Total neoadjuvant therapy in rectal cancer: The FOREST Protocol, a patient-centered approach that clusters two cohorts with different outcomes

Rectal cancer treatment has evolved toward individualized strategies that emphasize organ preservation and tailored therapeutic approaches. The FOREST protocol combines total neoadjuvant therapy (TNT), early response evaluation, and prehabilitation within a comprehensive framework designed to optimi...

Descripción completa

Detalles Bibliográficos
Autores: Guadalajara Labajo, Héctor, Dominguez Tristancho, José Luis, Fuentes Mateo, Raquel, León Arellano, Miguel, Sanz Baro, Raquel, Geraldi, Eleonora, Hormigo Sánchez, Ana Isabel, Castellano Megías, Víctor Manuel, Pérez Cobos, Marta, Mellado Miras, Patricia, López-Botet Zulueta, Begoña, García Arranz, Mariano Andrés, García-Foncillas López, Jesús Miguel, Caramés, Cristina, García Olmo, Damián
Tipo de recurso: artículo
Fecha de publicación:2025
País:España
Institución:Universidad Autónoma de Madrid
Repositorio:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:inglés
OAI Identifier:oai:repositorio.uam.es:10486/732440
Acceso en línea:https://hdl.handle.net/10486/732440
https://dx.doi.org/10.1002/ijc.70126
Access Level:acceso abierto
Palabra clave:local surgery
organ preservation
rectal cancer
total neoadjuvant therapy
Medicina
Descripción
Sumario:Rectal cancer treatment has evolved toward individualized strategies that emphasize organ preservation and tailored therapeutic approaches. The FOREST protocol combines total neoadjuvant therapy (TNT), early response evaluation, and prehabilitation within a comprehensive framework designed to optimize outcomes while minimizing overtreatment. In this single-center prospective study, 67 patients with rectal cancer (T1–T4, any N) were enrolled between April 2020 and December 2022. Treatment decisions—radical surgery (RS), watch and wait (WW), or local surgery (LS)—were guided by early and final response assessments. Outcomes were analyzed under an intention-to-treat (ITT) approach, with a median follow-up of 968 days (range: 440–2015). Final treatments included RS in 47.8% (n = 32), WW in 50.7% (n = 34), and LS in 1.5% (n = 1). Completion of TNT was achieved in 79.1% of patients. Organ preservation was accomplished in 44.8% (30/67 = 44.8%, with 34 WW and 1 LS). Systemic recurrence occurred in 22.4% of patients, surpassing the rate of local regrowth or persistence (17.9%). DFS in the WW group (65.7%) was comparable to that of the RS group (71.4%), while OS significantly favored WW (100% vs. 80.7%, p = .014). The FOREST protocol demonstrates that integrating TNT with response- guided strategies is feasible and can lead to high organ preservation rates and favorable oncologic outcomes. A key strength of the protocol is its ability to identify two distinct patient cohorts based on response evaluation. Treatment strategies for rectal cancer are increasingly focused on organ preservation and tai-lored therapy. Total neoadjuvant therapy (TNT), which integrates radiotherapy and systemic chemotherapy prior to surgery, is especially promising in this regard. Here, impacts on rectal cancer patient outcomes were assessed following TNT, wherein decisions to perform local or radical surgery or to watch and wait (WW) were determined by treatment response assessment. Analyses show that nearly 45% of patients who underwent TNT experienced organ preservation. Disease-free survival was comparable between WW and radical surgery groups. Mean while, WW had significantly better overall survival, highlighting possible benefits with TNT