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Interventions to Prevent Nonmelanoma Skin Cancers in Recipients of a Solid Organ Transplant

Systematic Review of Randomized Controlled Trials

Chung, Edmund Y.M., MD1,2; Palmer, Suetonia C., PhD3; Strippoli, Giovanni F.M., MD, PhD4–7

doi: 10.1097/TP.0000000000002641
Original Clinical Science—General
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Background. Organ transplant recipients are at high risk of developing skin cancer. The benefits and harms of interventions to prevent nonmelanoma skin cancer in solid organ transplant recipients have not been summarized.

Methods. We searched MEDLINE, Embase, and CENTRAL through April 2018. Risk of bias was assessed using the Cochrane tool, and evidence certainty was evaluated using the Grades of Recommendation, Assessment, Development, and Evaluation process. Prespecified outcomes were nonmelanoma skin cancer, clearance and prevention of keratotic skin lesions, and intervention-specific adverse events.

Results. Ninety-two trials (20 012 participants) were included. The evaluated treatments were cancer-specific interventions (acitretin, imiquimod, photodynamic therapy, nicotinamide, topical diclofenac, and selenium) and immunosuppression regimes (azathioprine, mycophenolate mofetil, calcineurin inhibitors, mammalian target of rapamycin [mTOR] inhibitors, belatacept, induction agents, and withdrawal of calcineurin inhibitors or corticosteroids). Effects on nonmelanoma skin cancer were uncertain for photodynamic therapy (3 trials, 93 participants, risk ratio [RR] 1.42 [95% confidence interval (CI), 0.65–3.11]; low certainty evidence), nicotinamide (2 trials, 60 participants), acitretin (2 trials, 61 participants), and imiquimod (1 trial, 20 participants) compared to control. mTOR inhibitors probably reduced skin cancer compared to calcineurin inhibitors (12 trials, 2225 participants, RR 0.62 [95% CI, 0.45–0.85]; moderate certainty evidence). Photodynamic therapy may cause pain at the treatment site (4 trials, 95 patients, RR 17.09 [95% CI, 4.22–69.26]; low certainty evidence).

Conclusions. There is limited evidence for the efficacy and safety of specific treatments to prevent nonmelanoma skin cancers among solid organ transplant recipients.

1 Department of Medicine, Royal North Shore Hospital, Sydney, NSW, Australia.

2 Northern Sydney Clinical School, The University of Sydney, Sydney, NSW, Australia.

3 Department of Medicine, University of Otago Christchurch, Christchurch, New Zealand.

4 Sydney School of Public Health, The University of Sydney, Sydney, NSW, Australia.

5 Cochrane Kidney and Transplant, Centre for Kidney Research, The Children’s Hospital at Westmead, Westmead, Australia.

6 Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy.

7 Medical Scientific Office and Diaverum Academy, Diaverum, Lund, Sweden.

Received 8 December 2018. Revision received 16 January 2019.

Accepted 16 January 2019.

G.F.M.S., S.C.P., and E.Y.M.C. contributed important intellectual content during manuscript drafting or revision, accepted accountability for the overall work by ensuring that questions pertaining to the accuracy or integrity of any portion of the work are appropriately investigated and resolved, conceived of and designed the review and developed the search strategy, and contributed to data analysis and the writing of the review. E.Y.M.C. and S.C.P. identified studies for inclusion and exclusion, assessed study quality, and performed or checked data extraction.

The authors declare no funding or conflicts of interest.

Supplemental digital content (SDC) is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal’s Web site (www.transplantjournal.com).

Correspondence: Giovanni F.M. Strippoli, MD, PhD, Sydney School of Public Health, The University of Sydney, Sydney, NSW 2006, Australia. (Giovanni.Strippoli@diaverum.com).

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