Clinical Equipoise and Unimproved Outcomes following Posttransplant Cutaneous Squamous Cell Carcinoma

Introduction: Cutaneous squamous cell carcinoma (CSCC) is the most common malignancy following solid organ transplantation. Historical data suggest that 25% of kidney transplant recipients (KTRs) develop additional CSCC within a year of their first lesion, with significantly increased risks of metastasis and mortality. However, contemporary outcomes and optimal secondary prevention strategies remain unclear. Methods: We conducted a multicenter retrospective cohort study across 8 UK transplant centers, identifying 136 KTRs diagnosed with first-ever CSCC between 2016 and 2020. Results: Over a median follow-up of 39 months, 48.5% developed further CSCC, and 23.3% died, most commonly from malignancy. Poor outcomes were confirmed in another, international cohort. Management varied within and between UK centers and 28.7% underwent immunosuppression reduction, though specific approaches were inconsistent. Distinct clinical and histopathological features were associated with recurrence risk and poorer outcomes, including multiple index lesions, high-risk histopathology, and current smoking. Conclusion: These findings confirm that contemporary post-CSCC outcomes remain unchanged from historic outcomes, despite advances in transplant care. The variability in management after first CSCC highlights the need for prospective studies to define effective interventions for secondary prevention. Importantly, we identify important clinical features present at first CSCC that may guide the targeting of such interventions to the highest risk patients.