The right study design is needed to find out which patients benefit from preoperative chemoradiotherapy for intermediate staged rectal cancer.

BACKGROUND The aim of this study was to identify subgroups that benefit from preoperative or postoperative chemoradiotherapy (CRT) for rectal cancer of intermediate stage. PATIENTS AND METHODS Between 1999 and 2004, 118 and 177 patients matched with respect to clinical T stage, circumferential tumor extent (= 60% / > 60%), lymph node metastasis, and lymph node size (< 1 cm / ≥ 1 cm), were allocated to preoperative CRT and postoperative CRT, respectively. In preoperative CRT, a total of 45 Gy was delivered with chemotherapy, and then surgery followed. In postoperative CRT, 45-51 Gy was delivered with chemotherapy following primary surgery. RESULTS Local recurrence, distant metastasis, disease-free survival, and disease-specific survival were not different between the two schemes. For a circumferential tumor extent of = 60%, local recurrence in preoperative CRT (3.6%) was lower than in postoperative CRT (11.9%) (p = 0.084, hazard ratio (HR) = 0.274, 95% confidence interval (CI) = 0.058-1.032). For a tumor located < 5cm from the anal verge, distant metastasis in preoperative CRT (18.9%) was lower than in postoperative CRT (34.4%) (p = 0.061, HR = 0.444, 95% CI = 0.188- 1.047), and 5-year disease-free survival rates in preoperative and postoperative CRT were 72.0 and 59.0%, respectively (p = 0.078). CONCLUSIONS Our findings suggest that preoperative CRT might be appropriate in rectal cancer involving the limited circumferential lumen and located in the low rectum. However, further prospective studies are required.