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Total Neoadjuvant Therapy for Locally Advanced Rectal Cancer
Author(s)
Université Libre de Bruxelles
Chiara Gallio
Université Libre de Bruxelles
Vaneja Velenik
Institute of Oncology Ljubljana
Hélène Meillat
Institut Paoli-Calmettes
Erika Ruíz‐García
Instituto Nacional de Cancerología
María Carmen Riesco Martínez
Hospital Universitario 12 De Octubre
Javier Suárez Alecha
Universidad de Navarra
Gertjan Rasschaert
Universitair Ziekenhuis Leuven
Carlos Carvalho
Centro Champalimaud
Violaine Randrian
Centre Hospitalier Universitaire de Poitiers
Iva Kirac
Sisters of Charity Hospital
Jorge Hernando
Vall d'Hebron Hospital Universitari
Mehmet Artaç
Necmettin Erbakan University
Juan Manuel O’Connor
Instituto Alexander Fleming
Ithai Waldhorn
Rambam Health Care Campus
Pètra M. Braam
Radboud University Medical Center
Ali Shamseddine
American University of Beirut Medical Center
Roberto Moretto
Azienda Ospedaliera Universitaria Pisana
Carolina de la Pinta
Instituto Ramón y Cajal de Investigación Sanitaria
Francesca De Felice
Policlinico Umberto I
Audrius Dulskas
Vilnius University
D. Páez López-Bravo
Hospital de Sant Pau
Alexander Vanden Bulcke
AZ Groeninge
Felix Bock
Universitätsmedizin Rostock
Amélie Deleporte
Centre Hospitalier Universitaire de Saint-Pierre
Marc Van den Eynde
Cliniques Universitaires Saint-Luc
Karen Geboes
Ghent University Hospital
Mauro Loi
Azienda Ospedaliero-Universitaria Careggi
Marco Messina
Constance Houlzé-Laroye
Centre Hospitalier Universitaire de Lille
Alberto Puccini
Humanitas University
Alessandro Pastorino
Ospedale Policlinico San Martino
Demetris Papamichael
Bank of Cyprus Oncology Center
Michele Fiore
Università Campus Bio-Medico
Daniel Sur
Iuliu Hațieganu University of Medicine and Pharmacy
Michal Eid
Masaryk University
Claire Antoun
Centre Hospitalier Universitaire de Besançon
Massimiliano Salati
University of Modena and Reggio Emilia
Ingrid Garajová
University of Parma
Matas Jakubauskas
Vilnius University
Jiří Tomášek
Masaryk Memorial Cancer Institute
Cidália Pinto
Jérôme Schwingel
cts CaritasKlinikum Saarbrücken
Federica Morano
Fondazione IRCCS Istituto Nazionale dei Tumori
Richard Adams
Velindre Cancer Centre
Alexandre Dermine
Hôpital de Jolimont
Amélie Chau
Ahsan Javed
Liverpool University Hospitals NHS Foundation Trust
Michele Ghidini
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
Francesco Fiorica
Paola Montenegro
Angelica Petrillo
Gaya Spolverato
University of Padua
N. Mulet Margalef
Institut Català d'Oncologia
Marie Diaz
CHU Ambroise Paré
Chiara Baratelli
Ospedale San Luigi Gonzaga
Francesco Puleo
Centre Hospitalier Interrégional Edith Cavell
Athanasios Karampeazis
401 General Military Hospital of Athens
Fatma Sert
Ege University
Quentin Gilliaux
CHU Dinant Godinne UCL Namur
Alfonso De Stefano
Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale"
Gabriel Liberale
Université Libre de Bruxelles
Luigi Moretti
Université Libre de Bruxelles
Philippe Martinive
Université Libre de Bruxelles
Vaiva Deltuvaite Thomas
International Drug Development Institute (Belgium)
Vincent S. Staggs
International Drug Development Institute (Belgium)
Everardo D. Saad
International Drug Development Institute (Belgium)
Jean-Luc Van Laethem
Université Libre de Bruxelles
Francesco Sclafani
Université Libre de Bruxelles
Nada Benhima
Irene Assaf
Gianluca Ricco
Roberta Fazio
Fatima-Zahra Abbassi
Giacomo Bregni
Ana Veron
María Gómez Galdón
Maria Antonietta Bali
Ernestas Sileika
Edita Baltruškevičienė
Laura Miceviciute
Laudy Chehade
Annamaria Pessino
Chiara Pirrone
Greta Catani
Ana Fortuna
David Tougeron
Valentina Daprà
Michela Bartolini
María Alsina
Oğuzhan Yıldız
Maria E. Gallego
A.C. Virgili Manrique
M. Carmen Martínez
Josep Balart
Juan Carlos Pernas
Berta Martín-Cullell
Edith A. Fernández-Figueroa
Rogelio Cuervo-Campos
Antonio Moreno-Avendaño
Laura Galeani
Geneviève Van Ooteghem
Astrid De Cuyper
Christopthe Remue
R Bachmann
Daniel Léonard
Anca Dragean
Marie-Laure Castella
Paméla Baldin
Valeria Pavese
Beatrice Borelli
Elvira Rampello
Carlos Orlando Salsaña Reyes
Jennifer Aoun
Mariana Figueiredo
Martina Manni
Christos Cortas
Martina Benincasa
Marius Kryžauskas
Tomas Poškus
Carlo Messina
Nuno Couto
Ana Clara
Catarina Freitas
Joaquim Gago
G. Atalaia
S Soares Brandao
José Azevedo
Laura M. Fernández
Pedro Vieira
Hugo Domingos
Oriol Parés
Miguel Borges
Bernd Frerker
Francesco Celotto
Eva Pape
Gabriëlle H. van Ramshorst
Jhanzeb Ihsan
Victoria Shallcross
Shakil Ahmed
José María Fernández Cebrián
Ana Ferrer‐Gomez
E. Canales Lachén
Raquel García Latorre
Íñigo Martínez Delfrade
Beatriz Peñas García
M. Martín
B. Frutos
B.I. Morón
Reyes Ferreiro
Sofía Parejo
Juan Carlos García‐Ruiz
Pedro Abadía
Javier Díe Trill
Elena Mendía
Juan Ocaña Jiménez
E Tobaruela
Araceli Ballestero Pérez
Gloria M. Rodriguez
S. Sancho
André D’Hoore
Albert Wolthuis
Gabriele Bislenghi
Karin Haustermans
Sabine Tejpar
Filip Van Herpe
Jeroen Dekervel
Eric Van Cutsem
Raphaëla C. Dresen
Xavier Sagaert
Gert De Hertogh
Philippe Leclercq
Lynn Debrun
M. Amin Dalia
Andrea Modrego
Guillaume Piessen
Date Issued
10 de julio de 2025
Type
Article
Volume
11
Issue
9
Series/Report No.
JAMA Oncology
Start Page
1045
End Page
1045
ISSN
2374-2437
2374-2445
Abstract
Importance: This was a clinical study of total neoadjuvant therapy (TNT) for rectal cancer. Objective: To assess the use and outcomes of TNT in routine practice. Design, Setting, and Participants: This international, multicenter study was conducted at 61 centers across 21 countries and included consecutive patients treated off trial with TNT for stage II/III rectal adenocarcinoma from September 2012 to December 2023. Data were analyzed between August and October 2024. Exposure: TNT, defined as the delivery of radiotherapy and nonradiosensitizing chemotherapy before surgery or watch and wait. Main Outcomes and Measures: The primary outcome was type of TNT administered. Secondary outcomes were patient characteristics, treatment adherence, safety, and efficacy overall and by type of TNT in the entire population and after propensity vector matching. Results: A total of 1585 patients (588 female [37.1%]; median [IQR] age, 61 [53-68] years) were included, 1260 (79.5%) of whom had 1 or more high-risk features (eg, cT4, cN2, extramural venous invasion, threatened/involved mesorectal fascia, and lateropelvic lymphadenopathy). Patients were treated with the PRODIGE 23-like regimen (FOLFIRINOX/FOLFOXIRI followed by long-course chemoradiotherapy) (271 [17.7%]), RAPIDO-like regimen (short-course radiotherapy followed by consolidation FOLFOX/CAPOX) (529 [33.4%]), OPRA induction-like (induction FOLFOX/CAPOX followed by long-course chemoradiotherapy) (190 [12.0%]), OPRA consolidation-like (long-course chemoradiotherapy followed by consolidation FOLFOX/CAPOX) (257 [16.2%]), and other regimens (360 [22.7%]). After TNT, 192 (12.1%) underwent watch and wait, and 30 (1.9%) underwent local excision. Pathological or clinical complete response was reported in 23.2% of cases. At treatment failure, 8.5% was local and 16.4% was distant progression. Three-year event-free survival (EFS) was 68% (95% CI, 64%-71%), and 5-year overall survival (OS) was 79% (95% CI, 75%-83%). In the overall population, patients treated with the PRODIGE 23-like regimen were most likely to have serious adverse events (61 [23.5%]) but had better local control and survival outcomes than those treated with the RAPIDO-like (EFS: hazard ratio [HR], 0.68; 95% CI, 0.49-0.95; P = .03; OS: HR, 0.51; 95% CI, 0.27-0.97; P = .04), OPRA induction-like (EFS: HR, 0.66; 95% CI, 0.44-0.98; P = .04; OS: HR, 0.35; 95% CI, 0.18-0.70; P = .003), and OPRA consolidation-like (EFS: HR, 0.64; 95% CI, 0.44-0.93; P = .02; OS: HR, 0.50; 95% CI, 0.25-1.00; P = .05) regimens. In the matched population (928 patients [58.5%]), no differences in survival outcomes were observed between the TNT regimens. Conclusions and Relevance: The findings of this case series study show substantial variation in the choice of the TNT regimen and were overall aligned with those reported in clinical trials, suggesting the efficacy of TNT in a clinical setting regardless of the specific regimen.
Keywords