Preoperative chemoradiation therapy

The German Rectal Cancer Study Group (CAO/ARO/AIO-94 [Working Group of Surgical Oncology/Working Group of Radiation Oncology/Working Group of Medical Oncology of the Germany Cancer Society]) randomly assigned 823 patients with ultrasound-staged T3 or T4 or lymph node-positive rectal cancer to either preoperative chemoradiation therapy or postoperative chemoradiation therapy (50.4 Gy in 28 daily fractions to the tumor and pelvic lymph nodes concurrent with infusional 5-FU 1,000 mg/m2 daily for 5 days during the first and fifth weeks of radiation therapy).[2][Level of evidence A1] All patients underwent total mesorectal excision and received four additional cycles of 5-FU–based chemotherapy.

The German Rectal Cancer Study Group (CAO/ARO/AIO-94 [Working Group of Surgical Oncology/Working Group of Radiation Oncology/Working Group of Medical Oncology of the Germany Cancer Society]) randomly assigned 823 patients with ultrasound-staged T3 or T4 or lymph node-positive rectal cancer to either preoperative chemoradiation therapy or postoperative chemoradiation therapy (50.4 Gy in 28 daily fractions to the tumor and pelvic lymph nodes concurrent with infusional 5-FU 1,000 mg/m2 daily for 5 days during the first and fifth weeks of radiation therapy).[2][Level of evidence A1] All patients underwent total mesorectal excision and received four additional cycles of 5-FU–based chemotherapy.

The 5-year overall survival (OS) rates were 76% for preoperative chemoradiation therapy and 74% for postoperative chemoradiation therapy (P = .80). The 5-year cumulative incidence of local relapse was 6% for patients assigned to the preoperative chemoradiation therapy group and 13% for patients in the postoperative chemoradiation therapy group (P = .006).

The German Rectal Cancer Study Group (CAO/ARO/AIO-94 [Working Group of Surgical Oncology/Working Group of Radiation Oncology/Working Group of Medical Oncology of the Germany Cancer Society]) randomly assigned 823 patients with ultrasound-staged T3 or T4 or lymph node-positive rectal cancer to either preoperative chemoradiation therapy or postoperative chemoradiation therapy (50.4 Gy in 28 daily fractions to the tumor and pelvic lymph nodes concurrent with infusional 5-FU 1,000 mg/m2 daily for 5 days during the first and fifth weeks of radiation therapy).[2][Level of evidence A1] All patients underwent total mesorectal excision and received four additional cycles of 5-FU–based chemotherapy.

Grade 3 or 4 acute toxic effects occurred in 27% of patients in the preoperative-treatment group and in 40% of patients in the postoperative-treatment group (P = .001). The corresponding rates of long-term toxic effects were 14% and 24%, respectively (P = .01).

The German Rectal Cancer Study Group (CAO/ARO/AIO-94 [Working Group of Surgical Oncology/Working Group of Radiation Oncology/Working Group of Medical Oncology of the Germany Cancer Society]) randomly assigned 823 patients with ultrasound-staged T3 or T4 or lymph node-positive rectal cancer to either preoperative chemoradiation therapy or postoperative chemoradiation therapy (50.4 Gy in 28 daily fractions to the tumor and pelvic lymph nodes concurrent with infusional 5-FU 1,000 mg/m2 daily for 5 days during the first and fifth weeks of radiation therapy).[2][Level of evidence A1] All patients underwent total mesorectal excision and received four additional cycles of 5-FU–based chemotherapy.

The same number of patients underwent abdominoperineal resection in each arm. However, among the 194 patients with tumors that were determined by the surgeon before randomization to require an abdominoperineal excision, a statistically significant increase in sphincter preservation was achieved among patients who received preoperative chemoradiation therapy (P = .004). These results have now been updated with a median follow-up of 11 years.[3]

The German Rectal Cancer Study Group (CAO/ARO/AIO-94 [Working Group of Surgical Oncology/Working Group of Radiation Oncology/Working Group of Medical Oncology of the Germany Cancer Society]) randomly assigned 823 patients with ultrasound-staged T3 or T4 or lymph node-positive rectal cancer to either preoperative chemoradiation therapy or postoperative chemoradiation therapy (50.4 Gy in 28 daily fractions to the tumor and pelvic lymph nodes concurrent with infusional 5-FU 1,000 mg/m2 daily for 5 days during the first and fifth weeks of radiation therapy).[2][Level of evidence A1] All patients underwent total mesorectal excision and received four additional cycles of 5-FU–based chemotherapy.

The 10-year OS was equivalent in both arms, (59.6% in the preoperative group vs. 59.9% in the postoperative group; P = .85). However, a local control benefit persists among patients treated with preoperative chemoradiation therapy compared with patients treated with postoperative chemoradiation therapy (10-year cumulative incidence of local relapse: 7.1% in the preoperative group vs. 10.1% in the postoperative group; P = .048). There were no significant differences detected for 10-year cumulative incidence of distant metastases or disease-free survival (DFS).[3]

The German Rectal Cancer Study Group (CAO/ARO/AIO-94 [Working Group of Surgical Oncology/Working Group of Radiation Oncology/Working Group of Medical Oncology of the Germany Cancer Society]) randomly assigned 823 patients with ultrasound-staged T3 or T4 or lymph node-positive rectal cancer to either preoperative chemoradiation therapy or postoperative chemoradiation therapy (50.4 Gy in 28 daily fractions to the tumor and pelvic lymph nodes concurrent with infusional 5-FU 1,000 mg/m2 daily for 5 days during the first and fifth weeks of radiation therapy).[2][Level of evidence A1] All patients underwent total mesorectal excision and received four additional cycles of 5-FU–based chemotherapy.

Among the patients assigned to the postoperative chemoradiation therapy treatment arm, 18% actually had pathologically determined stage I disease and were overestimated by endorectal ultrasound to have T3 or T4 or N1 disease. A similar number of patients were possibly overtreated in the preoperative treatment group.

The NSABP R-03 trial (NCT00410579) similarly compared preoperative versus postoperative chemoradiation therapy for patients with clinically staged T3 or T4 or lymph node-positive rectal cancer. Chemotherapy consisted of 5-FU/LV with 45 Gy in 25 fractions with a 5.4 Gy boost. Although the intended sample size was 900 patients, the study with 267 patients closed early because of poor accrual.[4][Level of evidence A1]

The NSABP R-03 trial (NCT00410579) similarly compared preoperative versus postoperative chemoradiation therapy for patients with clinically staged T3 or T4 or lymph node-positive rectal cancer. Chemotherapy consisted of 5-FU/LV with 45 Gy in 25 fractions with a 5.4 Gy boost. Although the intended sample size was 900 patients, the study with 267 patients closed early because of poor accrual.[4][Level of evidence A1]

With a median follow-up of 8.4 years, preoperative chemoradiation therapy was found to confer a significant improvement in 5-year DFS (64.7% vs. 53.4% for postoperative patients; P = .011).

The NSABP R-03 trial (NCT00410579) similarly compared preoperative versus postoperative chemoradiation therapy for patients with clinically staged T3 or T4 or lymph node-positive rectal cancer. Chemotherapy consisted of 5-FU/LV with 45 Gy in 25 fractions with a 5.4 Gy boost. Although the intended sample size was 900 patients, the study with 267 patients closed early because of poor accrual.[4][Level of evidence A1]

Similar to the German Rectal Cancer Study, there was no significant difference in OS between treatment arms (74.5% for preoperative chemoradiation therapy vs. 65.6% for postoperative chemoradiation therapy; P =. 065).