Molecular Biomarkers for Melanoma Screening, Diagnosis and Prognosis: Current State and Future Prospects

Despite significant progress in the development of treatment options, melanoma remains a leading cause of death due to skin cancer. Advances in our understanding of the genetic, transcriptomic, and morphologic spectrum of benign and malignant melanocytic neoplasia have enabled the field to propose biomarkers with potential diagnostic, prognostic, and predictive value. While these proposed biomarkers have the potential to improve clinical decision making at multiple critical intervention points, most remain unvalidated. Clinical validation of even the most commonly assessed biomarkers will require substantial resources, including limited clinical specimens. It is therefore important to consider the properties that constitute a relevant and clinically-useful biomarker-based test prior to engaging in large validation studies. In this review article we adapt an established framework for determining minimally-useful biomarker test characteristics, and apply this framework to a discussion of currently used and proposed biomarkers designed to aid melanoma detection, staging, prognosis, and choice of treatment.

Melanoma Prevention: Comparison of Different Screening Methods for the Selection of a High Risk Population

Background: Guidelines recommend limiting melanoma screening in a population with known risk factors, but none indicates methods for efficient recruitment. The purpose of this study is to compare three different methods of recruiting subjects to be screened for melanoma to detect which, if any, is the most efficient. Methods: From 2010 to 2019, subjects were recruited as follows: (1) regular skin examinations (RS), mainly conducted through the Associazione Contro il Melanoma network; (2) occasional melanoma screening (OS), during annual public campaigns; (3) and selective screening (SS), where people were invited to undergo a skin check after filling in a risk evaluation questionnaire, in cases where the assigned outcome was intermediate/high risk. Melanoma risk factors were compared across different screening methods. Generalized Linear Mixed Models were used for multivariable analysis. Results: A total of 2238 subjects (62.7% women) were recruited, median age 44 years (2–85), and 1094 (48.9 %) records were collected through RS, 826 (36.9 %) through OS, and 318 (14.2 %) through SS. A total of 131 suspicious non-melanoma skin cancers were clinically diagnosed, 20 pathologically confirmed, and 2 melanomas detected. SS performed significantly better at selecting subjects with a family history of melanoma and I-II phototypes compared to OS. Conclusions: Prior evaluation of melanoma known risk factors allowed for effective selection of a population to screen at higher risk of developing a melanoma.

Assessment of Raman Spectroscopy for Reducing Unnecessary Biopsies for Melanoma Screening

A key challenge in melanoma diagnosis is the large number of unnecessary biopsies on benign nevi, which requires significant amounts of time and money. To reduce unnecessary biopsies while still accurately detecting melanoma lesions, we propose using Raman spectroscopy as a non-invasive, fast, and inexpensive method for generating a “second opinion” for lesions being considered for biopsy. We collected in vivo Raman spectral data in the clinical skin screening setting from 52 patients, including 53 pigmented lesions and 7 melanomas. All lesions underwent biopsies based on clinical evaluation. Principal component analysis and logistic regression models with leave one lesion out cross validation were applied to classify melanoma and pigmented lesions for biopsy recommendations. Our model achieved an area under the receiver operating characteristic (ROC) curve (AUROC) of 0.903 and a specificity of 58.5% at perfect sensitivity. The number needed to treat for melanoma could have been decreased from 8.6 (60/7) to 4.1 (29/7). This study in a clinical skin screening setting shows the potential of Raman spectroscopy for reducing unnecessary skin biopsies with in vivo Raman data and is a significant step toward the application of Raman spectroscopy for melanoma screening in the clinic.