Combined modality therapy for rectal cancer: too much too often?

The refinement and implementation of multimodal therapy for rectal cancer, including surgery, radiotherapy, and chemotherapy, is certainly one of the most meaningful achievements in the history of clinical cancer research to date. It is thus important to set any harsh critique of current treatment methods and outcomes within this context. Just 30 years ago, the risk of local recurrence after rectal resection ranged from 20 to 40 %. It was often lethal and was associated with significant morbidity, pain, and suffering. This began to change with the report from the National Surgical Adjuvant Breast and Bowel Project (NSABP) Cooperative Group R01 trial in 1985, which demonstrated a reduction in local recurrence from 25 to 16 % with the addition of postoperative long-course chemoradiotherapy. The NSABP trial was followed by serial studies designed to improve results through addition and resequencing. The Gastrointestinal Tumor Study Group (GITSG) reported a 55–33 % reduction in all recurrence with the addition of adjuvant chemotherapy and radiotherapy, leading the National Institutes of Health to generate a consensus statement asserting that chemoradiotherapy should be delivered postoperatively for all stage II and III tumors. The German Rectal Cancer Study later demonstrated improved outcome when long-course chemoradiotherapy was delivered preoperatively rather than postoperatively to clinical stage II and III rectal cancers. Local recurrence at 46 months was reduced from 13 to 6 % without change in distant recurrence. At 10 years, the difference in local recurrence was of a lower magnitude but remained significant (7 vs. 10 %). Disease-free and overall survival did not differ between the groups. This changed the standard of practice to preoperative rather than postoperative long-course chemoradiotherapy for stage II and III rectal cancers. While North America and Central Europe employed a regimen of long-course postoperative chemoradiotherapy administered over 5–6 weeks, Northern Europe was utilizing short-course radiotherapy delivered over 5 days before surgery, and demonstrating similar improvements in outcome. The Swedish Rectal Cancer Trial showed that preoperative short-course radiotherapy reduced local recurrence from 27 to 11 % and increased survival from 65 to 74 % compared with surgery alone. This brings us to 2013, when patients are much less likely to experience local recurrence and more likely to retain sphincter function than decades ago. However, two reports in this issue of Annals of Surgical Oncology remind us that more is not necessarily better, and that one size does not fit all. Lange et al. report on a series of rectal cancer patients treated traditionally under the supervision of Warren Enker, an international leader and pioneer who has spent his career spreading the word about the methodical techniques of anatomic rectal resection and the benefits of total mesorectal excision. In total, 368 patients underwent rectal resection, with a median follow-up of 8 years. Seventy percent underwent sphincter-preserving surgery, with an average anastomotic height of 5.4 cm. Only 5 % of patients undergoing low anterior resection experienced anastomotic leak. The oncologic results are equally impressive. Five-year overall survival was 76 %: 92 % for stage I disease, 78 % for stage II disease, and 69 % for stage III disease. The 5-year local recurrence rate was 5.2 %: 0.8 % for stage I disease, 4.7 % for stage II disease, and 5.4 % for stage III disease. The 5-year rate of distant metastasis was 22 %: 3.9 % for stage I disease, 21 % for stage II disease, and 27 % for stage III disease. Analysis of functional outcome was measured in 50 patients. Irradiated patients had, on average, 3.2 bowel movements per day, compared to 1.2 in nonirradiated Society of Surgical Oncology 2013