A Delphi panel comprising 48 transplant dermatologists across 13 countries has published new recommendations for the prevention of cutaneous squamous cell carcinoma (cSCC) in solid organ transplant recipients. The recent consensus statement was published online in JAMA Dermatology.
According to the panel, there exists little clinical evidence to guide clinicians in their efforts to prevent cSCC in solid organ transplant recipients. To address this lack of guidance, the expert panel, which consisted of dermatologists who had more than 5 years of experience treating solid organ transplant recipients, convened to develop a survey to identify consensus statements regarding cSCC prevention in the solid organ transplant population.
The design of the survey relied on a novel actinic damage and skin cancer index (AD-SCI), which was developed by the working group and consisted of 6 ordinal stages. Each stage represented a frequently encountered clinical scenario in which the management of the case could be modified to reduce the risk for further cSCC. The first round included open-ended questions that were tailored to each AD-SCI stage of cSCC development. Respondents were given multiple-choice answers to choose management options for each stage.
Consensus-based management recommendations for optimal prevention of cSCC in solid organ transplant recipients were made across 5 of the 6 AD-SCI stages. Routine skin surveillance and sunscreen were recommended for all patients, based on evidence of targeted screening in patients at high risk for melanoma as well as previous recommendations for sunscreen use in reducing the incidence of actinic keratosis (AK) and cSCC in organ transplant recipients. These recommendations were made for AD-SCI stage 1, which was focused on only photodamaged skin.
For AD-SCI stage 2, the panel recommended cryotherapy as first-line management for thin scattered AKs. If cryotherapy fails initially, the guideline panel recommended that clinicians should repeat cryotherapy. In cases of thick scattered AKs, cryotherapy should also be used as first-line therapy, but lesion-directed therapy should be repeated if cryotherapy initially fails. Oral chemoprevention is not recommended for either thin or thick AKs.
In grouped AKs of AD-SCI stage 2, the panel recommended field therapy as first-line treatment for thin AKs. For thick AKs, the panel recommended lesion-directed therapy with cryotherapy followed by field therapy. The initiation of field therapy with fluorouracil was recommended as first-line treatment in scenarios that involved anatomically grouped AK or field cancerized skin.
A recommendation for fluorouracil did not reach a full consensus across the panel, nor did any field agent reach the 80% or greater consensus threshold at the AD-SCI stage. Reviewed data which supported fluorouracil-based therapy in immunocompetent patients led to 87% of respondents stating they believed fluorouracil is the most effective field agent; however, concerns among 78% of respondents regarding adherence to therapy may limit broader use, the panel stated.
The sole oral chemoprevention agent that was recommended by the expert panel was acitretin, based on responses to scenarios describing transplant recipients who developed cSCC at a high rate (10 cSCCs per year) or those who developed high-risk cSCC (≥20% risk of nodal metastasis). Acitretin was also recommended as oral chemoprevention after development of multiple low-risk cSCCs, with the panel recommending clinicians discuss with transplant teams regarding immunosuppression modification.
According to the guideline authors, the recommendation for acitretin is based on randomized clinical trials of renal transplant recipients. The expert panel noted that no randomized controlled trials to date have compared the benefits of acitretin in solid organ transplant recipients with high vs low rates of CSCC development.
In addition, the expert panel recommended the discussion of immunosuppression modification with transplant physicians in patients with advanced cSCC. A recommendation was not made on the most optimal immunosuppression modification strategy in these patients. Likewise, the panel made no recommendation on discussion immunosuppression reduction or conversion to mammalian target of rapamycin inhibition with transplant physicians.
Limitations and Additional Questions
According to the guideline panel, the AD-SCI used in the development of the consensus statement was based on expert opinion and does not represent a validated instrument. In addition, the chosen criteria for consensus (≥80%) were strict, suggesting “more areas of consensus may have been reported with a lower standard,” the expert panel wrote.
The guideline authors noted that there was no consensus regarding the management of solid organ transplant recipients who have an initial low-risk cSCC, indicating more studies and clinical trials are needed to guide management in the broader patient population. The expert panel noted that this future research work should involve transplant medicine colleagues.
“These recommendations will assist physicians in implementing prevention strategies for management of CSCC in SOTRs while awaiting high level-of-evidence data to guide best practices,” the guideline authors wrote.
Disclosure: Several authors declared affiliations with the pharmaceutical industry. Please refer to the original article for a full list of disclosures.
Massey PR, Schmults CD, Li SJ, et al. Consensus-based recommendations on the prevention of squamous cell carcinoma in solid organ transplant recipients: A Delphi consensus statement. JAMA Dermatol. 2021;157(10):1219-1226. doi:10.1001/jamadermatol.2021.3180