Clinical and treatment-related predictors of complete response after total neoadjuvant therapy for rectal cancer in a large multicenter analysis

Wurschi GW, Schneider M, Becker JN, Frerker B, Vorbach SM, Ehret F, Diefenhardt M, Schunn F, von Gruben ME, Büttner M, Hoffmann E, Rühle A, Beier J, Ferdinandus S, Trommer M, Sahin EC, Hlouschek J, Aninditha K, von Ohlen DS, Kaufmann J, Depardon A, Ha HM, Kessler C, Cieslak A, Trommer S, Fabian A, Sonnhoff M, Rißner F, Römer M, Pietschmann K (2026)

Publication Type: Journal article

Publication year: 2026

Journal

Book Volume: 58

Article Number: 101120

DOI: 10.1016/j.ctro.2026.101120

Abstract

Introduction: Complete response (CR) after total neoadjuvant therapy (TNT) in rectal cancer is linked to favorable local control and enables non-operative management (NOM). Achieving high CR rates is crucial. As no standard TNT protocol exists, we aimed to assess the impact of clinical factors and different protocols on CR rates. Methods: Rectal cancer patients undergoing TNT with curative intent between 2015 and 2024 were included in this retrospective multicenter analysis (DRKS00033000). The primary endpoint was CR. Predefined clinical and therapeutic variables were treated as covariates and evaluated as potential predictors of CR in a multivariable logistic regression model. Results: Among 245 included patients (181 men) with a median age of 62 (Q1-Q3: 54–67) years, 113 (46.1%) reached a CR. Of those, 69 (28.2%) were active smokers. Short-course radiotherapy (SCRT) was applied in 107 (43.7%) patients. Chemoradiotherapy with pyrimidine-based monotherapy or concomitant oxaliplatin was used in 65 (26.5%) and 73 (29.8%) of patients, respectively. A median of 8 (Q1-Q3: 6–9) cycles of consolidation chemotherapy was administered. The CR likelihood increased with each additional chemotherapy cycle (OR 1.19, 95%-CI: 1.04–1.38). SCRT was associated with lower CR rates (OR 0.34, 95%-CI: 0.16–0.74) compared with concomitant pyrimidine-based chemoradiotherapy. Adding concomitant oxaliplatin to 5-FU did not further increase CR rates (OR 1.06, 95%-CI: 0.50–2.27). CR was more likely in non-smokers (OR 1.92, 95%-CI: 1.03–3.57). ESMO tumor classification and treatment duration were not associated with CR. Conclusion: More intensive TNT protocols were associated with higher CR rates. Smoking cessation may be beneficial but requires external validation.

Authors with CRIS profile

Involved external institutions

Universitätsklinikum Jena Germany (DE) Medizinische Universität Innsbruck Austria (AT) Charité - Universitätsmedizin Berlin Germany (DE) Universitätsklinikum Frankfurt am Main (KGU) Germany (DE) Klinikum Stuttgart Germany (DE) Universitätsklinikum Schleswig-Holstein (UKSH) Germany (DE) Universitätsmedizin der Johannes Gutenberg-Universität Mainz Germany (DE) Otto-von-Guericke-Universität Magdeburg Germany (DE) Klinikum rechts der Isar Germany (DE) Universitätsklinikum Mannheim / University Medical Centre Mannheim (Universitätsmedizin Mannheim) Germany (DE) Universitätsklinikum Halle (Saale) Germany (DE) Medizinische Hochschule Hannover (MHH) / Hannover Medical School Germany (DE) Universitätsklinikum Heidelberg Germany (DE) Universitätsklinikum Carl Gustav Carus Dresden Germany (DE) Universitätsklinikum Hamburg-Eppendorf (UKE) Germany (DE) Universitätsklinikum Tübingen Germany (DE) Universitätsmedizin Rostock Germany (DE) Universitätsklinikum Freiburg Germany (DE) Universitätsklinikum Leipzig Germany (DE) Universitätsklinikum Köln Germany (DE) Universitätsklinikum Essen Germany (DE)

How to cite

APA:

Wurschi, G.W., Schneider, M., Becker, J.N., Frerker, B., Vorbach, S.M., Ehret, F.,... Pietschmann, K. (2026). Clinical and treatment-related predictors of complete response after total neoadjuvant therapy for rectal cancer in a large multicenter analysis. Clinical and Translational Radiation Oncology, 58. https://doi.org/10.1016/j.ctro.2026.101120

MLA:

Wurschi, Georg W., et al. "Clinical and treatment-related predictors of complete response after total neoadjuvant therapy for rectal cancer in a large multicenter analysis." Clinical and Translational Radiation Oncology 58 (2026).

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