Treatments of Primary Basal Cell Carcinoma of the Skin: A Systematic Review and Network Meta-analysis

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Background:Most interventions for basal cell carcinoma (BCC) have not been compared in head-to-head randomized trials.Purpose:To evaluate the comparative effectiveness and safety of treatments of primary BCC in adults.Data Sources:English-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 in August 2016.Study Selection:Comparative studies of treatments currently used in adults with primary BCC.Data Extraction:One 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 Synthesis:Forty 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.Limitation:Data are sparse, and effect estimates are imprecise and informed by indirect comparisons.Conclusion:Surgical 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 Source:Agency for Healthcare Research and Quality. (PROSPERO: CRD42016043353).

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