A recent study published in Clinical Cancer Research, “Development of a Prognostic Genetic Signature to Predict the Metastatic Risk Associated with Cutaneous Melanoma,” used Texas-based Castle Bioscience’s DecisionDx-Melanoma test for cutaneous melanoma. The gene test, which is indicated to predict a patient’s risk for developing Stage I or II metastatic melanoma, was clinically validated by this new study.
“[The results of this study] demonstrate that a gene signature can accurately predict metastasis, particularly in tumors that were assumed to be lower risk due to stage, size, and other characteristics,” said Pedram Gerami, MD, lead author on the study at Northwestern Skin Cancer Institute, in a news release. “This test can have a significant impact on the management and potentially long term outcomes of these melanoma patients.”
Ultimately, Dr. Gerami and colleagues demonstrated how Castle Bioscience’s genetic test for melanoma metastasis accurately predicts the chance for metastasis in patients affected by Stage I or II melanoma, regardless of signs of spread beyond the original tumor. Data were generated from over 200 patients in the validation study cohort.
DecisionDx-Melanoma is based on a 28-gene signature for prognosis. Tumor samples from patients’ primary cutaneous melanoma tissue is processed to extract genes, which are evaluated using radial basis machine modeling to indicate risk for metastasis. One of two outcomes is assigned to each patient: low risk (class 1) or high risk (class 2) for metastasis. Receiver operating characteristic (ROC) curves showed ROC = 0.91 during the validation study, compared to ROC = 0.93 identified during development. Five-year disease-free survival rates proved to be 97% in predicted class 1 patients and 31% in predicted class 2 patients, compared to 100% and 38%, respectively, during development.
Another important feature of the study was validation of American Joint Committee on Cancer stage as an independent predictor of metastatic risk. “The behavior of melanoma tumors is highly variable, and often cannot be accurately predicted using traditional staging methods,” said Dr. Gerami. The same validation applied to Breslow thickness, ulceration, and age, according to Cox regression analysis.
Finally, DecisionDx-Melanoma correctly identified known cases of Stage I and IIA metastasis with an accuracy of 80%. The gene expression profile test also identified 95% of non-metastatic Stage I patients as class 1 with an accuracy of 95% and metastatic Stage I patients as class 2 with an accuracy of 56%.
“The ability to more accurately stratify patients based on actual risk can have a significant impact on patients diagnosed with Stage I or II cutaneous melanoma,” said study author David H. Lawson of Winship Cancer Institute at Emory University. “Patients identified as high risk may choose to be monitored as if they were Stage III. Additionally, the psychological and emotional burden of a melanoma diagnosis may be lessened for patients receiving a Class 1, low risk diagnosis. This test, in combination with AJCC staging, provides caregivers with the most accurate prognostic tools currently available for managing patients diagnosed with melanoma.”
Dr. Lawson further described future applications of DecisionDx-Melanoma, stating, “Ongoing studies will further define how this test can best be used in conjunction with the current AJCC staging system and to determine whether adjuvant therapy for the higher risk patients can alter the natural history of this disease.”