Surgical re-excision versus observation for histologically dysplastic nevi: a systematic review of associated clinical outcomes K.T. Vuong1, J. Walker2, H. Powell1, N.E. Thomas3,4, D.E. Jonas5,6, A.S. Adamson3,5,6 1University of North Carolina School of Medicine, Chapel Hill, NC, USA 2Health Sciences Library, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA 3Department of Dermatology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA 4Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA 5Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA 6Cecil G. Sheps Center for Health Services Research, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA British Journal of Dermatology. DOI: 10.1111/bjd.16557

Kimmy Vuong, MD, MPH Lead researcher

Introduction Management of histologically dysplastic nevi (HDN) with re-excision versus observation remains controversial. A number of studies have suggested that observation may be a reasonable alternative to re-excision; however, no systematic review summarizing the available data has been conducted.

Objective To summarize and analyze the literature available regarding the development of biopsy site melanoma among HDN managed with either re-excision or observation.

Methods Used Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Searched MEDLINE via PubMed, EMBASE, and Cochrane Library (Wiley) for original research articles published from date of each database inception through April 20, 2017. Primary outcome: Development of melanoma at site of HDN biopsy site.

Methods Study criteria Inclusion criteria: human studies, English language, histological diagnosis of dysplastic nevi. Exclusion criteria: non-empirical studies, non-English studies, studies not reporting outcomes of interest, studies without full text available, populations without histologic diagnosis of dysplastic nevus. Study designs: Randomized controlled trials (RCTs), non-RCTs, case- control, cohort, cross-sectional, case-series.

Methods Quality assessment and risk of bias Modified Oxford Centre for Evidence-Based Medicine rating scale. Risk Of Bias in Non-randomized Studies – of Interventions (ROBINS-I) assessment tool.

Results

Results Study characteristics No trials were identified, all studies were observational; eleven (11/12, 91.7%) retrospective chart reviews; and one was both cross sectional and cohort. Follow up was not reported in 3 studies, but varied between 2 weeks and 30 years. 2 studies reported re-excised lesions only, 5 reported observation only, 5 reported both. Analysis included 2,673 total HDN of all grades. Eleven biopsy site melanomas developed across 3 of the studies, 6/1535 (0.39%) among observed lesions and 5/1138 (0.44%) among re-excised lesions.

Results Study quality and bias assessment Oxford Centre for Evidence-Based Medicine rating scale: All studies with evidence rating level of 3 or 4 (low quality). Risk Of Bias in Non-randomized Studies – of Interventions (ROBINS-I) assessment tool: All studies with overall serious risk of bias or not enough information to assess bias. Serious risk of bias was found in many domains, especially selection bias and confounding.

Discussion Study limitations: Most studies were retrospective, did not include demographic patient data, and 4 did not directly assess the primary outcome. Patients who underwent re-excision vs. observation may differ in their risk of the outcome (e.g. family history, larger HDN burden, other risk factors, etc.). Melanomas developing in only 3 of the studies may reflect differences in proportion of severe HDNs or in patient populations recruited.

Discussion Other limitations: Diagnosis and HDN grading can have significant inter-pathologist variability. There are negative effects of overly aggressive HDN management: worry, infection, scarring, unnecessary healthcare costs, etc. Most studies had zero events or did not compare observation to re-excision head-to-head  high risk for selection bias and confounding.

Discussion Further studies including controlled prospective cohort studies and/or randomized trials are warranted. A large RCT would be ideal, but to date, no such trial has been conducted and is unlikely given costs.

Conclusions What does this study add? Current evidence suggests that both re-excised and observed HDN have low rates of melanoma development. Clinical observation of most HDNs is likely a safe practice. However, the evidence is of low quality and is limited by imprecision because of few total observations and events.

Research team Jennifer Walker Nancy Thomas Kimmy Vuong Adewole Adamson Helen Powell Daniel Jonas

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