title: Downstaging of hepatocellular cancer before liver transplant: long-term outcome compared to tumors within Milan criteria.
abstract: We report on the long-term intention-to-treat (ITT) outcome of 118 patients with hepatocellular carcinoma (HCC) undergoing downstaging to within Milan/United Network for Organ Sharing T2 criteria before liver transplantation (LT) since 2002 and compare the results with 488 patients listed for LT with HCC meeting T2 criteria at listing in the same period. The downstaging subgroups include 1 lesion >5 and ≤8 cm (n = 43), 2 or 3 lesions at least one >3 and ≤5 cm with total tumor diameter ≤8 cm (n = 61), or 4-5 lesions each ≤3 cm with total tumor diameter ≤8 cm (n = 14). In the downstaging group, 64 patients (54.2%) had received LT and 5 (7.5%) developed HCC recurrence. Two of the five patients with HCC recurrence had 4-5 tumors at presentation. The 1- and 2-year cumulative probabilities for dropout (competing risk) were 24.1% and 34.2% in the downstaging group versus 20.3% and 25.6% in the T2 group (P = 0.04). Kaplan-Meier's 5-year post-transplant survival and recurrence-free probabilities were 77.8% and 90.8%, respectively, in the downstaging group versus 81% and 88%, respectively, in the T2 group (P = 0.69 and P = 0.66, respectively). The 5-year ITT survival was 56.1% in the downstaging group versus 63.3% in the T2 group (P = 0.29). Factors predicting dropout in the downstaging group included pretreatment alpha-fetoprotein ≥1,000 ng/mL (multivariate hazard ratio [HR]: 2.42; P = 0.02) and Child's B versus Child's A cirrhosis (multivariate HR: 2.19; P = 0.04).
  
  
  CONCLUSIONS
  Successful downstaging of HCC to within T2 criteria was associated with a low rate of HCC recurrence and excellent post-transplant survival, comparable to those meeting T2 criteria without downstaging. Owing to the small number of patients with 4-5 tumors, further investigations are needed to confirm the efficacy of downstaging in this subgroup.
authors.affiliation: Division of Gastroenterology, Department of Medicine, University of California San Francisco, San Francisco, CA.|Division of Transplant Surgery, Department of Surgery, University of California San Francisco, San Francisco, CA.
authors.forename: Francis Y
authors.initials: FY
authors.lastname: Yao
authors.affiliation: Division of Gastroenterology, Department of Medicine, University of California San Francisco, San Francisco, CA.
authors.forename: Neil
authors.initials: N
authors.lastname: Mehta
authors.affiliation: Division of Gastroenterology, Department of Medicine, University of California San Francisco, San Francisco, CA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Flemming
authors.affiliation: Division of Transplant Surgery, Department of Surgery, University of California San Francisco, San Francisco, CA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Dodge
authors.affiliation: Division of Gastroenterology, Department of Medicine, University of California San Francisco, San Francisco, CA.
authors.forename: Bilal
authors.initials: B
authors.lastname: Hameed
authors.affiliation: Division of Gastroenterology, Department of Medicine, University of California San Francisco, San Francisco, CA.
authors.forename: Oren
authors.initials: O
authors.lastname: Fix
authors.affiliation: Division of Transplant Surgery, Department of Surgery, University of California San Francisco, San Francisco, CA.
authors.forename: Ryutaro
authors.initials: R
authors.lastname: Hirose
authors.affiliation: Division of Interventional Radiology, Department of Radiology, University of California, San Francisco.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Fidelman
authors.affiliation: Division of Interventional Radiology, Department of Radiology, University of California, San Francisco.
authors.forename: Robert K
authors.initials: RK
authors.lastname: Kerlan
authors.affiliation: Division of Transplant Surgery, Department of Surgery, University of California San Francisco, San Francisco, CA.
authors.forename: John P
authors.initials: JP
authors.lastname: Roberts
mesh_terms: D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D006801:Humans; D008099:Liver / Q000473:pathology*; D008113:Liver Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology*; D009367:Neoplasm Staging; D018579:Patient Selection; D012189:Retrospective Studies; D012495:San Francisco / Q000453:epidemiology; D055815:Young Adult