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Peer-reviewedCC BY-NC-NDJAMA network open

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

  • Markus Diefenhardt1
  • Emmanouil Fokas1
  • Rebekka Kosmala2
  • Bülent Polat2
  • Christoph Thomas Germer3
  • Anke Schlenska-Lange4
  • Thomas Kuhnt5
  • Michael Ghadimi6
  • Stefan Rieken7
  • Armin Wiegering8
  • Matthias Schwarzbach9
  • Maximilian Fleischmann1
8 more authors
  • Robert Grützmann10
  • Oliver J. Ott11
  • Peter Martus12
  • Alfred Königsrainer13
  • Daniel Zips14
  • Ralf-Dieter Hofheinz15
  • Cihan Gani16
  • Claus Rödel1
16 affiliations
  1. 1Department of Radiotherapy and Oncology, Goethe University Frankfurt, University Hospital, Frankfurt, Germany
  2. 2Department of Radiation Oncology, University Hospital Würzburg, Julius-Maximilians-University Würzburg, Würzburg, Germany
  3. 3Department of General and Visceral Surgery, University Hospital Würzburg, Julius-Maximilians-University Würzburg, Würzburg, Germany
  4. 4Department of Haematology and Oncology, Barmherzige Brüder Hospital, Regensburg, Germany
  5. 5Department of Radiation Therapy, University of Leipzig, Leipzig, German
  6. 6Department of General, Visceral and Pediatric Surgery, University Hospital, University of Göttingen, Göttingen, Germany
  7. 7Department of Radiotherapy and Radiation Oncology, University Medical Center Göttingen, Göttingen, Germany
  8. 8Department of General, Visceral, Transplantation, and Thoracic Surgery, University Hospital Frankfurt, Goethe University Frankfurt, Frankfurt, Germany
  9. 9Department of General and Visceral Surgery, Varisano Hospital Frankfurt Hoechst, Frankfurt, Germany
  10. 10Department of General and Visceral Surgery, University of Erlangen-Nürnberg, Erlangen, Germany
  11. 11Department of Radiation Oncology, University of Erlangen-Nürnberg, Erlangen, Germany
  12. 12Institute for Clinical Epidemiology and Applied Biometry, University and Faculty of Medicine, University of Tübingen, Tübingen, Germany
  13. 13Department of General, Visceral and Transplant Surgery, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, Germany
  14. 14Department of Radiation Oncology, Charité–Universitätsmedizin Berlin, Freie Universität Berlin, and Humboldt-Universität Berlin, Berlin, Germany
  15. 15Department of Medical Oncology, University Hospital Mannheim, Heidelberg University, Mannheim, Germany
  16. 16Department of Radiation Oncology, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, Germany
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Abstract

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

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Cite

BibTeXRIS
BibTeX
@article{diefenhardt2026organ,
  title = {{Organ Preservation and Quality of Life After Total Neoadjuvant Treatment in Rectal Cancer}},
  author = {Markus Diefenhardt and Emmanouil Fokas and Rebekka Kosmala and Bülent Polat and Christoph Thomas Germer and Anke Schlenska-Lange and Thomas Kuhnt and Michael Ghadimi and Stefan Rieken and Armin Wiegering and Matthias Schwarzbach and Maximilian Fleischmann and Robert Grützmann and Oliver J. Ott and Peter Martus and Alfred Königsrainer and Daniel Zips and Ralf-Dieter Hofheinz and Cihan Gani and Claus Rödel},
  journal = {JAMA network open},
  year = {2026},
  month = oct,
  doi = {10.1001/jamanetworkopen.2026.39063},
  url = {https://europepmc.org/article/PMC/PMC13673318},
  note = {CC BY-NC-ND},
}
RIS
TY  - JOUR
TI  - Organ Preservation and Quality of Life After Total Neoadjuvant Treatment in Rectal Cancer
AU  - Markus Diefenhardt
AU  - Emmanouil Fokas
AU  - Rebekka Kosmala
AU  - Bülent Polat
AU  - Christoph Thomas Germer
AU  - Anke Schlenska-Lange
AU  - Thomas Kuhnt
AU  - Michael Ghadimi
AU  - Stefan Rieken
AU  - Armin Wiegering
AU  - Matthias Schwarzbach
AU  - Maximilian Fleischmann
AU  - Robert Grützmann
AU  - Oliver J. Ott
AU  - Peter Martus
AU  - Alfred Königsrainer
AU  - Daniel Zips
AU  - Ralf-Dieter Hofheinz
AU  - Cihan Gani
AU  - Claus Rödel
PY  - 2026
DA  - 2026/10/01
JO  - JAMA network open
DO  - 10.1001/jamanetworkopen.2026.39063
UR  - https://europepmc.org/article/PMC/PMC13673318
AB  - 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
SN  - 2574-3805
ER  -