Immunosuppressive regimens and skin cancer risk in solid-organ transplant recipients

Solid organ transplant recipients (SOTRs) are at increased risk of developing skin cancer due to long-term immunosuppressive (IS) therapy. Calcineurin inhibitors (CNIs), particularly tacrolimus and ciclosporin, are associated with elevated skin cancer risk. Mammalian -target of rapamycin inhibitors (mTORis) are considered protective, but real-life evidence of their effectiveness, especially when combined with reduced-dose CNIs, is limited. Understanding the impact of current IS regimens on skin cancer risk is essential for improving patient outcomes.

To evaluate the relative risk of different IS drugs and regimens on skin cancer development in SOTRs.

We conducted a prospective observational study at Vall d'Hebron University Hospital, Barcelona, Spain, from 2011 to 2021. The study included 1055 SOTRs from a mixed-organ cohort, with a combined follow-up of 3336 person-years. Real-life IS drug regimens were recorded during scheduled posttransplant screenings or dermatological follow-ups. Cox proportional hazards models with shared frailty were used to assess skin cancer risk, accounting for multiple events and adjusting for time-varying drug exposure.

Skin cancer occurred in 131 of 1055 SOTRs (12.4%). A total of 450 skin cancer events were registered, including 317 squamous cell carcinomas (70%), 118 basal cell carcinomas (26%) and 15 melanomas (3%). mTORi-based regimens were associated with significantly lower skin cancer rates [hazard ratio (HR) 0.66, 95% confidence interval (CI) 0.47-0.92; P = 0.01]. Everolimus appeared more protective than sirolimus (HR 0.38, 95% CI 0.21-0.69; P < 0.001). Reduced-dose CNIs combined with mTORis were linked to a 37% reduction in skin cancer rates in high-risk patients (HR 0.63, 95% CI 0.42-0.93; P = 0.02) and a 32% reduction in patients with posttransplant events (HR 0.68, 95% CI 0.47-0.98; P = 0.04). The reduction was mainly driven by decreased squamous cell carcinoma incidence.

mTORi-based regimens, particularly with reduced-dose tacrolimus, appear to offer a safer and more effective alternative to CNI-heavy regimens for skin cancer prevention in SOTRs. Real-life data support the integration of mTORis into IS strategies to reduce skin cancer risk, particularly for high-risk patients and those who developed skin malignancies. An author video to accompany this article is available online.