D. Goéré, Laurent Ghouti, S. Durand-Fontanier, Gérard Lorimier, Reza Kianmanesh, Pascale Mariani, Olivier Glehen, Amandine Pinto, Pierre Meeus, M. Ducreux, Charles Sabbagh, Emilie Thibaudeau, Catherine Arvieux, Zaher Lakkis, Cécile Brigand, Michel Carretier, Ellen Benhamou, Jean-Jacques Tuech, François Quenet, Valeria Loi, David Malka, Nicolas Pirro, J.M. Bereder, Jean-Marc Guilloit, Dominique Elias, Patrick Rat, M. Texier, Valérie Boige, Frédéric Marchal, Institut Gustave Roussy (IGR), Département de chirurgie viscérale [Gustave Roussy], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut du Cancer de Montpellier (ICM), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Centre Paul Papin(Angers), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service de chirurgie digestive [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Service de Chirurgie Générale, Digestive et Endocrine [CHU Reims], Centre Hospitalier Universitaire de Reims (CHU Reims), Génétique Expérimentale en Productions Animales (GEPA), Institut National de la Recherche Agronomique (INRA), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), Centre Hospitalier Universitaire [Grenoble] (CHU), Hôpital de Hautepierre [Strasbourg], Centre Léon Bérard [Lyon], Service de Chirurgie Digestive, Cancérologique, Générale, Endocrinienne et Urgences (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service de Chirurgie digestive, endocrinienne et générale [CHU Limoges], CHU Limoges, Institut Curie [Paris], Service de Chirurgie Digestive [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital de la Timone [CHU - APHM] (TIMONE), CHU Amiens-Picardie, Simplification des soins chez les patients complexes - UR UPJV 7518 (SSPC), Université de Picardie Jules Verne (UPJV), Embedded Computing Laboratory [Gif-sur-Yvette], Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Service de biostatistique et d'épidémiologie (SBE), Direction de la recherche clinique [Gustave Roussy], and Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR)
International audience; Background Diagnosis and treatment of colorectal peritoneal metastases at an early stage, before the onset of signs, could improve patient survival. We aimed to compare the survival benefit of systematic second-look surgery plus hyperthermic intraperitoneal chemotherapy (HIPEC), with surveillance, in patients at high risk of developing colorectal peritoneal metastases. Methods We did an open-label, randomised, phase 3 study in 23 hospitals in France. Eligible patients were aged 18-70 years and had a primary colorectal cancer with synchronous and localised colorectal peritoneal metastases removed during tumour resection, resected ovarian metastases, or a perforated tumour. Patients were randomly assigned (1:1) to surveillance or second-look surgery plus oxaliplatin-HIPEC (oxaliplatin 460 mg/m(2), or oxaliplatin 300 mg/m(2) plus irinotecan 200 mg/m(2), plus intravenous fluorouracil 400 mg/m(2)), or mitomycin-HIPEC (mitomycin 35 mg/m(2)) alone in case of neuropathy, after 6 months of adjuvant systemic chemotherapy with no signs of disease recurrence. Randomisation was done via a web-based system, with stratification by treatment centre, nodal status, and risk factors for colorectal peritoneal metastases. Second-look surgery consisted of a complete exploration of the abdominal cavity via xyphopubic incision, and resection of all peritoneal implants if resectable. Surveillance after resection of colorectal cancer was done according to the French Guidelines. The primary outcome was 3-year disease free survival, defined as the time from randomisation to peritoneal or distant disease recurrence, or death from any cause, whichever occurred first, analysed by intention to treat. Surgical complications were assessed in the second look surgery group only. This study was registered at ClinicalTrials.gov, NCT01226394. Findings Between June 11, 2010, and March 31, 2015, 150 patients were recruited and randomly assigned to a treatment group (75 per group). After a median follow-up of 50.8 months (IQR 47.0-54.8), 3-year disease-free survival was 53% (95% CI 41-64) in the surveillance group versus 44% (33-56) in the second-look surgery group (hazard ratio 0.97, 95% CI 0.61-1.56). No treatment-related deaths were reported. 29 (41%) of 71 patients in the second-look surgery group had grade 3-4 complications. The most common grade 3-4 complications were intra-abdominal adverse events (haemorrhage, digestive leakage) in 12 (23%) of 71 patients and haematological adverse events in 13 (18%) of 71 patients. Interpretation Systematic second-look surgery plus oxaliplatin-HIPEC did not improve disease-free survival compared with standard surveillance. Currently, essential surveillance of patients at high risk of developing colorectal peritoneal metastases appears to be adequate and effective in terms of survival outcomes. Copryright (C) 2020 Elsevier Ltd. All rights reserved.