Pre-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 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.In 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.These 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.
An important goal in the treatment of locally advanced rectal cancer is to reduce the risk of metastases and increase quality of life. Four chapters of this dissertation describe the results of the RAPIDO trial. This study compares 2 types of treatment for locally advanced rectal cancer. The standard treatment consists of long-term chemoradiotherapy, surgery, and possibly chemotherapy. The experimental treatment consists of short-course radiation followed by chemotherapy and then surgery. The experimental treatment showed a significant improvement in disease-related treatment failure at 3 and 5 years after surgery. This difference was explained by a significant decrease in the number of metastases. However, after 5 years, there are a fraction more patients with local recurrence of disease in the experimental treatment. In addition, this study shows that there is no difference in quality of life after 3 years. However, those in the experimental group do experience tingling in the toes and fingers more often. Furthermore, this dissertation shows that during surgery in case of the primary tumour in 58.3% of cases we gave radiotherapy too often when it was not necessary, and in the case of recurrence of disease in 26.5% of cases we gave it too little.In addition, we have shown that it is safe to provide chemoradiotherapy again to a patient who has local recurrence of disease and has also initially received chemoradiotherapy for their primary tumour.
The authors regret that in the original publication reference 1 was given in correctly. The correct reference is as follows:1.J. Socha, W. Michalski, K. Bujko, Does the RAPIDO trial suggest a benefit of post-operative chemotherapy after preoperative chemoradiation in rectal cancer? No, it does not., ESMO Open, Volume 8, Issue 5, 2023, 101644, https://doi.org/10.1016/j.esmoop.2023.101644 The authors would like to apologise for any inconvenience caused. Authors' reply—Does the RAPIDO trial suggest a benefit of post-operative chemotherapy after preoperative chemoradiation in rectal cancer? No, it does notESMO OpenVol. 8Issue 5PreviewWe thank Socha et al.1 for their interest in our article regarding the value of post-operative chemotherapy (pCT) after preoperative chemoradiotherapy in the RAPIDO trial. We indeed carried out three analyses within the standard-of-care treatment and used propensity score stratification (PSS) in analyses 2 (per-protocol analysis) and 3 (compliance with pCT analysis) to correct for confounders and assure groups with balanced baseline characteristics.2 Full-Text PDF Open Access
4006 Background: Local control in locally advanced rectal cancer (LARC) has improved. However, systemic relapses remain high even with postoperative chemotherapy, possibly due to low compliance. Short-course radiotherapy (SCRT) followed by delayed surgery with, in the waiting period, chemotherapy, may lead to better compliance, downstaging and fewer distant metastases. The main objective of the international multicenter phase III RAPIDO trial is to decrease Disease-related Treatment Failure (DrTF), defined as locoregional failure, distant metastasis, a new primary colon tumor or treatment-related death, by reducing the risk of systemic relapse without compromising local control. Methods: MRI-diagnosed LARC patients with either cT4a/b, extramural vascular invasion, cN2, involved mesorectal fascia or enlarged lateral lymph nodes considered to be metastatic were randomly assigned to SCRT (5x5 Gy) with subsequent six cycles of CAPOX or nine cycles of FOLFOX4 followed by total mesorectal excision (TME) (experimental arm) or, capecitabine-based chemoradiotherapy (25-28 x 2.0-1.8 Gy) followed by TME and optional, predefined by hospital policy, postoperative eight cycles of CAPOX or twelve cycles of FOLFOX4 (standard arm). Results: Between June 2011 and June 2016, 920 patients were randomized. Pathological complete response rates were 27.7% vs 13.8% (OR 2.40 [1.70 – 3.39]; p < 0.001) in the experimental and standard arms, respectively. At three years, cumulative probability of DrTF was 23.7% in the experimental arm and 30.4% in the standard arm (HR 0.76 [0.60 – 0.96]; p = 0.02). Probability at three years of distant metastasis and locoregional failure were, in the experimental and standard arms, 19.8% vs 26.6% (HR 0.69 [0.53 – 0.89]; p = 0.004) and 8.7% vs 6.0% (HR 1.45 [0.93 – 2.25]; p = 0.10), respectively. No differences in DrTF between hospitals with or without policy for postoperative chemotherapy were found (p = 0.37). Overall health ( p = 0.192), quality of life ( p = 0.125) and low anterior resection syndrome score ( p = 0.136) were comparable between the two treatment arms. Conclusions: A lower rate of DrTF, as a result of a lower rate of distant metastases, in high-risk LARC patients can be achieved with preoperative short-course radiotherapy, followed by chemotherapy and TME than by conventional chemoradiotherapy. In addition, the high pCR rate, achieved with the experimental treatment regimen can contribute to organ preservation. This treatment can be considered as a new standard of care. Clinical trial information: NCT01558921 .
