COG and SIOP approaches to Wilms tumor treatment

COG RTC (includes the previous NWTS group): The NWTS group established standard treatment for Wilms tumor in North America, consisting of initial nephrectomy (when feasible) followed by chemotherapy and, in some patients, radiation therapy.[219-221] This approach allows for early and accurate histological diagnosis, collection of biological materials unaltered by therapy, and staging information, such as the presence of tumor spill or tumor involvement in lymph nodes, before chemotherapy is administered.

SIOP: SIOP is a European consortium whose trials provide preoperative chemotherapy before definitive resection for patients with renal tumors. This results in fewer tumor spills during surgery and lower postoperative stage.[222] When the histological features of Wilms tumors from patients who underwent immediate surgery were compared with the histological features of patients who received preoperative chemotherapy, preoperative chemotherapy was shown to significantly alter the histology, with fewer blastemal and mixed histology types in the tumors. Additionally, there were fewer stage III tumors in the preoperative chemotherapy group.[223]

Both SIOP and COG treat infants younger than 6 months with a primary nephrectomy.[224]

Routine, postoperative radiation therapy of the flank is not necessary for children with stage I tumors or stage II tumors with FH when postnephrectomy combination chemotherapy consisting of vincristine and dactinomycin is administered.[221]

The prognosis for patients with stage III FH is best when treatment includes either (a) dactinomycin, vincristine, doxorubicin, and 10.8 Gy of radiation therapy to the flank; or (b) dactinomycin, vincristine, and 20 Gy of radiation therapy to the flank. Whole-abdominal radiation is indicated for extensive intraperitoneal disease or widespread intraperitoneal tumor spill with possible boost to gross residual disease.[221]

The addition of cyclophosphamide at the protocol dose (10 mg/kg/d for 3 days every 6 weeks) to the combination of vincristine, dactinomycin, and doxorubicin does not improve prognosis for patients with stage IV FH tumors.[221]

A single dose of dactinomycin per course (stages I–II FH, stage I anaplastic histology, stage III FH, stages III–IV, or stages I–IV clear cell sarcoma of the kidney) is equivalent to the divided-dose courses, results in the same EFS, achieves greater dose intensity, and is associated with less toxicity and expense.[225]

Eighteen weeks of therapy is adequate for patients with stage I and stage II FH, and stage III and IV patients can be treated with 6 months of therapy instead of 15 months.[180,219,225-227]

Gain of 1q is associated with inferior survival in patients with unilateral FH Wilms tumor. It is the single most powerful predictor of outcome, and in the presence of 1q gain, neither 1p nor 16q loss is significant. In the absence of 1q gain in unilateral FH Wilms tumor, 1p and/or 16q loss retain some prognostic significance and are associated with a higher risk of recurrence.[107,110]