Organ Preservation and Quality of Life After Total Neoadjuvant Treatment in Rectal Cancer.

Importance: Data on quality of life (QOL) after total neoadjuvant therapy (TNT) are important for counseling patients on the benefits of watch-and-wait (WW) vs total mesorectal excision (TME) for rectal cancer. A thorough understanding of both options and their long-term impact on bowel, urinary, sexual function, and other QOL domains remains limited. Objective: To examine the association of organ preservation with QOL and functional outcomes among patients with rectal cancer treated in 2 phase 2 clinical trials. Design, Setting, and Participants: This unplanned, post hoc, cohort study used data from the CAO/ARO/AIO-12 and CAO/ARO/AIO-16 trials, recruiting participants from June 15, 2015, through October 7, 2020, from 19 centers in Germany. Included patients had cT3 to cT4 or node-positive rectal adenocarcinoma. Total neoadjuvant treatment included chemoradiation therapy combined with induction or consolidation chemotherapy. The statistical analysis was performed from March 6 to December 23, 2025. Main Outcomes and Measures: The association of WW with functional outcomes and QOL was assessed using prospectively recorded EORTC QLQ-C30, EORTC QLQ-CR29, and Wexner score questionnaires. Differences in QOL scores were estimated using adjusted longitudinal and cross-sectional analyses with a predefined clinically meaningful difference of at least 5 points. Results: Baseline questionnaires were available from 346 of 385 eligible patients (89.9%; median [range] age, 60 [19-80] years; 257 male [67%]), while available QOL questionnaires decreased over time to 185 (48.1%) at 5 years. Using the longitudinal analytic approach, statistically significant and clinically meaningful differences in favor of WW were noted for fecal incontinence (-21.2 [95% CI, -30.0 to -12.3]; P < .001); stool frequency (-19.8 [95% CI, -27.6 to -11.9]; P < .001); embarrassment (-17.0 [95% CI, -27.4 to -6.6]; P = .002); flatulence (-15.2 [95% CI, -24.4 to -6.0]; P < .001), buttock pain (-11.9 [95% CI, -20.8 to -3.0]; P = .01); social (9.7 [95% CI, 1.1-18.3]; P = .03), physical (10.2 [95% CI, 4.1-16.3]; P = .002), and role (13.9 [95% CI, 4.9-22.9]; P = .003) functioning; and global health status (9.2 [95% CI, 3.2-15.2]; P = .004). These clinically meaningful differences were detectable in both the intended organ preservation and disease-free groups. Patients with sustained clinical complete response at 3 years (n = 29) vs those with pathologic complete response or matched baseline characteristics favored WW for fecal incontinence (-24.0 and -11.6, respectively), stool frequency (-34.6 and -19.1), sore skin (-18.0 and -18.1), buttock pain (-14.7 and -17.6), embarrassment (-41.1 and -20.5), role functioning (19.1 and 10.9), and social functioning (20.0 and 8.4). Conclusions and Relevance: In the absence of prospective randomized trials, this study provides evidence suggesting long-term clinically meaningful benefits for organ preservation regarding QOL, especially for most gastrointestinal subscales, social functioning, and global health status, over a 5-year period among patients with rectal cancer. As treatment options for patients with rectal cancer now routinely include WW in cases of clinical complete response after TNT, patient-reported QOL measures have become paramount for informed shared decision-making. Trial Registration: ClinicalTrials.gov Identifiers: NCT02363374 and NCT03561142.