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

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.