De novo malignancies after liver transplantation: A 30-year multicenter Brazilian cohort

INTRODUCTION AND OBJECTIVES: De novo malignancy (DNM) is a major late hazard after liver transplantation (LT), usually due to cumulative immunosuppression, viral oncogenesis, and host/environmental factors. Robust Brazilian multicenter data remain scarce. This study assessed burden, spectrum, timing, and post-cancer outcomes in a long-horizon national cohort. MATERIALS AND METHODS: Retrospective cohort of all orthotopic LT recipients from three Brazilian programs (1991-2022), with follow-up through June 1, 2024. Primary epidemiology used competing-risk methods (Aalen-Johansen with death as a competing event) for non-cutaneous DNM; Kaplan-Meier (KM) was reported for cross-study comparability. Overall survival (OS) was estimated from the first eligible DNM diagnosis in a prespecified clinical subset (excludes non-melanoma skin cancer [NMSC] and recurrent hepatocellular carcinoma; melanoma included). RESULTS: The analytic cohort comprised 1234 recipients; 142 developed post-LT malignancy, of whom 121 had ≥1 DNM. NMSC led the spectrum, followed by gastrointestinal neoplasms. Ten-year cumulative incidence of non-cutaneous DNM by Aalen-Johansen was 3.5% (95% CI 2.6-4.6); KM risks at 10 years were 9.8% for any DNM and 6.3% for non-cutaneous DNM. In the OS subset (n = 80), survival from first cancer diagnosis declined over time (primary: 1y 80.5%, 3y 69.8%, 5y 47.3%; sensitivity: 1y 78.0%, 3y 67.2%, 5y 44.0%). Temporal patterns showed sustained incidence beyond 5-10 years. CONCLUSIONS: In a 30-year multicenter Brazilian cohort, DNM constituted a major late complication after LT with persistent risk into late survivorship and clinically meaningful attrition after non-cutaneous cancers. These findings support lifelong, risk-adapted and oncologically mindful immunosuppression, tailored to regional epidemiology and access to longitudinal care.