GEP test enables accurate staging of metastatic risk
While uveal melanoma is the most common intra-ocular tumor in adults, it is a rare cancer with an annual U.S. incidence ≈ 2,000. Despite a 93% to 98% primary tumor “cure” rate, nearly 50% of all patients will likely develop metastatic disease within five years, primarily to the liver. However, less than 4% of patients present with metastatic disease at the time of diagnosis.
Following treatment for the primary eye tumor, the main clinical issue in uveal melanoma is determining a patient’s metastatic risk so that a risk-appropriate surveillance and management plan can be implemented.
DecisionDx-UM Test Is Standard of Care
The DecisionDx-UM™ gene expression profile (GEP) test enables accurate staging of five-year metastatic risk in uveal melanoma. Since its introduction in late 2009, it has been adopted as standard of care by the overwhelming majority of ocular oncology specialists in the U.S. in the management of eye cancer.
The test identifies the molecular signature of an individual’s tumor and its likelihood of metastasis within five years. Specifically, the assay determines the activity or “expression” of 15 genes which indicate a patient’s individual risk, or Class.
Based upon the clinical outcomes from the prospective, 5-year multi-center Collaborative Ocular Oncology Group (COOG) study, the DecisionDx-UM test reports Class 1A, Class 1B and Class 2 phenotype:
- Class 1A: Very low risk, with a 2% chance of the eye cancer spreading over the next five years;
- Class 1B: Low risk, with a 21% chance of metastasis over five years;
- Class 2: High risk, with 72% odds of metastasis within five years.
Meets Highest Levels of Validation
DecisionDx-UM is the only prognostic test for uveal melanoma that has been clinically validated by an independent prospective, multi-center study, as well as multiple retrospective and prospective single-center studies (see Scientific References).
According to results reported from the prospective 494 patient study conducted by the Collaborative Ocular Oncology Group (COOG), DecisionDx-UM is clinically and statistically superior to all other prognostic factors—including clinical factors, pathologic factors, and chromosome 3 testing (Onken, 2012). Furthermore, chromosome 3 status did not contribute additional prognostic information that was independent of the DecisionDx-UM test. The study also showed that the GEP test is technically robust, with a 97% success rate of returning a result. These results are comparable to the earlier single-center prospective and retrospective studies (Chappell, 2012; Gill, 2012; Onken, 2010; Worley, 2007).
The National Comprehensive Cancer Network (NCCN), a group of the most recognized and respected comprehensive cancer centers in the U.S., recommends that the clinical utility of tumor markers in oncology be determined in a prospective clinical trial, similar to the type of study required for new drugs (Febbo, 2011). Though the NCCN has not specifically evaluated DecisionDx-UM, it is the only prognostic test in uveal melanoma that would meet this strict standard for the highest level of evidence as it is the only such test to be validated in a prospective, multi-center study.
Additionally the American Joint Committee on Cancer recommends gene expression profile testing for use as the results are “clinically significant.” The American Joint Committee on Cancer (AJCC, version 7, 2010) is the only national organization that reviews uveal melanoma and the DecisionDx-UM test is the only clinically available gene expression profile test for use in the U.S.
Clinical use of the DecisionDx-UM test has been well documented in both medical records review and the literature to direct therapy. The primary clinical use is to implement a risk-appropriate surveillance plan. Additional documented uses include referrals to medical oncology for initiation of adjuvant therapy and clinical trial consideration for high risk patients.
Patients at low risk of metastasis, for instance, may receive a low intensity surveillance program, such as alternating semi-annual liver function tests and ultrasound or other imaging techniques. If a patient is at high risk, a high intensity surveillance program, such as quarterly MRI or CT scans, quarterly liver function tests, and referral to a medical oncologist for adjuvant treatment interventions could be considered as well as participation in clinical trials.
Earlier Prognostic Methods Found Insufficient
Prior to the test’s availability, patients were evaluated based on traditional cytopathology. A couple of clinics evaluated chromosome 3 status–largely using investigational techniques. Both methods provided insufficient information to accurately stage the risk of metastatic disease. As a result, patients were often given a “one size fits all” surveillance plan, with strong potential for either under-treatment or over-treatment. As well, because risk could not be precisely ascertained, many patients were not referred for adjuvant treatment.
The DecisionDx-UM assay was discovered, developed and clinically validated by Dr. J. William Harbour, while at Washington University in St. Louis. He is currently Professor of Ophthalmology, Vice Chairman for Translational Research and Director of the Ocular Oncology Service at the Bascom Palmer Eye Institute in Miami.
Castle Biosciences Inc. exclusively licensed the assay from the Washington University, completed technical validation studies and subsequently made it available for routine clinical use through a CAP-accredited/CLIA-certified laboratory. It is only available through Castle Biosciences Inc.