title: Early Recurrence After Hepatectomy for Colorectal Liver Metastases: What Optimal Definition and What Predictive Factors?
abstract: The purpose of this study was to determine the optimal definition and elucidate the predictive factors of early recurrence after surgery for colorectal liver metastases (CRLM).
  
  
  
  Among 987 patients who underwent curative surgery for CRLM from 1990 to 2012, 846 with a minimum follow-up period of 24 months were eligible for this study. The minimum p value approach of survival after initial recurrence was used to determine the optimal cutoff for the definition of early recurrence. The predictive factors of early recurrence and prognostic factors of survival were analyzed.
  
  
  
  For 667 patients (79%) who developed recurrence, the optimal cutoff point of early recurrence was determined to be 8 months after surgery. The impact of early recurrence on survival was demonstrated mainly in patients who received preoperative chemotherapy. Among the 691 patients who received preoperative chemotherapy, recurrence was observed in 562 (81%), and survival in patients with early recurrence was significantly worse than in those with late recurrence (5-year survival 18.5% vs. 53.4%, p < .0001). Multivariate logistic analysis identified age ≤57 years (p = .0022), >1 chemotherapy line (p = .03), disease progression during last-line chemotherapy (p = .024), >3 tumors (p = .0014), and carbohydrate antigen 19-9 >60 U/mL (p = .0003) as independent predictors of early recurrence. Salvage surgery for recurrence significantly improved survival, even in patients with early recurrence.
  
  
  
  The optimal cutoff point of early recurrence was determined to be 8 months. The preoperative prediction of early recurrence is possible and crucial for designing effective perioperative chemotherapy regimens.
  
  
  
  In this study, the optimal cutoff point of early recurrence was determined to be 8 months after surgery based on the minimum p value approach, and its prognostic impact was demonstrated mainly in patients who received preoperative chemotherapy. Five factors, including age, number of preoperative chemotherapy lines, response to last-line chemotherapy, number of tumors, and carbohydrate antigen 19-9 concentrations, were identified as predictors of early recurrence. Salvage surgery for recurrence significantly improved survival, even in patients with early recurrence. For better selection of patients who could truly benefit from surgery and should also receive strong postoperative chemotherapy, the accurate preoperative prediction of early recurrence is crucial.
authors.affiliation: Centre Hépato-Biliaire, Assistance Publique-Hôpitaux de Paris, Hôpital Universitaire Paul Brousse, Villejuif, France INSERM, Unité 935, Villejuif, France Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Katsunori
authors.initials: K
authors.lastname: Imai
authors.affiliation: Centre Hépato-Biliaire, Assistance Publique-Hôpitaux de Paris, Hôpital Universitaire Paul Brousse, Villejuif, France INSERM, Unité 935, Villejuif, France Université Paris-Sud, Villejuif, France.
authors.forename: Marc-Antoine
authors.initials: MA
authors.lastname: Allard
authors.affiliation: Centre Hépato-Biliaire, Assistance Publique-Hôpitaux de Paris, Hôpital Universitaire Paul Brousse, Villejuif, France INSERM, Unité 935, Villejuif, France Université Paris-Sud, Villejuif, France.
authors.forename: Carlos Castro
authors.initials: CC
authors.lastname: Benitez
authors.affiliation: Centre Hépato-Biliaire, Assistance Publique-Hôpitaux de Paris, Hôpital Universitaire Paul Brousse, Villejuif, France INSERM Unité 785, Villejuif, France Université Paris-Sud, Villejuif, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Vibert
authors.affiliation: Centre Hépato-Biliaire, Assistance Publique-Hôpitaux de Paris, Hôpital Universitaire Paul Brousse, Villejuif, France INSERM, Unité 935, Villejuif, France Université Paris-Sud, Villejuif, France.
authors.forename: Antonio
authors.initials: A
authors.lastname: Sa Cunha
authors.affiliation: Centre Hépato-Biliaire, Assistance Publique-Hôpitaux de Paris, Hôpital Universitaire Paul Brousse, Villejuif, France INSERM Unité 785, Villejuif, France Université Paris-Sud, Villejuif, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Cherqui
authors.affiliation: Centre Hépato-Biliaire, Assistance Publique-Hôpitaux de Paris, Hôpital Universitaire Paul Brousse, Villejuif, France INSERM Unité 785, Villejuif, France Université Paris-Sud, Villejuif, France.
authors.forename: Denis
authors.initials: D
authors.lastname: Castaing
authors.affiliation: Centre Hépato-Biliaire, Assistance Publique-Hôpitaux de Paris, Hôpital Universitaire Paul Brousse, Villejuif, France.
authors.forename: Henri
authors.initials: H
authors.lastname: Bismuth
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Baba
authors.affiliation: Centre Hépato-Biliaire, Assistance Publique-Hôpitaux de Paris, Hôpital Universitaire Paul Brousse, Villejuif, France INSERM, Unité 935, Villejuif, France Université Paris-Sud, Villejuif, France rene.adam@pbr.aphp.fr.
authors.forename: René
authors.initials: R
authors.lastname: Adam
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000473:pathology*; D005260:Female; D006498:Hepatectomy; D006801:Humans; D008113:Liver Neoplasms / Q000401:mortality / Q000556:secondary* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000209:etiology*; D011379:Prognosis; D016879:Salvage Therapy
keywords: Colorectal liver metastasis; Early recurrence; Hepatectomy; Minimum p value approach; Salvage surgery