Abstract
BACKGROUND: Skin cancer is the most common post-transplant malignancy. We aimed to determine the incidence, timing, risk factors, and survival impact of skin cancer in heart transplant (HTx) recipients over long-term follow-up. METHODS: This retrospective, single-center cohort study analyzed 568 HTx patients surviving >1 year (1990-2024). Patients with ≥1 histologically confirmed skin malignancy were compared to matched controls without skin cancer. Demographics, transplant characteristics, and immunosuppressive regimens were assessed. Logistic regression and Cox models identified independent risk factors for skin cancer and survival. RESULTS: Of 568 eligible patients, 42 (7.4%) developed skin cancer after a median of 15.5 years. Basal cell carcinoma was most common (54.7%), followed by squamous cell carcinoma (SCC, 33.3%). Immunosuppression with calcineurin inhibitor (CNI) plus azathioprine (AZA) was independently associated with increased skin cancer risk (odds ratio [OR] 9.41, p = 0.044), especially for SCC (OR 6.6, p = 0.027). Median time to first skin tumor onset was shortest with CNI + AZA (6 years, p = 0.0014) compared to other AZA-free immunosuppressive regimens. Overall survival (OS) did not differ significantly between skin cancer and control groups (p = 0.485), but SCC was independently associated with reduced OS (HR 2.14, p = 0.05). CONCLUSIONS: Skin cancer is a relevant long-term complication after HTx, particularly SCC in patients receiving AZA. Our findings support limiting AZA use and reinforce the importance of structured dermatologic surveillance and early mammalian target of rapamycin conversion strategies to improve long-term outcomes.