Timing of surgery after short course radiotherapy for rectal cancer: real-world evidence

Background: A prolonged interval between short course radiotherapy (SCRT, 25 Gy in 5 fractions) and surgery for rectal cancer (4-8 weeks, SCRT-delay) has been associated with a lower postoperative complication rate and higher pathological complete response (pCR) rate than SCRT and surgery within a week (SCRT-direct surgery). The current study sought to confirm these associations in nationwide real-world data of Dutch rectal cancer patients. Method: Patients with intermediate risk rectal cancer (T3(MRF-)N0M0 and T1-3(MRF-)N1M0) treated with either SCRT-delay (4-12 weeks) or SCRT-direct surgery in 2018-2021 were selected from a nationwide Dutch cohort. Confounders were eliminated using inverse probability of treatment weighting (IPTW). The 90-day postoperative complication rate and pathological complete response (pCR) rate were compared using log-binomial and Poisson regression. Results: 664 patients were included in the SCRT-direct surgery and 238 in the SCRT-delay group. After IPTW, the 90-day postoperative complication rate was comparable between SCRT-direct surgery and SCRT-delay (40% vs. 42%, RR = 1.1 [95%confidence interval (CI): 0.9; 1.3], p=0.6). pCR occurred more often following SCRT-delay than following SCRT-direct surgery (10% vs. 0.3%, RR = 39 [95%CI: 11, 139], p < 0.001). Conclusion: Real-world evidence could not confirm an advantage in postoperative complications following SCRT-delay compared to SCRT-direct surgery, but did confirm the increased pCR rate following SCRT-delay. SCRT-delay followed by a response assessment should be offered to patients who are interested in watch & wait strategy. SCRT-direct surgery still is a valid option for patients who prefer surgical management.