Unlike colon cancer, primary cancers of the rectum are prone to local recurrence; the consequences of such recurrences (severe pain and altered bowel function) are serious and affect both the duration and quality of life. Since 1990, the routine treatment approach to patients with stage II and III rectal cancer has involved the use of postoperative adjuvant chemotherapy plus radiation therapy, a practice that reduced local recurrence rates from 20-25% to about 15%. A similar reduction in recurrence rate was observed as a consequence of the adoption of a novel surgical technique called total mesorectal resection, in which the rectum is excised with its mesentery. Together, these two techniques (adjuvant therapy plus total mesorectal resection) have reduced recurrence rates to about 10%.
Preoperative or neoadjuvant therapy has several potential advantages over postoperative adjuvant therapy. Effective preoperative therapy may reduce tumor bulk and make the surgical procedure technically easier and result in better sphincter preservation. Such therapy may result in downstaging of the tumor. Preoperative radiation therapy may be more effective because it avoids irradiating tissue that may have been rendered hypoxic by the surgical procedure. Furthermore, radiation complications may be minimized because the unoperated bowel (particularly the small bowel) retains the capacity to move away from the radiation field, an adaptation that is lost when the bowel forms postoperative adhesions anchoring it in place.
The German Rectal Cancer Study Group conducted a prospective randomized comparison of preoperative vs postoperative chemoradiotherapy in 823 patients with stage II or III rectal cancer (Sauer et al, 2004) . The group receiving preoperative treatment received 5040 cGy of radiation therapy delivered in 180-cGy fractions 5 days a week plus 5-fluorouracil (5FU) by 120-h continuous infusion at 1000 mg/m2 per day during weeks 1 and 5 of the radiation therapy. Surgery was performed 6 weeks after completion of the preoperative therapy and 1 month after the surgery; patients received four 5-day cycles of 5FU by continuous infusion at 500 mg/m2 per day. In patients randomly assigned to the postoperative adjuvant therapy arm, the identical regimen of chemoradiotherapy was begun 4 weeks after the surgery and the adjuvant 5FU started 4 weeks after the chemoradiotherapy was completed. In addition, the latter group received a 540-cGy boost to the tumor bed.
With a median follow-up of nearly 4 years, overall 5-year survival was the same on the two arms: 76% for preoperative therapy and 74% for postoperative therapy. However, the preoperative group had less than half the number of local recurrences compared with the postoperative group (6% vs 13%; p > = .006). In addition, 8% of the preoperative group had a pathologic complete response to the chemoradiotherapy, a higher percentage of patients were able to complete the prescribed treatment, and the acute and chronic toxicities were less severe.
Thus, current recommendations for rectal cancer include the following: patients should be clinically staged with endorectal ultrasonography or magnetic resonance imaging; those with clinical stage II or ...