Neoadjuvant Chemotherapy with FOLFIRINOX and Preoperative Chemoradiotherapy for Patients with Locally Advanced Rectal Cancer (UNICANCER PRODIGE 23): Health-related Quality of Life Longitudinal Analysis

Background: Results from the phase 3 PRODIGE 23 study showed that neoad-juvant chemotherapy (NAC) with mFOLFIRINOX and preoperative chemoradiotherapy improved disease-free survival compared with preoperative chemoradiotherapy in patients with locally advanced rectal cancer. We aimed to assess the health-related quality of life (HRQOL) outcomes from this study.Patients and methods: A total of 461 patients (231 versus 230 patients) from 35 French hos-pitals were randomly assigned to either NAC with FOLFIRINOX (oxaliplatin 85 mg/m2, irinotecan 180 mg/m2, leucovorin 400 mg/m2, fluorouracil 2400 mg/m2 over 46 h intravenously every 2 weeks for 6 cycles) followed by preoperative chemoradiotherapy or chemoradiotherapy only. HRQOL was assessed at baseline, during treatments and at 2-year follow-up using the European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-CR29 questionnaires.Results: Compared to baseline, HRQOL scores during NAC were better for tumour symp-toms but worse for global health status, functional domains, fatigue, nausea/vomiting and appetite loss. During follow-up, improved emotional functioning was observed, but dete-rioration of body image, increased urinary incontinence, and lower male sexual function were observed. Linear mixed model exhibited a treatment-by-time interaction effect for nausea/ vomiting and insomnia symptoms showing a greater deterioration in the standard-of-care group. Only treatment arm and baseline physical functioning were independent significant favourable prognostic factors. Conclusion: NAC improved tumour-related symptoms and transitorily reduced most func-tional scores. Adding NAC before chemoradiotherapy and increased physical functioning at baseline were independent significant prognostic factors for longer disease-free survival.(c) 2023 Elsevier Ltd. All rights reserved.