A recent article by de Gruijl and Armstrong focuses on potential causes for the increased incidence of melanoma diagnoses in Europe, Australia, and the United States, such as increased sun exposure at a young age and increased use of ultraviolet (UV) tanning beds (1, 2); however, they note that, similar to commentary by Welch et al. (1, 2), the increased risk from additional UV exposure does not account for the even larger increase in incidence seen over the past three or four decades. Both reports posit that melanoma is being overdiagnosed but most of the additional cases are thin tumors and other lower-risk melanomas (1, 2). De Gruijl and Armstrong conclude that dermatologists are unlikely to adopt suggestions that not all suspicious thin lesions need biopsy since they are responsible for their patients’ outcomes and note that the overdiagnosis issue “will only be resolved by advances in histopathological diagnosis, or novel molecular analyses that can distinguish between potentially lethal and non-lethal melanomas” (1). They end by noting, “to the best of our knowledge there is no such solution in sight” (1).
We take issue with this final statement, as gene-expression profile (GEP) tests are currently validated and available to provide diagnostic and prognostic information for patients with suspected or confirmed malignant cutaneous melanoma. To combat the overdiagnosis of melanoma, molecular tools can be used to appropriately guide dermatopathologists in the definitive diagnosis of suspicious melanocytic lesions in addition to histopathological features (3). The 23-GEP (MyPath; Castle Biosciences, Inc., Houston, TX, USA) and 35-GEP (DiffDx-Melanoma; Castle Biosciences, Inc.) tests analyze gene-expression levels to provide increased diagnostic clarity for difficult-to-diagnose melanocytic lesions (4, 5). These objective tests can provide clinicians with peace of mind that pathologically ambiguous lesions are benign or malignant, allowing physicians to guide appropriate patient follow-up care and treatment plans.
Regarding prognostication, molecular biology-based solutions are already available to address the concerns of separating low-risk and high-risk tumors to guide appropriate physician management of patients with cutaneous melanoma. For those with a diagnosis of melanoma, well-validated prognostic tools (i.e. able to “distinguish between potentially lethal and non-lethal” cancers) have been available in the United States for nearly a decade. The 31-GEP test (DecisionDx-Melanoma; Castle Biosciences, Inc.) provides precise risk stratification information for patients diagnosed with stage I-III melanoma (6-8). Algorithms integrating 31-GEP results with clinicopathological features (i31-GEP) are validated for predicting the risk of a positive sentinel lymph node biopsy (9) and of recurrence or metastasis (10). Utilizing GEP testing with standard clinicopathological staging can improve patient risk stratification, allowing physicians to provide personalized, risk-aligned treatment and surveillance management for patients, even in the context of potential overdiagnosis.
- Received January 10, 2023.
- Revision received January 19, 2023.
- Accepted January 24, 2023.
- Copyright © 2023 The Author(s). Published by the International Institute of Anticancer Research.
This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY-NC-ND) 4.0 international license (https://creativecommons.org/licenses/by-nc-nd/4.0).
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