The DecisionDx™-Melanoma gene test was designed to identify those Stage I or II cutaneous melanoma patients whose tumor biology suggests they are at higher risk of metastasis than their stage, or sentinel lymph node biopsy status, might indicate.
As with all cancers, one of the primary challenges for doctors in managing skin melanoma is predicting the course of their patients’ disease, or prognosis. Having an accurate picture of whether or not the cancer has already, or is likely to spread, is critical to determining treatment and follow-up care.
We know that a certain percentage of the 60,000 Stage I and II patients diagnosed each year will ultimately see their disease progress at some point after the primary tumor is removed. While traditional staging provides valuable prognostic information, it does miss many patients. In addition, while sentinel lymph node biopsy status has been reported as the most accurate prognostic factor for predicting metastasis (McMasters, 2004), two of three patients who metastasize are SLNB negative (SLNB-). These patients would have missed the opportunity to receive the increased surveillance and treatment options afforded those thought to be at higher risk by current standards (Coit, et al, v.2, 2013).
Addressing a need for a more accurate picture of individual risk, the DecisionDx-Melanoma test was developed to help predict the five-year risk of recurrence based on the biology of a patient’s tumor. The test uses a small sample of the melanoma to measure the activity of specific genes found by rigorous studies to be most associated with progression in this cancer. Based on the tumor’s “expression” levels—also called the “gene expression” profile or signature—the tumor is classified as either Class 1 “low risk” or Class 2 “high risk.”
Stage II patients with Class 2 gene test result at higher risk than most Stage III patients
Multi-center studies of the DecisionDx-Melanoma gene test found that there are a number of Stage I and II patients with high risk tumor biology who are missed by staging and SLNB. In fact, patients with Class 2 biology were shown to have a significantly higher metastatic risk than most Stage III patients and it is thought that they should be considered for more aggressive management to avoid under-treatment relative to their risk.
The additional, personalized information from the gene test can enable doctors to more accurately match their patients’ metastatic risk to the appropriate surveillance and treatment plans. Patients receiving a “low risk” Class 1 result have about a 3% chance of their cancer spreading within 5 years. These patients are usually recommended to have routine follow-up care, which includes periodic examinations of the skin and lymph nodes.
For patients with a Class 2 result, the risk of the cancer spreading is much higher–at about 69% within 5 years. For example, for those Stage II patients who receive a Class 2 gene test result with a higher risk for recurrence than a Stage III patient, a physician may recommend “upstaging” the patient to Stage III for care purposes. Stage III patients usually receive more frequent monitoring and may be referred to a surgical and/or medical oncologist to be considered for further treatment or participation in clinical trials. But it is up to the patient and their healthcare team to decide how best to proceed.
DecisionDx-Melanoma was validated in the largest melanoma biomarker study of its kind. Using archival tumor samples, the GEP test identified the majority of Stage I and II patients whose tumor biology had put them at higher risk of metastasis than their stage had suggested (see Clinical Validation). The study showed that the gene test is a highly accurate and independent predictor of individual metastatic risk in Stage I and II disease.
A second study, published in 2015 in the Journal of the American Academy of Dermatology, found that DecisionDx-Melanoma significantly improved upon the prognostic accuracy of sentinel lymph node biopsy in identifying patients (archival samples) at high risk of their cancer spreading. The GEP test was able to identify as high risk a large number of patients whose sentinel lymph node biopsy results did not indicate any increased risk, but who subsequently developed metastatic disease (see GEP/SLNB Study Publication). SLNB status historically has been considered the most accurate tool for staging melanoma.