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

Consensus Statement 

September 1, 2021

A Delphi Consensus Statement

Paul R. Massey, MD, MPH¹; Chrysalyne D. Schmults, MD, MSCE¹; Sara J. Li, BS¹; et alSarah T. Arron, MD, PhD²; Maryam M. Asgari, MD, MPH^3,4; Jan Nico Bouwes Bavinck, MD, PhD⁵; Elizabeth Billingsley, MD⁶; Travis W. Blalock, MD⁷; Katie Blasdale, MBBS⁸; Bryan T. Carroll, MD, PhD^9,10; John A. Carucci, MD, PhD¹¹; Alvin H. Chong, MBBS, MMed^12,13; Sean R. Christensen, MD, PhD¹⁴; Christina Lee Chung, MD^15,16; Jennifer A. DeSimone, MD¹⁷; Emilie Ducroux, MD¹⁸; Begoña Escutia-Muñoz, MD, PhD¹⁹; Carla Ferrándiz-Pulido, MD, PhD^20,21; Matthew C. Fox, MD²²; Roel E. Genders, MD, PhD⁵; Alexandra Geusau, MD²³; Petter Gjersvik, MD, PhD^24,25; Allison M. Hanlon, MD, PhD²⁶; Edit B. Olasz Harken, MD, PhD²⁷; Günther F.L. Hofbauer, MD²⁸; R. Samuel Hopkins, MD²⁹; Justin J. Leitenberger, MD²⁹; Manisha J. Loss, MD³⁰; Veronique Del Marmol, MD, PhD³¹; José M. Mascaró Jr, MD³²; Sarah A. Myers, MD³³; Bichchau T. Nguyen, MD, MPH^34,35; Walmar R. P. Oliveira, MD, PhD³⁶; Clark C. Otley, MD³⁷; Charlotte M. Proby, MA³⁸; Emőke Rácz, MD, PhD³⁹; Veronica Ruiz-Salas, MD, PhD⁴⁰; Faramarz H. Samie, MD, PhD⁴¹; Deniz Seçkin, MD⁴²; Syed N. Shah, MBBS⁴³; Thuzar M. Shin, MD, PhD⁴⁴; Stephen P. Shumack, MBBS⁴⁵; Seaver L. Soon, MD⁴⁶; Thomas Stasko, MD⁴⁷; Elisa Zavattaro, MD, PhD⁴⁸; Nathalie C. Zeitouni, MD^49,50; Fiona O'Reilly Zwald, MD^51,52,53; Catherine A. Harwood, MBBS, PhD^54,55; Anokhi Jambusaria-Pahlajani, MD, MSCE²²

Author Affiliations

JAMA Dermatol. 2021;157(10):1219-1226. doi:10.1001/jamadermatol.2021.3180

Key Points

Question  What are the recommended medical interventions for skin cancer prevention in solid organ transplant recipients?

Findings  On the basis of the results of the Delphi study, cryotherapy is recommended as first-line therapy for actinic keratosis, with the exception of thin actinic keratoses grouped in 1 area. In that scenario and for field cancerization, field therapy should be performed.

Meaning  Oral chemoprevention and discussion with the transplant team regarding modification of immunosuppression should be initiated when the patient develops multiple low-risk cutaneous squamous cell carcinoma (>10 tumors per year) or a high-risk cutaneous squamous cell carcinoma.

Abstract

Importance  There 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 ≥20% 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.

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Benjamin Hidalgo-Matlock
Skin Care Physicians of Costa Rica

Clinica Victoria en San Pedro: 4000-1054
Momentum Escazu: 2101-9574

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