{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T15:45:20Z","timestamp":1792079120187,"version":"4.4.0"},"reference-count":24,"publisher":"American Medical Association (AMA)","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"\n Importance<\/jats:title>\n 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.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To examine the association of organ preservation with QOL and functional outcomes among patients with rectal cancer treated in 2 phase 2 clinical trials.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n 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.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n 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.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n 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 (\u221221.2 [95% CI,\u2009\u221230.0 to \u201312.3];\n P<\/jats:italic>\n \u2009&amp;lt;\u2009.001); stool frequency (\u221219.8 [95% CI,\u2009\u221227.6 to \u221211.9];\n P<\/jats:italic>\n \u2009&amp;lt;\u2009.001); embarrassment (\u221217.0 [95% CI,\u2009\u221227.4 to \u22126.6];\n P<\/jats:italic>\n \u2009=\u2009.002); flatulence (\u221215.2 [95% CI,\u2009\u221224.4 to \u22126.0];\n P<\/jats:italic>\n \u2009&amp;lt;\u2009.001), buttock pain (\u221211.9 [95% CI,\u2009\u221220.8 to \u22123.0];\n P<\/jats:italic>\n \u2009=\u2009.01); social (9.7 [95% CI, 1.1-18.3];\n P<\/jats:italic>\n \u2009=\u2009.03), physical (10.2 [95% CI, 4.1-16.3];\n P<\/jats:italic>\n \u2009=\u2009.002), and role (13.9 [95% CI, 4.9-22.9];\n P<\/jats:italic>\n \u2009=\u2009.003) functioning; and global health status (9.2 [95% CI, 3.2-15.2];\n P<\/jats:italic>\n \u2009=\u2009.004). 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\u2009=\u200929) vs those with pathologic complete response or matched baseline characteristics favored WW for fecal incontinence (\u221224.0 and \u221211.6, respectively), stool frequency (\u221234.6 and \u221219.1), sore skin (\u221218.0 and \u221218.1), buttock pain (\u221214.7 and \u221217.6), embarrassment (\u221241.1 and \u221220.5), role functioning (19.1 and 10.9), and social functioning (20.0 and 8.4).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n 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.<\/jats:p>\n <\/jats:sec>\n \n Trial Registration<\/jats:title>\n \n ClinicalTrials.gov Identifiers:\n NCT02363374<\/jats:ext-link>\n and\n NCT03561142<\/jats:ext-link>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2026.39063","type":"journal-article","created":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T15:00:31Z","timestamp":1792076431000},"page":"e2639063","source":"Crossref","is-referenced-by-count":0,"title":["Organ Preservation and Quality of Life After Total Neoadjuvant Treatment in Rectal Cancer"],"prefix":"10.1001","volume":"9","author":[{"given":"Markus","family":"Diefenhardt","sequence":"first","affiliation":[{"name":"Department of Radiotherapy and Oncology, Goethe University Frankfurt, University Hospital, Frankfurt, 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Radiation Oncology, University of Erlangen-N\u00fcrnberg, Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Martus","sequence":"additional","affiliation":[{"name":"Institute for Clinical Epidemiology and Applied Biometry, University and Faculty of Medicine, University of T\u00fcbingen, T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfred","family":"K\u00f6nigsrainer","sequence":"additional","affiliation":[{"name":"Department of General, Visceral and Transplant Surgery, University Hospital T\u00fcbingen, Eberhard Karls University T\u00fcbingen, T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Zips","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, Freie Universit\u00e4t Berlin, and Humboldt-Universit\u00e4t Berlin, Berlin, Germany"},{"name":"Partner Site 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