Quality of life and anorectal function in rectal cancer patients undergoing immunotherapy-based total neoadjuvant therapy: a comparison of organ preservation and radical surgery

PURPOSE: Immunotherapy-based total neoadjuvant therapy (iTNT) improves clinical complete response rates and increases organ preservation (OP) opportunities in rectal cancer, while its long-term impacts on quality of life (QoL) and anorectal function remain unclear. This study aimed to evaluate long-term QoL and anorectal function after iTNT, and to clarify how OP versus radical surgery affects patient-reported outcomes and functional recovery, providing evidence for individualized clinical decision-making. MATERIAL AND METHODS: This prospective longitudinal cohort study enrolled rectal cancer patients receiving iTNT from 2021 to 2024. Patient-reported outcomes were dynamically evaluated using the EORTC QLQ-C30/CR29, Low Anterior Resection Syndrome (LARS), Wexner, and Memorial Sloan Kettering Cancer Center Bowel Function Instrument (MSKCC-BFI) questionnaires. Longitudinal changes were analyzed using linear mixed-effects models accounting for within-patient correlation. A separate conventional TNT cohort was included for exploratory cross-sectional comparison of long-term outcomes. Risk factors for major LARS were evaluated using univariable and multivariable logistic regression with multiple imputation and complete-case sensitivity analyses. RESULTS: Of 172 patients receiving iTNT, 142 were eligible for QoL analysis and 137 for anorectal function assessment after excluding five patients with permanent stomas. Patients managed with OP were associated with better global health status, lower symptom burden, and better anorectal function than those undergoing total mesorectal excision (TME), with lower LARS and Wexner scores during follow-up. Compared with conventional TNT, poorer QoL and anorectal outcomes after iTNT were mainly observed in patients undergoing TME, whereas outcomes were largely comparable among those managed with OP. Multivariate analysis identified TME and shorter tumor distance from the anal verge as independent risk factors for major LARS. CONCLUSION: OP following iTNT was associated with more favorable long-term QoL and anorectal functional outcomes than TME. These findings support OP strategies as an important approach for optimizing long-term patient-reported outcomes in appropriately selected patients with rectal cancer.