Survival Benefit of Preoperative Versus Postoperative Radiotherapy in Metastatic Rectal Cancer Treated With Definitive Surgical Resection of Primary Tumor: A Population Based, Propensity Score-Matched Study

Preoperative chemoradiation followed by surgery has been recommended as a standard treatment for patients with stage II/III rectal cancer. However, the optimal sequencing of radiotherapy for metastatic rectal cancer remains unclear. Between 2004 and 2014, patients diagnosed with metastatic rectal cancer who underwent the resection of primary site and received radiotherapy were retrospectively selected using the Surveillance, Epidemiology, and End Results (SEER) database. The propensity score matching analyses were used to lessen the effects of confounding factors including age, sex, race, marital status, serum carcinoembryonic antigen level, histologic type, differentiation status, tumor size, T stage, N stage and resection of the distant lesions. The cancer-specific survival (CSS) were compared based on the sequencing of radiotherapy. Ultimately, 686 matched pairs were formed for comparison of preoperative versus postoperative radiotherapy. The 5-year CSS estimates were 33.4% (95% CI: 28.9%-37.9%) and 26.8% (95% CI: 22.7%-30.9%) for patients underwent preoperative radiotherapy followed by resection of primary lesion and postoperative radiotherapy after surgery, respectively. Patients underwent preoperative radiotherapy had better CSS as compared to patients received postoperative radiotherapy (p<0.001 for log-rank test). Multivariate analysis demonstrated that preoperative radiotherapy group was associated with significantly decreased risk for cancer death (HR=0.820, 95% CI: 0.712-0.945, p=0.006). Preoperative radiotherapy was superior to postoperative radiotherapy in patients with metastatic rectal cancer. Therapeutic strategy for these patients should be further explored.