Consensus-Based Recommendations on the Prevention of Squamous Cell Carcinoma in Solid Organ Transplant Recipients

Abstract

IMPORTANCEThere is a paucity of evidence to guide physicians regarding prevention strategies for cutaneous squamous cell carcinoma (CSCC) in solid organ transplant recipients (SOTRs).OBJECTIVE To examine the development and results of a Delphi process initiated to identify consensus-based medical management recommendations for prevention of CSCC in SOTRs.EVIDENCE REVIEW Dermatologists with more than 5 years' experience treating SOTRs were invited to participate. A novel actinic damage and skin cancer index (AD-SCI), consisting of 6 ordinal stages corresponding to an increasing burden of actinic damage and CSCC, was used to guide survey design. Three sequential web-based surveys were administered from January 1, 2019, to December 31, 2020. Pursuant to Delphi principles, respondents thoroughly reviewed all peer responses between rounds. Supplemental questions were also asked to better understand panelists' rationale for their responses.FINDINGS The Delphi panel comprised 48 dermatologists. Respondents represented 13 countries, with 27 (56%) from the US. Twenty-nine respondents (60%) were Mohs surgeons. Consensus was reached with 80% or higher concordance among respondents when presented with a statement, question, or management strategy pertaining to prevention of CSCC in SOTRs. A near-consensus category of 70% to less than 80% concordance was also defined. The AD-SCI stage-based recommendations were established if consensus or near-consensus was achieved. The panel was able to make recommendations for 5 of 6 AD-SCI stages. Key recommendations include the following: cryotherapy for scattered actinic keratosis (AK); field therapy for AK when grouped in 1 anatomical area, unless AKs are thick in which case field therapy and cryotherapy were recommended; combination lesion directed and field therapy with fluorouracil for field cancerized skin; and initiation of acitretin therapy and discussion of immunosuppression reduction or modification for patients who develop multiple skin cancers at a high rate (10 CSCCs per year) or develop high-risk CSCC (defined by a tumor with approximately Ն20% risk of nodal metastasis). No consensus recommendation was achieved for SOTRs with a first low risk CSCC.CONCLUSIONS AND RELEVANCE Physicians may consider implementation of panel recommendations for prevention of CSCC in SOTRs while awaiting high-level-of-evidence data. Additional clinical trials are needed in areas where consensus was not reached.

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

“…We summarize staging of disease prevention for posttransplant skin cancer in Table 1 (20,21). Primary and secondary prevention strategies for CSCC in OTR include patient education, photoprotection, clinical skin surveillance and topical and oral chemoprevention (22), though data in transplant cohorts are limited with recommendations extrapolated from relatively small studies (23)(24)(25), expert opinion (26,27), or studies in ICP (28)(29)(30).…”

“…Dermatologists may consider oral chemoprevention for patients at high risk of subsequent CSCC, with options including oral retinoids (acitretin) or nicotinamide ( 26 ). Acitretin is effective with up to 42% reduction in rates of CSCC in kidney transplant recipients in RCTs ( 23 , 25 ).…”

“…Uncertainty about optimal timing of these interventions led to formulation of expert consensus-based recommendations for management, including a recent international Delphi panel of transplant dermatologists ( 26 ). While consensus was reached regarding topical and systemic agents in primary and secondary prevention of CSCC, consensus was not reached for optimal interventions after a first low-risk CSCC (LRCSCC; defined in this study, and this paper, as Brigham and Women’s Hospital Stage T1 or T2a, or American Joint Committee on Cancer T1 or T2).…”

A long‐term cohort study of acitretin for prevention of keratinocyte carcinoma in solid organ transplant recipients

“…3 A recent Delphi consensus statement recommended acitretin as chemoprophylaxis in SOTR who develop one high-risk cutaneous squamous cell carcinoma (SCC) after multiple low-risk SCCs, or more than 10 low-risk SCCs per year. 4 Acitretin is a synthetic retinoid thought to affect cellcycle control, induce apoptosis, promote cellular differentiation and immunomodulation, and inhibit ornithine decarboxylase, cellular proliferation and keratinisation. 5 Retinoids also inhibit growth of human papilloma virus (HPV)-16-immortalised keratinocytes compared with noninfected cells, and there is a high prevalence of HPV in KC of SOTR.…”

“…Strategies for prevention include photoprotection, systemic acitretin chemoprophylaxis, reduction of immunosuppression and substitution of immunosuppressive agent(s) with mammalian target of rapamycin (mTOR) inhibitors 3 . A recent Delphi consensus statement recommended acitretin as chemoprophylaxis in SOTR who develop one high‐risk cutaneous squamous cell carcinoma (SCC) after multiple low‐risk SCCs, or more than 10 low‐risk SCCs per year 4 …”