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Publications

Journal Article Ahead of print

PubMed: 42407299 DOI: 10.1016/j.ejca.2026.116911

Mismatch repair deficiency or microsatellite instability in locally advanced rectal cancer patients treated with total neoadjuvant therapy.

Eur J Cancer 245:116911

Authors: Nada Benhima, Alessandro Audisio, Chiara Gallio, Gianluca Ricco, Hélène Meillat, Vaneja Velenik, Maria Carmen Riesco, Javier Suárez Alecha, Gertjan Rasschaert, David Páez López-Bravo, David Tougeron, Carlos Carvalho, Beatrice Borelli, Federico Famiglietti, Carolina De la Pinta, Juan Manuel O'Connor, Mehmet Artaç, Pètra M Braam, Alberto Puccini, Ithai Waldhorn, Alexander Vanden Bulcke, Mauro Loi, Francesca De Felice, Michal Eid, Amélie Deleporte, Chiara Rossini, Paola Montenegro, Michele Fiore, Marc Van Den Eynde, Ali Shamseddine, Karen P Geboes, Marco Messina, Núria Mulet Margalef, Constance Houlzé-Laroye, Iva Kirac, Alessandro Pastorino, Massimiliano Salati, Soňa Argalácsová, Federica Morano, Jaume Capdevila, Ingrid Garajovà, Claire Antoun, Cidália Maria Sousa Pinto, Manfred P Lutz, Richard A Adams, Amélie Chau, Alexander Siebenhuener, Alexandre Dermine, Michele Ghidini, Audrius Dulskas … and 32 other authors

Affiliations

  • Université libre de Bruxelles (ULB), Hôpital Universitaire de Bruxelles (HUB), Institut Jules Bordet - Hôpital Erasme, Brussels, Belgium.
  • Université libre de Bruxelles (ULB), Hôpital Universitaire de Bruxelles (HUB), Institut Jules Bordet - Hôpital Erasme, Brussels, Belgium; Azienda Ospedaliera S.Croce e Carle, Cuneo, Italy.
  • Université libre de Bruxelles (ULB), Hôpital Universitaire de Bruxelles (HUB), Institut Jules Bordet - Hôpital Erasme, Brussels, Belgium; IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy.
  • Université libre de Bruxelles (ULB), Hôpital Universitaire de Bruxelles (HUB), Institut Jules Bordet - Hôpital Erasme, Brussels, Belgium; Policlinico S.Orsola-Malpighi, Bologna, Italy.
  • Institut Paoli-Calmettes, Marseille, France.
  • Institute of Oncology Ljubljana, Ljubljana, Slovenia.
  • Hospital Universitario 12 de Octubre, Madrid, Spain.
  • Hospital Universitario de Navarra, Pamplona, Spain.
  • University Hospitals Leuven - Campus Gasthuisberg, Leuven, Belgium.
  • Hospital de la Santa Creu i Sant Pau, IR SANT PAU, Barcelona, Spain.
  • CHU de Poitiers, Poitiers, France.
  • Champalimaud Clinical Centre, Lisbon, Portugal.
  • Azienda Ospedaliera Universitaria Pisana, Pisa, Italy.
  • CHU Charleroi, Charleroi, Belgium.
  • Ramón y Cajal University Hospital, IRYCIS, Madrid, Spain.
  • Instituto Alexander Fleming, Buenos Aires, Argentina.
  • Necmettin Erbakan University, Faculty of Medicine, Konya, Turkey.
  • Radboud University Medical Centre, Nijmegen, the Netherlands.
  • Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy; IRCCS Humanitas Research Hospital, Medical Oncology and Hematology Unit, Humanitas Cancer Center, Rozzano, Milan, Italy.
  • Rambam Health Care Campus, Haifa, Israel.
  • AZ Groeninge, Kortrijk, Belgium.
  • Azienda Ospedaliero Universitaria Careggi, Firenze, Italy.
  • Policlinico Umberto I "Sapienza" University of Rome, Rome, Italy.
  • University Hospital Brno, Faculty of Medicine, Masaryk University, Brno, Czech Republic; Center for Precision Medicine, University Hospital Brno, Brno, Czech Republic.
  • CHU Saint-Pierre, University Hospital, Brussels, Belgium.
  • ASST Ovest Milanese Presidi Legnano, Cuggiono, Milan, Italy.
  • Auna-Oncosalud, Lima, Peru.
  • Università Campus Bio-Medico di Roma, &, Fondazione Policlinico Universitario Campus Bio-Medico, Roma, Italy.
  • Institut Roi Albert II, Cliniques Universitaires Saint-Luc, UCLouvain, Brussels, Belgium.
  • American University of Beirut Medical Center, Beirut, Lebanon.
  • Ghent University Hospital, Ghent, Belgium.
  • ARNAS Civico, Palermo, Italy.
  • Institut Català d'Oncologia - Badalona and Germans Trias i Pujol Research Institute, Badalona, Spain.
  • Claude Huriez Hospital, CHU Lille, Lille, France.
  • IGET - Institute for Gastroenterological Tumours, and, University Hospital for Tumors, Sestre Milosrdnice University Hospital Center, Zagreb, Croatia.
  • Ospedale Policlinico San Martino - IRCCS, Genoa, Italy.
  • University Hospital Modena, Modena, Italy.
  • General University Hospital and, First Faculty of Medicine, Prague, Czech Republic.
  • Fondazione IRCCS, Istituto Nazionale dei Tumori di Milano, Milan, Italy.
  • Vall d'Hebron University Hospital, Barcelona, Spain.
  • University Hospital of Parma, Parma, Italy.
  • University Hospital of Besançon, Besançon, France.
  • Centro Hospitalar Universitário do Algarve-Hospital de Faro, Faro, Portugal.
  • Caritasklinikum St. Theresia, Saarbruecken, Germany.
  • Cardiff University and, Velindre Cancer Centre, Cardiff, UK.
  • Polyclinique Hénin-Beaumont, Group Ahnac, Haut-de-France, France.
  • Klinik für Hämatologie und Onkologie, Hirslanden Zurich AG, Zurich, Switzerland.
  • CHU Helora Hospital La Louvière Site Jolimont, La Louvière, Belgium.
  • Fondazione IRCCS, Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
  • Vilnius University Vilnius, Lithuania; National Cancer Institute, Vilnius, Lithuania.

Abstract

BACKGROUND

Data on the prognostic value of dMMR/MSI-H in locally advancer rectal cancer (LARC) are inconsistent and mostly from patients treated with conventional neoadjuvant therapy. We sought to evaluate oncological outcomes by mismatch repair/microsatellite (MMR/MS) status in LARC patients treated with total neoadjuvant therapy (TNT).

METHODS

Patients from the International Real-World Study of TNT in Rectal Cancer tested for dMMR/MSI-H by immunohistochemistry and/or molecular testing were included. Pathological complete response (pCR), complete response (CR, pCR + clinical complete response), event-free survival (EFS) and overall survival (OS) were assessed by MMR/MS status in the overall and matched populations. For the latter, variable-ratio matching according to nine variables (age, year of diagnosis, tumour location, staging modality, cT stage, cN stage, presence of lateropelvic lymphadenopathy, distance from the mesorectal fascia, TNT regimen) was applied.

RESULTS

Of 1911 patients, 1320 (69.1%) (09/2012-09/2025) had information on the MMR/MS status, 46 (3.5%) having dMMR/MSI-H tumours. No outcome differences were found by MMR/MS status in the overall population. In the matched population (n = 372), pCR was 14.2% among patients with pMMR/MSS tumours versus 12.5% among those with dMMR/MSI-H tumours (adjusted OR 1.07, 95%CI 0.39-2.91, p = 0.899), while CR was 18.9% and 16.7%, respectively (adjusted OR 0.95, 95%CI 0.35-2.58, p = 0.917). 3-year EFS and 5-year OS were 65.8% and 79.2%, and 67.6% and 93.5% in patients with pMMR/MSS and in those with dMMR/MSI-H tumours, respectively (adjusted HR EFS 1.30, 95%CI 0.57-2.89, p = 0.527; adjusted HR OS 2.52, 95%CI 0.67-9.42, p = 0.171).

CONCLUSIONS

In this study, the dMMR/MSI-H phenotype did not hold prognostic value in LARC patients treated with TNT.

MeSH

Dna Mismatch Repair, Microsatellite Repeats, Neoplasms, Neoadjuvant Therapy, Rectal Neoplasms, Therapeutics, Microsatellite Instability