Quality of life and late toxicity after total neoadjuvant treatment for locally advanced rectal cancer – LARCT-US

INTRODUCTION: Total neoadjuvant therapy (TNT) is increasingly used to treat locally advanced rectal cancer (LARC) due to more complete responses and fewer systemic recurrences. However, its impact on quality-of-life (QoL) or late toxicity remains under-investigated. This study evaluates this in a large real-world Swedish cohort treated with an abbreviated RAPIDO-TNT-protocol (LARCT-US). MATERIAL AND METHODS: In the prospective LARCT-US study, 273 LARC patients from 16 Swedish hospitals received short-course radiotherapy (5x5 Gy) followed by four cycles of CAPOX (or six cycles of mFOLFOX-6). An additional 189 patients who received similar treatment were included (ad modum LARCT-US, AdmL). QoL was assessed three years post-treatment using EORTC QLQ-C30, QLQ-CR29 and bowel function using the LARS-score. Physician-reported grade 3+ late toxicity was recorded at three- and five-years follow-up. RESULTS: Of curatively treated recurrence-free LARCT-US patients, 144/176 (82%) were included in the QoL assessment. Global health score (GHS) and all functioning scores were high (mean 73 and ∼86, respectively). Flatulence, urinary frequency, and fatigue were the most commonly reported symptoms. LARS was present in 79% of patients (n = 42/53), with 47% experiencing major LARS. Grade 3+ late toxicity occurred in 12% (n = 33/265) of LARCT-US/AdmL patients after three years and in 8% (n = 16/254) after five years. Patients with late toxicity reported worse scores for GHS, fatigue, dysuria, financial difficulties, and role and social functioning. CONCLUSIONS: An abbreviated TNT schedule, compared with the RAPIDO-study, used in LARCT-US, achieves favourable oncological outcomes with low risk of late toxicity, and an acceptable QoL similar to other less effective neoadjuvant treatments.