Mismatch repair deficiency or microsatellite instability in locally advanced rectal cancer patients treated with total neoadjuvant therapy.
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Benhima Nada, Audisio Alessandro, Gallio Chiara, Ricco Gianluca, Meillat Hélène, Velenik Vaneja, Riesco Maria Carmen, Suárez Alecha Javier, Rasschaert Gertjan, Páez López-Bravo David, Tougeron David, Carvalho Carlos, Borelli Beatrice, Famiglietti Federico, De la Pinta Carolina, O'Connor Juan Manuel, Artaç Mehmet, Braam Pètra M, Puccini Alberto, Waldhorn Ithai, Vanden Bulcke Alexander, Loi Mauro, De Felice Francesca, Eid Michal, Deleporte Amélie, Rossini Chiara, Montenegro Paola, Fiore Michele, Van Den Eynde Marc, Shamseddine Ali, Geboes Karen P, Messina Marco, Mulet Margalef Núria, Houlzé-Laroye Constance, Kirac Iva, Pastorino Alessandro, Salati Massimiliano, Argalácsová Soňa, Morano Federica, Capdevila Jaume, Garajovà Ingrid, Antoun Claire, Sousa Pinto Cidália Maria, Lutz Manfred P, Adams Richard A, Chau Amélie, Siebenhuener Alexander, Dermine Alexandre, Ghidini Michele, Dulskas Audrius, Papamichael Demetris, Javed Muhammad Ahsan, Ruiz-Garcia Erika, Tomášek Jiří, Petrillo Angelica, Baratelli Chiara, Vandamme Timon, Spolverato Gaya, Bock Felix, Diaz Marie, Campana Luca Giovanni, Sur Daniel, Karampeazis Athanasios, Patsko Veronika, Puleo Francesco, Bounedjar Adda, Fiorica Francesco, Gilliaux Quentin, Bernardini Ilaria, De Stefano Alfonso, Grønlie Guren Marianne, Jakubauskas Matas, Sert Fatma, Gomez Galdon Maria, Veron Sanchez Ana, Vierasu Ortansa-Irina, Assaf Irene, Moretti Luigi, Martinive Philippe, Liberale Gabriel, Van Laethem Jean-Luc, Sclafani Francesco, International Real-World TNT Study Consortium
Аннотация
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.