Total Neoadjuvant Therapy for Locally Advanced Rectal Cancer
Author(s)
Chiara Gallio
Vaneja Velenik
Hélène Meillat
Erika Ruíz‐García
María Carmen Riesco Martínez
Javier Suárez Alecha
Gertjan Rasschaert
Carlos Carvalho
Violaine Randrian
Iva Kirac
Jorge Hernando
Mehmet Artaç
Juan Manuel O’Connor
Ithai Waldhorn
Pètra M. Braam
Ali Shamseddine
Roberto Moretto
Carolina de la Pinta
Francesca De Felice
Audrius Dulskas
D. Páez López-Bravo
Alexander Vanden Bulcke
Felix Bock
Amélie Deleporte
Marc Van den Eynde
Karen Geboes
Mauro Loi
Marco Messina
Constance Houlzé-Laroye
Alberto Puccini
Alessandro Pastorino
Demetris Papamichael
Michele Fiore
Daniel Sur
Michal Eid
Claire Antoun
Massimiliano Salati
Ingrid Garajová
Matas Jakubauskas
Jiří Tomášek
Cidália Pinto
Jérôme Schwingel
Federica Morano
Richard Adams
Alexandre Dermine
Amélie Chau
Ahsan Javed
Michele Ghidini
Francesco Fiorica
Paola Montenegro
Angelica Petrillo
Gaya Spolverato
N. Mulet Margalef
Marie Diaz
Chiara Baratelli
Francesco Puleo
Athanasios Karampeazis
Fatma Sert
Quentin Gilliaux
Alfonso De Stefano
Gabriel Liberale
Luigi Moretti
Philippe Martinive
Vaiva Deltuvaite Thomas
Vincent S. Staggs
Everardo D. Saad
Jean-Luc Van Laethem
Francesco Sclafani
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
Start Page
1045
End Page
1045
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.
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