Impact of Sex on the Survival of Patients With Hepatocellular Carcinoma: A Surveillance, Epidemiology, and End Results Analysis

BACKGROUNDMen are 4 to 8 times more likely to develop hepatocellular carcinoma (HCC) than women. Preclinical models have suggested a role for sex hormones in the development of HCC. In the current study, the authors investigated the impact of age, sex, race, and ethnicity on the survival of patients with HCC using the Surveillance, Epidemiology, and End Results (SEER) database. METHODSPatients diagnosed with HCC from 1988 through 2010 were identified from the SEER registry. Hazard ratios (HR) for overall survival (OS) were derived using the Cox regression model adjusted for race, year of diagnosis, marital status, treatment, birthplace, tumor differentiation, and tumor size. RESULTSA total of 39,345 patients were identified; 76% were men and 34% were women (50% white, 12% African American, 21% Asian, 16% Hispanic, and 1% Native American). The median age at the time of diagnosis was 61 years for men and 67 years for women. Approximately 84% of patients had liver-limited disease and 16% had metastatic disease. Treatment information was available for patients diagnosed after 1998 (34,674 patients): 11% received liver-directed therapy, 11% underwent surgical resection, and 7% underwent liver transplantation. The HR for the OS of women versus men was 0.83 (95% confidence interval [95% CI], 0.77-0.88) for patients aged <55 years. The protective effect of sex on OS was found to be greatest in patients aged 18 to 44 years (HR, 0.75; 95% CI, 0.65-0.86 [P<.001]), especially those with surgically resected tumors (HR, 0.68; 95% CI, 0.54-0.86 [P=.001]) and those who were African American (HR, 0.85; 95% CI, 0.78-0.92 [P<.001]). There was no survival difference between sexes noted among Hispanics or patients aged >65 years. CONCLUSIONSSex appears to be associated with survival in patients with HCC. The role of androgens and estrogens in the development and progression of HCC warrants further investigation. Cancer 2014;120:3707-3716. (c) 2014 American Cancer Society. Men and women diagnosed with hepatocellular carcinoma have significantly different overall survival rates after adjusting for tumor-related and treatment-related variables. These survival differences are age-dependent and potentially related to hormonal influences on tumor biology.