These results have now been updated with a median follow-up of 11 years. The 10-year overall survival (OS) is equivalent in both arms (10-year OS, 59.6% vs. 59.9%, respectively P = .85). However, a local-control benefit persists among patients treated with preoperative chemoradiation compared with postoperative chemoradiation (10-year cumulative of local relapse, 7.1% vs. 10.1%, respectively; P = .048). There were no significant differences detected for a 10-year cumulative incidence of distant metastases or disease-free survival (DFS). Among the patients assigned to the postoperative chemoradiation 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.
National Surgical Adjuvant Breast and Bowel Project (NSABP)
The NSABP R-03 trial similarly compared preoperative with postoperative chemoradiation therapy for patients with clinical T3 or T4 or node-positive rectal cancer. Chemotherapy consisted of fluorouracil and leucovorin with 45 Gy in 25 fractions with a 5.4 Gy boost. Although the intended sample size was 900 patients, the study closed early because of poor accrual, with 267 patients. With a median follow-up of 8.4 years, preoperative chemoradiation was found to confer a significant improvement in 5-year DFS (64.7% vs. 53.4% for postoperative patients, P = .011). Similar to the German Rectal Study, there was no significant difference seen in OS between treatment arms (74.5% vs. 65.6%, P = .065 for preoperative vs. postoperative chemoradiation).[Level of evidence: 1iiA]
Postoperative Chemoradiation Therapy
Recent progress in adjuvant postoperative treatment regimens relates to the integration of systemic therapy with radiation therapy, as well as redefining the techniques for both modalities. The efficacy of postoperative radiation therapy and 5-FU-based chemotherapy for stage II and III rectal cancer was established by a series of prospective, randomized clinical trials from the Gastrointestinal Tumor Study Group (GITSG-7175), the Mayo/North Central Cancer Treatment Group (NCCTG-794751), and the National Surgical Adjuvant Breast and Bowel Project (NSABP-R-01).[10,11,12][Level of evidence: 1iiA] These studies demonstrated an increase in both disease-free survival (DFS) interval and OS when radiation therapy was combined with chemotherapy after surgical resection. Following publication of the results of these trials, experts at a National Cancer Institute-sponsored Consensus Development Conference in 1990 concluded that postoperative combined-modality treatment is recommended for patients with stage II and III rectal carcinoma.