Stage III Rectal Cancer
The German Rectal Cancer Study Group randomly assigned 823 patients with ultrasound (US)-staged T3/T4 or node-positive rectal cancer to either preoperative chemoradiation or postoperative chemoradiation (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). All patients received a TME and an additional four cycles of 5-FU-based chemotherapy. The 5-year OS rates were 76% and 74% for preoperative and postoperative chemoradiation, respectively (P = .80). The 5-year cumulative incidence of local relapse was 6% for patients assigned to preoperative chemoradiation therapy and 13% in the postoperative-treatment group (P = .006). Grade 3 or 4 acute toxic effects occurred in 27% of the patients in the preoperative-treatment group as compared with 40% of the patients in the postoperative-treatment group (P = .001); the corresponding rates of long-term toxic effects were 14% and 24%, respectively (P = .01).[Level of evidence: 1iA] There was no difference in the number of patients receiving an 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).
Of the patients assigned to the postoperative chemoradiation arm, 18% actually had pathologically determined stage I disease and were overestimated by endorectal US to have T3/T4 or node-positive disease. A similar number of patients may have been overtreated in the preoperative treatment group. Nevertheless, on the basis of this study, preoperative chemoradiation therapy has become the standard of care for patients with clinically staged T3/T4 or node-positive disease.
Current Clinical Trials
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage III rectal cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
O'Connell MJ, Martenson JA, Wieand HS, et al.: Improving adjuvant therapy for rectal cancer by combining protracted-infusion fluorouracil with radiation therapy after curative surgery. N Engl J Med 331 (8): 502-7, 1994.
Tepper JE, O'Connell M, Niedzwiecki D, et al.: Adjuvant therapy in rectal cancer: analysis of stage, sex, and local control--final report of intergroup 0114. J Clin Oncol 20 (7): 1744-50, 2002.
Smalley SR, Benedetti JK, Williamson SK, et al.: Phase III trial of fluorouracil-based chemotherapy regimens plus radiotherapy in postoperative adjuvant rectal cancer: GI INT 0144. J Clin Oncol 24 (22): 3542-7, 2006.
Sauer R, Becker H, Hohenberger W, et al.: Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med 351 (17): 1731-40, 2004.