Comparison of short course radiotherapy with chemoradiotherapy for locally advanced rectal cancers in the elderly: A multicentre, randomised, non-blinded, phase 3 trial

Background: There is no specific guideline for the treatment of locally advanced rectal cancers in the elderly. Here we compared R0 resection rate and degradation of auton-omy based on the instrumental activities of daily living score between neoadjuvant, short course radiotherapy and chemoradiotherapy in this specific population.Patients and methods: Patients >75 years with resectable T3-T4 rectal adenocarcinoma within 12 cm of the anal verge or T2 of the very low rectum were randomised between short course radiotherapy (5 x 5 Gy in one week) and chemoradiotherapy (50 Gy, 2 Gy/f, 5 weeks with capecitabine: 800 mg/m2 twice daily, 5 days per week), with delayed surgery 7 +/- 1 weeks for the two arms.Results: One hundred and three eligible patients were enrolled between January 2016 and December 2019 when the trial was closed due to poor accrual. The R0 resection rate (first co-primary objective) was 84.3%; confidence interval 95% [73.26-94.18] in the short course group and 88%; confidence interval 95% [77.77-96.60] in the chemoradiotherapy group (non-inferiority p = 0.28). The deterioration of the instrumental activities of daily living score was not different during the pre-operative phase, it was significantly more deteriorated in the chemoradiotherapy group at 3 months post-operative (44.8% versus 14.8%; p = 0.032) but was not different at 12 months post-operative (second co-primary objective). During pre-operative phase, 9.8% of patients in short course group and 22% of patients in chemora-diotherapy group presented a serious adverse event, but we observed no difference during the post-operative phase between the two groups.Conclusion: Although the main objectives of the study were not achieved, the short course radiotherapy followed by delayed surgery could represent a preferred treatment option in pa-tients >75 years with locally advanced rectal cancer; a new study must be performed to confirm the improvement in overall and specific survival results. 2022 Elsevier Ltd. All rights reserved.