Findings on Value of Pre- Versus Post-Operative Therapy for
Sauer R, Becker H, Hohenberger W, et al.
N Engl J Med. 2004;351:1731-1740.

Postoperative chemoradiotherapy is recommended as the standard treatment for locally advanced rectal cancer. Encouraging results recently have been reported with preoperative radiotherapy as well. To gauge usefulness and superiority in locally advanced rectal cancer, we compared these 2 treatment protocols. The primary end point of the study was overall survival.

Patients with clinical stage T3 or T4 or node-positive disease were randomly assigned to receive either preoperative chemoradiotherapy (n = 421) or postoperative chemoradiotherapy (n = 402). The preoperative regimen, which was completed 6 weeks before surgery, consisted of 5040 cGy delivered in fractions of 180 cGy per day, 5 days per week, and a 120-hour continuous intravenous infusion of fluorouracil 1000 mg/m of body surface area per day during the first and fifth weeks of radiotherapy. A month following surgery, patients in both study groups received four 5-day cycles of fluorouracil (500 mg/m/d). Chemoradiotherapy was identical in the postoperative-treatment group, except for the delivery of a boost of 540 cGy.

The overall 5-year survival rates were comparable: 76% among patients randomized to preoperative chemoradiotherapy and 74% among patients only receiving chemoradiotherapy postoperatively (P = .80). However, the 5-year cumulative incidence of local relapse was 6% for patients assigned to the preoperative regimen and 13% for those only receiving postoperative treatment (P = .006). Grade 3 or 4 acute toxic effects occurred more frequently among patients in the postoperative-treatment group: 40% versus 27% in the preoperative-treatment group (P = .001). Corresponding rates of long-term toxic effects also were observed: 24% among patients receiving only postoperative treatment and 14% among those receiving preoperative chemoradiotherapy (P = .01).

The findings suggest that preoperative chemoradiotherapy provides improved local control and reduces incidence of acute and long-term toxic effects but does not result in a survival advantage over standard postoperative chemoradiotherapy.