Natural History of Untreated Hepatocellular Carcinoma in a US Cohort and the Role of Cancer Surveillance

BACKGROUND & AIMS: Determining the natural history and predictors of survival in patients with untreated hepatocellular carcinoma (HCC) in the United States is useful to test existing tumor classifications, identify subgroups of patients likely to benefit from treatment, and estimate lead time related to HCC surveillance. METHODS: We identified a national cohort of 518 veterans diagnosed with HCC from 2004 through 2011, with follow-up ending in 2014, who received no palliative or curative treatment. We examined the association between postdiagnosis survival and patient factors, tumor characteristics, and prediagnosis surveillance. RESULTS: The mean age at HCC diagnosis was 65.7 years and most patients had hepatitis C (60.6%). Almost all patients (99%) died within the observation period; the median overall survival time was 3.6 months and survival times were 13.4, 9.5, 3.4, and 1.6 months for patients of Barcelona Clinic Liver Cancer stages 0/A,B, C, and D, respectively. In addition, model for end-stage liver disease and levels of alpha-fetoprotein were predictive of survival. Nearly 28% received prediagnosis HCC surveillance, which was associated with detection of disease at an earlier stage (Barcelona Clinic Liver Cancer 0/A/B; 26.4% vs 14.4%; P = .0006) and slightly longer survival than patients with no surveillance overall (5.2 months vs 3.4 months; P = .021); there was no difference in survival times of patients with 0/A stage who did versus did not receive surveillance (10.3 months vs 10.5 months). CONCLUSIONS: Patients with HCCs, including those detected through surveillance, survived for short time periods in the absence of treatment, irrespective of their initial stage at diagnosis. Model for end- stage liver disease scores and levels of a- fetoprotein were prognostic factors, independent of Barcelona Clinic Liver Cancer stage. The lead time related to detection by surveillance was modest (< 2 months) and therefore unlikely to explain the survival benefit associated with surveillance in previous studies.