Interventions After First Post-Transplant Cutaneous Squamous Cell Carcinoma: A Proposed Decision Framework

Abstract

Cutaneous squamous cell carcinoma (CSCC) is a major cause of morbidity and mortality after organ transplant. Many patients subsequently develop multiple CSCC following a first CSCC, and the risk of metastasis and death is significantly increased compared to the general population. Post-transplant CSCC represents a disease at the interface of dermatology and transplant medicine. Both systemic chemoprevention and modulation of immunosuppression are frequently employed in patients with multiple CSCC, yet there is little consensus on their use after first CSCC to reduce risk of subsequent tumors. While relatively few controlled trials have been undertaken, extrapolation of observational data suggests the most effective interventions may be at the time of first CSCC. We review the need for intervention after a first post-transplant CSCC and evidence for use of various approaches as secondary prevention, before discussing barriers preventing engagement with this approach and finally highlight areas for future research. Close collaboration between specialties to ensure prompt deployment of these interventions after a first CSCC may improve patient outcomes.

Updates in Skin Cancer in Transplant Recipients and Immunosuppressed Patients: Review of the 2022–2023 Scientific Symposium of the International Immunosuppression and Transplant Skin Cancer Collaborative

“…This study found an incidence rate ratio (IRR) of 0.44 (p = 0.03, 95% CI = 0.21-0.92) when SOTRs were switched from cyclosporine to tacrolimus, as well as an IRR of 1.66 (p = 0.01, 95% CI = 1.16-2.36%) with azathioprine compared to an IRR of 0.78 with mycophenolate (p = 0.18, 95% CI = 0.54-1.12) [9]. Additionally, transition from azathioprine to mycophenolate appears to reduce the risk of developing a first cutaneous SCC post solid organ transplantation with mycophenolate having an IRR of 0.49 (p = 0, 95% CI = 0.32-0.75) compared to azathioprine in this setting [9][10][11].…”

“…These clinical findings are supported by transitional research showing that cutaneous SCC in SOTRs taking azathioprine show unique mutational signatures caused by UVA absorption by DNA [ 7 , 8 ]. While azathioprine is now less commonly used as a primary immunosuppression regimen for SOTRs, it is still used in patients who are intolerant to mycophenolate therapy or who may be planning to become pregnant [ 9 ].…”

“…A recent large retrospective control-matched cohort study by Gibson et al published in 2021 found a significant reduction in skin cancer development with the use of tacrolimus and mycophenolate when compared to cyclosporine and azathioprine, respectively [ 10 ]. This study found an incidence rate ratio (IRR) of 0.44 ( p = 0.03, 95% CI = 0.21–0.92) when SOTRs were switched from cyclosporine to tacrolimus, as well as an IRR of 1.66 ( p = 0.01, 95% CI = 1.16–2.36%) with azathioprine compared to an IRR of 0.78 with mycophenolate ( p = 0.18, 95% CI = 0.54–1.12) [ 9 ]. Additionally, transition from azathioprine to mycophenolate appears to reduce the risk of developing a first cutaneous SCC post solid organ transplantation with mycophenolate having an IRR of 0.49 ( p = 0, 95% CI = 0.32–0.75) compared to azathioprine in this setting [ 9 – 11 ].…”

“…As discussed above in the Massey et al publication, the development of multiple invasive low risk cutaneous SCC or the development of a high-risk cutaneous SCC should prompt discussion of alteration of immunosuppression regimen with the patient’s transplant team. The two secondary prevention strategies used in this situation are to change the immunosuppressive regimen or change the immunosuppressive intensity, and individual patient assessment must be used to determine the best course of action [ 9 ]. As immunosuppression regimens continue to evolve, more research is needed to determine best therapy and dose to balance maintaining the function of the transplanted organ and decreasing the risk of secondary malignancies.…”