Beyond the first graft: skin cancer risk and risk stratification in retransplanted solid organ recipients.

Abstract

Solid organ transplant recipients (SOTRs) face a markedly elevated risk of post-transplant skin cancer, particularly cutaneous squamous cell carcinoma (cSCC). This risk is driven by chronic immunosuppression, including the direct oncogenic effects of some immunosuppressive drugs, and cumulative carcinogenic risk factors including ultraviolet radiation exposure. Retransplanted SOTRs (R-SOTRs) represent a growing yet under-recognized subgroup, carrying additional vulnerability as the second or third transplant will often require more profound immunosuppression. Despite this, no retransplant-specific dermatological surveillance guidelines currently exist. Risk-stratification tools, including the Skin and Ultraviolet Neoplasia Transplant Risk Assessment Calculator, do not incorporate retransplantation status or cumulative immunosuppressive burden. Given the plausibly amplified risk profile of this population, a conceptual framework for skin cancer risk stratification in the context of retransplantation remains an unmet clinical need. To address this, we conducted a narrative review of studies published between January 2000 and February 2026, synthesizing primary studies alongside relevant guidelines and consensus statements. Kidney and heart registry data identify retransplantation as a risk indicator for post-transplant skin cancer outcomes, while the only cohort that reported cutaneous outcomes after retransplantation, comprising highly selected kidney recipients with prior cSCC, demonstrated higher rates of aggressive cSCC after retransplantation. Therefore, we propose a conceptual framework stratifying R-SOTRs into five risk categories according to prior skin cancer history, acknowledging the limited direct evidence currently available: no prior skin cancer, prior single nonaggressive cSCC, prior multiple cSCC, prior histologically aggressive cSCC and prior metastatic cSCC. This framework is intended to support individualized risk assessment and to identify patients likely to warrant closer dermatological follow-up, rather than to prescribe specific surveillance intervals. Prospective studies evaluating the impact of risk-stratified surveillance on skin cancer outcomes in this population are urgently needed.