Are genetic expression profiling tests ready for widespread use in melanoma?
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Yes.
The use of genetic expression profiling (GEP) assays is standard of care for the management of many cancers, including breast, prostate and thyroid cancers, and uveal melanoma. They are coming into standard use for melanoma.
A commercially available 23-gene GEP assay is commonly used as an adjunct to indeterminate histopathology when melanoma is in the differential of a pigmented lesion, and a 31-gene GEP assay is now Medicare approved as an adjunct to American Joint Committee on Cancer (AJCC) staging to better determine the relapse risk of a given melanoma. This 31-gene assay has been validated retrospectively, prospectively and in a meta-analysis, and it now is listed as an option for risk assessment by National Comprehensive Cancer Network guidelines.
In my practice, I use this assay to identify patients who may be at higher risk than predicted by their AJCC stage, and those who are at particularly low risk and may not require either sentinel node staging or close surgical follow-up. These uses are supported by a fair amount of level-two data.
Although many cling to the old ways of histopathology and AJCC staging only and demand level-one data for GEP assays, I believe that the era of using genetic expression to diagnose and risk-assess melanomas has arrived. I am hopeful that those who care for patients with melanoma learn to use GEP assays, understand their possible applications and limitations, and push in the future for a next generation of GEP assays that will ask more specific diagnostic and clinical questions.
References:
Gastman BR, et al. J Am Acad Dermatol. 2019;doi:10.1016/j.jaad.2018.07.028.
Keller J, et al. Cancer Med. 2019;doi:10.1002/cam4.2128.
John Vetto, MD, is professor of surgery in the division of surgical oncology at Oregon Health & Science University. He can be reached at 3181 S.W. Sam Jackson Park Road, Portland, OR 97239-3098.
No.
The melanoma treatment landscape has changed dramatically over the past decade. On the heels of the now well-defined benefits of sentinel node biopsy, there are now highly effective systemic treatments for advanced disease. This has led to several questions. Which patients will benefit from additional therapy? Which therapy should be used?
Conceptually, GEP technologies hold the promise of answering some of these pressing questions by examining the molecular makeup of the primary melanoma to determine likelihood of recurrence or death due to disease. This strategy has proved valuable in breast cancer, where rigorous prospective trials have demonstrated the ability of GEP to determine which patients can benefit from adjuvant chemotherapy. The hope is that similar beneficial GEP tests can be validated for patients with melanoma.
However, significant work remains to reach that end. Several GEP tests have been developed and one is commercially available. These tests primarily have been aimed to improve risk stratification (ie, prognostic) rather than determine which therapies are best for a particular patient (ie, predictive).
As a prognostic test, GEP appears to hold promise. The available evidence probably falls short of demonstrating prognostic value independent of traditional staging, but it seems likely there will be independent value in testing for some patients. Surprisingly, there is little overlap in the genes in the various GEP tests, which raises the question of whether the ideal test or contextual application is yet to be identified.
There is promise that GEP testing will enable better selection of patients for therapies — including sentinel node biopsy — although additional prospective validation with larger sample sizes will be needed. More information also will be needed to determine how to handle discordant anatomic and molecular findings, such as patients with stage I melanoma but a high-risk molecular score, and vice versa. With refinements in AJCC staging, GEP faces a higher bar in demonstrating added value to what is available via routine clinicopathological data.
It also is important to remember that even the best prognostic GEP test will not be therapeutic, in distinction to staging procedures such as sentinel node biopsy. Patients with positive sentinel nodes not only gain that prognostic information, they also are rendered free of regional nodal disease in the vast majority of cases. Finally, GEP testing will need to be significantly refined so it will have predictive value for response to adjuvant therapy. A test that could help select patients for adjuvant therapy and help choose between targeted therapy and checkpoint blockade would be incredibly valuable.
Everyone should be eager to contribute to acquiring the knowledge needed to determine where these tests fit into decision-making for melanoma treatment, but we should be careful not to get ahead of the data.
Reference:
Marchetti MA, et al. J Am Acad Dermatol. 2019;doi:10.1016/j.jaad.2018.11.063.
Keith A. Delman, MD, is professor of surgery in the division of surgical oncology at Emory University. He can be reached at kdelman@emory.edu. Mark B. Faries, MD, can be reached at mfaries@theangelesclinic.org. Giorgos C. Karakousis, MD, can be reached at giorgos.karakousis@pennmedicine.upenn.edu. Sandra L. Wong, MD, can be reached at sandra.l.wong@hitchcock.org. Jonathan S. Zager, MD, can be reached at jonathan.zager@moffitt.org.
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