Hepatocellular carcinoma with extrahepatic metastasis: Clinical features and prognostic factors

Koji Uchino, Ryosuke Tateishi, Shuichiro Shiina, Miho Kanda, Ryota Masuzaki, Yuji Kondo, Tadashi Goto, Masao Omata, Haruhiko Yoshida, Kazuhiko Koike

Research output: Contribution to journalArticlepeer-review

332 Citations (Scopus)


BACKGROUND: Despite significant advances in the treatment of intrahepatic lesions, the prognosis for patients with hepatocellular carcinoma (HCC) who have extrahepatic metastasis remains poor. The objective of this study was to further elucidate the clinical course and prognostic determinants of patients with this disease. METHODS: In total, 342 patients who had HCC with extrahepatic metastasis were enrolled. The metastases were diagnosed at initial presentation with HCC in 28 patients and during follow-up in the remaining patients. The authors analyzed clinical features, prognoses, and treatments and established a scoring system to predict prognosis using a split-sample method with a testing set and a training set. RESULTS: The most frequent site of extrahepatic metastasis was the lung followed by lymph nodes, bone, and adrenal glands. These metastases were related directly to death in only 23 patients (7.6%). The median survival after diagnosis of extrahepatic metastasis was 8.1 months (range, 0.03-108.7 months). In univariate analysis of the training set (n = 171), performance status, Child-Pugh classification, the number and size of intrahepatic lesions, macroscopic vascular invasion, symptomatic extrahepatic metastases, α-fetoprotein levels, and complete responses to treatment were associated significantly with prognosis. On the basis of multivariate analysis, a scoring system was developed to predict prognosis that assessed uncontrollable intrahepatic lesions, extent of vascular invasion, and performance status. This scoring system was validated in the testing set (n = 171) and produced a concordance index of 0.73. CONCLUSIONS: The controllability of intrahepatic lesions and performance status were identified as important prognostic factors in patients with advanced HCC who had extrahepatic metastasis.

Original languageEnglish
Pages (from-to)4475-4483
Number of pages9
Issue number19
Publication statusPublished - 1 Oct 2011
Externally publishedYes


  • clinical course
  • extrahepatic metastasis
  • hepatocellular carcinoma
  • prognosis


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