Efficacy and Safety of Intraoperative Hyperthermic Intraperitoneal Chemotherapy for Locally Advanced Colon Cancer
Authors: Arjona-Sánchez Alvaro , Espinosa-Redondo Esther , Gutiérrez-Calvo Alberto , Segura-Sampedro Juan J. , Pérez-Viejo Estibalitz , Concepción-Martín Vanessa , Sánchez-García Susana , García-Fadrique Alfonso , Prieto-Nieto Isabel , Barrios-Sanchez Pedro , Torres-Melero Juan , Ramírez Faraco Maria , Prada-Villaverde Arancha , Carrasco-Campos Joaquin , Artiles-Armas Manuel , Villarejo-Campos Pedro , Ortega-Pérez Gloria , Boldo-Roda Emrique , Sánchez-Hidalgo Juan-Manuel , Casado-Adam Angela , Rodríguez-Ortiz Lidia , Aranda Enrique , Cano-Osuna Maria Teresa , Díaz-López Cesar , Romero-Ruiz Antonio , Briceño-Delgado Javier , Rufián-Peña Sebastian ,   Grupo Español de Carcinomatosis Peritoneal, Lorenzo Liñán Miguel A. , Gallarín Salamanca Isabel M. , Gónzalez Cordero Marta , Ramos Isabel , Crusellas Maña Oriol , Mayol Oltra Araceli , Granados Rodríguez Melissa , Vázquez Borrego Mari C. , Gómez España Auxiliadora , Ortega Salas Rosa M. , Martínez López Ana , Villar Carlos , Garzas Martín de Almagro Cruces , Triviño Tarradas Francisco , Torres Tordera Eva M. , Rufián Andujar Blanca , Valenzuela Molina Francisca , Gordon Suarez Antonio , Medina Fernández Francisco J. , Diéz Alonso Manuel , Hernández Juara Pilar , Molina Villaverde Raquel , Castillo Torres Carolina , Busteros Moraza Jose I. , Lasa Unzué Inmaculada , Gómez Sanz Remedios , López García Alberto , Heras Garceau María A. , Serrano del Moral Ángel , Manzanedo Israel , Pereira Fernando , González Moreno Santiago , Titos García Alberto , Parra Baños Pedro A. , Carrasco Prats Milagros , Ruíz Marín Miguel , Terol Garaulet Emilio , García Molina Francisco , Morales Soriano Rafael , Pineño Flores Cristina , Pérez Rodríguez Raquel , Hernández Pérez Carolina , Afonso Gómez Ruth , Viña Romero María Micaela , Muñoz Hernández Amelia , Castro López-Tarruella Victoria , Moneva Arce Modesto E. , Gianchandani Moorjani Rajesh , Sánchez González Juan M. , Díaz López Carmen , Hernández Hernández Guillermo , Díaz Mejías José G. , Hernández Barroso Moisés J. , Abreu Falcon  
Published: April 2023

Importance

Peritoneal metastasis in patients with locally advanced colon cancer (T4 stage) is estimated to recur at a rate of approximately 25% at 3 years from surgical resection and is associated with poor prognosis. There is controversy regarding the clinical benefit of prophylactic hyperthermic intraperitoneal chemotherapy (HIPEC) in these patients.

Objective

To assess the efficacy and safety of intraoperative HIPEC in patients with locally advanced colon cancer.

Design, Setting, and Participants

This open-label, phase 3 randomized clinical trial was conducted in 17 Spanish centers from November 15, 2015, to March 9, 2021. Enrolled patients were aged 18 to 75 years with locally advanced primary colon cancer diagnosed preoperatively (cT4N02M0).

Interventions

Patients were randomly assigned 1:1 to receive cytoreduction plus HIPEC with mitomycin C (30 mg/m2 over 60 minutes; investigational group) or cytoreduction alone (comparator group), both followed by systemic adjuvant chemotherapy. Randomization of the intention-to-treat population was done via a web-based system, with stratification by treatment center and sex.

Main Outcomes and Measures

The primary outcome was 3-year locoregional control (LC) rate, defined as the proportion of patients without peritoneal disease recurrence analyzed by intention to treat. Secondary end points were disease-free survival, overall survival, morbidity, and rate of toxic effects.

Results

A total of 184 patients were recruited and randomized (investigational group, n = 89; comparator group, n = 95). The mean (SD) age was 61.5 (9.2) years, and 111 (60.3%) were male. Median duration of follow-up was 36 months (IQR, 27-36 months). Demographic and clinical characteristics were similar between groups. The 3-year LC rate was higher in the investigational group (97.6%) than in the comparator group (87.6%) (log-rank P = .03; hazard ratio [HR], 0.21; 95% CI, 0.05-0.95). No differences were observed in disease-free survival (investigational, 81.2%; comparator, 78.0%; log-rank P = .22; HR, 0.71; 95% CI, 0.41-1.22) or overall survival (investigational, 91.7%; comparator, 92.9%; log-rank P = .68; HR, 0.79; 95% CI, 0.26-2.37). The definitive subgroup with pT4 disease showed a pronounced benefit in 3-year LC rate after investigational treatment (investigational: 98.3%; comparator: 82.1%; log-rank P = .003; HR, 0.09; 95% CI, 0.01-0.70). No differences in morbidity or toxic effects between groups were observed.

Conclusions and Relevance

In this randomized clinical trial, the addition of HIPEC to complete surgical resection for locally advanced colon cancer improved the 3-year LC rate compared with surgery alone. This approach should be considered for patients with locally advanced colorectal cancer.

Trial Registration

ClinicalTrials.gov Identifier: NCT02614534