Clinical and treatment-related predictors of complete response after total neoadjuvant therapy for rectal cancer in a large multicenter analysis
Year: 2026
Type: article
Study design: Observational Study
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: Georg W. Wurschi, Melanie Schneider, Jan-Niklas Becker, Bernd Frerker, Samuel M. Vorbach, Felix Ehret, Markus Diefenhardt, Fabian Schunn, Maria-Elena von Gruben, Marcel Büttner, Elgin Hoffmann, Alexander Rühle, Josephine Beier, Simone Ferdinandus, Maike Trommer, Ezgi Ceren Sahin, Julian Hlouschek, Kynann Aninditha, Daphne Schepers von Ohlen, Justus Kaufmann, Alina Depardon, Hai Minh Ha, Christopher Kessler, Adrianna Cieslak, Simon Trommer, Alexander Fabian, Mathias Sonnhoff, Florian Rißner, Maximilian Römer, Klaus Pietschmann
Institutions: Jena University Hospital, University Hospital Carl Gustav Carus, Technische Universität Dresden, Medizinische Hochschule Hannover, Universitätsmedizin Rostock, Innsbruck Medical University, Universität Innsbruck, Humboldt-Universität zu Berlin, Deutsches Konsortium für Translationale Krebsforschung, Freie Universität Berlin, Charité - Universitätsmedizin Berlin, Goethe University Frankfurt, University Hospital Frankfurt, Frankfurt Cancer Institute, University Hospital Heidelberg, University Medical Center Hamburg-Eppendorf, German Cancer Research Center, Universitätsklinikum Tübingen, University of Tübingen, University of Freiburg, University Medical Center Freiburg, University Hospital Leipzig, University of Cologne, University Hospital Cologne, Essen University Hospital, Klinikum Stuttgart, University of Lübeck, University Medical Center of the Johannes Gutenberg University Mainz, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsklinikum Erlangen, Otto-von-Guericke-Universität Magdeburg, TUM Klinikum, Technical University of Munich, Heidelberg University, University Medical Centre Mannheim, Medizinische Fakultät Mannheim, University Hospital in Halle, University Hospital Schleswig-Holstein
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,430
OpenAlex ID: W7127959798