The value of post-operative chemotherapy after chemoradiotherapy in patients with high-risk locally advanced rectal cancerdresults from the RAPIDO trial

Dijkstra, E.A.; Zwart, W.H.; Nilsson, P.J.; Putter, H.; Roodvoets, A.G.H.; Kranenbarg, E.M.K.; ... ; Glimelius, B. (2023)

Article / Letter to editor

BackgroundPre-operative chemoradiotherapy (CRT) rather than radiotherapy (RT) has resulted in fewer locoregional recurrences (LRRs), but no decrease in distant metastasis (DM) rate for patients with locally advanced rectal cancer (LARC). In many countries, patients receive post-operative chemotherapy (pCT) to improve oncological outcomes. We investigated the value of pCT after pre-operative CRT in the RAPIDO trial.Patients and methodsPatients were randomised between experimental (short-course RT, chemotherapy and surgery) and standard-of-care treatment (CRT, surgery and pCT depending on hospital policy). In this substudy, we compared curatively resected patients from the standard-of-care group who received pCT (pCT+ group) with those who did not (pCT− group). Subsequently, patients from the pCT+ group who received at least 75% of the prescribed chemotherapy cycles (pCT ≥75% group) were compared with patients who did not receive pCT (pCT−/− group). By propensity score stratification (PSS), we adjusted for the following unbalanced confounders: age, clinical extramural vascular invasion, distance to the anal verge, ypT stage, ypN stage, residual tumour, serious adverse event (SAE) and/or readmission within 6 weeks after surgery and SAE related to pre-operative CRT. Cumulative probability of disease-free survival (DFS), DM, LRR and overall survival (OS) was analysed by Cox regression.ResultsIn total, 396/452 patients had a curative resection. The number of patients in the pCT+, pCT >75%, pCT− and pCT−/− groups was 184, 112, 154 and 149, respectively. The PSS-adjusted analyses for all endpoints demonstrated hazard ratios between approximately 0.7 and 0.8 (pCT+ versus pCT−), and 0.5 and 0.8 (pCT ≥75% versus pCT−/−). However, all 95% confidence intervals included 1.ConclusionsThese data suggest a benefit of pCT after pre-operative CRT for patients with high-risk LARC, with approximately 20%-25% improvement in DFS and OS and 20%-25% risk reductions in DM and LRR. Compliance with pCT additionally reduces or improves all endpoints by 10%-20%. However, differences are not statistically significant.

• locally advanced rectal cancer
• post-operative chemotherapy
• oncological outcomes
• propensity score stratification
• adjuvant chemotherapy

• All authors: Dijkstra, E.A.; Zwart, W.H.; Nilsson, P.J.; Putter, H.; Roodvoets, A.G.H.; Kranenbarg, E.M.K.; Froedin, J.E.; Nygren, P.; Ostergaard, L.; Kersten, C.; Verbiene, I.; Cervantes, A.; Hendriks, M.P.; Capdevila, J.; Edhemovic, I.; Velde, C.J.H. van de; Marijnen, C.A.M.; Etten, B. van; Hospers, G.A.P.; Glimelius, B.
• Date: 2023-03-03
• Journal: ESMO Open
• Volume: 8
• Issue: 2
• DOI: doi:10.1016/j.esmoop.2023.101158
• Link: https://www.esmoopen.com/article/S2059-7029(23)00378-2/fulltext