A pathologic complete response of rectal cancer to preoperative combined-modality therapy results in improved oncological outcome compared with those who achieve no downstaging on the basis of preoperative endorectal ultrasonography

Background: Preoperative combined-modality therapy (CMT) is the preferred treatment for locally advanced rectal cancer (endorectal ultrasonography [ERUS] T3-4, N1, or clinically bulky) and achieves a pathologic complete response (pCR) in 4% to 33% of patients. However, the prognostic significance of pCR remains unclear. Methods: A prospectively collected database was queried to identify 200 patients with locally advanced disease treated from 1992 to 2002. The pCR group was defined as having no evidence of viable tumor on pathologic analysis. The no-downstaging group was defined as no difference between the pre-CMT ERUS stage and the pathologic stage. Those achieving some downstaging but not pCR were excluded. Patients were treated with CMT (5040 cGy of radiation and 5-fluorouracil-based chemotherapy) followed by surgery, and 51 (85%) in the pCR group and 129 (92%) in the no-downstaging group (P = .1) received postoperative chemotherapy. Recurrence-free survival (RFS) and overall survival (OS) were determined by using the Kaplan-Meier method. Results: The median follow-up was 38.6 months (range, 18.2-124.9 months). The pCR (n = 60) and control (n = 140) groups were similar in age (P = .6), sex (P = .4), distance of the tumor from the anal verge (P = .3), pre-CMT ERUS stage (P = .2), and comorbidities (P = .2). The 5-year RFS was 96% and 54% in the pCR and control groups, respectively (P < .00001); the 5-year OS was 90% and 68% (P = .009). Sphincter-preservation rates were higher in the pCR group (P = .01). Conclusions: Rectal cancer patients with pCR after preoperative CMT have improved RFS, OS, and sphincter preservation compared with patients without downstaging. Because pCR seems to be associated with better outcome, an understanding of the factors governing the response to CMT should be pursued.