Aaron M. Drucker, MD, ScM; Gaelen P. Adam, MLIS; Valerie Rofeberg, ScM; Abhilash Gazula, MPH; Bryant Smith, MPH; Farah Moustafa, MD; Martin A. Weinstock, MD, PhD; Thomas A. Trikalinos, MD
Disclaimer: This report is based on research conducted by the Brown Evidence-based Practice Center under contract to the AHRQ. The findings and conclusions in this document are those of the authors, who are responsible for its contents, and do not necessarily represent the views of AHRQ. Therefore, no statement in this report should be construed as an official position of AHRQ or of the U.S. Department of Health and Human Services.
Financial Support: By contract 290-2015-00002-I from the AHRQ.
Disclosures: Dr. Drucker reports grants from AHRQ during the conduct of the study; having served as an investigator and received research funding from Sanofi and Regeneron; and having been a consultant for Sanofi, RTI Health Solutions, Canadian Agency for Drugs and Technology in Health, and Eczema Society of Canada. He has received honoraria from Astellas Canada, Prime Inc., Spire Learning, CME Outfitters, and Eczema Society of Canada. None of the disclosures outside this work are relevant to the treatment of primary basal cell carcinoma. Ms. Adam reports grants from AHRQ during the conduct of the study. Dr. Weinstock reports grants from AHRQ during the conduct of the study. Authors not named here have disclosed no conflicts of interest. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M18-0678.
Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that her spouse has stock options/holdings with Targeted Diagnostics and Therapeutics. Darren B. Taichman, MD, PhD, Executive Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Deborah Cotton, MD, MPH, Deputy Editor, reports that she has no financial relationships or interest to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Catharine B. Stack, PhD, MS, Deputy Editor for Statistics, reports that she has stock holdings in Proctor & Gamble, Pfizer, and Johnson & Johnson.
Reproducible Research Statement:Study protocol: Available at https://effectivehealthcare.ahrq.gov/topics/skin-cancer/research-protocol and on PROSPERO (CRD42016043353). Statistical code: Available at www.brown.edu/academics/public-health/research/evidence-synthesis-in-health/research-initiatives/code-and-data, under Technical Appendix for NMSC. Data set: Available at https://srdr.ahrq.gov and at www.brown.edu/academics/public-health/research/evidence-synthesis-in-health/research-initiatives/code-and-data, under Technical Appendix for NMSC.
Corresponding Author: Aaron M. Drucker, MD, ScM, Room 6343, Women's College Hospital, 76 Grenville Street, Toronto, Ontario M5S 1B2, Canada; e-mail, Aaron.Drucker@wchospital.ca.
Current Author Addresses: Dr. Drucker: Room 6343, Women's College Hospital, 76 Grenville Street, Toronto, Ontario M5S 1B2, Canada.
Ms. Adam, Ms. Rofeberg, Mr. Gazula, Mr. Smith, and Dr. Trikalinos: Center for Evidence Synthesis in Health, 121 South Main Street, Providence, RI 02912.
Drs. Moustafa and Weinstock: Department of Dermatology, APC-10, Rhode Island Hospital, 593 Eddy Street, Providence, RI 02903.
Author Contributions: Conception and design: A.M. Drucker, G.P. Adam, F. Moustafa, M.A. Weinstock, T.A. Trikalinos.
Analysis and interpretation of the data: A.M. Drucker, G.P. Adam, V. Rofeberg, B. Smith, F. Moustafa, T.A. Trikalinos.
Drafting of the article: A.M. Drucker, G.P. Adam, V. Rofeberg, T.A. Trikalinos.
Critical revision of the article for important intellectual content: A.M. Drucker, G.P. Adam, V. Rofeberg, A. Gazula, F. Moustafa, M.A. Weinstock, T.A. Trikalinos.
Final approval of the article: A.M. Drucker, G.P. Adam, V. Rofeberg, A. Gazula, B. Smith, F. Moustafa, M.A. Weinstock, T.A. Trikalinos.
Provision of study materials or patients: G.P. Adam.
Statistical expertise: V. Rofeberg, T.A. Trikalinos.
Obtaining of funding: G.P. Adam, T.A. Trikalinos.
Administrative, technical, or logistic support: G.P. Adam, A. Gazula, T.A. Trikalinos.
Collection and assembly of data: A.M. Drucker, G.P. Adam, V. Rofeberg, A. Gazula, B. Smith, F. Moustafa, T.A. Trikalinos.
Most interventions for basal cell carcinoma (BCC) have not been compared in head-to-head randomized trials.
To evaluate the comparative effectiveness and safety of treatments of primary BCC in adults.
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 ClinicalTrials.gov in August 2016.
Comparative studies of treatments currently used in adults with primary BCC.
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.
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.
Data are sparse, and effect estimates are imprecise and informed by indirect comparisons.
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.
Agency for Healthcare Research and Quality. (PROSPERO: CRD42016043353).
Drucker AM, Adam GP, Rofeberg V, et al. Treatments of Primary Basal Cell Carcinoma of the Skin: A Systematic Review and Network Meta-analysis. Ann Intern Med. 2018;169:456–466. [Epub ahead of print 18 September 2018]. doi: https://doi.org/10.7326/M18-0678
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Published: Ann Intern Med. 2018;169(7):456-466.
Published at www.annals.org on 18 September 2018
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