Impact of Duration of Neoadjuvant Radiation on Rectal Cancer Survival: A Real World Multi-center Retrospective Cohort Study

The optimal duration of neoadjuvant radiotherapy in rectal cancer remains controversial. This is a multi-center retrospective cohort study. Appropriate preoperative selection of radiotherapy duration was not associated with survival differences. Background: The utility of neoadjuvant radiotherapy (nRT) for the treatment of stage II and III rectal cancer is well-established. However, the optimal duration of nRT in this setting remains controversial. Using a population-based cohort of patients with stage II and III rectal cancer (RC) treated with curative intent, our aims were to (1) examine the patterns of nRT use and (2) explore the relationship between different nRT schedules and survival in the real-world setting. Methods: This is a multi-center retrospective cohort study based on population-based data from 5 regional comprehensive cancer centers in British Columbia, Canada. We analyzed patients diagnosed with clinical stage II or III RC from 2006 to 2010 and treated with either short-course (SC) or long-course (LC) nRT prior to curative intent surgery. Logistic regression models were constructed to determine the factors associated with the course of nRT delivered to patients. Kaplan-Meier methods and Cox regression that accounted for known prognostic factors were used to evaluate the relationship between nRT schedule and overall (OS), disease-free (DFS), local recurrence-free (LRFS), and distant recurrence-free survival (DRFS). Results: We identified 427 patients: the median age was 65 years (range, 31 to 94 years), 67% were men, 87% had T3 or T4 tumors, and 74% had N1 or N2 disease. Among them, 241 (56%) received SC and 186 (44%) received LC. Adjusting for confounders, patients with N1 or N2 disease were more likely to undergo LC (odds ratio [OR], 5.08; 95% confidence interval [CI], 2.51-11.22; P < .0001 and OR, 8.35; 95% CI, 3.35-22.39; P < .0001, respectively), whereas older age patients were less likely to receive LC (OR, 0.95; 95% CI, 0.94-0.98; P < .0001). In Kaplan-Meier analysis, there were no significant differences observed in OS, DFS, LRFS, and DRFS between SC and LC. Likewise, multivariate analyses demonstrated that OS (hazard ratio [HR], 0.91; 95% CI, 0.61-1.37; P = .66), DFS (HR, 1.06; 95% CI, 0.68-1.64; P = .80), LRFS (HR, 0.79; 95% CI, 0.39-1.57; P = .50) and DRFS (HR, 0.99; 95% CI, 0.60-1.61; P = .95) were similar regardless of nRT schedules. Additional baseline clinical and tumor characteristics did not influence outcomes (all P > .05). Conclusion: Appropriate preoperative selection of SC versus LC nRT for locally advanced RC based on patient and tumor characteristics was not associated with differences in survival outcomes in the real-world setting.