Downstaging after preoperative chemoradiation for locally advanced rectal cancer is associated with better survival than pathologic stage 0–1 disease treated with upfront surgery

Abstract

Abstract Background and objectives It is unknown how patients with locally advanced rectal cancer with significant response to preoperative radiotherapy/chemoradiotherapy fare relative to patients with true pathologic 0–1 disease undergoing upfront surgery. We aimed to determine whether survival is improved in locally advanced rectal cancer downstaged to pathologic stage 0–1 disease compared to true pathologic stage 0–1 tumors. Methods A retrospective review of the National Cancer Database between 2004 and 2016 was conducted. Three groups were identified: (1) clinical stage 2–3 disease downstaged to pathologic stage 0–1 disease after radiotherapy, (2) clinical stage 2–3 disease not downstaged after radiotherapy, and (3) true pathologic 0–1 tumors undergoing upfront surgery. The primary endpoint was overall survival and was compared using Kaplan–Meier and multivariate Cox regression analyses. Results The study population consisted of 59,884 patients. Of the 40,130 patients with locally advanced rectal cancer treated with preoperative radiation, 12,670 (31.5%) had significant downstaging (group 1), while 27,460 (68.4%) had no significant downstaging (group 2). A total of 19,754 had pathologic 0–1 disease treated with upfront resection (group 3). On Kaplan–Meier analysis, downstaged patients had significantly better overall survival compared to both non-downstaged and true pathologic stage 0–1 patients (median 156 vs. 99 and 136 months, respectively, p < 0.001). On multivariate analysis, downstaged patients had significantly better survival (HR 0.88, p < 0.001) compared to true pathologic 0–1 patients. Conclusions Locally advanced rectal cancer downstaged after preoperative radiotherapy has significantly better survival compared to true pathologic stage 0–1 disease treated with upfront surgery. Response to chemoradiotherapy likely identifies a subset of patients with a particularly good prognosis.