Impact of multiple primary cancers on overall survival of patients with hepatocellular carcinoma

The increasing occurrence of multiple primary cancers (MPC) is a long-term trend, but the prevalence of MPC in patients with hepatocellular carcinoma (HCC) and its impact on overall survival (OS) remains unknown. We retrospectively analyzed 497 patients with HCC treated at two tertiary centers. The cohort was divided into two subgroups - liver transplant (LT, 324 patients) and non-liver transplant (non-LT, 173 patients). We analyzed MPC occurrence, its impact on survival, and identified variables predicting unfavorable outcomes. The MPC were detected in 88 patients (18%). The most common MPC were prostate (17%), skin (15.9%), kidney (12.5%), and lung (10.2%). The median OS of the whole cohort and the LT and non-LT subgroups were 70, 116, and 17 months, respectively (p<0.0001). The median OS in patients with HCC only and HCC with another cancer was 77 (95% CI, 67-96) and 50 months (95% CI, 37-62), respectively (p=0.25). The OS of LT patients was significantly better than that of those in whom LT had been contraindicated owing to concomitant MPC (116 vs. 35 months, p<0.0009). Autoimmune etiology, non-alcoholic steatohepatitis (NASH), HCC as the first diagnosed malignancy, and male sex were identified as factors significantly influencing the patients' outcomes (HR 0.43, 3.2326, 0.70, and 1.43, respectively). The MPC frequency was 18%. The impact of MPC on OS was not significant, except for individuals contraindicated for LT because of MPC. A better prognosis is associated with the autoimmune etiology of cirrhosis, and when HCC is diagnosed as the first malignancy. Male sex and NASH worsened the outcomes.