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