Genitourinary system sites

Testis or spermatic cord (paratesticular). Recommendations for paratesticular primary tumors are primarily based on the results from cooperative group trials and a recent INSTRuCT consensus opinion.[122] Lesions occurring adjacent to the testis or spermatic cord and up to the internal inguinal ring should be removed by orchiectomy with resection of the spermatic cord, using an inguinal incision with proximal vascular control (i.e., radical orchiectomy).[123] Resection of hemiscrotal skin is required when there is tumor fixation or invasion. Hemiscrotectomy had been recommended by the COG, German groups, and Italian groups when a previous transscrotal biopsy had been performed. A retrospective German CWS study of 28 patients with embryonal rhabdomyosarcoma found a 5-year EFS rate of 91.7% in 12 patients with an initial transscrotal excision followed by hemiscrotectomy, while the 5-year EFS rate was 93.8% in 16 patients without subsequent hemiscrotectomy. All of these patients also received chemotherapy with vincristine, dactinomycin, an alkylating agent, and other agents.[124][Level of evidence C2] A retrospective study examined 842 patients with localized paratesticular rhabdomyosarcoma who were enrolled in COG, CWS, EpSSG, Italian Cooperative Group, and MMT studies from 1988 to 2013. Of all patients, 7.7% had a transscrotal resection; however, this surgical factor did not contribute to an inferior EFS in stratified univariable and multivariable analysis.[125] A COG study evaluated 279 patients with paratesticular rhabdomyosarcoma. The study also found that hemiscrotectomy did not improve outcome after transscrotal violation.[126][Level of evidence C1] These findings support the consensus statement from INSTRuCT that hemiscrotectomy is no longer recommended for scrotal violation.[122] The EpSSG RMS-2005 (NCT00379457) study enrolled 237 patients with paratesticular tumors. Seventy-five patients (32%) had an inappropriate first surgery, defined as tumorectomy without orchidectomy, transscrotal orchidectomy without an inguinal approach, or biopsy in a resectable tumor. These patients required intensified therapy to maintain excellent OS and EFS. Ten patients required additional local surgery and intensified chemotherapy.[127] For patients with incompletely removed paratesticular tumors that require RT, temporarily repositioning the contralateral testicle into the adjacent thigh before scrotal radiation may preserve hormone production; however, more data are needed.[128][Level of evidence C1] A retrospective review of 49 patients with paratestis rhabdomyosarcoma referred to Memorial Sloan Kettering Cancer Center found that 20 patients had scrotal violation as a part of their original surgery. Fifteen of these patients underwent salvage surgery or RT. Eleven of these patients had continuous PFS, whereas four of the five patients who were treated without a salvage procedure developed recurrent disease.[129][Level of evidence C2] Paratesticular tumors have a relatively high incidence of lymphatic spread (26% in IRS-I and IRS-II).[90] All patients with paratesticular primary tumors should have thin-cut abdominal and pelvic CT scans with intravenous contrast to evaluate nodal involvement. For patients who have Group I disease, are younger than 10 years, and in whom CT scans show no evidence of lymph node enlargement, retroperitoneal node biopsy/sampling is unnecessary, but a repeat CT scan every 3 months is recommended.[130,131] For patients with suggestive or positive CT scans, retroperitoneal, ipsilateral, infra-renal vein lymph node sampling of 10 to 12 nodes (but not formal node dissection) is recommended, and treatment is based on the findings of this procedure.[4,39,132] Patients with suspicious or documented retroperitoneal/pelvic lymph nodes require nodal RT. In patients aged 10 years and older, only 9% will have clinical or radiological evidence of retroperitoneal node enlargement. However, pathological evaluation has shown that imaging alone will miss 50% of nodal disease. Therefore, patients aged 10 years and older should have an ipsilateral, nerve-sparing retroperitoneal node dissection, regardless of imaging findings.[133] Staging ipsilateral retroperitoneal lymph node sampling is currently required for all children aged 10 years and older with paratesticular rhabdomyosarcoma on COG-STS studies. Many European investigators relied on radiographic, rather than surgical-pathological assessment, for retroperitoneal lymph node involvement.[123,130] European studies, as well as an international pooled data analysis, demonstrated worse outcomes in this patient population when surgical lymph node evaluation was not performed.[125,127,134] On the basis of these results and with the high relapse rate and worse EFS in Stage N0 patients, investigators from SIOP, EpSSG, and COG recommended surgical resection, in the form of ipsilateral retroperitoneal lymph node sampling of clinically normal nodes (not enlarged by CT or MRI), in patients aged 10 years and older with paratesticular rhabdomyosarcoma.[125] A consensus document regarding paratesticular rhabdomyosarcoma from all North American and European cooperative groups concurred that all patients aged 10 years or older should undergo ipsilateral, infra-renal vein, retroperitoneal surgical lymph node evaluation by sampling 7 to 12 nodes or a nerve-sparing dissection.[122] Evidence (lymph node sampling): RT should be considered for patients whose nodes are biopsy positive.

Testis or spermatic cord (paratesticular). Recommendations for paratesticular primary tumors are primarily based on the results from cooperative group trials and a recent INSTRuCT consensus opinion.[122] Lesions occurring adjacent to the testis or spermatic cord and up to the internal inguinal ring should be removed by orchiectomy with resection of the spermatic cord, using an inguinal incision with proximal vascular control (i.e., radical orchiectomy).[123] Resection of hemiscrotal skin is required when there is tumor fixation or invasion. Hemiscrotectomy had been recommended by the COG, German groups, and Italian groups when a previous transscrotal biopsy had been performed. A retrospective German CWS study of 28 patients with embryonal rhabdomyosarcoma found a 5-year EFS rate of 91.7% in 12 patients with an initial transscrotal excision followed by hemiscrotectomy, while the 5-year EFS rate was 93.8% in 16 patients without subsequent hemiscrotectomy. All of these patients also received chemotherapy with vincristine, dactinomycin, an alkylating agent, and other agents.[124][Level of evidence C2] A retrospective study examined 842 patients with localized paratesticular rhabdomyosarcoma who were enrolled in COG, CWS, EpSSG, Italian Cooperative Group, and MMT studies from 1988 to 2013. Of all patients, 7.7% had a transscrotal resection; however, this surgical factor did not contribute to an inferior EFS in stratified univariable and multivariable analysis.[125] A COG study evaluated 279 patients with paratesticular rhabdomyosarcoma. The study also found that hemiscrotectomy did not improve outcome after transscrotal violation.[126][Level of evidence C1] These findings support the consensus statement from INSTRuCT that hemiscrotectomy is no longer recommended for scrotal violation.[122] The EpSSG RMS-2005 (NCT00379457) study enrolled 237 patients with paratesticular tumors. Seventy-five patients (32%) had an inappropriate first surgery, defined as tumorectomy without orchidectomy, transscrotal orchidectomy without an inguinal approach, or biopsy in a resectable tumor. These patients required intensified therapy to maintain excellent OS and EFS. Ten patients required additional local surgery and intensified chemotherapy.[127] For patients with incompletely removed paratesticular tumors that require RT, temporarily repositioning the contralateral testicle into the adjacent thigh before scrotal radiation may preserve hormone production; however, more data are needed.[128][Level of evidence C1] A retrospective review of 49 patients with paratestis rhabdomyosarcoma referred to Memorial Sloan Kettering Cancer Center found that 20 patients had scrotal violation as a part of their original surgery. Fifteen of these patients underwent salvage surgery or RT. Eleven of these patients had continuous PFS, whereas four of the five patients who were treated without a salvage procedure developed recurrent disease.[129][Level of evidence C2] Paratesticular tumors have a relatively high incidence of lymphatic spread (26% in IRS-I and IRS-II).[90] All patients with paratesticular primary tumors should have thin-cut abdominal and pelvic CT scans with intravenous contrast to evaluate nodal involvement. For patients who have Group I disease, are younger than 10 years, and in whom CT scans show no evidence of lymph node enlargement, retroperitoneal node biopsy/sampling is unnecessary, but a repeat CT scan every 3 months is recommended.[130,131] For patients with suggestive or positive CT scans, retroperitoneal, ipsilateral, infra-renal vein lymph node sampling of 10 to 12 nodes (but not formal node dissection) is recommended, and treatment is based on the findings of this procedure.[4,39,132] Patients with suspicious or documented retroperitoneal/pelvic lymph nodes require nodal RT. In patients aged 10 years and older, only 9% will have clinical or radiological evidence of retroperitoneal node enlargement. However, pathological evaluation has shown that imaging alone will miss 50% of nodal disease. Therefore, patients aged 10 years and older should have an ipsilateral, nerve-sparing retroperitoneal node dissection, regardless of imaging findings.[133] Staging ipsilateral retroperitoneal lymph node sampling is currently required for all children aged 10 years and older with paratesticular rhabdomyosarcoma on COG-STS studies. Many European investigators relied on radiographic, rather than surgical-pathological assessment, for retroperitoneal lymph node involvement.[123,130] European studies, as well as an international pooled data analysis, demonstrated worse outcomes in this patient population when surgical lymph node evaluation was not performed.[125,127,134] On the basis of these results and with the high relapse rate and worse EFS in Stage N0 patients, investigators from SIOP, EpSSG, and COG recommended surgical resection, in the form of ipsilateral retroperitoneal lymph node sampling of clinically normal nodes (not enlarged by CT or MRI), in patients aged 10 years and older with paratesticular rhabdomyosarcoma.[125] A consensus document regarding paratesticular rhabdomyosarcoma from all North American and European cooperative groups concurred that all patients aged 10 years or older should undergo ipsilateral, infra-renal vein, retroperitoneal surgical lymph node evaluation by sampling 7 to 12 nodes or a nerve-sparing dissection.[122] Evidence (lymph node sampling): RT should be considered for patients whose nodes are biopsy positive.

In the SIOP-MMT-89 and -95 studies, patients with paratesticular rhabdomyosarcoma were evaluated with imaging but did not undergo routine ipsilateral lymph node sampling.[135][Level of evidence B4]

Testis or spermatic cord (paratesticular). Recommendations for paratesticular primary tumors are primarily based on the results from cooperative group trials and a recent INSTRuCT consensus opinion.[122] Lesions occurring adjacent to the testis or spermatic cord and up to the internal inguinal ring should be removed by orchiectomy with resection of the spermatic cord, using an inguinal incision with proximal vascular control (i.e., radical orchiectomy).[123] Resection of hemiscrotal skin is required when there is tumor fixation or invasion. Hemiscrotectomy had been recommended by the COG, German groups, and Italian groups when a previous transscrotal biopsy had been performed. A retrospective German CWS study of 28 patients with embryonal rhabdomyosarcoma found a 5-year EFS rate of 91.7% in 12 patients with an initial transscrotal excision followed by hemiscrotectomy, while the 5-year EFS rate was 93.8% in 16 patients without subsequent hemiscrotectomy. All of these patients also received chemotherapy with vincristine, dactinomycin, an alkylating agent, and other agents.[124][Level of evidence C2] A retrospective study examined 842 patients with localized paratesticular rhabdomyosarcoma who were enrolled in COG, CWS, EpSSG, Italian Cooperative Group, and MMT studies from 1988 to 2013. Of all patients, 7.7% had a transscrotal resection; however, this surgical factor did not contribute to an inferior EFS in stratified univariable and multivariable analysis.[125] A COG study evaluated 279 patients with paratesticular rhabdomyosarcoma. The study also found that hemiscrotectomy did not improve outcome after transscrotal violation.[126][Level of evidence C1] These findings support the consensus statement from INSTRuCT that hemiscrotectomy is no longer recommended for scrotal violation.[122] The EpSSG RMS-2005 (NCT00379457) study enrolled 237 patients with paratesticular tumors. Seventy-five patients (32%) had an inappropriate first surgery, defined as tumorectomy without orchidectomy, transscrotal orchidectomy without an inguinal approach, or biopsy in a resectable tumor. These patients required intensified therapy to maintain excellent OS and EFS. Ten patients required additional local surgery and intensified chemotherapy.[127] For patients with incompletely removed paratesticular tumors that require RT, temporarily repositioning the contralateral testicle into the adjacent thigh before scrotal radiation may preserve hormone production; however, more data are needed.[128][Level of evidence C1] A retrospective review of 49 patients with paratestis rhabdomyosarcoma referred to Memorial Sloan Kettering Cancer Center found that 20 patients had scrotal violation as a part of their original surgery. Fifteen of these patients underwent salvage surgery or RT. Eleven of these patients had continuous PFS, whereas four of the five patients who were treated without a salvage procedure developed recurrent disease.[129][Level of evidence C2] Paratesticular tumors have a relatively high incidence of lymphatic spread (26% in IRS-I and IRS-II).[90] All patients with paratesticular primary tumors should have thin-cut abdominal and pelvic CT scans with intravenous contrast to evaluate nodal involvement. For patients who have Group I disease, are younger than 10 years, and in whom CT scans show no evidence of lymph node enlargement, retroperitoneal node biopsy/sampling is unnecessary, but a repeat CT scan every 3 months is recommended.[130,131] For patients with suggestive or positive CT scans, retroperitoneal, ipsilateral, infra-renal vein lymph node sampling of 10 to 12 nodes (but not formal node dissection) is recommended, and treatment is based on the findings of this procedure.[4,39,132] Patients with suspicious or documented retroperitoneal/pelvic lymph nodes require nodal RT. In patients aged 10 years and older, only 9% will have clinical or radiological evidence of retroperitoneal node enlargement. However, pathological evaluation has shown that imaging alone will miss 50% of nodal disease. Therefore, patients aged 10 years and older should have an ipsilateral, nerve-sparing retroperitoneal node dissection, regardless of imaging findings.[133] Staging ipsilateral retroperitoneal lymph node sampling is currently required for all children aged 10 years and older with paratesticular rhabdomyosarcoma on COG-STS studies. Many European investigators relied on radiographic, rather than surgical-pathological assessment, for retroperitoneal lymph node involvement.[123,130] European studies, as well as an international pooled data analysis, demonstrated worse outcomes in this patient population when surgical lymph node evaluation was not performed.[125,127,134] On the basis of these results and with the high relapse rate and worse EFS in Stage N0 patients, investigators from SIOP, EpSSG, and COG recommended surgical resection, in the form of ipsilateral retroperitoneal lymph node sampling of clinically normal nodes (not enlarged by CT or MRI), in patients aged 10 years and older with paratesticular rhabdomyosarcoma.[125] A consensus document regarding paratesticular rhabdomyosarcoma from all North American and European cooperative groups concurred that all patients aged 10 years or older should undergo ipsilateral, infra-renal vein, retroperitoneal surgical lymph node evaluation by sampling 7 to 12 nodes or a nerve-sparing dissection.[122] Evidence (lymph node sampling): RT should be considered for patients whose nodes are biopsy positive. › In the SIOP-MMT-89 and -95 studies, patients with paratesticular rhabdomyosarcoma were evaluated with imaging but did not undergo routine ipsilateral lymph node sampling.[135][Level of evidence B4]

Thirty-one percent of Stage N0 patients aged 10 years and older developed node relapse, compared with 8% of Stage N0 patients younger than 10 years (P = .0005).

Testis or spermatic cord (paratesticular). Recommendations for paratesticular primary tumors are primarily based on the results from cooperative group trials and a recent INSTRuCT consensus opinion.[122] Lesions occurring adjacent to the testis or spermatic cord and up to the internal inguinal ring should be removed by orchiectomy with resection of the spermatic cord, using an inguinal incision with proximal vascular control (i.e., radical orchiectomy).[123] Resection of hemiscrotal skin is required when there is tumor fixation or invasion. Hemiscrotectomy had been recommended by the COG, German groups, and Italian groups when a previous transscrotal biopsy had been performed. A retrospective German CWS study of 28 patients with embryonal rhabdomyosarcoma found a 5-year EFS rate of 91.7% in 12 patients with an initial transscrotal excision followed by hemiscrotectomy, while the 5-year EFS rate was 93.8% in 16 patients without subsequent hemiscrotectomy. All of these patients also received chemotherapy with vincristine, dactinomycin, an alkylating agent, and other agents.[124][Level of evidence C2] A retrospective study examined 842 patients with localized paratesticular rhabdomyosarcoma who were enrolled in COG, CWS, EpSSG, Italian Cooperative Group, and MMT studies from 1988 to 2013. Of all patients, 7.7% had a transscrotal resection; however, this surgical factor did not contribute to an inferior EFS in stratified univariable and multivariable analysis.[125] A COG study evaluated 279 patients with paratesticular rhabdomyosarcoma. The study also found that hemiscrotectomy did not improve outcome after transscrotal violation.[126][Level of evidence C1] These findings support the consensus statement from INSTRuCT that hemiscrotectomy is no longer recommended for scrotal violation.[122] The EpSSG RMS-2005 (NCT00379457) study enrolled 237 patients with paratesticular tumors. Seventy-five patients (32%) had an inappropriate first surgery, defined as tumorectomy without orchidectomy, transscrotal orchidectomy without an inguinal approach, or biopsy in a resectable tumor. These patients required intensified therapy to maintain excellent OS and EFS. Ten patients required additional local surgery and intensified chemotherapy.[127] For patients with incompletely removed paratesticular tumors that require RT, temporarily repositioning the contralateral testicle into the adjacent thigh before scrotal radiation may preserve hormone production; however, more data are needed.[128][Level of evidence C1] A retrospective review of 49 patients with paratestis rhabdomyosarcoma referred to Memorial Sloan Kettering Cancer Center found that 20 patients had scrotal violation as a part of their original surgery. Fifteen of these patients underwent salvage surgery or RT. Eleven of these patients had continuous PFS, whereas four of the five patients who were treated without a salvage procedure developed recurrent disease.[129][Level of evidence C2] Paratesticular tumors have a relatively high incidence of lymphatic spread (26% in IRS-I and IRS-II).[90] All patients with paratesticular primary tumors should have thin-cut abdominal and pelvic CT scans with intravenous contrast to evaluate nodal involvement. For patients who have Group I disease, are younger than 10 years, and in whom CT scans show no evidence of lymph node enlargement, retroperitoneal node biopsy/sampling is unnecessary, but a repeat CT scan every 3 months is recommended.[130,131] For patients with suggestive or positive CT scans, retroperitoneal, ipsilateral, infra-renal vein lymph node sampling of 10 to 12 nodes (but not formal node dissection) is recommended, and treatment is based on the findings of this procedure.[4,39,132] Patients with suspicious or documented retroperitoneal/pelvic lymph nodes require nodal RT. In patients aged 10 years and older, only 9% will have clinical or radiological evidence of retroperitoneal node enlargement. However, pathological evaluation has shown that imaging alone will miss 50% of nodal disease. Therefore, patients aged 10 years and older should have an ipsilateral, nerve-sparing retroperitoneal node dissection, regardless of imaging findings.[133] Staging ipsilateral retroperitoneal lymph node sampling is currently required for all children aged 10 years and older with paratesticular rhabdomyosarcoma on COG-STS studies. Many European investigators relied on radiographic, rather than surgical-pathological assessment, for retroperitoneal lymph node involvement.[123,130] European studies, as well as an international pooled data analysis, demonstrated worse outcomes in this patient population when surgical lymph node evaluation was not performed.[125,127,134] On the basis of these results and with the high relapse rate and worse EFS in Stage N0 patients, investigators from SIOP, EpSSG, and COG recommended surgical resection, in the form of ipsilateral retroperitoneal lymph node sampling of clinically normal nodes (not enlarged by CT or MRI), in patients aged 10 years and older with paratesticular rhabdomyosarcoma.[125] A consensus document regarding paratesticular rhabdomyosarcoma from all North American and European cooperative groups concurred that all patients aged 10 years or older should undergo ipsilateral, infra-renal vein, retroperitoneal surgical lymph node evaluation by sampling 7 to 12 nodes or a nerve-sparing dissection.[122] Evidence (lymph node sampling): RT should be considered for patients whose nodes are biopsy positive. › In the SIOP-MMT-89 and -95 studies, patients with paratesticular rhabdomyosarcoma were evaluated with imaging but did not undergo routine ipsilateral lymph node sampling.[135][Level of evidence B4]

The SIOP-MMT group subsequently recommended ipsilateral lymph node sampling for all patients aged 10 years and older.

Testis or spermatic cord (paratesticular). Recommendations for paratesticular primary tumors are primarily based on the results from cooperative group trials and a recent INSTRuCT consensus opinion.[122] Lesions occurring adjacent to the testis or spermatic cord and up to the internal inguinal ring should be removed by orchiectomy with resection of the spermatic cord, using an inguinal incision with proximal vascular control (i.e., radical orchiectomy).[123] Resection of hemiscrotal skin is required when there is tumor fixation or invasion. Hemiscrotectomy had been recommended by the COG, German groups, and Italian groups when a previous transscrotal biopsy had been performed. A retrospective German CWS study of 28 patients with embryonal rhabdomyosarcoma found a 5-year EFS rate of 91.7% in 12 patients with an initial transscrotal excision followed by hemiscrotectomy, while the 5-year EFS rate was 93.8% in 16 patients without subsequent hemiscrotectomy. All of these patients also received chemotherapy with vincristine, dactinomycin, an alkylating agent, and other agents.[124][Level of evidence C2] A retrospective study examined 842 patients with localized paratesticular rhabdomyosarcoma who were enrolled in COG, CWS, EpSSG, Italian Cooperative Group, and MMT studies from 1988 to 2013. Of all patients, 7.7% had a transscrotal resection; however, this surgical factor did not contribute to an inferior EFS in stratified univariable and multivariable analysis.[125] A COG study evaluated 279 patients with paratesticular rhabdomyosarcoma. The study also found that hemiscrotectomy did not improve outcome after transscrotal violation.[126][Level of evidence C1] These findings support the consensus statement from INSTRuCT that hemiscrotectomy is no longer recommended for scrotal violation.[122] The EpSSG RMS-2005 (NCT00379457) study enrolled 237 patients with paratesticular tumors. Seventy-five patients (32%) had an inappropriate first surgery, defined as tumorectomy without orchidectomy, transscrotal orchidectomy without an inguinal approach, or biopsy in a resectable tumor. These patients required intensified therapy to maintain excellent OS and EFS. Ten patients required additional local surgery and intensified chemotherapy.[127] For patients with incompletely removed paratesticular tumors that require RT, temporarily repositioning the contralateral testicle into the adjacent thigh before scrotal radiation may preserve hormone production; however, more data are needed.[128][Level of evidence C1] A retrospective review of 49 patients with paratestis rhabdomyosarcoma referred to Memorial Sloan Kettering Cancer Center found that 20 patients had scrotal violation as a part of their original surgery. Fifteen of these patients underwent salvage surgery or RT. Eleven of these patients had continuous PFS, whereas four of the five patients who were treated without a salvage procedure developed recurrent disease.[129][Level of evidence C2] Paratesticular tumors have a relatively high incidence of lymphatic spread (26% in IRS-I and IRS-II).[90] All patients with paratesticular primary tumors should have thin-cut abdominal and pelvic CT scans with intravenous contrast to evaluate nodal involvement. For patients who have Group I disease, are younger than 10 years, and in whom CT scans show no evidence of lymph node enlargement, retroperitoneal node biopsy/sampling is unnecessary, but a repeat CT scan every 3 months is recommended.[130,131] For patients with suggestive or positive CT scans, retroperitoneal, ipsilateral, infra-renal vein lymph node sampling of 10 to 12 nodes (but not formal node dissection) is recommended, and treatment is based on the findings of this procedure.[4,39,132] Patients with suspicious or documented retroperitoneal/pelvic lymph nodes require nodal RT. In patients aged 10 years and older, only 9% will have clinical or radiological evidence of retroperitoneal node enlargement. However, pathological evaluation has shown that imaging alone will miss 50% of nodal disease. Therefore, patients aged 10 years and older should have an ipsilateral, nerve-sparing retroperitoneal node dissection, regardless of imaging findings.[133] Staging ipsilateral retroperitoneal lymph node sampling is currently required for all children aged 10 years and older with paratesticular rhabdomyosarcoma on COG-STS studies. Many European investigators relied on radiographic, rather than surgical-pathological assessment, for retroperitoneal lymph node involvement.[123,130] European studies, as well as an international pooled data analysis, demonstrated worse outcomes in this patient population when surgical lymph node evaluation was not performed.[125,127,134] On the basis of these results and with the high relapse rate and worse EFS in Stage N0 patients, investigators from SIOP, EpSSG, and COG recommended surgical resection, in the form of ipsilateral retroperitoneal lymph node sampling of clinically normal nodes (not enlarged by CT or MRI), in patients aged 10 years and older with paratesticular rhabdomyosarcoma.[125] A consensus document regarding paratesticular rhabdomyosarcoma from all North American and European cooperative groups concurred that all patients aged 10 years or older should undergo ipsilateral, infra-renal vein, retroperitoneal surgical lymph node evaluation by sampling 7 to 12 nodes or a nerve-sparing dissection.[122] Evidence (lymph node sampling): RT should be considered for patients whose nodes are biopsy positive.

The North American and European cooperative groups performed a pooled analysis of 12 studies from five cooperative groups.[125][Level of evidence C1]

Testis or spermatic cord (paratesticular). Recommendations for paratesticular primary tumors are primarily based on the results from cooperative group trials and a recent INSTRuCT consensus opinion.[122] Lesions occurring adjacent to the testis or spermatic cord and up to the internal inguinal ring should be removed by orchiectomy with resection of the spermatic cord, using an inguinal incision with proximal vascular control (i.e., radical orchiectomy).[123] Resection of hemiscrotal skin is required when there is tumor fixation or invasion. Hemiscrotectomy had been recommended by the COG, German groups, and Italian groups when a previous transscrotal biopsy had been performed. A retrospective German CWS study of 28 patients with embryonal rhabdomyosarcoma found a 5-year EFS rate of 91.7% in 12 patients with an initial transscrotal excision followed by hemiscrotectomy, while the 5-year EFS rate was 93.8% in 16 patients without subsequent hemiscrotectomy. All of these patients also received chemotherapy with vincristine, dactinomycin, an alkylating agent, and other agents.[124][Level of evidence C2] A retrospective study examined 842 patients with localized paratesticular rhabdomyosarcoma who were enrolled in COG, CWS, EpSSG, Italian Cooperative Group, and MMT studies from 1988 to 2013. Of all patients, 7.7% had a transscrotal resection; however, this surgical factor did not contribute to an inferior EFS in stratified univariable and multivariable analysis.[125] A COG study evaluated 279 patients with paratesticular rhabdomyosarcoma. The study also found that hemiscrotectomy did not improve outcome after transscrotal violation.[126][Level of evidence C1] These findings support the consensus statement from INSTRuCT that hemiscrotectomy is no longer recommended for scrotal violation.[122] The EpSSG RMS-2005 (NCT00379457) study enrolled 237 patients with paratesticular tumors. Seventy-five patients (32%) had an inappropriate first surgery, defined as tumorectomy without orchidectomy, transscrotal orchidectomy without an inguinal approach, or biopsy in a resectable tumor. These patients required intensified therapy to maintain excellent OS and EFS. Ten patients required additional local surgery and intensified chemotherapy.[127] For patients with incompletely removed paratesticular tumors that require RT, temporarily repositioning the contralateral testicle into the adjacent thigh before scrotal radiation may preserve hormone production; however, more data are needed.[128][Level of evidence C1] A retrospective review of 49 patients with paratestis rhabdomyosarcoma referred to Memorial Sloan Kettering Cancer Center found that 20 patients had scrotal violation as a part of their original surgery. Fifteen of these patients underwent salvage surgery or RT. Eleven of these patients had continuous PFS, whereas four of the five patients who were treated without a salvage procedure developed recurrent disease.[129][Level of evidence C2] Paratesticular tumors have a relatively high incidence of lymphatic spread (26% in IRS-I and IRS-II).[90] All patients with paratesticular primary tumors should have thin-cut abdominal and pelvic CT scans with intravenous contrast to evaluate nodal involvement. For patients who have Group I disease, are younger than 10 years, and in whom CT scans show no evidence of lymph node enlargement, retroperitoneal node biopsy/sampling is unnecessary, but a repeat CT scan every 3 months is recommended.[130,131] For patients with suggestive or positive CT scans, retroperitoneal, ipsilateral, infra-renal vein lymph node sampling of 10 to 12 nodes (but not formal node dissection) is recommended, and treatment is based on the findings of this procedure.[4,39,132] Patients with suspicious or documented retroperitoneal/pelvic lymph nodes require nodal RT. In patients aged 10 years and older, only 9% will have clinical or radiological evidence of retroperitoneal node enlargement. However, pathological evaluation has shown that imaging alone will miss 50% of nodal disease. Therefore, patients aged 10 years and older should have an ipsilateral, nerve-sparing retroperitoneal node dissection, regardless of imaging findings.[133] Staging ipsilateral retroperitoneal lymph node sampling is currently required for all children aged 10 years and older with paratesticular rhabdomyosarcoma on COG-STS studies. Many European investigators relied on radiographic, rather than surgical-pathological assessment, for retroperitoneal lymph node involvement.[123,130] European studies, as well as an international pooled data analysis, demonstrated worse outcomes in this patient population when surgical lymph node evaluation was not performed.[125,127,134] On the basis of these results and with the high relapse rate and worse EFS in Stage N0 patients, investigators from SIOP, EpSSG, and COG recommended surgical resection, in the form of ipsilateral retroperitoneal lymph node sampling of clinically normal nodes (not enlarged by CT or MRI), in patients aged 10 years and older with paratesticular rhabdomyosarcoma.[125] A consensus document regarding paratesticular rhabdomyosarcoma from all North American and European cooperative groups concurred that all patients aged 10 years or older should undergo ipsilateral, infra-renal vein, retroperitoneal surgical lymph node evaluation by sampling 7 to 12 nodes or a nerve-sparing dissection.[122] Evidence (lymph node sampling): RT should be considered for patients whose nodes are biopsy positive. › The North American and European cooperative groups performed a pooled analysis of 12 studies from five cooperative groups.[125][Level of evidence C1]

For patients with paratesticular rhabdomyosarcoma (N = 842), age 10 years and older at diagnosis and tumor size larger than 5 cm were unfavorable prognostic features.

Testis or spermatic cord (paratesticular). Recommendations for paratesticular primary tumors are primarily based on the results from cooperative group trials and a recent INSTRuCT consensus opinion.[122] Lesions occurring adjacent to the testis or spermatic cord and up to the internal inguinal ring should be removed by orchiectomy with resection of the spermatic cord, using an inguinal incision with proximal vascular control (i.e., radical orchiectomy).[123] Resection of hemiscrotal skin is required when there is tumor fixation or invasion. Hemiscrotectomy had been recommended by the COG, German groups, and Italian groups when a previous transscrotal biopsy had been performed. A retrospective German CWS study of 28 patients with embryonal rhabdomyosarcoma found a 5-year EFS rate of 91.7% in 12 patients with an initial transscrotal excision followed by hemiscrotectomy, while the 5-year EFS rate was 93.8% in 16 patients without subsequent hemiscrotectomy. All of these patients also received chemotherapy with vincristine, dactinomycin, an alkylating agent, and other agents.[124][Level of evidence C2] A retrospective study examined 842 patients with localized paratesticular rhabdomyosarcoma who were enrolled in COG, CWS, EpSSG, Italian Cooperative Group, and MMT studies from 1988 to 2013. Of all patients, 7.7% had a transscrotal resection; however, this surgical factor did not contribute to an inferior EFS in stratified univariable and multivariable analysis.[125] A COG study evaluated 279 patients with paratesticular rhabdomyosarcoma. The study also found that hemiscrotectomy did not improve outcome after transscrotal violation.[126][Level of evidence C1] These findings support the consensus statement from INSTRuCT that hemiscrotectomy is no longer recommended for scrotal violation.[122] The EpSSG RMS-2005 (NCT00379457) study enrolled 237 patients with paratesticular tumors. Seventy-five patients (32%) had an inappropriate first surgery, defined as tumorectomy without orchidectomy, transscrotal orchidectomy without an inguinal approach, or biopsy in a resectable tumor. These patients required intensified therapy to maintain excellent OS and EFS. Ten patients required additional local surgery and intensified chemotherapy.[127] For patients with incompletely removed paratesticular tumors that require RT, temporarily repositioning the contralateral testicle into the adjacent thigh before scrotal radiation may preserve hormone production; however, more data are needed.[128][Level of evidence C1] A retrospective review of 49 patients with paratestis rhabdomyosarcoma referred to Memorial Sloan Kettering Cancer Center found that 20 patients had scrotal violation as a part of their original surgery. Fifteen of these patients underwent salvage surgery or RT. Eleven of these patients had continuous PFS, whereas four of the five patients who were treated without a salvage procedure developed recurrent disease.[129][Level of evidence C2] Paratesticular tumors have a relatively high incidence of lymphatic spread (26% in IRS-I and IRS-II).[90] All patients with paratesticular primary tumors should have thin-cut abdominal and pelvic CT scans with intravenous contrast to evaluate nodal involvement. For patients who have Group I disease, are younger than 10 years, and in whom CT scans show no evidence of lymph node enlargement, retroperitoneal node biopsy/sampling is unnecessary, but a repeat CT scan every 3 months is recommended.[130,131] For patients with suggestive or positive CT scans, retroperitoneal, ipsilateral, infra-renal vein lymph node sampling of 10 to 12 nodes (but not formal node dissection) is recommended, and treatment is based on the findings of this procedure.[4,39,132] Patients with suspicious or documented retroperitoneal/pelvic lymph nodes require nodal RT. In patients aged 10 years and older, only 9% will have clinical or radiological evidence of retroperitoneal node enlargement. However, pathological evaluation has shown that imaging alone will miss 50% of nodal disease. Therefore, patients aged 10 years and older should have an ipsilateral, nerve-sparing retroperitoneal node dissection, regardless of imaging findings.[133] Staging ipsilateral retroperitoneal lymph node sampling is currently required for all children aged 10 years and older with paratesticular rhabdomyosarcoma on COG-STS studies. Many European investigators relied on radiographic, rather than surgical-pathological assessment, for retroperitoneal lymph node involvement.[123,130] European studies, as well as an international pooled data analysis, demonstrated worse outcomes in this patient population when surgical lymph node evaluation was not performed.[125,127,134] On the basis of these results and with the high relapse rate and worse EFS in Stage N0 patients, investigators from SIOP, EpSSG, and COG recommended surgical resection, in the form of ipsilateral retroperitoneal lymph node sampling of clinically normal nodes (not enlarged by CT or MRI), in patients aged 10 years and older with paratesticular rhabdomyosarcoma.[125] A consensus document regarding paratesticular rhabdomyosarcoma from all North American and European cooperative groups concurred that all patients aged 10 years or older should undergo ipsilateral, infra-renal vein, retroperitoneal surgical lymph node evaluation by sampling 7 to 12 nodes or a nerve-sparing dissection.[122] Evidence (lymph node sampling): RT should be considered for patients whose nodes are biopsy positive. › The North American and European cooperative groups performed a pooled analysis of 12 studies from five cooperative groups.[125][Level of evidence C1]

At 7.5 years of median follow-up, the EFS rate was 87.7%, and the OS rate was 94.8% at 5 years.

Testis or spermatic cord (paratesticular). Recommendations for paratesticular primary tumors are primarily based on the results from cooperative group trials and a recent INSTRuCT consensus opinion.[122] Lesions occurring adjacent to the testis or spermatic cord and up to the internal inguinal ring should be removed by orchiectomy with resection of the spermatic cord, using an inguinal incision with proximal vascular control (i.e., radical orchiectomy).[123] Resection of hemiscrotal skin is required when there is tumor fixation or invasion. Hemiscrotectomy had been recommended by the COG, German groups, and Italian groups when a previous transscrotal biopsy had been performed. A retrospective German CWS study of 28 patients with embryonal rhabdomyosarcoma found a 5-year EFS rate of 91.7% in 12 patients with an initial transscrotal excision followed by hemiscrotectomy, while the 5-year EFS rate was 93.8% in 16 patients without subsequent hemiscrotectomy. All of these patients also received chemotherapy with vincristine, dactinomycin, an alkylating agent, and other agents.[124][Level of evidence C2] A retrospective study examined 842 patients with localized paratesticular rhabdomyosarcoma who were enrolled in COG, CWS, EpSSG, Italian Cooperative Group, and MMT studies from 1988 to 2013. Of all patients, 7.7% had a transscrotal resection; however, this surgical factor did not contribute to an inferior EFS in stratified univariable and multivariable analysis.[125] A COG study evaluated 279 patients with paratesticular rhabdomyosarcoma. The study also found that hemiscrotectomy did not improve outcome after transscrotal violation.[126][Level of evidence C1] These findings support the consensus statement from INSTRuCT that hemiscrotectomy is no longer recommended for scrotal violation.[122] The EpSSG RMS-2005 (NCT00379457) study enrolled 237 patients with paratesticular tumors. Seventy-five patients (32%) had an inappropriate first surgery, defined as tumorectomy without orchidectomy, transscrotal orchidectomy without an inguinal approach, or biopsy in a resectable tumor. These patients required intensified therapy to maintain excellent OS and EFS. Ten patients required additional local surgery and intensified chemotherapy.[127] For patients with incompletely removed paratesticular tumors that require RT, temporarily repositioning the contralateral testicle into the adjacent thigh before scrotal radiation may preserve hormone production; however, more data are needed.[128][Level of evidence C1] A retrospective review of 49 patients with paratestis rhabdomyosarcoma referred to Memorial Sloan Kettering Cancer Center found that 20 patients had scrotal violation as a part of their original surgery. Fifteen of these patients underwent salvage surgery or RT. Eleven of these patients had continuous PFS, whereas four of the five patients who were treated without a salvage procedure developed recurrent disease.[129][Level of evidence C2] Paratesticular tumors have a relatively high incidence of lymphatic spread (26% in IRS-I and IRS-II).[90] All patients with paratesticular primary tumors should have thin-cut abdominal and pelvic CT scans with intravenous contrast to evaluate nodal involvement. For patients who have Group I disease, are younger than 10 years, and in whom CT scans show no evidence of lymph node enlargement, retroperitoneal node biopsy/sampling is unnecessary, but a repeat CT scan every 3 months is recommended.[130,131] For patients with suggestive or positive CT scans, retroperitoneal, ipsilateral, infra-renal vein lymph node sampling of 10 to 12 nodes (but not formal node dissection) is recommended, and treatment is based on the findings of this procedure.[4,39,132] Patients with suspicious or documented retroperitoneal/pelvic lymph nodes require nodal RT. In patients aged 10 years and older, only 9% will have clinical or radiological evidence of retroperitoneal node enlargement. However, pathological evaluation has shown that imaging alone will miss 50% of nodal disease. Therefore, patients aged 10 years and older should have an ipsilateral, nerve-sparing retroperitoneal node dissection, regardless of imaging findings.[133] Staging ipsilateral retroperitoneal lymph node sampling is currently required for all children aged 10 years and older with paratesticular rhabdomyosarcoma on COG-STS studies. Many European investigators relied on radiographic, rather than surgical-pathological assessment, for retroperitoneal lymph node involvement.[123,130] European studies, as well as an international pooled data analysis, demonstrated worse outcomes in this patient population when surgical lymph node evaluation was not performed.[125,127,134] On the basis of these results and with the high relapse rate and worse EFS in Stage N0 patients, investigators from SIOP, EpSSG, and COG recommended surgical resection, in the form of ipsilateral retroperitoneal lymph node sampling of clinically normal nodes (not enlarged by CT or MRI), in patients aged 10 years and older with paratesticular rhabdomyosarcoma.[125] A consensus document regarding paratesticular rhabdomyosarcoma from all North American and European cooperative groups concurred that all patients aged 10 years or older should undergo ipsilateral, infra-renal vein, retroperitoneal surgical lymph node evaluation by sampling 7 to 12 nodes or a nerve-sparing dissection.[122] Evidence (lymph node sampling): RT should be considered for patients whose nodes are biopsy positive. › The North American and European cooperative groups performed a pooled analysis of 12 studies from five cooperative groups.[125][Level of evidence C1]

The only treatment variable that was associated with EFS in patients aged 10 years or older was surgical assessment of regional nodes, which may most accurately identify patients who can benefit from RT.

Testis or spermatic cord (paratesticular). Recommendations for paratesticular primary tumors are primarily based on the results from cooperative group trials and a recent INSTRuCT consensus opinion.[122] Lesions occurring adjacent to the testis or spermatic cord and up to the internal inguinal ring should be removed by orchiectomy with resection of the spermatic cord, using an inguinal incision with proximal vascular control (i.e., radical orchiectomy).[123] Resection of hemiscrotal skin is required when there is tumor fixation or invasion. Hemiscrotectomy had been recommended by the COG, German groups, and Italian groups when a previous transscrotal biopsy had been performed. A retrospective German CWS study of 28 patients with embryonal rhabdomyosarcoma found a 5-year EFS rate of 91.7% in 12 patients with an initial transscrotal excision followed by hemiscrotectomy, while the 5-year EFS rate was 93.8% in 16 patients without subsequent hemiscrotectomy. All of these patients also received chemotherapy with vincristine, dactinomycin, an alkylating agent, and other agents.[124][Level of evidence C2] A retrospective study examined 842 patients with localized paratesticular rhabdomyosarcoma who were enrolled in COG, CWS, EpSSG, Italian Cooperative Group, and MMT studies from 1988 to 2013. Of all patients, 7.7% had a transscrotal resection; however, this surgical factor did not contribute to an inferior EFS in stratified univariable and multivariable analysis.[125] A COG study evaluated 279 patients with paratesticular rhabdomyosarcoma. The study also found that hemiscrotectomy did not improve outcome after transscrotal violation.[126][Level of evidence C1] These findings support the consensus statement from INSTRuCT that hemiscrotectomy is no longer recommended for scrotal violation.[122] The EpSSG RMS-2005 (NCT00379457) study enrolled 237 patients with paratesticular tumors. Seventy-five patients (32%) had an inappropriate first surgery, defined as tumorectomy without orchidectomy, transscrotal orchidectomy without an inguinal approach, or biopsy in a resectable tumor. These patients required intensified therapy to maintain excellent OS and EFS. Ten patients required additional local surgery and intensified chemotherapy.[127] For patients with incompletely removed paratesticular tumors that require RT, temporarily repositioning the contralateral testicle into the adjacent thigh before scrotal radiation may preserve hormone production; however, more data are needed.[128][Level of evidence C1] A retrospective review of 49 patients with paratestis rhabdomyosarcoma referred to Memorial Sloan Kettering Cancer Center found that 20 patients had scrotal violation as a part of their original surgery. Fifteen of these patients underwent salvage surgery or RT. Eleven of these patients had continuous PFS, whereas four of the five patients who were treated without a salvage procedure developed recurrent disease.[129][Level of evidence C2] Paratesticular tumors have a relatively high incidence of lymphatic spread (26% in IRS-I and IRS-II).[90] All patients with paratesticular primary tumors should have thin-cut abdominal and pelvic CT scans with intravenous contrast to evaluate nodal involvement. For patients who have Group I disease, are younger than 10 years, and in whom CT scans show no evidence of lymph node enlargement, retroperitoneal node biopsy/sampling is unnecessary, but a repeat CT scan every 3 months is recommended.[130,131] For patients with suggestive or positive CT scans, retroperitoneal, ipsilateral, infra-renal vein lymph node sampling of 10 to 12 nodes (but not formal node dissection) is recommended, and treatment is based on the findings of this procedure.[4,39,132] Patients with suspicious or documented retroperitoneal/pelvic lymph nodes require nodal RT. In patients aged 10 years and older, only 9% will have clinical or radiological evidence of retroperitoneal node enlargement. However, pathological evaluation has shown that imaging alone will miss 50% of nodal disease. Therefore, patients aged 10 years and older should have an ipsilateral, nerve-sparing retroperitoneal node dissection, regardless of imaging findings.[133] Staging ipsilateral retroperitoneal lymph node sampling is currently required for all children aged 10 years and older with paratesticular rhabdomyosarcoma on COG-STS studies. Many European investigators relied on radiographic, rather than surgical-pathological assessment, for retroperitoneal lymph node involvement.[123,130] European studies, as well as an international pooled data analysis, demonstrated worse outcomes in this patient population when surgical lymph node evaluation was not performed.[125,127,134] On the basis of these results and with the high relapse rate and worse EFS in Stage N0 patients, investigators from SIOP, EpSSG, and COG recommended surgical resection, in the form of ipsilateral retroperitoneal lymph node sampling of clinically normal nodes (not enlarged by CT or MRI), in patients aged 10 years and older with paratesticular rhabdomyosarcoma.[125] A consensus document regarding paratesticular rhabdomyosarcoma from all North American and European cooperative groups concurred that all patients aged 10 years or older should undergo ipsilateral, infra-renal vein, retroperitoneal surgical lymph node evaluation by sampling 7 to 12 nodes or a nerve-sparing dissection.[122] Evidence (lymph node sampling): RT should be considered for patients whose nodes are biopsy positive.

In the EpSSG RMS-2005 (NCT00379457) cooperative group study (n = 237) of patients with paratesticular rhabdomyosarcoma, retroperitoneal lymph node staging was based on conventional imaging with ultrasonography, CT, or MRI, not systematic surgical staging.[127][Level of evidence B4]

Testis or spermatic cord (paratesticular). Recommendations for paratesticular primary tumors are primarily based on the results from cooperative group trials and a recent INSTRuCT consensus opinion.[122] Lesions occurring adjacent to the testis or spermatic cord and up to the internal inguinal ring should be removed by orchiectomy with resection of the spermatic cord, using an inguinal incision with proximal vascular control (i.e., radical orchiectomy).[123] Resection of hemiscrotal skin is required when there is tumor fixation or invasion. Hemiscrotectomy had been recommended by the COG, German groups, and Italian groups when a previous transscrotal biopsy had been performed. A retrospective German CWS study of 28 patients with embryonal rhabdomyosarcoma found a 5-year EFS rate of 91.7% in 12 patients with an initial transscrotal excision followed by hemiscrotectomy, while the 5-year EFS rate was 93.8% in 16 patients without subsequent hemiscrotectomy. All of these patients also received chemotherapy with vincristine, dactinomycin, an alkylating agent, and other agents.[124][Level of evidence C2] A retrospective study examined 842 patients with localized paratesticular rhabdomyosarcoma who were enrolled in COG, CWS, EpSSG, Italian Cooperative Group, and MMT studies from 1988 to 2013. Of all patients, 7.7% had a transscrotal resection; however, this surgical factor did not contribute to an inferior EFS in stratified univariable and multivariable analysis.[125] A COG study evaluated 279 patients with paratesticular rhabdomyosarcoma. The study also found that hemiscrotectomy did not improve outcome after transscrotal violation.[126][Level of evidence C1] These findings support the consensus statement from INSTRuCT that hemiscrotectomy is no longer recommended for scrotal violation.[122] The EpSSG RMS-2005 (NCT00379457) study enrolled 237 patients with paratesticular tumors. Seventy-five patients (32%) had an inappropriate first surgery, defined as tumorectomy without orchidectomy, transscrotal orchidectomy without an inguinal approach, or biopsy in a resectable tumor. These patients required intensified therapy to maintain excellent OS and EFS. Ten patients required additional local surgery and intensified chemotherapy.[127] For patients with incompletely removed paratesticular tumors that require RT, temporarily repositioning the contralateral testicle into the adjacent thigh before scrotal radiation may preserve hormone production; however, more data are needed.[128][Level of evidence C1] A retrospective review of 49 patients with paratestis rhabdomyosarcoma referred to Memorial Sloan Kettering Cancer Center found that 20 patients had scrotal violation as a part of their original surgery. Fifteen of these patients underwent salvage surgery or RT. Eleven of these patients had continuous PFS, whereas four of the five patients who were treated without a salvage procedure developed recurrent disease.[129][Level of evidence C2] Paratesticular tumors have a relatively high incidence of lymphatic spread (26% in IRS-I and IRS-II).[90] All patients with paratesticular primary tumors should have thin-cut abdominal and pelvic CT scans with intravenous contrast to evaluate nodal involvement. For patients who have Group I disease, are younger than 10 years, and in whom CT scans show no evidence of lymph node enlargement, retroperitoneal node biopsy/sampling is unnecessary, but a repeat CT scan every 3 months is recommended.[130,131] For patients with suggestive or positive CT scans, retroperitoneal, ipsilateral, infra-renal vein lymph node sampling of 10 to 12 nodes (but not formal node dissection) is recommended, and treatment is based on the findings of this procedure.[4,39,132] Patients with suspicious or documented retroperitoneal/pelvic lymph nodes require nodal RT. In patients aged 10 years and older, only 9% will have clinical or radiological evidence of retroperitoneal node enlargement. However, pathological evaluation has shown that imaging alone will miss 50% of nodal disease. Therefore, patients aged 10 years and older should have an ipsilateral, nerve-sparing retroperitoneal node dissection, regardless of imaging findings.[133] Staging ipsilateral retroperitoneal lymph node sampling is currently required for all children aged 10 years and older with paratesticular rhabdomyosarcoma on COG-STS studies. Many European investigators relied on radiographic, rather than surgical-pathological assessment, for retroperitoneal lymph node involvement.[123,130] European studies, as well as an international pooled data analysis, demonstrated worse outcomes in this patient population when surgical lymph node evaluation was not performed.[125,127,134] On the basis of these results and with the high relapse rate and worse EFS in Stage N0 patients, investigators from SIOP, EpSSG, and COG recommended surgical resection, in the form of ipsilateral retroperitoneal lymph node sampling of clinically normal nodes (not enlarged by CT or MRI), in patients aged 10 years and older with paratesticular rhabdomyosarcoma.[125] A consensus document regarding paratesticular rhabdomyosarcoma from all North American and European cooperative groups concurred that all patients aged 10 years or older should undergo ipsilateral, infra-renal vein, retroperitoneal surgical lymph node evaluation by sampling 7 to 12 nodes or a nerve-sparing dissection.[122] Evidence (lymph node sampling): RT should be considered for patients whose nodes are biopsy positive. › In the EpSSG RMS-2005 (NCT00379457) cooperative group study (n = 237) of patients with paratesticular rhabdomyosarcoma, retroperitoneal lymph node staging was based on conventional imaging with ultrasonography, CT, or MRI, not systematic surgical staging.[127][Level of evidence B4]

Twenty-one of 26 recurrences were in patients older than 10 years and were mainly locoregional in 16 of the 26 patients.

Testis or spermatic cord (paratesticular). Recommendations for paratesticular primary tumors are primarily based on the results from cooperative group trials and a recent INSTRuCT consensus opinion.[122] Lesions occurring adjacent to the testis or spermatic cord and up to the internal inguinal ring should be removed by orchiectomy with resection of the spermatic cord, using an inguinal incision with proximal vascular control (i.e., radical orchiectomy).[123] Resection of hemiscrotal skin is required when there is tumor fixation or invasion. Hemiscrotectomy had been recommended by the COG, German groups, and Italian groups when a previous transscrotal biopsy had been performed. A retrospective German CWS study of 28 patients with embryonal rhabdomyosarcoma found a 5-year EFS rate of 91.7% in 12 patients with an initial transscrotal excision followed by hemiscrotectomy, while the 5-year EFS rate was 93.8% in 16 patients without subsequent hemiscrotectomy. All of these patients also received chemotherapy with vincristine, dactinomycin, an alkylating agent, and other agents.[124][Level of evidence C2] A retrospective study examined 842 patients with localized paratesticular rhabdomyosarcoma who were enrolled in COG, CWS, EpSSG, Italian Cooperative Group, and MMT studies from 1988 to 2013. Of all patients, 7.7% had a transscrotal resection; however, this surgical factor did not contribute to an inferior EFS in stratified univariable and multivariable analysis.[125] A COG study evaluated 279 patients with paratesticular rhabdomyosarcoma. The study also found that hemiscrotectomy did not improve outcome after transscrotal violation.[126][Level of evidence C1] These findings support the consensus statement from INSTRuCT that hemiscrotectomy is no longer recommended for scrotal violation.[122] The EpSSG RMS-2005 (NCT00379457) study enrolled 237 patients with paratesticular tumors. Seventy-five patients (32%) had an inappropriate first surgery, defined as tumorectomy without orchidectomy, transscrotal orchidectomy without an inguinal approach, or biopsy in a resectable tumor. These patients required intensified therapy to maintain excellent OS and EFS. Ten patients required additional local surgery and intensified chemotherapy.[127] For patients with incompletely removed paratesticular tumors that require RT, temporarily repositioning the contralateral testicle into the adjacent thigh before scrotal radiation may preserve hormone production; however, more data are needed.[128][Level of evidence C1] A retrospective review of 49 patients with paratestis rhabdomyosarcoma referred to Memorial Sloan Kettering Cancer Center found that 20 patients had scrotal violation as a part of their original surgery. Fifteen of these patients underwent salvage surgery or RT. Eleven of these patients had continuous PFS, whereas four of the five patients who were treated without a salvage procedure developed recurrent disease.[129][Level of evidence C2] Paratesticular tumors have a relatively high incidence of lymphatic spread (26% in IRS-I and IRS-II).[90] All patients with paratesticular primary tumors should have thin-cut abdominal and pelvic CT scans with intravenous contrast to evaluate nodal involvement. For patients who have Group I disease, are younger than 10 years, and in whom CT scans show no evidence of lymph node enlargement, retroperitoneal node biopsy/sampling is unnecessary, but a repeat CT scan every 3 months is recommended.[130,131] For patients with suggestive or positive CT scans, retroperitoneal, ipsilateral, infra-renal vein lymph node sampling of 10 to 12 nodes (but not formal node dissection) is recommended, and treatment is based on the findings of this procedure.[4,39,132] Patients with suspicious or documented retroperitoneal/pelvic lymph nodes require nodal RT. In patients aged 10 years and older, only 9% will have clinical or radiological evidence of retroperitoneal node enlargement. However, pathological evaluation has shown that imaging alone will miss 50% of nodal disease. Therefore, patients aged 10 years and older should have an ipsilateral, nerve-sparing retroperitoneal node dissection, regardless of imaging findings.[133] Staging ipsilateral retroperitoneal lymph node sampling is currently required for all children aged 10 years and older with paratesticular rhabdomyosarcoma on COG-STS studies. Many European investigators relied on radiographic, rather than surgical-pathological assessment, for retroperitoneal lymph node involvement.[123,130] European studies, as well as an international pooled data analysis, demonstrated worse outcomes in this patient population when surgical lymph node evaluation was not performed.[125,127,134] On the basis of these results and with the high relapse rate and worse EFS in Stage N0 patients, investigators from SIOP, EpSSG, and COG recommended surgical resection, in the form of ipsilateral retroperitoneal lymph node sampling of clinically normal nodes (not enlarged by CT or MRI), in patients aged 10 years and older with paratesticular rhabdomyosarcoma.[125] A consensus document regarding paratesticular rhabdomyosarcoma from all North American and European cooperative groups concurred that all patients aged 10 years or older should undergo ipsilateral, infra-renal vein, retroperitoneal surgical lymph node evaluation by sampling 7 to 12 nodes or a nerve-sparing dissection.[122] Evidence (lymph node sampling): RT should be considered for patients whose nodes are biopsy positive. › In the EpSSG RMS-2005 (NCT00379457) cooperative group study (n = 237) of patients with paratesticular rhabdomyosarcoma, retroperitoneal lymph node staging was based on conventional imaging with ultrasonography, CT, or MRI, not systematic surgical staging.[127][Level of evidence B4]

The 5-year OS and EFS rates were both significantly worse in patients older than 10 years, compared with those younger than 10 years (OS rates, 86.7% vs. 98.1%, respectively; P = .0013; EFS rates, 79.6% vs. 95.8%, respectively; P = .0004).

Testis or spermatic cord (paratesticular). Recommendations for paratesticular primary tumors are primarily based on the results from cooperative group trials and a recent INSTRuCT consensus opinion.[122] Lesions occurring adjacent to the testis or spermatic cord and up to the internal inguinal ring should be removed by orchiectomy with resection of the spermatic cord, using an inguinal incision with proximal vascular control (i.e., radical orchiectomy).[123] Resection of hemiscrotal skin is required when there is tumor fixation or invasion. Hemiscrotectomy had been recommended by the COG, German groups, and Italian groups when a previous transscrotal biopsy had been performed. A retrospective German CWS study of 28 patients with embryonal rhabdomyosarcoma found a 5-year EFS rate of 91.7% in 12 patients with an initial transscrotal excision followed by hemiscrotectomy, while the 5-year EFS rate was 93.8% in 16 patients without subsequent hemiscrotectomy. All of these patients also received chemotherapy with vincristine, dactinomycin, an alkylating agent, and other agents.[124][Level of evidence C2] A retrospective study examined 842 patients with localized paratesticular rhabdomyosarcoma who were enrolled in COG, CWS, EpSSG, Italian Cooperative Group, and MMT studies from 1988 to 2013. Of all patients, 7.7% had a transscrotal resection; however, this surgical factor did not contribute to an inferior EFS in stratified univariable and multivariable analysis.[125] A COG study evaluated 279 patients with paratesticular rhabdomyosarcoma. The study also found that hemiscrotectomy did not improve outcome after transscrotal violation.[126][Level of evidence C1] These findings support the consensus statement from INSTRuCT that hemiscrotectomy is no longer recommended for scrotal violation.[122] The EpSSG RMS-2005 (NCT00379457) study enrolled 237 patients with paratesticular tumors. Seventy-five patients (32%) had an inappropriate first surgery, defined as tumorectomy without orchidectomy, transscrotal orchidectomy without an inguinal approach, or biopsy in a resectable tumor. These patients required intensified therapy to maintain excellent OS and EFS. Ten patients required additional local surgery and intensified chemotherapy.[127] For patients with incompletely removed paratesticular tumors that require RT, temporarily repositioning the contralateral testicle into the adjacent thigh before scrotal radiation may preserve hormone production; however, more data are needed.[128][Level of evidence C1] A retrospective review of 49 patients with paratestis rhabdomyosarcoma referred to Memorial Sloan Kettering Cancer Center found that 20 patients had scrotal violation as a part of their original surgery. Fifteen of these patients underwent salvage surgery or RT. Eleven of these patients had continuous PFS, whereas four of the five patients who were treated without a salvage procedure developed recurrent disease.[129][Level of evidence C2] Paratesticular tumors have a relatively high incidence of lymphatic spread (26% in IRS-I and IRS-II).[90] All patients with paratesticular primary tumors should have thin-cut abdominal and pelvic CT scans with intravenous contrast to evaluate nodal involvement. For patients who have Group I disease, are younger than 10 years, and in whom CT scans show no evidence of lymph node enlargement, retroperitoneal node biopsy/sampling is unnecessary, but a repeat CT scan every 3 months is recommended.[130,131] For patients with suggestive or positive CT scans, retroperitoneal, ipsilateral, infra-renal vein lymph node sampling of 10 to 12 nodes (but not formal node dissection) is recommended, and treatment is based on the findings of this procedure.[4,39,132] Patients with suspicious or documented retroperitoneal/pelvic lymph nodes require nodal RT. In patients aged 10 years and older, only 9% will have clinical or radiological evidence of retroperitoneal node enlargement. However, pathological evaluation has shown that imaging alone will miss 50% of nodal disease. Therefore, patients aged 10 years and older should have an ipsilateral, nerve-sparing retroperitoneal node dissection, regardless of imaging findings.[133] Staging ipsilateral retroperitoneal lymph node sampling is currently required for all children aged 10 years and older with paratesticular rhabdomyosarcoma on COG-STS studies. Many European investigators relied on radiographic, rather than surgical-pathological assessment, for retroperitoneal lymph node involvement.[123,130] European studies, as well as an international pooled data analysis, demonstrated worse outcomes in this patient population when surgical lymph node evaluation was not performed.[125,127,134] On the basis of these results and with the high relapse rate and worse EFS in Stage N0 patients, investigators from SIOP, EpSSG, and COG recommended surgical resection, in the form of ipsilateral retroperitoneal lymph node sampling of clinically normal nodes (not enlarged by CT or MRI), in patients aged 10 years and older with paratesticular rhabdomyosarcoma.[125] A consensus document regarding paratesticular rhabdomyosarcoma from all North American and European cooperative groups concurred that all patients aged 10 years or older should undergo ipsilateral, infra-renal vein, retroperitoneal surgical lymph node evaluation by sampling 7 to 12 nodes or a nerve-sparing dissection.[122] Evidence (lymph node sampling): RT should be considered for patients whose nodes are biopsy positive. › In the EpSSG RMS-2005 (NCT00379457) cooperative group study (n = 237) of patients with paratesticular rhabdomyosarcoma, retroperitoneal lymph node staging was based on conventional imaging with ultrasonography, CT, or MRI, not systematic surgical staging.[127][Level of evidence B4]

Eight of ten nodal relapses were in patients older than 10 years.

Testis or spermatic cord (paratesticular). Recommendations for paratesticular primary tumors are primarily based on the results from cooperative group trials and a recent INSTRuCT consensus opinion.[122] Lesions occurring adjacent to the testis or spermatic cord and up to the internal inguinal ring should be removed by orchiectomy with resection of the spermatic cord, using an inguinal incision with proximal vascular control (i.e., radical orchiectomy).[123] Resection of hemiscrotal skin is required when there is tumor fixation or invasion. Hemiscrotectomy had been recommended by the COG, German groups, and Italian groups when a previous transscrotal biopsy had been performed. A retrospective German CWS study of 28 patients with embryonal rhabdomyosarcoma found a 5-year EFS rate of 91.7% in 12 patients with an initial transscrotal excision followed by hemiscrotectomy, while the 5-year EFS rate was 93.8% in 16 patients without subsequent hemiscrotectomy. All of these patients also received chemotherapy with vincristine, dactinomycin, an alkylating agent, and other agents.[124][Level of evidence C2] A retrospective study examined 842 patients with localized paratesticular rhabdomyosarcoma who were enrolled in COG, CWS, EpSSG, Italian Cooperative Group, and MMT studies from 1988 to 2013. Of all patients, 7.7% had a transscrotal resection; however, this surgical factor did not contribute to an inferior EFS in stratified univariable and multivariable analysis.[125] A COG study evaluated 279 patients with paratesticular rhabdomyosarcoma. The study also found that hemiscrotectomy did not improve outcome after transscrotal violation.[126][Level of evidence C1] These findings support the consensus statement from INSTRuCT that hemiscrotectomy is no longer recommended for scrotal violation.[122] The EpSSG RMS-2005 (NCT00379457) study enrolled 237 patients with paratesticular tumors. Seventy-five patients (32%) had an inappropriate first surgery, defined as tumorectomy without orchidectomy, transscrotal orchidectomy without an inguinal approach, or biopsy in a resectable tumor. These patients required intensified therapy to maintain excellent OS and EFS. Ten patients required additional local surgery and intensified chemotherapy.[127] For patients with incompletely removed paratesticular tumors that require RT, temporarily repositioning the contralateral testicle into the adjacent thigh before scrotal radiation may preserve hormone production; however, more data are needed.[128][Level of evidence C1] A retrospective review of 49 patients with paratestis rhabdomyosarcoma referred to Memorial Sloan Kettering Cancer Center found that 20 patients had scrotal violation as a part of their original surgery. Fifteen of these patients underwent salvage surgery or RT. Eleven of these patients had continuous PFS, whereas four of the five patients who were treated without a salvage procedure developed recurrent disease.[129][Level of evidence C2] Paratesticular tumors have a relatively high incidence of lymphatic spread (26% in IRS-I and IRS-II).[90] All patients with paratesticular primary tumors should have thin-cut abdominal and pelvic CT scans with intravenous contrast to evaluate nodal involvement. For patients who have Group I disease, are younger than 10 years, and in whom CT scans show no evidence of lymph node enlargement, retroperitoneal node biopsy/sampling is unnecessary, but a repeat CT scan every 3 months is recommended.[130,131] For patients with suggestive or positive CT scans, retroperitoneal, ipsilateral, infra-renal vein lymph node sampling of 10 to 12 nodes (but not formal node dissection) is recommended, and treatment is based on the findings of this procedure.[4,39,132] Patients with suspicious or documented retroperitoneal/pelvic lymph nodes require nodal RT. In patients aged 10 years and older, only 9% will have clinical or radiological evidence of retroperitoneal node enlargement. However, pathological evaluation has shown that imaging alone will miss 50% of nodal disease. Therefore, patients aged 10 years and older should have an ipsilateral, nerve-sparing retroperitoneal node dissection, regardless of imaging findings.[133] Staging ipsilateral retroperitoneal lymph node sampling is currently required for all children aged 10 years and older with paratesticular rhabdomyosarcoma on COG-STS studies. Many European investigators relied on radiographic, rather than surgical-pathological assessment, for retroperitoneal lymph node involvement.[123,130] European studies, as well as an international pooled data analysis, demonstrated worse outcomes in this patient population when surgical lymph node evaluation was not performed.[125,127,134] On the basis of these results and with the high relapse rate and worse EFS in Stage N0 patients, investigators from SIOP, EpSSG, and COG recommended surgical resection, in the form of ipsilateral retroperitoneal lymph node sampling of clinically normal nodes (not enlarged by CT or MRI), in patients aged 10 years and older with paratesticular rhabdomyosarcoma.[125] A consensus document regarding paratesticular rhabdomyosarcoma from all North American and European cooperative groups concurred that all patients aged 10 years or older should undergo ipsilateral, infra-renal vein, retroperitoneal surgical lymph node evaluation by sampling 7 to 12 nodes or a nerve-sparing dissection.[122] Evidence (lymph node sampling): RT should be considered for patients whose nodes are biopsy positive. › In the EpSSG RMS-2005 (NCT00379457) cooperative group study (n = 237) of patients with paratesticular rhabdomyosarcoma, retroperitoneal lymph node staging was based on conventional imaging with ultrasonography, CT, or MRI, not systematic surgical staging.[127][Level of evidence B4]

The EpSSG group advocates surgical staging for patients aged 10 years and older.

Testis or spermatic cord (paratesticular). Recommendations for paratesticular primary tumors are primarily based on the results from cooperative group trials and a recent INSTRuCT consensus opinion.[122] Lesions occurring adjacent to the testis or spermatic cord and up to the internal inguinal ring should be removed by orchiectomy with resection of the spermatic cord, using an inguinal incision with proximal vascular control (i.e., radical orchiectomy).[123] Resection of hemiscrotal skin is required when there is tumor fixation or invasion. Hemiscrotectomy had been recommended by the COG, German groups, and Italian groups when a previous transscrotal biopsy had been performed. A retrospective German CWS study of 28 patients with embryonal rhabdomyosarcoma found a 5-year EFS rate of 91.7% in 12 patients with an initial transscrotal excision followed by hemiscrotectomy, while the 5-year EFS rate was 93.8% in 16 patients without subsequent hemiscrotectomy. All of these patients also received chemotherapy with vincristine, dactinomycin, an alkylating agent, and other agents.[124][Level of evidence C2] A retrospective study examined 842 patients with localized paratesticular rhabdomyosarcoma who were enrolled in COG, CWS, EpSSG, Italian Cooperative Group, and MMT studies from 1988 to 2013. Of all patients, 7.7% had a transscrotal resection; however, this surgical factor did not contribute to an inferior EFS in stratified univariable and multivariable analysis.[125] A COG study evaluated 279 patients with paratesticular rhabdomyosarcoma. The study also found that hemiscrotectomy did not improve outcome after transscrotal violation.[126][Level of evidence C1] These findings support the consensus statement from INSTRuCT that hemiscrotectomy is no longer recommended for scrotal violation.[122] The EpSSG RMS-2005 (NCT00379457) study enrolled 237 patients with paratesticular tumors. Seventy-five patients (32%) had an inappropriate first surgery, defined as tumorectomy without orchidectomy, transscrotal orchidectomy without an inguinal approach, or biopsy in a resectable tumor. These patients required intensified therapy to maintain excellent OS and EFS. Ten patients required additional local surgery and intensified chemotherapy.[127] For patients with incompletely removed paratesticular tumors that require RT, temporarily repositioning the contralateral testicle into the adjacent thigh before scrotal radiation may preserve hormone production; however, more data are needed.[128][Level of evidence C1] A retrospective review of 49 patients with paratestis rhabdomyosarcoma referred to Memorial Sloan Kettering Cancer Center found that 20 patients had scrotal violation as a part of their original surgery. Fifteen of these patients underwent salvage surgery or RT. Eleven of these patients had continuous PFS, whereas four of the five patients who were treated without a salvage procedure developed recurrent disease.[129][Level of evidence C2] Paratesticular tumors have a relatively high incidence of lymphatic spread (26% in IRS-I and IRS-II).[90] All patients with paratesticular primary tumors should have thin-cut abdominal and pelvic CT scans with intravenous contrast to evaluate nodal involvement. For patients who have Group I disease, are younger than 10 years, and in whom CT scans show no evidence of lymph node enlargement, retroperitoneal node biopsy/sampling is unnecessary, but a repeat CT scan every 3 months is recommended.[130,131] For patients with suggestive or positive CT scans, retroperitoneal, ipsilateral, infra-renal vein lymph node sampling of 10 to 12 nodes (but not formal node dissection) is recommended, and treatment is based on the findings of this procedure.[4,39,132] Patients with suspicious or documented retroperitoneal/pelvic lymph nodes require nodal RT. In patients aged 10 years and older, only 9% will have clinical or radiological evidence of retroperitoneal node enlargement. However, pathological evaluation has shown that imaging alone will miss 50% of nodal disease. Therefore, patients aged 10 years and older should have an ipsilateral, nerve-sparing retroperitoneal node dissection, regardless of imaging findings.[133] Staging ipsilateral retroperitoneal lymph node sampling is currently required for all children aged 10 years and older with paratesticular rhabdomyosarcoma on COG-STS studies. Many European investigators relied on radiographic, rather than surgical-pathological assessment, for retroperitoneal lymph node involvement.[123,130] European studies, as well as an international pooled data analysis, demonstrated worse outcomes in this patient population when surgical lymph node evaluation was not performed.[125,127,134] On the basis of these results and with the high relapse rate and worse EFS in Stage N0 patients, investigators from SIOP, EpSSG, and COG recommended surgical resection, in the form of ipsilateral retroperitoneal lymph node sampling of clinically normal nodes (not enlarged by CT or MRI), in patients aged 10 years and older with paratesticular rhabdomyosarcoma.[125] A consensus document regarding paratesticular rhabdomyosarcoma from all North American and European cooperative groups concurred that all patients aged 10 years or older should undergo ipsilateral, infra-renal vein, retroperitoneal surgical lymph node evaluation by sampling 7 to 12 nodes or a nerve-sparing dissection.[122] Evidence (lymph node sampling): RT should be considered for patients whose nodes are biopsy positive.

The COG reviewed 279 patients with localized paratesticular rhabdomyosarcoma enrolled in one of four COG studies (D9602, ARST0331, D9803, or ARST0531 [NCT00354835]). Surgical resection of the primary tumor before chemotherapy and RT was encouraged, when possible, with retroperitoneal lymph node dissection (RPLND) recommended for patients aged 10 years and older. Most tumors were resected with negative margins (78.5%), and most patients did not have radiographic enlargement of regional lymph nodes (90.3%). Of 270 analyzed patients, 121 were older than 10 years. Of these patients, 25 (20.9%) underwent template RPLND, 35 (28.9%) had RPLN sampling, and for 12 of the patients (9.9%), the RPLN technique was unknown.[126][Level of evidence B4]

Testis or spermatic cord (paratesticular). Recommendations for paratesticular primary tumors are primarily based on the results from cooperative group trials and a recent INSTRuCT consensus opinion.[122] Lesions occurring adjacent to the testis or spermatic cord and up to the internal inguinal ring should be removed by orchiectomy with resection of the spermatic cord, using an inguinal incision with proximal vascular control (i.e., radical orchiectomy).[123] Resection of hemiscrotal skin is required when there is tumor fixation or invasion. Hemiscrotectomy had been recommended by the COG, German groups, and Italian groups when a previous transscrotal biopsy had been performed. A retrospective German CWS study of 28 patients with embryonal rhabdomyosarcoma found a 5-year EFS rate of 91.7% in 12 patients with an initial transscrotal excision followed by hemiscrotectomy, while the 5-year EFS rate was 93.8% in 16 patients without subsequent hemiscrotectomy. All of these patients also received chemotherapy with vincristine, dactinomycin, an alkylating agent, and other agents.[124][Level of evidence C2] A retrospective study examined 842 patients with localized paratesticular rhabdomyosarcoma who were enrolled in COG, CWS, EpSSG, Italian Cooperative Group, and MMT studies from 1988 to 2013. Of all patients, 7.7% had a transscrotal resection; however, this surgical factor did not contribute to an inferior EFS in stratified univariable and multivariable analysis.[125] A COG study evaluated 279 patients with paratesticular rhabdomyosarcoma. The study also found that hemiscrotectomy did not improve outcome after transscrotal violation.[126][Level of evidence C1] These findings support the consensus statement from INSTRuCT that hemiscrotectomy is no longer recommended for scrotal violation.[122] The EpSSG RMS-2005 (NCT00379457) study enrolled 237 patients with paratesticular tumors. Seventy-five patients (32%) had an inappropriate first surgery, defined as tumorectomy without orchidectomy, transscrotal orchidectomy without an inguinal approach, or biopsy in a resectable tumor. These patients required intensified therapy to maintain excellent OS and EFS. Ten patients required additional local surgery and intensified chemotherapy.[127] For patients with incompletely removed paratesticular tumors that require RT, temporarily repositioning the contralateral testicle into the adjacent thigh before scrotal radiation may preserve hormone production; however, more data are needed.[128][Level of evidence C1] A retrospective review of 49 patients with paratestis rhabdomyosarcoma referred to Memorial Sloan Kettering Cancer Center found that 20 patients had scrotal violation as a part of their original surgery. Fifteen of these patients underwent salvage surgery or RT. Eleven of these patients had continuous PFS, whereas four of the five patients who were treated without a salvage procedure developed recurrent disease.[129][Level of evidence C2] Paratesticular tumors have a relatively high incidence of lymphatic spread (26% in IRS-I and IRS-II).[90] All patients with paratesticular primary tumors should have thin-cut abdominal and pelvic CT scans with intravenous contrast to evaluate nodal involvement. For patients who have Group I disease, are younger than 10 years, and in whom CT scans show no evidence of lymph node enlargement, retroperitoneal node biopsy/sampling is unnecessary, but a repeat CT scan every 3 months is recommended.[130,131] For patients with suggestive or positive CT scans, retroperitoneal, ipsilateral, infra-renal vein lymph node sampling of 10 to 12 nodes (but not formal node dissection) is recommended, and treatment is based on the findings of this procedure.[4,39,132] Patients with suspicious or documented retroperitoneal/pelvic lymph nodes require nodal RT. In patients aged 10 years and older, only 9% will have clinical or radiological evidence of retroperitoneal node enlargement. However, pathological evaluation has shown that imaging alone will miss 50% of nodal disease. Therefore, patients aged 10 years and older should have an ipsilateral, nerve-sparing retroperitoneal node dissection, regardless of imaging findings.[133] Staging ipsilateral retroperitoneal lymph node sampling is currently required for all children aged 10 years and older with paratesticular rhabdomyosarcoma on COG-STS studies. Many European investigators relied on radiographic, rather than surgical-pathological assessment, for retroperitoneal lymph node involvement.[123,130] European studies, as well as an international pooled data analysis, demonstrated worse outcomes in this patient population when surgical lymph node evaluation was not performed.[125,127,134] On the basis of these results and with the high relapse rate and worse EFS in Stage N0 patients, investigators from SIOP, EpSSG, and COG recommended surgical resection, in the form of ipsilateral retroperitoneal lymph node sampling of clinically normal nodes (not enlarged by CT or MRI), in patients aged 10 years and older with paratesticular rhabdomyosarcoma.[125] A consensus document regarding paratesticular rhabdomyosarcoma from all North American and European cooperative groups concurred that all patients aged 10 years or older should undergo ipsilateral, infra-renal vein, retroperitoneal surgical lymph node evaluation by sampling 7 to 12 nodes or a nerve-sparing dissection.[122] Evidence (lymph node sampling): RT should be considered for patients whose nodes are biopsy positive. › The COG reviewed 279 patients with localized paratesticular rhabdomyosarcoma enrolled in one of four COG studies (D9602, ARST0331, D9803, or ARST0531 [NCT00354835]). Surgical resection of the primary tumor before chemotherapy and RT was encouraged, when possible, with retroperitoneal lymph node dissection (RPLND) recommended for patients aged 10 years and older. Most tumors were resected with negative margins (78.5%), and most patients did not have radiographic enlargement of regional lymph nodes (90.3%). Of 270 analyzed patients, 121 were older than 10 years. Of these patients, 25 (20.9%) underwent template RPLND, 35 (28.9%) had RPLN sampling, and for 12 of the patients (9.9%), the RPLN technique was unknown.[126][Level of evidence B4]

In patients older than 10 years, imaging alone will miss over 51.5% of nodal disease.

Testis or spermatic cord (paratesticular). Recommendations for paratesticular primary tumors are primarily based on the results from cooperative group trials and a recent INSTRuCT consensus opinion.[122] Lesions occurring adjacent to the testis or spermatic cord and up to the internal inguinal ring should be removed by orchiectomy with resection of the spermatic cord, using an inguinal incision with proximal vascular control (i.e., radical orchiectomy).[123] Resection of hemiscrotal skin is required when there is tumor fixation or invasion. Hemiscrotectomy had been recommended by the COG, German groups, and Italian groups when a previous transscrotal biopsy had been performed. A retrospective German CWS study of 28 patients with embryonal rhabdomyosarcoma found a 5-year EFS rate of 91.7% in 12 patients with an initial transscrotal excision followed by hemiscrotectomy, while the 5-year EFS rate was 93.8% in 16 patients without subsequent hemiscrotectomy. All of these patients also received chemotherapy with vincristine, dactinomycin, an alkylating agent, and other agents.[124][Level of evidence C2] A retrospective study examined 842 patients with localized paratesticular rhabdomyosarcoma who were enrolled in COG, CWS, EpSSG, Italian Cooperative Group, and MMT studies from 1988 to 2013. Of all patients, 7.7% had a transscrotal resection; however, this surgical factor did not contribute to an inferior EFS in stratified univariable and multivariable analysis.[125] A COG study evaluated 279 patients with paratesticular rhabdomyosarcoma. The study also found that hemiscrotectomy did not improve outcome after transscrotal violation.[126][Level of evidence C1] These findings support the consensus statement from INSTRuCT that hemiscrotectomy is no longer recommended for scrotal violation.[122] The EpSSG RMS-2005 (NCT00379457) study enrolled 237 patients with paratesticular tumors. Seventy-five patients (32%) had an inappropriate first surgery, defined as tumorectomy without orchidectomy, transscrotal orchidectomy without an inguinal approach, or biopsy in a resectable tumor. These patients required intensified therapy to maintain excellent OS and EFS. Ten patients required additional local surgery and intensified chemotherapy.[127] For patients with incompletely removed paratesticular tumors that require RT, temporarily repositioning the contralateral testicle into the adjacent thigh before scrotal radiation may preserve hormone production; however, more data are needed.[128][Level of evidence C1] A retrospective review of 49 patients with paratestis rhabdomyosarcoma referred to Memorial Sloan Kettering Cancer Center found that 20 patients had scrotal violation as a part of their original surgery. Fifteen of these patients underwent salvage surgery or RT. Eleven of these patients had continuous PFS, whereas four of the five patients who were treated without a salvage procedure developed recurrent disease.[129][Level of evidence C2] Paratesticular tumors have a relatively high incidence of lymphatic spread (26% in IRS-I and IRS-II).[90] All patients with paratesticular primary tumors should have thin-cut abdominal and pelvic CT scans with intravenous contrast to evaluate nodal involvement. For patients who have Group I disease, are younger than 10 years, and in whom CT scans show no evidence of lymph node enlargement, retroperitoneal node biopsy/sampling is unnecessary, but a repeat CT scan every 3 months is recommended.[130,131] For patients with suggestive or positive CT scans, retroperitoneal, ipsilateral, infra-renal vein lymph node sampling of 10 to 12 nodes (but not formal node dissection) is recommended, and treatment is based on the findings of this procedure.[4,39,132] Patients with suspicious or documented retroperitoneal/pelvic lymph nodes require nodal RT. In patients aged 10 years and older, only 9% will have clinical or radiological evidence of retroperitoneal node enlargement. However, pathological evaluation has shown that imaging alone will miss 50% of nodal disease. Therefore, patients aged 10 years and older should have an ipsilateral, nerve-sparing retroperitoneal node dissection, regardless of imaging findings.[133] Staging ipsilateral retroperitoneal lymph node sampling is currently required for all children aged 10 years and older with paratesticular rhabdomyosarcoma on COG-STS studies. Many European investigators relied on radiographic, rather than surgical-pathological assessment, for retroperitoneal lymph node involvement.[123,130] European studies, as well as an international pooled data analysis, demonstrated worse outcomes in this patient population when surgical lymph node evaluation was not performed.[125,127,134] On the basis of these results and with the high relapse rate and worse EFS in Stage N0 patients, investigators from SIOP, EpSSG, and COG recommended surgical resection, in the form of ipsilateral retroperitoneal lymph node sampling of clinically normal nodes (not enlarged by CT or MRI), in patients aged 10 years and older with paratesticular rhabdomyosarcoma.[125] A consensus document regarding paratesticular rhabdomyosarcoma from all North American and European cooperative groups concurred that all patients aged 10 years or older should undergo ipsilateral, infra-renal vein, retroperitoneal surgical lymph node evaluation by sampling 7 to 12 nodes or a nerve-sparing dissection.[122] Evidence (lymph node sampling): RT should be considered for patients whose nodes are biopsy positive. › The COG reviewed 279 patients with localized paratesticular rhabdomyosarcoma enrolled in one of four COG studies (D9602, ARST0331, D9803, or ARST0531 [NCT00354835]). Surgical resection of the primary tumor before chemotherapy and RT was encouraged, when possible, with retroperitoneal lymph node dissection (RPLND) recommended for patients aged 10 years and older. Most tumors were resected with negative margins (78.5%), and most patients did not have radiographic enlargement of regional lymph nodes (90.3%). Of 270 analyzed patients, 121 were older than 10 years. Of these patients, 25 (20.9%) underwent template RPLND, 35 (28.9%) had RPLN sampling, and for 12 of the patients (9.9%), the RPLN technique was unknown.[126][Level of evidence B4]

Sampling of ≥7 to 12 nodes appeared optimal.

Testis or spermatic cord (paratesticular). Recommendations for paratesticular primary tumors are primarily based on the results from cooperative group trials and a recent INSTRuCT consensus opinion.[122] Lesions occurring adjacent to the testis or spermatic cord and up to the internal inguinal ring should be removed by orchiectomy with resection of the spermatic cord, using an inguinal incision with proximal vascular control (i.e., radical orchiectomy).[123] Resection of hemiscrotal skin is required when there is tumor fixation or invasion. Hemiscrotectomy had been recommended by the COG, German groups, and Italian groups when a previous transscrotal biopsy had been performed. A retrospective German CWS study of 28 patients with embryonal rhabdomyosarcoma found a 5-year EFS rate of 91.7% in 12 patients with an initial transscrotal excision followed by hemiscrotectomy, while the 5-year EFS rate was 93.8% in 16 patients without subsequent hemiscrotectomy. All of these patients also received chemotherapy with vincristine, dactinomycin, an alkylating agent, and other agents.[124][Level of evidence C2] A retrospective study examined 842 patients with localized paratesticular rhabdomyosarcoma who were enrolled in COG, CWS, EpSSG, Italian Cooperative Group, and MMT studies from 1988 to 2013. Of all patients, 7.7% had a transscrotal resection; however, this surgical factor did not contribute to an inferior EFS in stratified univariable and multivariable analysis.[125] A COG study evaluated 279 patients with paratesticular rhabdomyosarcoma. The study also found that hemiscrotectomy did not improve outcome after transscrotal violation.[126][Level of evidence C1] These findings support the consensus statement from INSTRuCT that hemiscrotectomy is no longer recommended for scrotal violation.[122] The EpSSG RMS-2005 (NCT00379457) study enrolled 237 patients with paratesticular tumors. Seventy-five patients (32%) had an inappropriate first surgery, defined as tumorectomy without orchidectomy, transscrotal orchidectomy without an inguinal approach, or biopsy in a resectable tumor. These patients required intensified therapy to maintain excellent OS and EFS. Ten patients required additional local surgery and intensified chemotherapy.[127] For patients with incompletely removed paratesticular tumors that require RT, temporarily repositioning the contralateral testicle into the adjacent thigh before scrotal radiation may preserve hormone production; however, more data are needed.[128][Level of evidence C1] A retrospective review of 49 patients with paratestis rhabdomyosarcoma referred to Memorial Sloan Kettering Cancer Center found that 20 patients had scrotal violation as a part of their original surgery. Fifteen of these patients underwent salvage surgery or RT. Eleven of these patients had continuous PFS, whereas four of the five patients who were treated without a salvage procedure developed recurrent disease.[129][Level of evidence C2] Paratesticular tumors have a relatively high incidence of lymphatic spread (26% in IRS-I and IRS-II).[90] All patients with paratesticular primary tumors should have thin-cut abdominal and pelvic CT scans with intravenous contrast to evaluate nodal involvement. For patients who have Group I disease, are younger than 10 years, and in whom CT scans show no evidence of lymph node enlargement, retroperitoneal node biopsy/sampling is unnecessary, but a repeat CT scan every 3 months is recommended.[130,131] For patients with suggestive or positive CT scans, retroperitoneal, ipsilateral, infra-renal vein lymph node sampling of 10 to 12 nodes (but not formal node dissection) is recommended, and treatment is based on the findings of this procedure.[4,39,132] Patients with suspicious or documented retroperitoneal/pelvic lymph nodes require nodal RT. In patients aged 10 years and older, only 9% will have clinical or radiological evidence of retroperitoneal node enlargement. However, pathological evaluation has shown that imaging alone will miss 50% of nodal disease. Therefore, patients aged 10 years and older should have an ipsilateral, nerve-sparing retroperitoneal node dissection, regardless of imaging findings.[133] Staging ipsilateral retroperitoneal lymph node sampling is currently required for all children aged 10 years and older with paratesticular rhabdomyosarcoma on COG-STS studies. Many European investigators relied on radiographic, rather than surgical-pathological assessment, for retroperitoneal lymph node involvement.[123,130] European studies, as well as an international pooled data analysis, demonstrated worse outcomes in this patient population when surgical lymph node evaluation was not performed.[125,127,134] On the basis of these results and with the high relapse rate and worse EFS in Stage N0 patients, investigators from SIOP, EpSSG, and COG recommended surgical resection, in the form of ipsilateral retroperitoneal lymph node sampling of clinically normal nodes (not enlarged by CT or MRI), in patients aged 10 years and older with paratesticular rhabdomyosarcoma.[125] A consensus document regarding paratesticular rhabdomyosarcoma from all North American and European cooperative groups concurred that all patients aged 10 years or older should undergo ipsilateral, infra-renal vein, retroperitoneal surgical lymph node evaluation by sampling 7 to 12 nodes or a nerve-sparing dissection.[122] Evidence (lymph node sampling): RT should be considered for patients whose nodes are biopsy positive. › The COG reviewed 279 patients with localized paratesticular rhabdomyosarcoma enrolled in one of four COG studies (D9602, ARST0331, D9803, or ARST0531 [NCT00354835]). Surgical resection of the primary tumor before chemotherapy and RT was encouraged, when possible, with retroperitoneal lymph node dissection (RPLND) recommended for patients aged 10 years and older. Most tumors were resected with negative margins (78.5%), and most patients did not have radiographic enlargement of regional lymph nodes (90.3%). Of 270 analyzed patients, 121 were older than 10 years. Of these patients, 25 (20.9%) underwent template RPLND, 35 (28.9%) had RPLN sampling, and for 12 of the patients (9.9%), the RPLN technique was unknown.[126][Level of evidence B4]

The 5-year EFS rate was 92%.

Testis or spermatic cord (paratesticular). Recommendations for paratesticular primary tumors are primarily based on the results from cooperative group trials and a recent INSTRuCT consensus opinion.[122] Lesions occurring adjacent to the testis or spermatic cord and up to the internal inguinal ring should be removed by orchiectomy with resection of the spermatic cord, using an inguinal incision with proximal vascular control (i.e., radical orchiectomy).[123] Resection of hemiscrotal skin is required when there is tumor fixation or invasion. Hemiscrotectomy had been recommended by the COG, German groups, and Italian groups when a previous transscrotal biopsy had been performed. A retrospective German CWS study of 28 patients with embryonal rhabdomyosarcoma found a 5-year EFS rate of 91.7% in 12 patients with an initial transscrotal excision followed by hemiscrotectomy, while the 5-year EFS rate was 93.8% in 16 patients without subsequent hemiscrotectomy. All of these patients also received chemotherapy with vincristine, dactinomycin, an alkylating agent, and other agents.[124][Level of evidence C2] A retrospective study examined 842 patients with localized paratesticular rhabdomyosarcoma who were enrolled in COG, CWS, EpSSG, Italian Cooperative Group, and MMT studies from 1988 to 2013. Of all patients, 7.7% had a transscrotal resection; however, this surgical factor did not contribute to an inferior EFS in stratified univariable and multivariable analysis.[125] A COG study evaluated 279 patients with paratesticular rhabdomyosarcoma. The study also found that hemiscrotectomy did not improve outcome after transscrotal violation.[126][Level of evidence C1] These findings support the consensus statement from INSTRuCT that hemiscrotectomy is no longer recommended for scrotal violation.[122] The EpSSG RMS-2005 (NCT00379457) study enrolled 237 patients with paratesticular tumors. Seventy-five patients (32%) had an inappropriate first surgery, defined as tumorectomy without orchidectomy, transscrotal orchidectomy without an inguinal approach, or biopsy in a resectable tumor. These patients required intensified therapy to maintain excellent OS and EFS. Ten patients required additional local surgery and intensified chemotherapy.[127] For patients with incompletely removed paratesticular tumors that require RT, temporarily repositioning the contralateral testicle into the adjacent thigh before scrotal radiation may preserve hormone production; however, more data are needed.[128][Level of evidence C1] A retrospective review of 49 patients with paratestis rhabdomyosarcoma referred to Memorial Sloan Kettering Cancer Center found that 20 patients had scrotal violation as a part of their original surgery. Fifteen of these patients underwent salvage surgery or RT. Eleven of these patients had continuous PFS, whereas four of the five patients who were treated without a salvage procedure developed recurrent disease.[129][Level of evidence C2] Paratesticular tumors have a relatively high incidence of lymphatic spread (26% in IRS-I and IRS-II).[90] All patients with paratesticular primary tumors should have thin-cut abdominal and pelvic CT scans with intravenous contrast to evaluate nodal involvement. For patients who have Group I disease, are younger than 10 years, and in whom CT scans show no evidence of lymph node enlargement, retroperitoneal node biopsy/sampling is unnecessary, but a repeat CT scan every 3 months is recommended.[130,131] For patients with suggestive or positive CT scans, retroperitoneal, ipsilateral, infra-renal vein lymph node sampling of 10 to 12 nodes (but not formal node dissection) is recommended, and treatment is based on the findings of this procedure.[4,39,132] Patients with suspicious or documented retroperitoneal/pelvic lymph nodes require nodal RT. In patients aged 10 years and older, only 9% will have clinical or radiological evidence of retroperitoneal node enlargement. However, pathological evaluation has shown that imaging alone will miss 50% of nodal disease. Therefore, patients aged 10 years and older should have an ipsilateral, nerve-sparing retroperitoneal node dissection, regardless of imaging findings.[133] Staging ipsilateral retroperitoneal lymph node sampling is currently required for all children aged 10 years and older with paratesticular rhabdomyosarcoma on COG-STS studies. Many European investigators relied on radiographic, rather than surgical-pathological assessment, for retroperitoneal lymph node involvement.[123,130] European studies, as well as an international pooled data analysis, demonstrated worse outcomes in this patient population when surgical lymph node evaluation was not performed.[125,127,134] On the basis of these results and with the high relapse rate and worse EFS in Stage N0 patients, investigators from SIOP, EpSSG, and COG recommended surgical resection, in the form of ipsilateral retroperitoneal lymph node sampling of clinically normal nodes (not enlarged by CT or MRI), in patients aged 10 years and older with paratesticular rhabdomyosarcoma.[125] A consensus document regarding paratesticular rhabdomyosarcoma from all North American and European cooperative groups concurred that all patients aged 10 years or older should undergo ipsilateral, infra-renal vein, retroperitoneal surgical lymph node evaluation by sampling 7 to 12 nodes or a nerve-sparing dissection.[122] Evidence (lymph node sampling): RT should be considered for patients whose nodes are biopsy positive. › The COG reviewed 279 patients with localized paratesticular rhabdomyosarcoma enrolled in one of four COG studies (D9602, ARST0331, D9803, or ARST0531 [NCT00354835]). Surgical resection of the primary tumor before chemotherapy and RT was encouraged, when possible, with retroperitoneal lymph node dissection (RPLND) recommended for patients aged 10 years and older. Most tumors were resected with negative margins (78.5%), and most patients did not have radiographic enlargement of regional lymph nodes (90.3%). Of 270 analyzed patients, 121 were older than 10 years. Of these patients, 25 (20.9%) underwent template RPLND, 35 (28.9%) had RPLN sampling, and for 12 of the patients (9.9%), the RPLN technique was unknown.[126][Level of evidence B4]

There was a trend toward improved EFS among those who underwent template RPLND (P = .068).

Testis or spermatic cord (paratesticular). Recommendations for paratesticular primary tumors are primarily based on the results from cooperative group trials and a recent INSTRuCT consensus opinion.[122] Lesions occurring adjacent to the testis or spermatic cord and up to the internal inguinal ring should be removed by orchiectomy with resection of the spermatic cord, using an inguinal incision with proximal vascular control (i.e., radical orchiectomy).[123] Resection of hemiscrotal skin is required when there is tumor fixation or invasion. Hemiscrotectomy had been recommended by the COG, German groups, and Italian groups when a previous transscrotal biopsy had been performed. A retrospective German CWS study of 28 patients with embryonal rhabdomyosarcoma found a 5-year EFS rate of 91.7% in 12 patients with an initial transscrotal excision followed by hemiscrotectomy, while the 5-year EFS rate was 93.8% in 16 patients without subsequent hemiscrotectomy. All of these patients also received chemotherapy with vincristine, dactinomycin, an alkylating agent, and other agents.[124][Level of evidence C2] A retrospective study examined 842 patients with localized paratesticular rhabdomyosarcoma who were enrolled in COG, CWS, EpSSG, Italian Cooperative Group, and MMT studies from 1988 to 2013. Of all patients, 7.7% had a transscrotal resection; however, this surgical factor did not contribute to an inferior EFS in stratified univariable and multivariable analysis.[125] A COG study evaluated 279 patients with paratesticular rhabdomyosarcoma. The study also found that hemiscrotectomy did not improve outcome after transscrotal violation.[126][Level of evidence C1] These findings support the consensus statement from INSTRuCT that hemiscrotectomy is no longer recommended for scrotal violation.[122] The EpSSG RMS-2005 (NCT00379457) study enrolled 237 patients with paratesticular tumors. Seventy-five patients (32%) had an inappropriate first surgery, defined as tumorectomy without orchidectomy, transscrotal orchidectomy without an inguinal approach, or biopsy in a resectable tumor. These patients required intensified therapy to maintain excellent OS and EFS. Ten patients required additional local surgery and intensified chemotherapy.[127] For patients with incompletely removed paratesticular tumors that require RT, temporarily repositioning the contralateral testicle into the adjacent thigh before scrotal radiation may preserve hormone production; however, more data are needed.[128][Level of evidence C1] A retrospective review of 49 patients with paratestis rhabdomyosarcoma referred to Memorial Sloan Kettering Cancer Center found that 20 patients had scrotal violation as a part of their original surgery. Fifteen of these patients underwent salvage surgery or RT. Eleven of these patients had continuous PFS, whereas four of the five patients who were treated without a salvage procedure developed recurrent disease.[129][Level of evidence C2] Paratesticular tumors have a relatively high incidence of lymphatic spread (26% in IRS-I and IRS-II).[90] All patients with paratesticular primary tumors should have thin-cut abdominal and pelvic CT scans with intravenous contrast to evaluate nodal involvement. For patients who have Group I disease, are younger than 10 years, and in whom CT scans show no evidence of lymph node enlargement, retroperitoneal node biopsy/sampling is unnecessary, but a repeat CT scan every 3 months is recommended.[130,131] For patients with suggestive or positive CT scans, retroperitoneal, ipsilateral, infra-renal vein lymph node sampling of 10 to 12 nodes (but not formal node dissection) is recommended, and treatment is based on the findings of this procedure.[4,39,132] Patients with suspicious or documented retroperitoneal/pelvic lymph nodes require nodal RT. In patients aged 10 years and older, only 9% will have clinical or radiological evidence of retroperitoneal node enlargement. However, pathological evaluation has shown that imaging alone will miss 50% of nodal disease. Therefore, patients aged 10 years and older should have an ipsilateral, nerve-sparing retroperitoneal node dissection, regardless of imaging findings.[133] Staging ipsilateral retroperitoneal lymph node sampling is currently required for all children aged 10 years and older with paratesticular rhabdomyosarcoma on COG-STS studies. Many European investigators relied on radiographic, rather than surgical-pathological assessment, for retroperitoneal lymph node involvement.[123,130] European studies, as well as an international pooled data analysis, demonstrated worse outcomes in this patient population when surgical lymph node evaluation was not performed.[125,127,134] On the basis of these results and with the high relapse rate and worse EFS in Stage N0 patients, investigators from SIOP, EpSSG, and COG recommended surgical resection, in the form of ipsilateral retroperitoneal lymph node sampling of clinically normal nodes (not enlarged by CT or MRI), in patients aged 10 years and older with paratesticular rhabdomyosarcoma.[125] A consensus document regarding paratesticular rhabdomyosarcoma from all North American and European cooperative groups concurred that all patients aged 10 years or older should undergo ipsilateral, infra-renal vein, retroperitoneal surgical lymph node evaluation by sampling 7 to 12 nodes or a nerve-sparing dissection.[122] Evidence (lymph node sampling): RT should be considered for patients whose nodes are biopsy positive. › The COG reviewed 279 patients with localized paratesticular rhabdomyosarcoma enrolled in one of four COG studies (D9602, ARST0331, D9803, or ARST0531 [NCT00354835]). Surgical resection of the primary tumor before chemotherapy and RT was encouraged, when possible, with retroperitoneal lymph node dissection (RPLND) recommended for patients aged 10 years and older. Most tumors were resected with negative margins (78.5%), and most patients did not have radiographic enlargement of regional lymph nodes (90.3%). Of 270 analyzed patients, 121 were older than 10 years. Of these patients, 25 (20.9%) underwent template RPLND, 35 (28.9%) had RPLN sampling, and for 12 of the patients (9.9%), the RPLN technique was unknown.[126][Level of evidence B4]

Reliance on imaging alone to detect nodal involvement will miss pathological node involvement and may result in undertreatment.

Bladder or prostate. Bladder preservation is a major goal of therapy for patients with tumors arising in the bladder and/or prostate. Two reviews provide information about the historical, current, and future treatment approaches for patients with bladder and prostate rhabdomyosarcomas.[136,137] The initial surgical procedure in most patients consists of a biopsy, which often can be performed using ultrasound guidance or cystoscopy, or by a direct-vision transanal route.[138] In rare cases, the tumor is confined to the dome of the bladder and can be completely resected, leaving a functional bladder intact. Otherwise, to preserve a functional bladder in patients with gross residual disease, chemotherapy and RT have been used in North America and some parts of Europe to reduce tumor bulk.[139,140] This is sometimes followed, when necessary, by a more limited surgical procedure such as partial cystectomy.[141] Early experience with this approach was disappointing, with only 20% to 40% of patients with bladder/prostate tumors alive and with functional bladders 3 years after diagnosis (3-year OS rate was 70% in IRS-II).[141,142] The later experience from the IRS-III and IRS-IV studies, which used more intensive chemotherapy and RT and had a greater emphasis on bladder preservation, showed 55% of patients alive with functional bladders at 3 years postdiagnosis, with 3-year OS rates exceeding 80%.[140,143,144] In a prospective registry study of 19 patients (median age, 1.8 years at diagnosis; range, 0.5–5.0 years) who were treated with proton therapy, the 5-year OS and PFS rates were 76%. The 5-year local-control rate was 76%. Tumor size predicted the local-control rate, with 5-year local-control rates of 43% for patients whose tumors were larger than 5 cm versus 100% for patients whose tumors were 5 cm or smaller (P = .006). The four patients who had a relapse all died.[145] Patients with a primary tumor of the bladder or prostate who present with a large pelvic mass, resulting from a distended bladder caused by outlet obstruction at diagnosis, receive RT. The RT volume is defined by imaging studies after initial chemotherapy to relieve outlet obstruction. This approach to therapy remains generally accepted, with the belief that more effective chemotherapy and RT will continue to increase the frequency of bladder salvage. For patients with biopsy-proven, residual malignant tumor after chemotherapy and RT, appropriate surgical management may include partial cystectomy, prostatectomy, or exenteration (usually approached anteriorly with preservation of the rectum). Very few studies report objective long-term assessment of bladder function. Urodynamic studies can accurately evaluate bladder function.[146] An alternative strategy, used in European SIOP protocols, has been to avoid major radical surgery when possible and omit EBRT if complete disappearance of tumor can be achieved by chemotherapy and conservative surgical procedures. The goal is to preserve a functional bladder and prostate without incurring the late effects of RT or having to perform a total cystectomy/prostatectomy. From 1984 to 2003, 172 patients with nonmetastatic bladder and/or bladder/prostate rhabdomyosarcoma were enrolled in a SIOP-MMT study. Of the 119 survivors, 50% had no significant local therapy, and only 26% received RT. The 5-year OS rate was 77%.[147][Level of evidence C1] Another alternative strategy in highly selected patients is to perform conservative surgery, followed by brachytherapy at a specialized center.[148]; [149][Level of evidence C2]; [150][Level of evidence C1] A prospective, nonrandomized analysis of this strategy reported the outcomes of 100 children. The 5-year disease-free survival rate was 84%, and the OS rate was 91%. At last follow-up, most survivors presented with only mild-to-moderate genitourinary sequelae and a normal diurnal urinary continence. Five patients required a secondary total cystectomy, three patients for a nonfunctional bladder and two patients for relapse. In another series, bladder-conserving surgery plus brachytherapy for boys with prostate or bladder-neck rhabdomyosarcoma led to excellent survival rates, bladder preservation, and short-term functional results.[46][Level of evidence C1] In patients who have been treated with chemotherapy and RT for rhabdomyosarcoma arising in the bladder or prostate region, the presence of well-differentiated rhabdomyoblasts in surgical specimens or biopsies obtained after treatment does not appear to be associated with a high risk of recurrence and is not an indication for a major surgical procedure such as total cystectomy.[143,151,152] One study suggested that in patients with residual bladder tumors with histological evidence of maturation, additional courses of chemotherapy should be given before cystectomy is considered.[143] Surgery should be considered if malignant tumor cells do not disappear over time after initial chemotherapy and RT. Because of limited data, it is unclear whether this situation is analogous for patients with rhabdomyosarcoma arising in other parts of the body.

Kidney. The kidney is rarely the primary site for sarcoma. Ten patients were identified among 5,746 eligible patients enrolled in IRSG protocols, including six with embryonal rhabdomyosarcoma and four with undifferentiated sarcoma. The tumors were large (mean widest diameter, 12.7 cm), and anaplasia was present in four (67%) patients. Of the patients with embryonal rhabdomyosarcoma, three Group I and Group II patients survived, one Group III patient died of infection, and two Group IV patients died of recurrent disease; these children were aged 5.8 and 6.1 years at diagnosis. This limited experience concluded that the kidney is an unfavorable site for primary sarcoma.[153]

Vulva, vagina, or uterus. For patients with genitourinary primary tumors of the vulva, vagina, or uterus, the initial surgical procedure is usually a vulvar or transvaginal biopsy. Initial radical surgery is not indicated for rhabdomyosarcoma of the vulva, vagina, or uterus.[4] Conservative surgical intervention for vaginal rhabdomyosarcoma, with primary chemotherapy and radiation (external beam or brachytherapy) for Group II or III disease results in excellent 5-year survival rates.[53,154,155][Level of evidence C1] In the COG-ARST0331 study, there was an unacceptably high rate of local recurrences in girls with Group III vaginal tumors who did not receive RT.[53][Level of evidence C2] In 21 girls with genitourinary tract disease who were not treated with RT (mostly Group III vaginal primary tumors), the 3-year FFS rate was 57%, compared with 77% in the other 45 patients with non–female genitourinary primary tumors (P = .02).[54][Level of evidence B4] Therefore, the COG-STS recommended that RT be administered to patients with residual viable vaginal tumor, beginning at week 12.[55][Level of evidence C1] Because of the small number of patients with uterine rhabdomyosarcoma, it is difficult to make a definitive treatment decision, but chemotherapy with or without RT is effective.[154,156] Twelve of 14 girls with primary cervical embryonal (mainly botryoid) rhabdomyosarcoma were disease-free after VAC chemotherapy and conservative surgery. Of note, two girls also had a pleuropulmonary blastoma and another had a Sertoli-Leydig cell tumor.[157] Exenteration is usually not required for primary tumors at these sites, but may be done if needed, with rectal preservation possible in most cases. Four cooperative groups in the United States and Europe evaluated patients with localized vaginal or uterine tumors (N = 427). Some patients received initial RT for local control of residual disease after induction chemotherapy, while others had it later, or not at all if no demonstrable disease was found. The 10-year EFS rate was 74%, and the 10-year OS rate was 92%. Unfavorable factors were positive lymph node disease and uterine corpus primary site. There was no statistical difference in outcomes between patients who received early RT and patients who received later RT. About one-half of these patients were cured without radical surgery or systematic RT.[45][Level of evidence C1] A study of five CWS trials (and one registry) included 67 patients with localized vaginal or uterine rhabdomyosarcoma diagnosed at a median age of 2.89 years (0.09–18.08). Multimodality treatment consisted of chemotherapy (n = 66), secondary surgery (n = 32), and RT (n = 11). The study reported the following results:[158][Level of evidence C1] The INSTRuCT group summarized its consensus expert opinion about local treatment of female genital tract tumors as follows:[159] For girls with genitourinary primary tumors who will receive pelvic irradiation, ovarian transposition (oophoropexy) before radiation therapy should be considered unless dose estimations suggest that ovarian function is likely to be preserved.[160] Alternatively, ovarian tissue preservation is under investigation and can be considered.[161]

Vulva, vagina, or uterus. For patients with genitourinary primary tumors of the vulva, vagina, or uterus, the initial surgical procedure is usually a vulvar or transvaginal biopsy. Initial radical surgery is not indicated for rhabdomyosarcoma of the vulva, vagina, or uterus.[4] Conservative surgical intervention for vaginal rhabdomyosarcoma, with primary chemotherapy and radiation (external beam or brachytherapy) for Group II or III disease results in excellent 5-year survival rates.[53,154,155][Level of evidence C1] In the COG-ARST0331 study, there was an unacceptably high rate of local recurrences in girls with Group III vaginal tumors who did not receive RT.[53][Level of evidence C2] In 21 girls with genitourinary tract disease who were not treated with RT (mostly Group III vaginal primary tumors), the 3-year FFS rate was 57%, compared with 77% in the other 45 patients with non–female genitourinary primary tumors (P = .02).[54][Level of evidence B4] Therefore, the COG-STS recommended that RT be administered to patients with residual viable vaginal tumor, beginning at week 12.[55][Level of evidence C1] Because of the small number of patients with uterine rhabdomyosarcoma, it is difficult to make a definitive treatment decision, but chemotherapy with or without RT is effective.[154,156] Twelve of 14 girls with primary cervical embryonal (mainly botryoid) rhabdomyosarcoma were disease-free after VAC chemotherapy and conservative surgery. Of note, two girls also had a pleuropulmonary blastoma and another had a Sertoli-Leydig cell tumor.[157] Exenteration is usually not required for primary tumors at these sites, but may be done if needed, with rectal preservation possible in most cases. Four cooperative groups in the United States and Europe evaluated patients with localized vaginal or uterine tumors (N = 427). Some patients received initial RT for local control of residual disease after induction chemotherapy, while others had it later, or not at all if no demonstrable disease was found. The 10-year EFS rate was 74%, and the 10-year OS rate was 92%. Unfavorable factors were positive lymph node disease and uterine corpus primary site. There was no statistical difference in outcomes between patients who received early RT and patients who received later RT. About one-half of these patients were cured without radical surgery or systematic RT.[45][Level of evidence C1] A study of five CWS trials (and one registry) included 67 patients with localized vaginal or uterine rhabdomyosarcoma diagnosed at a median age of 2.89 years (0.09–18.08). Multimodality treatment consisted of chemotherapy (n = 66), secondary surgery (n = 32), and RT (n = 11). The study reported the following results:[158][Level of evidence C1] The INSTRuCT group summarized its consensus expert opinion about local treatment of female genital tract tumors as follows:[159] For girls with genitourinary primary tumors who will receive pelvic irradiation, ovarian transposition (oophoropexy) before radiation therapy should be considered unless dose estimations suggest that ovarian function is likely to be preserved.[160] Alternatively, ovarian tissue preservation is under investigation and can be considered.[161]

Diagnosis at age 12 months or younger was the only significant negative prognostic factor influencing EFS.

Vulva, vagina, or uterus. For patients with genitourinary primary tumors of the vulva, vagina, or uterus, the initial surgical procedure is usually a vulvar or transvaginal biopsy. Initial radical surgery is not indicated for rhabdomyosarcoma of the vulva, vagina, or uterus.[4] Conservative surgical intervention for vaginal rhabdomyosarcoma, with primary chemotherapy and radiation (external beam or brachytherapy) for Group II or III disease results in excellent 5-year survival rates.[53,154,155][Level of evidence C1] In the COG-ARST0331 study, there was an unacceptably high rate of local recurrences in girls with Group III vaginal tumors who did not receive RT.[53][Level of evidence C2] In 21 girls with genitourinary tract disease who were not treated with RT (mostly Group III vaginal primary tumors), the 3-year FFS rate was 57%, compared with 77% in the other 45 patients with non–female genitourinary primary tumors (P = .02).[54][Level of evidence B4] Therefore, the COG-STS recommended that RT be administered to patients with residual viable vaginal tumor, beginning at week 12.[55][Level of evidence C1] Because of the small number of patients with uterine rhabdomyosarcoma, it is difficult to make a definitive treatment decision, but chemotherapy with or without RT is effective.[154,156] Twelve of 14 girls with primary cervical embryonal (mainly botryoid) rhabdomyosarcoma were disease-free after VAC chemotherapy and conservative surgery. Of note, two girls also had a pleuropulmonary blastoma and another had a Sertoli-Leydig cell tumor.[157] Exenteration is usually not required for primary tumors at these sites, but may be done if needed, with rectal preservation possible in most cases. Four cooperative groups in the United States and Europe evaluated patients with localized vaginal or uterine tumors (N = 427). Some patients received initial RT for local control of residual disease after induction chemotherapy, while others had it later, or not at all if no demonstrable disease was found. The 10-year EFS rate was 74%, and the 10-year OS rate was 92%. Unfavorable factors were positive lymph node disease and uterine corpus primary site. There was no statistical difference in outcomes between patients who received early RT and patients who received later RT. About one-half of these patients were cured without radical surgery or systematic RT.[45][Level of evidence C1] A study of five CWS trials (and one registry) included 67 patients with localized vaginal or uterine rhabdomyosarcoma diagnosed at a median age of 2.89 years (0.09–18.08). Multimodality treatment consisted of chemotherapy (n = 66), secondary surgery (n = 32), and RT (n = 11). The study reported the following results:[158][Level of evidence C1] The INSTRuCT group summarized its consensus expert opinion about local treatment of female genital tract tumors as follows:[159] For girls with genitourinary primary tumors who will receive pelvic irradiation, ovarian transposition (oophoropexy) before radiation therapy should be considered unless dose estimations suggest that ovarian function is likely to be preserved.[160] Alternatively, ovarian tissue preservation is under investigation and can be considered.[161]

The 10-year EFS rate for infants aged 12 months or younger was 50%, and the OS rate was 81%.

Vulva, vagina, or uterus. For patients with genitourinary primary tumors of the vulva, vagina, or uterus, the initial surgical procedure is usually a vulvar or transvaginal biopsy. Initial radical surgery is not indicated for rhabdomyosarcoma of the vulva, vagina, or uterus.[4] Conservative surgical intervention for vaginal rhabdomyosarcoma, with primary chemotherapy and radiation (external beam or brachytherapy) for Group II or III disease results in excellent 5-year survival rates.[53,154,155][Level of evidence C1] In the COG-ARST0331 study, there was an unacceptably high rate of local recurrences in girls with Group III vaginal tumors who did not receive RT.[53][Level of evidence C2] In 21 girls with genitourinary tract disease who were not treated with RT (mostly Group III vaginal primary tumors), the 3-year FFS rate was 57%, compared with 77% in the other 45 patients with non–female genitourinary primary tumors (P = .02).[54][Level of evidence B4] Therefore, the COG-STS recommended that RT be administered to patients with residual viable vaginal tumor, beginning at week 12.[55][Level of evidence C1] Because of the small number of patients with uterine rhabdomyosarcoma, it is difficult to make a definitive treatment decision, but chemotherapy with or without RT is effective.[154,156] Twelve of 14 girls with primary cervical embryonal (mainly botryoid) rhabdomyosarcoma were disease-free after VAC chemotherapy and conservative surgery. Of note, two girls also had a pleuropulmonary blastoma and another had a Sertoli-Leydig cell tumor.[157] Exenteration is usually not required for primary tumors at these sites, but may be done if needed, with rectal preservation possible in most cases. Four cooperative groups in the United States and Europe evaluated patients with localized vaginal or uterine tumors (N = 427). Some patients received initial RT for local control of residual disease after induction chemotherapy, while others had it later, or not at all if no demonstrable disease was found. The 10-year EFS rate was 74%, and the 10-year OS rate was 92%. Unfavorable factors were positive lymph node disease and uterine corpus primary site. There was no statistical difference in outcomes between patients who received early RT and patients who received later RT. About one-half of these patients were cured without radical surgery or systematic RT.[45][Level of evidence C1] A study of five CWS trials (and one registry) included 67 patients with localized vaginal or uterine rhabdomyosarcoma diagnosed at a median age of 2.89 years (0.09–18.08). Multimodality treatment consisted of chemotherapy (n = 66), secondary surgery (n = 32), and RT (n = 11). The study reported the following results:[158][Level of evidence C1] The INSTRuCT group summarized its consensus expert opinion about local treatment of female genital tract tumors as follows:[159] For girls with genitourinary primary tumors who will receive pelvic irradiation, ovarian transposition (oophoropexy) before radiation therapy should be considered unless dose estimations suggest that ovarian function is likely to be preserved.[160] Alternatively, ovarian tissue preservation is under investigation and can be considered.[161]

In contrast, children with local disease older than 1 year to age 10 years had a 10-year EFS rate of 78% and an OS rate of 94% (P = .038). Children older than 10 years had a 10-year EFS rate of 82% and an OS rate of 88% (P = .53).

Vulva, vagina, or uterus. For patients with genitourinary primary tumors of the vulva, vagina, or uterus, the initial surgical procedure is usually a vulvar or transvaginal biopsy. Initial radical surgery is not indicated for rhabdomyosarcoma of the vulva, vagina, or uterus.[4] Conservative surgical intervention for vaginal rhabdomyosarcoma, with primary chemotherapy and radiation (external beam or brachytherapy) for Group II or III disease results in excellent 5-year survival rates.[53,154,155][Level of evidence C1] In the COG-ARST0331 study, there was an unacceptably high rate of local recurrences in girls with Group III vaginal tumors who did not receive RT.[53][Level of evidence C2] In 21 girls with genitourinary tract disease who were not treated with RT (mostly Group III vaginal primary tumors), the 3-year FFS rate was 57%, compared with 77% in the other 45 patients with non–female genitourinary primary tumors (P = .02).[54][Level of evidence B4] Therefore, the COG-STS recommended that RT be administered to patients with residual viable vaginal tumor, beginning at week 12.[55][Level of evidence C1] Because of the small number of patients with uterine rhabdomyosarcoma, it is difficult to make a definitive treatment decision, but chemotherapy with or without RT is effective.[154,156] Twelve of 14 girls with primary cervical embryonal (mainly botryoid) rhabdomyosarcoma were disease-free after VAC chemotherapy and conservative surgery. Of note, two girls also had a pleuropulmonary blastoma and another had a Sertoli-Leydig cell tumor.[157] Exenteration is usually not required for primary tumors at these sites, but may be done if needed, with rectal preservation possible in most cases. Four cooperative groups in the United States and Europe evaluated patients with localized vaginal or uterine tumors (N = 427). Some patients received initial RT for local control of residual disease after induction chemotherapy, while others had it later, or not at all if no demonstrable disease was found. The 10-year EFS rate was 74%, and the 10-year OS rate was 92%. Unfavorable factors were positive lymph node disease and uterine corpus primary site. There was no statistical difference in outcomes between patients who received early RT and patients who received later RT. About one-half of these patients were cured without radical surgery or systematic RT.[45][Level of evidence C1] A study of five CWS trials (and one registry) included 67 patients with localized vaginal or uterine rhabdomyosarcoma diagnosed at a median age of 2.89 years (0.09–18.08). Multimodality treatment consisted of chemotherapy (n = 66), secondary surgery (n = 32), and RT (n = 11). The study reported the following results:[158][Level of evidence C1] The INSTRuCT group summarized its consensus expert opinion about local treatment of female genital tract tumors as follows:[159] For girls with genitourinary primary tumors who will receive pelvic irradiation, ovarian transposition (oophoropexy) before radiation therapy should be considered unless dose estimations suggest that ovarian function is likely to be preserved.[160] Alternatively, ovarian tissue preservation is under investigation and can be considered.[161]

Metastatic disease was observed in four patients, three of whom are alive.

Vulva, vagina, or uterus. For patients with genitourinary primary tumors of the vulva, vagina, or uterus, the initial surgical procedure is usually a vulvar or transvaginal biopsy. Initial radical surgery is not indicated for rhabdomyosarcoma of the vulva, vagina, or uterus.[4] Conservative surgical intervention for vaginal rhabdomyosarcoma, with primary chemotherapy and radiation (external beam or brachytherapy) for Group II or III disease results in excellent 5-year survival rates.[53,154,155][Level of evidence C1] In the COG-ARST0331 study, there was an unacceptably high rate of local recurrences in girls with Group III vaginal tumors who did not receive RT.[53][Level of evidence C2] In 21 girls with genitourinary tract disease who were not treated with RT (mostly Group III vaginal primary tumors), the 3-year FFS rate was 57%, compared with 77% in the other 45 patients with non–female genitourinary primary tumors (P = .02).[54][Level of evidence B4] Therefore, the COG-STS recommended that RT be administered to patients with residual viable vaginal tumor, beginning at week 12.[55][Level of evidence C1] Because of the small number of patients with uterine rhabdomyosarcoma, it is difficult to make a definitive treatment decision, but chemotherapy with or without RT is effective.[154,156] Twelve of 14 girls with primary cervical embryonal (mainly botryoid) rhabdomyosarcoma were disease-free after VAC chemotherapy and conservative surgery. Of note, two girls also had a pleuropulmonary blastoma and another had a Sertoli-Leydig cell tumor.[157] Exenteration is usually not required for primary tumors at these sites, but may be done if needed, with rectal preservation possible in most cases. Four cooperative groups in the United States and Europe evaluated patients with localized vaginal or uterine tumors (N = 427). Some patients received initial RT for local control of residual disease after induction chemotherapy, while others had it later, or not at all if no demonstrable disease was found. The 10-year EFS rate was 74%, and the 10-year OS rate was 92%. Unfavorable factors were positive lymph node disease and uterine corpus primary site. There was no statistical difference in outcomes between patients who received early RT and patients who received later RT. About one-half of these patients were cured without radical surgery or systematic RT.[45][Level of evidence C1] A study of five CWS trials (and one registry) included 67 patients with localized vaginal or uterine rhabdomyosarcoma diagnosed at a median age of 2.89 years (0.09–18.08). Multimodality treatment consisted of chemotherapy (n = 66), secondary surgery (n = 32), and RT (n = 11). The study reported the following results:[158][Level of evidence C1] The INSTRuCT group summarized its consensus expert opinion about local treatment of female genital tract tumors as follows:[159] For girls with genitourinary primary tumors who will receive pelvic irradiation, ovarian transposition (oophoropexy) before radiation therapy should be considered unless dose estimations suggest that ovarian function is likely to be preserved.[160] Alternatively, ovarian tissue preservation is under investigation and can be considered.[161]

Relapsed disease occurred in 5 of 12 infants aged 1 year or younger and 10 of 55 children at a median of 1.38 years (0.53–2.97) after initial diagnosis.

Vulva, vagina, or uterus. For patients with genitourinary primary tumors of the vulva, vagina, or uterus, the initial surgical procedure is usually a vulvar or transvaginal biopsy. Initial radical surgery is not indicated for rhabdomyosarcoma of the vulva, vagina, or uterus.[4] Conservative surgical intervention for vaginal rhabdomyosarcoma, with primary chemotherapy and radiation (external beam or brachytherapy) for Group II or III disease results in excellent 5-year survival rates.[53,154,155][Level of evidence C1] In the COG-ARST0331 study, there was an unacceptably high rate of local recurrences in girls with Group III vaginal tumors who did not receive RT.[53][Level of evidence C2] In 21 girls with genitourinary tract disease who were not treated with RT (mostly Group III vaginal primary tumors), the 3-year FFS rate was 57%, compared with 77% in the other 45 patients with non–female genitourinary primary tumors (P = .02).[54][Level of evidence B4] Therefore, the COG-STS recommended that RT be administered to patients with residual viable vaginal tumor, beginning at week 12.[55][Level of evidence C1] Because of the small number of patients with uterine rhabdomyosarcoma, it is difficult to make a definitive treatment decision, but chemotherapy with or without RT is effective.[154,156] Twelve of 14 girls with primary cervical embryonal (mainly botryoid) rhabdomyosarcoma were disease-free after VAC chemotherapy and conservative surgery. Of note, two girls also had a pleuropulmonary blastoma and another had a Sertoli-Leydig cell tumor.[157] Exenteration is usually not required for primary tumors at these sites, but may be done if needed, with rectal preservation possible in most cases. Four cooperative groups in the United States and Europe evaluated patients with localized vaginal or uterine tumors (N = 427). Some patients received initial RT for local control of residual disease after induction chemotherapy, while others had it later, or not at all if no demonstrable disease was found. The 10-year EFS rate was 74%, and the 10-year OS rate was 92%. Unfavorable factors were positive lymph node disease and uterine corpus primary site. There was no statistical difference in outcomes between patients who received early RT and patients who received later RT. About one-half of these patients were cured without radical surgery or systematic RT.[45][Level of evidence C1] A study of five CWS trials (and one registry) included 67 patients with localized vaginal or uterine rhabdomyosarcoma diagnosed at a median age of 2.89 years (0.09–18.08). Multimodality treatment consisted of chemotherapy (n = 66), secondary surgery (n = 32), and RT (n = 11). The study reported the following results:[158][Level of evidence C1] The INSTRuCT group summarized its consensus expert opinion about local treatment of female genital tract tumors as follows:[159] For girls with genitourinary primary tumors who will receive pelvic irradiation, ovarian transposition (oophoropexy) before radiation therapy should be considered unless dose estimations suggest that ovarian function is likely to be preserved.[160] Alternatively, ovarian tissue preservation is under investigation and can be considered.[161]

Treatment of patients with relapsed disease consisted of multimodality treatment (n = 13) or resection only (n = 2). Nine patients (60%) were alive in clinical remission at a median of 7.02 years (1.23–16.72) after diagnosis of relapsed disease.

Vulva, vagina, or uterus. For patients with genitourinary primary tumors of the vulva, vagina, or uterus, the initial surgical procedure is usually a vulvar or transvaginal biopsy. Initial radical surgery is not indicated for rhabdomyosarcoma of the vulva, vagina, or uterus.[4] Conservative surgical intervention for vaginal rhabdomyosarcoma, with primary chemotherapy and radiation (external beam or brachytherapy) for Group II or III disease results in excellent 5-year survival rates.[53,154,155][Level of evidence C1] In the COG-ARST0331 study, there was an unacceptably high rate of local recurrences in girls with Group III vaginal tumors who did not receive RT.[53][Level of evidence C2] In 21 girls with genitourinary tract disease who were not treated with RT (mostly Group III vaginal primary tumors), the 3-year FFS rate was 57%, compared with 77% in the other 45 patients with non–female genitourinary primary tumors (P = .02).[54][Level of evidence B4] Therefore, the COG-STS recommended that RT be administered to patients with residual viable vaginal tumor, beginning at week 12.[55][Level of evidence C1] Because of the small number of patients with uterine rhabdomyosarcoma, it is difficult to make a definitive treatment decision, but chemotherapy with or without RT is effective.[154,156] Twelve of 14 girls with primary cervical embryonal (mainly botryoid) rhabdomyosarcoma were disease-free after VAC chemotherapy and conservative surgery. Of note, two girls also had a pleuropulmonary blastoma and another had a Sertoli-Leydig cell tumor.[157] Exenteration is usually not required for primary tumors at these sites, but may be done if needed, with rectal preservation possible in most cases. Four cooperative groups in the United States and Europe evaluated patients with localized vaginal or uterine tumors (N = 427). Some patients received initial RT for local control of residual disease after induction chemotherapy, while others had it later, or not at all if no demonstrable disease was found. The 10-year EFS rate was 74%, and the 10-year OS rate was 92%. Unfavorable factors were positive lymph node disease and uterine corpus primary site. There was no statistical difference in outcomes between patients who received early RT and patients who received later RT. About one-half of these patients were cured without radical surgery or systematic RT.[45][Level of evidence C1] A study of five CWS trials (and one registry) included 67 patients with localized vaginal or uterine rhabdomyosarcoma diagnosed at a median age of 2.89 years (0.09–18.08). Multimodality treatment consisted of chemotherapy (n = 66), secondary surgery (n = 32), and RT (n = 11). The study reported the following results:[158][Level of evidence C1] The INSTRuCT group summarized its consensus expert opinion about local treatment of female genital tract tumors as follows:[159] For girls with genitourinary primary tumors who will receive pelvic irradiation, ovarian transposition (oophoropexy) before radiation therapy should be considered unless dose estimations suggest that ovarian function is likely to be preserved.[160] Alternatively, ovarian tissue preservation is under investigation and can be considered.[161]

Prognosis for female genital tract tumors is favorable, with an excellent response to chemotherapy.

Vulva, vagina, or uterus. For patients with genitourinary primary tumors of the vulva, vagina, or uterus, the initial surgical procedure is usually a vulvar or transvaginal biopsy. Initial radical surgery is not indicated for rhabdomyosarcoma of the vulva, vagina, or uterus.[4] Conservative surgical intervention for vaginal rhabdomyosarcoma, with primary chemotherapy and radiation (external beam or brachytherapy) for Group II or III disease results in excellent 5-year survival rates.[53,154,155][Level of evidence C1] In the COG-ARST0331 study, there was an unacceptably high rate of local recurrences in girls with Group III vaginal tumors who did not receive RT.[53][Level of evidence C2] In 21 girls with genitourinary tract disease who were not treated with RT (mostly Group III vaginal primary tumors), the 3-year FFS rate was 57%, compared with 77% in the other 45 patients with non–female genitourinary primary tumors (P = .02).[54][Level of evidence B4] Therefore, the COG-STS recommended that RT be administered to patients with residual viable vaginal tumor, beginning at week 12.[55][Level of evidence C1] Because of the small number of patients with uterine rhabdomyosarcoma, it is difficult to make a definitive treatment decision, but chemotherapy with or without RT is effective.[154,156] Twelve of 14 girls with primary cervical embryonal (mainly botryoid) rhabdomyosarcoma were disease-free after VAC chemotherapy and conservative surgery. Of note, two girls also had a pleuropulmonary blastoma and another had a Sertoli-Leydig cell tumor.[157] Exenteration is usually not required for primary tumors at these sites, but may be done if needed, with rectal preservation possible in most cases. Four cooperative groups in the United States and Europe evaluated patients with localized vaginal or uterine tumors (N = 427). Some patients received initial RT for local control of residual disease after induction chemotherapy, while others had it later, or not at all if no demonstrable disease was found. The 10-year EFS rate was 74%, and the 10-year OS rate was 92%. Unfavorable factors were positive lymph node disease and uterine corpus primary site. There was no statistical difference in outcomes between patients who received early RT and patients who received later RT. About one-half of these patients were cured without radical surgery or systematic RT.[45][Level of evidence C1] A study of five CWS trials (and one registry) included 67 patients with localized vaginal or uterine rhabdomyosarcoma diagnosed at a median age of 2.89 years (0.09–18.08). Multimodality treatment consisted of chemotherapy (n = 66), secondary surgery (n = 32), and RT (n = 11). The study reported the following results:[158][Level of evidence C1] The INSTRuCT group summarized its consensus expert opinion about local treatment of female genital tract tumors as follows:[159] For girls with genitourinary primary tumors who will receive pelvic irradiation, ovarian transposition (oophoropexy) before radiation therapy should be considered unless dose estimations suggest that ovarian function is likely to be preserved.[160] Alternatively, ovarian tissue preservation is under investigation and can be considered.[161]

Definitive local control can often be achieved by chemotherapy alone.

Vulva, vagina, or uterus. For patients with genitourinary primary tumors of the vulva, vagina, or uterus, the initial surgical procedure is usually a vulvar or transvaginal biopsy. Initial radical surgery is not indicated for rhabdomyosarcoma of the vulva, vagina, or uterus.[4] Conservative surgical intervention for vaginal rhabdomyosarcoma, with primary chemotherapy and radiation (external beam or brachytherapy) for Group II or III disease results in excellent 5-year survival rates.[53,154,155][Level of evidence C1] In the COG-ARST0331 study, there was an unacceptably high rate of local recurrences in girls with Group III vaginal tumors who did not receive RT.[53][Level of evidence C2] In 21 girls with genitourinary tract disease who were not treated with RT (mostly Group III vaginal primary tumors), the 3-year FFS rate was 57%, compared with 77% in the other 45 patients with non–female genitourinary primary tumors (P = .02).[54][Level of evidence B4] Therefore, the COG-STS recommended that RT be administered to patients with residual viable vaginal tumor, beginning at week 12.[55][Level of evidence C1] Because of the small number of patients with uterine rhabdomyosarcoma, it is difficult to make a definitive treatment decision, but chemotherapy with or without RT is effective.[154,156] Twelve of 14 girls with primary cervical embryonal (mainly botryoid) rhabdomyosarcoma were disease-free after VAC chemotherapy and conservative surgery. Of note, two girls also had a pleuropulmonary blastoma and another had a Sertoli-Leydig cell tumor.[157] Exenteration is usually not required for primary tumors at these sites, but may be done if needed, with rectal preservation possible in most cases. Four cooperative groups in the United States and Europe evaluated patients with localized vaginal or uterine tumors (N = 427). Some patients received initial RT for local control of residual disease after induction chemotherapy, while others had it later, or not at all if no demonstrable disease was found. The 10-year EFS rate was 74%, and the 10-year OS rate was 92%. Unfavorable factors were positive lymph node disease and uterine corpus primary site. There was no statistical difference in outcomes between patients who received early RT and patients who received later RT. About one-half of these patients were cured without radical surgery or systematic RT.[45][Level of evidence C1] A study of five CWS trials (and one registry) included 67 patients with localized vaginal or uterine rhabdomyosarcoma diagnosed at a median age of 2.89 years (0.09–18.08). Multimodality treatment consisted of chemotherapy (n = 66), secondary surgery (n = 32), and RT (n = 11). The study reported the following results:[158][Level of evidence C1] The INSTRuCT group summarized its consensus expert opinion about local treatment of female genital tract tumors as follows:[159] For girls with genitourinary primary tumors who will receive pelvic irradiation, ovarian transposition (oophoropexy) before radiation therapy should be considered unless dose estimations suggest that ovarian function is likely to be preserved.[160] Alternatively, ovarian tissue preservation is under investigation and can be considered.[161]

Adequate biopsy is required and should provide sufficient tissue to establish the diagnosis and for further molecular or genetic analysis.

Vulva, vagina, or uterus. For patients with genitourinary primary tumors of the vulva, vagina, or uterus, the initial surgical procedure is usually a vulvar or transvaginal biopsy. Initial radical surgery is not indicated for rhabdomyosarcoma of the vulva, vagina, or uterus.[4] Conservative surgical intervention for vaginal rhabdomyosarcoma, with primary chemotherapy and radiation (external beam or brachytherapy) for Group II or III disease results in excellent 5-year survival rates.[53,154,155][Level of evidence C1] In the COG-ARST0331 study, there was an unacceptably high rate of local recurrences in girls with Group III vaginal tumors who did not receive RT.[53][Level of evidence C2] In 21 girls with genitourinary tract disease who were not treated with RT (mostly Group III vaginal primary tumors), the 3-year FFS rate was 57%, compared with 77% in the other 45 patients with non–female genitourinary primary tumors (P = .02).[54][Level of evidence B4] Therefore, the COG-STS recommended that RT be administered to patients with residual viable vaginal tumor, beginning at week 12.[55][Level of evidence C1] Because of the small number of patients with uterine rhabdomyosarcoma, it is difficult to make a definitive treatment decision, but chemotherapy with or without RT is effective.[154,156] Twelve of 14 girls with primary cervical embryonal (mainly botryoid) rhabdomyosarcoma were disease-free after VAC chemotherapy and conservative surgery. Of note, two girls also had a pleuropulmonary blastoma and another had a Sertoli-Leydig cell tumor.[157] Exenteration is usually not required for primary tumors at these sites, but may be done if needed, with rectal preservation possible in most cases. Four cooperative groups in the United States and Europe evaluated patients with localized vaginal or uterine tumors (N = 427). Some patients received initial RT for local control of residual disease after induction chemotherapy, while others had it later, or not at all if no demonstrable disease was found. The 10-year EFS rate was 74%, and the 10-year OS rate was 92%. Unfavorable factors were positive lymph node disease and uterine corpus primary site. There was no statistical difference in outcomes between patients who received early RT and patients who received later RT. About one-half of these patients were cured without radical surgery or systematic RT.[45][Level of evidence C1] A study of five CWS trials (and one registry) included 67 patients with localized vaginal or uterine rhabdomyosarcoma diagnosed at a median age of 2.89 years (0.09–18.08). Multimodality treatment consisted of chemotherapy (n = 66), secondary surgery (n = 32), and RT (n = 11). The study reported the following results:[158][Level of evidence C1] The INSTRuCT group summarized its consensus expert opinion about local treatment of female genital tract tumors as follows:[159] For girls with genitourinary primary tumors who will receive pelvic irradiation, ovarian transposition (oophoropexy) before radiation therapy should be considered unless dose estimations suggest that ovarian function is likely to be preserved.[160] Alternatively, ovarian tissue preservation is under investigation and can be considered.[161]

Initial complete surgical resection before chemotherapy can be avoided in most cases:

Vulva, vagina, or uterus. For patients with genitourinary primary tumors of the vulva, vagina, or uterus, the initial surgical procedure is usually a vulvar or transvaginal biopsy. Initial radical surgery is not indicated for rhabdomyosarcoma of the vulva, vagina, or uterus.[4] Conservative surgical intervention for vaginal rhabdomyosarcoma, with primary chemotherapy and radiation (external beam or brachytherapy) for Group II or III disease results in excellent 5-year survival rates.[53,154,155][Level of evidence C1] In the COG-ARST0331 study, there was an unacceptably high rate of local recurrences in girls with Group III vaginal tumors who did not receive RT.[53][Level of evidence C2] In 21 girls with genitourinary tract disease who were not treated with RT (mostly Group III vaginal primary tumors), the 3-year FFS rate was 57%, compared with 77% in the other 45 patients with non–female genitourinary primary tumors (P = .02).[54][Level of evidence B4] Therefore, the COG-STS recommended that RT be administered to patients with residual viable vaginal tumor, beginning at week 12.[55][Level of evidence C1] Because of the small number of patients with uterine rhabdomyosarcoma, it is difficult to make a definitive treatment decision, but chemotherapy with or without RT is effective.[154,156] Twelve of 14 girls with primary cervical embryonal (mainly botryoid) rhabdomyosarcoma were disease-free after VAC chemotherapy and conservative surgery. Of note, two girls also had a pleuropulmonary blastoma and another had a Sertoli-Leydig cell tumor.[157] Exenteration is usually not required for primary tumors at these sites, but may be done if needed, with rectal preservation possible in most cases. Four cooperative groups in the United States and Europe evaluated patients with localized vaginal or uterine tumors (N = 427). Some patients received initial RT for local control of residual disease after induction chemotherapy, while others had it later, or not at all if no demonstrable disease was found. The 10-year EFS rate was 74%, and the 10-year OS rate was 92%. Unfavorable factors were positive lymph node disease and uterine corpus primary site. There was no statistical difference in outcomes between patients who received early RT and patients who received later RT. About one-half of these patients were cured without radical surgery or systematic RT.[45][Level of evidence C1] A study of five CWS trials (and one registry) included 67 patients with localized vaginal or uterine rhabdomyosarcoma diagnosed at a median age of 2.89 years (0.09–18.08). Multimodality treatment consisted of chemotherapy (n = 66), secondary surgery (n = 32), and RT (n = 11). The study reported the following results:[158][Level of evidence C1] The INSTRuCT group summarized its consensus expert opinion about local treatment of female genital tract tumors as follows:[159] For girls with genitourinary primary tumors who will receive pelvic irradiation, ovarian transposition (oophoropexy) before radiation therapy should be considered unless dose estimations suggest that ovarian function is likely to be preserved.[160] Alternatively, ovarian tissue preservation is under investigation and can be considered.[161] › Initial complete surgical resection before chemotherapy can be avoided in most cases:

Vaginal: Vaginectomy is unnecessary.

Vulva, vagina, or uterus. For patients with genitourinary primary tumors of the vulva, vagina, or uterus, the initial surgical procedure is usually a vulvar or transvaginal biopsy. Initial radical surgery is not indicated for rhabdomyosarcoma of the vulva, vagina, or uterus.[4] Conservative surgical intervention for vaginal rhabdomyosarcoma, with primary chemotherapy and radiation (external beam or brachytherapy) for Group II or III disease results in excellent 5-year survival rates.[53,154,155][Level of evidence C1] In the COG-ARST0331 study, there was an unacceptably high rate of local recurrences in girls with Group III vaginal tumors who did not receive RT.[53][Level of evidence C2] In 21 girls with genitourinary tract disease who were not treated with RT (mostly Group III vaginal primary tumors), the 3-year FFS rate was 57%, compared with 77% in the other 45 patients with non–female genitourinary primary tumors (P = .02).[54][Level of evidence B4] Therefore, the COG-STS recommended that RT be administered to patients with residual viable vaginal tumor, beginning at week 12.[55][Level of evidence C1] Because of the small number of patients with uterine rhabdomyosarcoma, it is difficult to make a definitive treatment decision, but chemotherapy with or without RT is effective.[154,156] Twelve of 14 girls with primary cervical embryonal (mainly botryoid) rhabdomyosarcoma were disease-free after VAC chemotherapy and conservative surgery. Of note, two girls also had a pleuropulmonary blastoma and another had a Sertoli-Leydig cell tumor.[157] Exenteration is usually not required for primary tumors at these sites, but may be done if needed, with rectal preservation possible in most cases. Four cooperative groups in the United States and Europe evaluated patients with localized vaginal or uterine tumors (N = 427). Some patients received initial RT for local control of residual disease after induction chemotherapy, while others had it later, or not at all if no demonstrable disease was found. The 10-year EFS rate was 74%, and the 10-year OS rate was 92%. Unfavorable factors were positive lymph node disease and uterine corpus primary site. There was no statistical difference in outcomes between patients who received early RT and patients who received later RT. About one-half of these patients were cured without radical surgery or systematic RT.[45][Level of evidence C1] A study of five CWS trials (and one registry) included 67 patients with localized vaginal or uterine rhabdomyosarcoma diagnosed at a median age of 2.89 years (0.09–18.08). Multimodality treatment consisted of chemotherapy (n = 66), secondary surgery (n = 32), and RT (n = 11). The study reported the following results:[158][Level of evidence C1] The INSTRuCT group summarized its consensus expert opinion about local treatment of female genital tract tumors as follows:[159] For girls with genitourinary primary tumors who will receive pelvic irradiation, ovarian transposition (oophoropexy) before radiation therapy should be considered unless dose estimations suggest that ovarian function is likely to be preserved.[160] Alternatively, ovarian tissue preservation is under investigation and can be considered.[161] › Initial complete surgical resection before chemotherapy can be avoided in most cases:

Cervix: Up-front vaginectomy/hysterectomy is usually not indicated.

Vulva, vagina, or uterus. For patients with genitourinary primary tumors of the vulva, vagina, or uterus, the initial surgical procedure is usually a vulvar or transvaginal biopsy. Initial radical surgery is not indicated for rhabdomyosarcoma of the vulva, vagina, or uterus.[4] Conservative surgical intervention for vaginal rhabdomyosarcoma, with primary chemotherapy and radiation (external beam or brachytherapy) for Group II or III disease results in excellent 5-year survival rates.[53,154,155][Level of evidence C1] In the COG-ARST0331 study, there was an unacceptably high rate of local recurrences in girls with Group III vaginal tumors who did not receive RT.[53][Level of evidence C2] In 21 girls with genitourinary tract disease who were not treated with RT (mostly Group III vaginal primary tumors), the 3-year FFS rate was 57%, compared with 77% in the other 45 patients with non–female genitourinary primary tumors (P = .02).[54][Level of evidence B4] Therefore, the COG-STS recommended that RT be administered to patients with residual viable vaginal tumor, beginning at week 12.[55][Level of evidence C1] Because of the small number of patients with uterine rhabdomyosarcoma, it is difficult to make a definitive treatment decision, but chemotherapy with or without RT is effective.[154,156] Twelve of 14 girls with primary cervical embryonal (mainly botryoid) rhabdomyosarcoma were disease-free after VAC chemotherapy and conservative surgery. Of note, two girls also had a pleuropulmonary blastoma and another had a Sertoli-Leydig cell tumor.[157] Exenteration is usually not required for primary tumors at these sites, but may be done if needed, with rectal preservation possible in most cases. Four cooperative groups in the United States and Europe evaluated patients with localized vaginal or uterine tumors (N = 427). Some patients received initial RT for local control of residual disease after induction chemotherapy, while others had it later, or not at all if no demonstrable disease was found. The 10-year EFS rate was 74%, and the 10-year OS rate was 92%. Unfavorable factors were positive lymph node disease and uterine corpus primary site. There was no statistical difference in outcomes between patients who received early RT and patients who received later RT. About one-half of these patients were cured without radical surgery or systematic RT.[45][Level of evidence C1] A study of five CWS trials (and one registry) included 67 patients with localized vaginal or uterine rhabdomyosarcoma diagnosed at a median age of 2.89 years (0.09–18.08). Multimodality treatment consisted of chemotherapy (n = 66), secondary surgery (n = 32), and RT (n = 11). The study reported the following results:[158][Level of evidence C1] The INSTRuCT group summarized its consensus expert opinion about local treatment of female genital tract tumors as follows:[159] For girls with genitourinary primary tumors who will receive pelvic irradiation, ovarian transposition (oophoropexy) before radiation therapy should be considered unless dose estimations suggest that ovarian function is likely to be preserved.[160] Alternatively, ovarian tissue preservation is under investigation and can be considered.[161] › Initial complete surgical resection before chemotherapy can be avoided in most cases:

Uterus: Up-front hysterectomy is usually not indicated.

Vulva, vagina, or uterus. For patients with genitourinary primary tumors of the vulva, vagina, or uterus, the initial surgical procedure is usually a vulvar or transvaginal biopsy. Initial radical surgery is not indicated for rhabdomyosarcoma of the vulva, vagina, or uterus.[4] Conservative surgical intervention for vaginal rhabdomyosarcoma, with primary chemotherapy and radiation (external beam or brachytherapy) for Group II or III disease results in excellent 5-year survival rates.[53,154,155][Level of evidence C1] In the COG-ARST0331 study, there was an unacceptably high rate of local recurrences in girls with Group III vaginal tumors who did not receive RT.[53][Level of evidence C2] In 21 girls with genitourinary tract disease who were not treated with RT (mostly Group III vaginal primary tumors), the 3-year FFS rate was 57%, compared with 77% in the other 45 patients with non–female genitourinary primary tumors (P = .02).[54][Level of evidence B4] Therefore, the COG-STS recommended that RT be administered to patients with residual viable vaginal tumor, beginning at week 12.[55][Level of evidence C1] Because of the small number of patients with uterine rhabdomyosarcoma, it is difficult to make a definitive treatment decision, but chemotherapy with or without RT is effective.[154,156] Twelve of 14 girls with primary cervical embryonal (mainly botryoid) rhabdomyosarcoma were disease-free after VAC chemotherapy and conservative surgery. Of note, two girls also had a pleuropulmonary blastoma and another had a Sertoli-Leydig cell tumor.[157] Exenteration is usually not required for primary tumors at these sites, but may be done if needed, with rectal preservation possible in most cases. Four cooperative groups in the United States and Europe evaluated patients with localized vaginal or uterine tumors (N = 427). Some patients received initial RT for local control of residual disease after induction chemotherapy, while others had it later, or not at all if no demonstrable disease was found. The 10-year EFS rate was 74%, and the 10-year OS rate was 92%. Unfavorable factors were positive lymph node disease and uterine corpus primary site. There was no statistical difference in outcomes between patients who received early RT and patients who received later RT. About one-half of these patients were cured without radical surgery or systematic RT.[45][Level of evidence C1] A study of five CWS trials (and one registry) included 67 patients with localized vaginal or uterine rhabdomyosarcoma diagnosed at a median age of 2.89 years (0.09–18.08). Multimodality treatment consisted of chemotherapy (n = 66), secondary surgery (n = 32), and RT (n = 11). The study reported the following results:[158][Level of evidence C1] The INSTRuCT group summarized its consensus expert opinion about local treatment of female genital tract tumors as follows:[159] For girls with genitourinary primary tumors who will receive pelvic irradiation, ovarian transposition (oophoropexy) before radiation therapy should be considered unless dose estimations suggest that ovarian function is likely to be preserved.[160] Alternatively, ovarian tissue preservation is under investigation and can be considered.[161]

Primary re-excision to achieve complete resection is usually not indicated.

Vulva, vagina, or uterus. For patients with genitourinary primary tumors of the vulva, vagina, or uterus, the initial surgical procedure is usually a vulvar or transvaginal biopsy. Initial radical surgery is not indicated for rhabdomyosarcoma of the vulva, vagina, or uterus.[4] Conservative surgical intervention for vaginal rhabdomyosarcoma, with primary chemotherapy and radiation (external beam or brachytherapy) for Group II or III disease results in excellent 5-year survival rates.[53,154,155][Level of evidence C1] In the COG-ARST0331 study, there was an unacceptably high rate of local recurrences in girls with Group III vaginal tumors who did not receive RT.[53][Level of evidence C2] In 21 girls with genitourinary tract disease who were not treated with RT (mostly Group III vaginal primary tumors), the 3-year FFS rate was 57%, compared with 77% in the other 45 patients with non–female genitourinary primary tumors (P = .02).[54][Level of evidence B4] Therefore, the COG-STS recommended that RT be administered to patients with residual viable vaginal tumor, beginning at week 12.[55][Level of evidence C1] Because of the small number of patients with uterine rhabdomyosarcoma, it is difficult to make a definitive treatment decision, but chemotherapy with or without RT is effective.[154,156] Twelve of 14 girls with primary cervical embryonal (mainly botryoid) rhabdomyosarcoma were disease-free after VAC chemotherapy and conservative surgery. Of note, two girls also had a pleuropulmonary blastoma and another had a Sertoli-Leydig cell tumor.[157] Exenteration is usually not required for primary tumors at these sites, but may be done if needed, with rectal preservation possible in most cases. Four cooperative groups in the United States and Europe evaluated patients with localized vaginal or uterine tumors (N = 427). Some patients received initial RT for local control of residual disease after induction chemotherapy, while others had it later, or not at all if no demonstrable disease was found. The 10-year EFS rate was 74%, and the 10-year OS rate was 92%. Unfavorable factors were positive lymph node disease and uterine corpus primary site. There was no statistical difference in outcomes between patients who received early RT and patients who received later RT. About one-half of these patients were cured without radical surgery or systematic RT.[45][Level of evidence C1] A study of five CWS trials (and one registry) included 67 patients with localized vaginal or uterine rhabdomyosarcoma diagnosed at a median age of 2.89 years (0.09–18.08). Multimodality treatment consisted of chemotherapy (n = 66), secondary surgery (n = 32), and RT (n = 11). The study reported the following results:[158][Level of evidence C1] The INSTRuCT group summarized its consensus expert opinion about local treatment of female genital tract tumors as follows:[159] For girls with genitourinary primary tumors who will receive pelvic irradiation, ovarian transposition (oophoropexy) before radiation therapy should be considered unless dose estimations suggest that ovarian function is likely to be preserved.[160] Alternatively, ovarian tissue preservation is under investigation and can be considered.[161]

Patients with tumors that are localized to the vagina or cervix and who demonstrate incomplete response after induction chemotherapy receive local RT (brachytherapy).

Vulva, vagina, or uterus. For patients with genitourinary primary tumors of the vulva, vagina, or uterus, the initial surgical procedure is usually a vulvar or transvaginal biopsy. Initial radical surgery is not indicated for rhabdomyosarcoma of the vulva, vagina, or uterus.[4] Conservative surgical intervention for vaginal rhabdomyosarcoma, with primary chemotherapy and radiation (external beam or brachytherapy) for Group II or III disease results in excellent 5-year survival rates.[53,154,155][Level of evidence C1] In the COG-ARST0331 study, there was an unacceptably high rate of local recurrences in girls with Group III vaginal tumors who did not receive RT.[53][Level of evidence C2] In 21 girls with genitourinary tract disease who were not treated with RT (mostly Group III vaginal primary tumors), the 3-year FFS rate was 57%, compared with 77% in the other 45 patients with non–female genitourinary primary tumors (P = .02).[54][Level of evidence B4] Therefore, the COG-STS recommended that RT be administered to patients with residual viable vaginal tumor, beginning at week 12.[55][Level of evidence C1] Because of the small number of patients with uterine rhabdomyosarcoma, it is difficult to make a definitive treatment decision, but chemotherapy with or without RT is effective.[154,156] Twelve of 14 girls with primary cervical embryonal (mainly botryoid) rhabdomyosarcoma were disease-free after VAC chemotherapy and conservative surgery. Of note, two girls also had a pleuropulmonary blastoma and another had a Sertoli-Leydig cell tumor.[157] Exenteration is usually not required for primary tumors at these sites, but may be done if needed, with rectal preservation possible in most cases. Four cooperative groups in the United States and Europe evaluated patients with localized vaginal or uterine tumors (N = 427). Some patients received initial RT for local control of residual disease after induction chemotherapy, while others had it later, or not at all if no demonstrable disease was found. The 10-year EFS rate was 74%, and the 10-year OS rate was 92%. Unfavorable factors were positive lymph node disease and uterine corpus primary site. There was no statistical difference in outcomes between patients who received early RT and patients who received later RT. About one-half of these patients were cured without radical surgery or systematic RT.[45][Level of evidence C1] A study of five CWS trials (and one registry) included 67 patients with localized vaginal or uterine rhabdomyosarcoma diagnosed at a median age of 2.89 years (0.09–18.08). Multimodality treatment consisted of chemotherapy (n = 66), secondary surgery (n = 32), and RT (n = 11). The study reported the following results:[158][Level of evidence C1] The INSTRuCT group summarized its consensus expert opinion about local treatment of female genital tract tumors as follows:[159] For girls with genitourinary primary tumors who will receive pelvic irradiation, ovarian transposition (oophoropexy) before radiation therapy should be considered unless dose estimations suggest that ovarian function is likely to be preserved.[160] Alternatively, ovarian tissue preservation is under investigation and can be considered.[161]

Hysterectomy is indicated for patients with tumors of the corpus uteri who have persistent tumor after definitive initial therapy.

Vulva, vagina, or uterus. For patients with genitourinary primary tumors of the vulva, vagina, or uterus, the initial surgical procedure is usually a vulvar or transvaginal biopsy. Initial radical surgery is not indicated for rhabdomyosarcoma of the vulva, vagina, or uterus.[4] Conservative surgical intervention for vaginal rhabdomyosarcoma, with primary chemotherapy and radiation (external beam or brachytherapy) for Group II or III disease results in excellent 5-year survival rates.[53,154,155][Level of evidence C1] In the COG-ARST0331 study, there was an unacceptably high rate of local recurrences in girls with Group III vaginal tumors who did not receive RT.[53][Level of evidence C2] In 21 girls with genitourinary tract disease who were not treated with RT (mostly Group III vaginal primary tumors), the 3-year FFS rate was 57%, compared with 77% in the other 45 patients with non–female genitourinary primary tumors (P = .02).[54][Level of evidence B4] Therefore, the COG-STS recommended that RT be administered to patients with residual viable vaginal tumor, beginning at week 12.[55][Level of evidence C1] Because of the small number of patients with uterine rhabdomyosarcoma, it is difficult to make a definitive treatment decision, but chemotherapy with or without RT is effective.[154,156] Twelve of 14 girls with primary cervical embryonal (mainly botryoid) rhabdomyosarcoma were disease-free after VAC chemotherapy and conservative surgery. Of note, two girls also had a pleuropulmonary blastoma and another had a Sertoli-Leydig cell tumor.[157] Exenteration is usually not required for primary tumors at these sites, but may be done if needed, with rectal preservation possible in most cases. Four cooperative groups in the United States and Europe evaluated patients with localized vaginal or uterine tumors (N = 427). Some patients received initial RT for local control of residual disease after induction chemotherapy, while others had it later, or not at all if no demonstrable disease was found. The 10-year EFS rate was 74%, and the 10-year OS rate was 92%. Unfavorable factors were positive lymph node disease and uterine corpus primary site. There was no statistical difference in outcomes between patients who received early RT and patients who received later RT. About one-half of these patients were cured without radical surgery or systematic RT.[45][Level of evidence C1] A study of five CWS trials (and one registry) included 67 patients with localized vaginal or uterine rhabdomyosarcoma diagnosed at a median age of 2.89 years (0.09–18.08). Multimodality treatment consisted of chemotherapy (n = 66), secondary surgery (n = 32), and RT (n = 11). The study reported the following results:[158][Level of evidence C1] The INSTRuCT group summarized its consensus expert opinion about local treatment of female genital tract tumors as follows:[159] For girls with genitourinary primary tumors who will receive pelvic irradiation, ovarian transposition (oophoropexy) before radiation therapy should be considered unless dose estimations suggest that ovarian function is likely to be preserved.[160] Alternatively, ovarian tissue preservation is under investigation and can be considered.[161]

Fertility preservation is a consideration for all patients.[159]