• Aaron M Drucker, Gaelen P Adam, Valerie Rofeberg, Abhilash Gazula, Bryant Smith, Farah Moustafa, Martin A Weinstock, and Thomas A Trikalinos.
• Alpert Medical School of Brown University, Providence, Rhode Island, and University of Toronto and Women's College Hospital, Toronto, Ontario, Canada (A.M.D.).
• Ann. Intern. Med. 2018 Oct 2; 169 (7): 456-466.

BackgroundMost interventions for basal cell carcinoma (BCC) have not been compared in head-to-head randomized trials.PurposeTo evaluate the comparative effectiveness and safety of treatments of primary BCC in adults.Data SourcesEnglish-language searches of MEDLINE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Embase from inception to May 2018; reference lists of guidelines and systematic reviews; and a search of ClinicalTrials.gov in August 2016.Study SelectionComparative studies of treatments currently used in adults with primary BCC.Data ExtractionOne investigator extracted data on recurrence, histologic clearance, clinical clearance, cosmetic outcomes, quality of life, and mortality, and a second reviewer verified extractions. Several investigators evaluated risk of bias for each study.Data SynthesisForty randomized trials and 5 nonrandomized studies compared 18 interventions in 9 categories. Relative intervention effects and mean outcome frequencies were estimated using frequentist network meta-analyses. Estimated recurrence rates were similar for excision (3.8% [95% CI, 1.5% to 9.5%]), Mohs surgery (3.8% [CI, 0.7% to 18.2%]), curettage and diathermy (6.9% [CI, 0.9% to 36.6%]), and external-beam radiation (3.5% [CI, 0.7% to 16.8%]). Recurrence rates were higher for cryotherapy (22.3% [CI, 10.2% to 42.0%]), curettage and cryotherapy (19.9% [CI, 4.6% to 56.1%]), 5-fluorouracil (18.8% [CI, 10.1% to 32.5%]), imiquimod (14.1% [CI, 5.4% to 32.4%]), and photodynamic therapy using methyl-aminolevulinic acid (18.8% [CI, 10.1% to 32.5%]) or aminolevulinic acid (16.6% [CI, 7.5% to 32.8%]). The proportion of patients reporting good or better cosmetic outcomes was better for photodynamic therapy using methyl-aminolevulinic acid (93.8% [CI, 79.2% to 98.3%]) or aminolevulinic acid (95.8% [CI, 84.2% to 99.0%]) than for excision (77.8% [CI, 44.8% to 93.8%]) or cryotherapy (51.1% [CI, 15.8% to 85.4%]). Data on quality of life and mortality were too sparse for quantitative synthesis.LimitationData are sparse, and effect estimates are imprecise and informed by indirect comparisons.ConclusionSurgical treatments and external-beam radiation have low recurrence rates for the treatment of low-risk BCC, but substantial uncertainty exists about their comparative effectiveness versus other treatments. Gaps remain regarding high-risk BCC subtypes and important outcomes, including costs.Primary Funding SourceAgency for Healthcare Research and Quality. (PROSPERO: CRD42016043353).

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