Quality of life and late toxicity after short-course radiotherapy followed by chemotherapy or chemoradiotherapy for locally advanced rectal cancer – The RAPIDO trial

Abstract

Locally advanced rectal cancer; Quality of life; Total neoadjuvant treatment

Cáncer de recto localmente avanzado; Calidad de vida; Tratamiento neoadyuvante total

Càncer de recte localment avançat; Qualitat de vida; Tractament neoadjuvant total

Background and purpose The RAPIDO trial demonstrated a decrease in disease-related treatment failure (DrTF) and an increase in pathological complete responses (pCR) in locally advanced rectal cancer (LARC) patients receiving total neoadjuvant treatment (TNT) compared to conventional chemoradiotherapy. This study examines health-related quality of life (HRQL), bowel function, and late toxicity in patients in the trial. Materials and methods Patients were randomized between short-course radiotherapy followed by pre-operative chemotherapy (EXP), or chemoradiotherapy and optional post-operative chemotherapy (STD). The STD group was divided into patients who did (STD+) and did not (STD−) receive post-operative chemotherapy. Three years after surgery patients received HRQL (EORTC QLQ-C30, QLQ-CR29 and QLQ-CIPN20) and LARS questionnaires. Patients who experienced a DrTF event before the toxicity assessments (6, 12, 24, or 36 months) were excluded from analyses. Results Of 574 eligible patients, 495 questionnaires were returned (86%) and 453 analyzed (79% completed within time limits). No significant differences were observed between the groups regarding QLQ-C30, QLQ-CR29 or LARS scores. Sensory-related symptoms occurred significantly more often in the EXP group compared to all STD patients, but not compared to STD+ patients. Any toxicity of any grade and grade ≥ 3 toxicity was comparable between the EXP and STD groups at all time-points. Neurotoxicity grade 1–2 occurred significantly more often in the EXP and STD+ group at all time-points compared to the STD− group. Conclusion The results demonstrate that TNT for LARC, yielding improved DrTF and pCRs, does not compromise HRQL, bowel functional or results in more grade ≥3 toxicity compared to standard chemoradiotherapy at three years after surgery in DrTF-free patients.

Funding for this study was acquired from the Dutch Cancer Foundation (CKS-2011-4997); the Swedish Cancer Society; the Swedish Research Council (project number K2014-99X-22481-01-3); the Spanish Ministry of Economy and Competitiveness through the Carlos III Health Institute EC11-423, and by the Spanish Clinical Research Network (SCReN-PT13/0002/0031; PT17/0017/0003; co-financed by European Regional Development Fund “A way to make Europe”).