Comparative effectiveness of postoperative chemotherapy among older patients with non-metastatic rectal cancer treated with preoperative chemoradiotherapy.

Abstract

Postoperative chemotherapy is standard following preoperative chemoradiation therapy (CRT) and curative resection for clinically staged II/III rectal cancer. Recent trials have questioned whether postoperative chemotherapy improves overall survival. The objective of the study was to evaluate the comparative effectiveness of postoperative chemotherapy following CRT or radiation therapy (RT) with specific attention to the impact of age on postoperative chemotherapy effectiveness. Patients treated with CRT or RT then resection of pathologically staged 0-III rectal cancer diagnosed from 2004 to 2009 were identified from the Surveillance, Epidemiology and End Results program-Medicare database. Propensity score weighted Cox proportional hazards models and Kaplan Meier methods were used to compare the effectiveness of 1) postoperative 5-fluorouracil (5-FU) or capecitabine to no treatment and 2) postoperative oxaliplatin+5-FU/capecitabine to 5-FU/capecitabine alone on mortality. Results were stratified by age. We identified 1316 patients; 49% received postoperative chemotherapy, 341 (52%) included oxaliplatin. After weighting, postoperative 5-FU/capecitabine alone was associated with decreased mortality in patients aged 66-74 (adjusted hazard ratio (aHR)=0.46, 95% CI: 0.30, 0.72), corresponding to a 5-year risk difference of -0.23, (95% CI: -0.33, -0.12). No further mortality reduction from adding oxaliplatin to 5-FU/capecitabine was seen in patients aged 66-74 (aHR=1.57, 95% CI: 0.93, 2.65). No mortality reduction for 5-FU/capecitabine alone was observed among patients aged 75+ (aHR=1.11, 95% CI: 0.76, 1.63). Among patients <75years, postoperative 5-FU/capecitabine was associated with reduced mortality after preoperative CRT/RT and surgical resection; however, the addition of oxaliplatin was not associated with further mortality reduction. Decisions regarding postoperative chemotherapy after age 75 warrant consideration of individual patient risks and preferences, as benefits may be limited.