title: Is primary tumour resection associated with survival improvement in patients with colorectal cancer and unresectable synchronous metastases? A pooled analysis of individual data from four randomised trials.
abstract: OBJECTIVE
  To evaluate the impact on survival of primary tumour resection in patients with unresectable synchronous metastases from colorectal cancer (CRC).
  
  
  BACKGROUND
  Primary tumour resection in this setting remains controversial.
  
  
  METHODS
  We retrieved individual data of 1155 patients with metastatic CRC included in four first-line chemotherapy trials: Fédération Francophone de Cancérologie Digestive (FFCD)-9601, FFCD-2000-05, Actions Concertées dans les cancers COloRectaux et Digestifs (ACCORD)-13, and ML-16987. Patients with unresectable synchronous metastases were eligible for this study. We used univariate and multivariate analyses (Cox models stratified on the trial) to assess the impact of primary tumour resection and other potential prognostic variables on overall survival (OS) (the primary endpoint).
  
  
  RESULTS
  Amongst the 1155 patients, 810 patients met the inclusion criteria and 59% (n = 478) underwent resection of their primary tumour, prior to trial entry (resection group). Compared to patients in the non-resection group (n =3 32 [41%]), those in the resection group were more likely to have a colonic primary, lower baseline carcinoembryonic antigen (CEA) and alkaline phosphatase levels, and normal white-blood-cell count (p < 0.001 each). Primary tumour resection was independently associated to better OS in multivariate analysis (hazard ratio (HR), 0.63 [0.53-0.75]; p < 0.001, with a more favourable impact of resection on OS in case of rectal primary and low CEA level. Primary tumour resection was also independently associated to a better progression-free survival in multivariate analysis (HR, 0.82 [0.70-0.95]; p < 0.001).
  
  
  CONCLUSIONS
  Primary tumour resection was independently associated to a better OS in patients with CRC and unresectable synchronous metastases.
authors.affiliation: Department of Biostatistics and Epidemiology, Gustave Roussy, Villejuif, France.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Faron
authors.affiliation: Department of Biostatistics and Epidemiology, Gustave Roussy, Villejuif, France. Electronic address: jppignon@gustaveroussy.fr.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Pignon
authors.affiliation: Department of Medical Oncology, Gustave Roussy, Villejuif, France.
authors.forename: David
authors.initials: D
authors.lastname: Malka
authors.affiliation: Department of Biostatistics and Epidemiology, Gustave Roussy, Villejuif, France.
authors.forename: Abderrahmane
authors.initials: A
authors.lastname: Bourredjem
authors.affiliation: Department of Medical and Translational Research, Centre René Gauducheau, Saint-Herblain, France.
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Douillard
authors.affiliation: Department of Urologic and Digestive Oncology, Centre Oscar Lambret, Lille, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Adenis
authors.affiliation: Department of Visceral Surgery, Gustave Roussy, Villejuif, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Elias
authors.affiliation: Department of Hepatogastroenterology and Digestive Oncology, Hôpital Robert Debré, Reims, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Bouché
authors.affiliation: Department of Medical Oncology, Gustave Roussy, Villejuif, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Ducreux
mesh_terms: D000368:Aged; D002272:Carcinoembryonic Antigen / Q000097:blood; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery*; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009362:Neoplasm Metastasis; D017063:Outcome Assessment, Health Care / Q000379:methods* / Q000592:standards; D011379:Prognosis; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic
chemical_list: D002272:Carcinoembryonic Antigen
keywords: Chemotherapy; Colorectal cancer; Meta-analysis; Metastasis; Prognosis; Surgery