DENVER — A diagnostic test that uses gene-expression profiles can help establish which primary cutaneous melanoma tumors are likely to metastasize, a new study shows.
This could help identify patients who could then be put on a more aggressive screening schedule, and perhaps even be given adjuvant therapies such as immune-modulating agents, said Pedram Gerami, MD, associate professor of dermatology and pathology and director of melanoma research at the Northwestern Skin Cancer Institute in Chicago.
Molecular diagnostics have begun to change prognostication in other tumors, and "people in the melanoma field are realizing that the time is right for it here, as well," he said.
Dr. Gerami presented the research here at the American Academy of Dermatology 72nd Annual Meeting.
Currently, results from sentinel lymph node biopsies are routinely used to determine which patients are most likely to develop metastases. Patients with negative results are considered low risk, but 2 of 3 patients who develop metastatic disease had negative results, according to Dr. Gerami.
The size and scope of this trial differentiate it from other studies of melanoma and molecular diagnostics. "This is one of the largest studies. It includes multiple major melanoma academic centers across the country, and compares the gene-expression test with the traditional type of testing, which is the parameter used by the American Joint Committee on Cancer," he explained.
The study involved 134 patients with stage I, II, or III cutaneous melanoma. All were participants in the initial clinical validation studies of the gene-expression test and had documented biopsy results.
Results from the gene-expression test were compared with results from the biopsy.
The gene-expression test evaluates the expression of 31 genes shown in previous studies to contribute to aggressiveness and metastasis. It ranks patients as low risk or high risk for metastases.
In patients considered low risk because of a negative biopsy, the gene-expression test identified most of the melanomas that progressed over the subsequent 5-year period.
Table 1. Accuracy of 5-Year Survival Predictions
| Results | n | Metastasis-Free, % | Overall, % |
| Biopsy | |||
| Negative | 106 | 55 | 67 |
| Positive | 28 | 37 | 55 |
| Gene expression test | |||
| Low risk | 43 | 87 | 92 |
| High risk | 91 | 31 | 49 |
The gene-expression test outperformed biopsy in the prediction of overall and metastasis-free survival.
The biopsy and gene-expression results were discordant in 49% of patients. In those cases, the gene-expression test more correctly predicted the clinical outcome. On Cox multivariate analysis, the gene-expression test was the only independent and highly significant prognostic factor (P < .000003).
Table 2. Accuracy of Survival Predictions With Combined Results
| Gene-Expression Results | n | Metastasis-Free, % | Overall, % |
| Low-risk | |||
| Negative biopsy | 42 | 86 | 92 |
| Positive biopsy | 1 | 100 | 100 |
| High-risk | |||
| Negative biopsy | 64 | 31 | 49 |
| Positive biopsy | 27 | 34 | 53 |
These results are interesting, but not yet conclusive, said Delphine Lee, MD, PhD, director of the Department of Translational Immunology at the John Wayne Cancer Institute at Saint John's Health Center in Santa Monica, California.
"In the end, no one has a crystal ball, but the more information we have, the better," she told Medscape Medical News.
"However, we have to balance that with the cost of healthcare. As a physician treating a patient one on one, I don't think about what it costs, but I'm not the policymaker trying to figure out how to care for all these people," Dr. Lee explained.
The key to the utility of the gene-expression test will be the tangible benefits it brings to a patient. "Is it really going to help us know more?" she asked.
To answer that question, prospective clinical trials are needed. "This study was retrospective, and the only way we're going to know if these things really work is to test them prospectively," Dr. Lee added.
The study was funded by Castle Biosciences. Dr. Gerami is a consultant with Castle. Dr. Lee has disclosed no relevant financial relationships.
American Academy of Dermatology (AAD) 72nd Annual Meeting. Presented March 22, 2014.
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Cite this: Gene Test Predicts Melanoma Metastases - Medscape - Mar 27, 2014.
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