Post-transplant malignancies in Taiwanese kidney transplant recipients: incidence, temporal trends, and immunosuppressive risk factors in a two-decade single-center cohort.

BACKGROUND: Post-transplant malignancies (PTMs) remain major late immune-related complications after kidney transplantation, but long-term Asian data integrating immunologic exposures are limited. METHODS: We retrospectively analyzed 1,808 kidney transplant recipients from 2002 to 2022 at Taichung Veterans General Hospital, Taiwan. After exclusions, 1,734 patients were eligible. Outcomes included PTM incidence, spectrum, latency, temporal trends, and survival, with prespecified analyses of longitudinal tacrolimus trough levels and cumulative immunosuppressive burden. RESULTS: PTM incidence was 11.7%. Urothelial (bladder 15.8%, upper tract 14.3%) and liver cancers predominated. One third occurred within 5 years with a median latency of 8.2 years. Bladder cancer declined after 2012 (26.7% vs. 11.2%, p = 0.010). Older age independently predicted PTM (HR 1.08 per year, p < 0.001) and mortality (HR 1.07 per year, p < 0.001). Higher long-term tacrolimus trough levels were independently associated with mortality in both the overall and PTM cohorts (HR 1.24 and 1.37, both p < 0.05). PTM patients had higher mortality (46.3% vs. 30.6%) with median post-diagnosis survival of 16.5 months. CONCLUSIONS: PTMs in Taiwan are frequent and immunologically shaped, with a distinct urothelial and hepatic predominance and a post 2012 decline in bladder cancer plausibly linked to evolving immunosuppression, surveillance, and reduced carcinogen exposure. Older age and cumulative immunosuppressive burden were associated with PTM development, whereas higher long-term tacrolimus trough levels independently predicted mortality, underscoring the need for individualized immunosuppressive management and cancer type specific surveillance.