Natural History of Small Untreated Hepatocellular Carcinoma in Cirrhosis: A Multivariate Analysis of Prognostic Factors of Tumor Growth Rate and Patient Survival

We analyzed the growth pattern of tumor masses and the survival of 39 asymptomatic Italian patients with a total of 59 small (less than or equal to 5 cm in diameter) hepatocellular carcinomas arising from cirrhosis. The total length of the observation period ranged from 90 to 962 days, with an average of 364 +/- 229 (mean +/- S.D.). Doubling time ranged from 27.2 to 605.6 days (mean +/- S.D., 204.2 +/- 135; median = 171.6 days). Three different growth patterns were recognized: (a) tumors with no or very slow initial growth pattern (doubling time greater than 200 days), 10 cases (37%); (b) tumors with declining growth rate over time, 9 cases (33.4%); and (c) tumors with almost constant growth rate, 8 cases (29.6%). Using the stepwise discriminant analysis, we found a score based on albumin, alcohol intake, number of nodules, echo pattern and histological type that allowed a correct prediction of short doubling time (less than or equal to 150 days) in 55.6%, medium doubling time (151 to 300 days) in 60% and long doubling time (greater than 300 days) in 100% of cases. The estimated survival rate of the 39 patients, calculated by the Kaplan-Meier method was 81% at 1 yr, 55.7% at 2 yr and 21% at 3 yr. Stepwise discriminant analysis showed that a score based on sex, HBsAg status, alcohol consumption, ascites, gamma-glutamyltranspeptidase, prothrombin time, Child-Pugh class and all the sonographical parameters could predict 2-yr survival in 100% of cases. We conclude that great variability of growth patterns exists among and within small hepatocellular carcinomas. Prediction of subsequent growth rate is unreliable in most cases.(ABSTRACT TRUNCATED AT 250 WORDS)