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Clinical manifestations between hepatocellular carcinoma (HCC) and extra-hepatic primary malignancy (EHPM) are lack of large-scale study. We enrolled 14555 HCC patients between 1986 and 2013 retrospectively. The EHPM was classified as prior, synchronous and metachronous group based on before, within and after 6 months of HCC diagnosis, respectively. The incidence rate of EHPM is 3.91% (95% confidence interval [CI]: 3.60–4.23%). Urogenital cancers, kidney and bladder, were at unexpected higher ranks. Older in age, Child-Pugh A cirrhosis, negativity of HBsAg and anti-HCV, and earlier BCLC staging are independent factors associated with EHPM. The survival rates of EHPM improve over time and also better than HCC-alone. Cox proportional-hazards regression shows independent poor prognostic factors are age >60, male, AFP levels ≥400 ng/ml, positivity of HBsAg, Child-Pugh B vs. A, Non-metachronous group, respectively, treated with local ablation, transcatheter arterial embolization, radiotherapy and supportive care vs. surgery, respectively, TNM stage IIIA vs. I, and BCLC stages A, B, C and D vs. 0, respectively. Survival of EHPM improve could be explained by early diagnosis and improve treatment of cancers.

Hepatocellular Carcinoma associated with Extra-hepatic Primary Malignancy: its Secular change, Clinical Manifestations and Survival