Short-course radiotherapy followed by preoperative chemotherapy and total mesorectal excision improved clinical outcomes for patients with high-risk locally advanced rectal cancer, according to the results of the randomized phase 3 Rectal Cancer And Preoperative Induction Therapy Followed by Dedicated Operation trial (RAPIDO; ClinicalTrials.gov Identifier: NCT01558921). The trial results were recently published in The Lancet.
A total of 920 patients with high-risk locally advanced rectal cancer were enrolled from 54 international sites, including sites in the United States. Patients were randomly assigned to receive either short-course radiotherapy followed by preoperative chemotherapy and total mesorectal excision or standard chemoradiotherapy, total mesorectal excision, and optional adjuvant chemotherapy.
The primary endpoint of the trial was disease-related treatment failure at 3 years, which was defined as the first occurrence of locoregional failure, distant metastasis, a new primary colorectal tumor, or treatment-related death.
The trial met the primary endpoint, showing that, at a median follow-up of 4.6 years, patients in the short-course radiotherapy with preoperative chemotherapy group had significantly lower likelihood of disease-related treatment failure at 3 years compared with the standard group (23.7% vs 30.4%, respectively; hazard ratio [HR], 0.75; 95% CI 0.60-0.95; P =.019).
Patients in the short-course radiotherapy with preoperative chemotherapy group spent 12 days receiving treatment in health care facilities while the standard group spent 25 to 28 days, which the study authors described as a “prominent benefit” of the short-course radiotherapy group, “especially in the context of the COVID-19 pandemic.”
Diarrhea was the most common grade 3 or worse adverse event during preoperative therapy for both groups, though it was more frequent in the short-course radiotherapy with preoperative chemotherapy group (18% vs 9%, respectively).
The frequency of serious adverse events was similar between patients who received short-course radiotherapy with preoperative chemotherapy (38%) and patients who received standard chemoradiotherapy with or without adjuvant chemotherapy (34% vs 34%, respectively).
A total of 4 patients in the short-course radiotherapy with preoperative chemotherapy group and 4 in the standard group died from reasons related to treatment.
The study authors concluded that short-course radiotherapy followed by preoperative chemotherapy and total mesorectal excision could be considered a “new standard of care” for patients with high-risk locally advanced rectal cancer.
Disclosures: Some of the authors disclosed financial relationships with the pharmaceutical industry and/or the medical device industry. For a full list of disclosures, please refer to the original study.
Bahadoer RR, Dijkstra EA, van Etten B, et al. Short-course radiotherapy followed by chemotherapy before total mesorectal excision (TME) versus preoperative chemoradiotherapy, TME, and optional adjuvant chemotherapy in locally advanced rectal cancer (RAPIDO): a randomised, open-label, phase 3 trial. Lancet Oncol. Published online December 7, 2020. doi:10.1016/S1470-2045(20)30555-6