The 28-year incidence of de novo malignancies after liver transplantation: A single-center analysis of risk factors and mortality in 1616 patients

BACKGROUND: De novo malignancies are one of the leading causes of late mortality after liver transplantation (LT). METHODS: We analyzed 1616 consecutive patients who underwent LT between 1988 and 2006 at our institution. All patients were prospectively observed over a study period of 28 years by our own outpatient clinic. Complete follow up data were available for 96% of patients, 3% were incomplete and only 1% were lost to follow-up. The median follow-up of the patients was 14.1 years. Variables with possible prognostic impact on the development of de novo malignancies (DNM) were analyzed, as was the incidence of malignancies compared to the non-transplant population by using standardized incidence ratios (SIRs). RESULTS: In total 266 patients (16,5%) developed 322 DNM of the following subgroups: hematological malignancies (n: 49), skin cancer (n: 83) and non-skin solid organ tumors (SOT) (n: 190). The probability of developing any DNM within 10 and 25 years was 12.9% and 23.0%, respectively. The respective probability of developing SOT was 7.8% and 16.2%. Mean age at time of diagnosis of SOT was 57.4 years (range, 18-82 years). In the multivariate analysis an increased recipient age (HR 1.03, P=0.001) and a history of smoking (HR 1.92, p= 0.001) were significantly associated with development of SOT. Moreover, the development of SOT was significantly increased in cyclosporine A- treated compared to tacrolimus- treated patients (HR 1.53, P= 0.03). CONCLUSION: The present analysis shows a disproportionate increase of de novo SOT with an increasing follow up period. Increased age and a history of smoking are confirmed as major risk factors. Moreover, the importance of immunosuppression is highlighted. This article is protected by copyright. All rights reserved.