Prognostic Test: Proven, Medically Necessary
The DecisionDx-Melanoma™ gene expression profile (GEP) test was discovered, developed, and validated by Castle Biosciences. Validation was completed in a prospectively planned, multi-center study using archival tissue.
Generally patients diagnosed with Stage I or II melanoma have surgical excision of the primary tumor followed by interval routine skin exams and clinical examination. There is rarely any systemic surveillance imaging, further lymph node interrogation or recommendation for adjuvant therapy. In contrast, patients diagnosed with Stage III melanoma receive complete lymph node dissection, active surveillance measures and often, referral to medical oncology for adjuvant medical therapy and clinical trial participation.
The overall segregation of care based upon Stage I/II vs Stage III makes sense from a population perspective. Specifically, approximately 50% of Stage III patients will develop metastatic disease within 5 years while approximately 14% of Stage I and II patients are at risk for metastatic disease. This 14% of patients represents nearly 8,500 people diagnosed annually who will metastasize. Based upon the validation study data, the DecisionDx-Melanoma can identify these high-risk patients such that the overall Class 2 metastatic risk is greater than that seen in a Stage III patient population.
The information provided by DecisionDx-Melanoma has significant implications for managing patients with cutaneous melanoma. It provides objective data with which the decision to more aggressively manage a Stage I or II patient can be supported. Patients with Class 2 biology have a higher risk than most Stage III patients and it is thought that they should be considered for similar management to avoid undertreatment relative to their risk.
The validation study demonstrated that the DecisionDx-Melanoma test identifies patients diagnosed with Stage I or II (sentinel lymph node negative, if performed) cutaneous melanoma who are at high risk for metastasis. The test reports a low risk Class 1 score in which the 5-year metastatic free survival rate was determined to be 97% and a high-risk Class 2 score in which the 5-year metastatic free survival rate was 31%. Using Cox proportional, multivariate analysis, the DecisionDx-Melanoma test was shown to be an independent and more powerful variable in predicting individual metastatic risk in patients with Stage I or II disease than Breslow’s thickness, mitotic rate and ulceration as well as AJCC staging. The validation study also contained patients who had been diagnosed with Stage III cutaneous melanoma—all but one of whom were classified as Class 2.
Based upon completion of both technical laboratory requirements and of the validation study, the test is available for clinical use in a CAP accredited / CLIA certified laboratory. Thus, the test is not experimental or investigational.
Appropriate Use: The DecisionDx-Melanoma test has been proven for use in patients with Stage I, II or III cutaneous melanoma. Use in patients diagnosed with Stage IV disease is not appropriate.
The DecisionDx-Melanoma test has been proven, and found to be superior to all other predictive factors in identifying individual metastatic risk:
- Clinically validated in a prospectively planned, archival study of 268 patients. The study is the largest biomarker study of its kind in cutaneous melanoma;
- Technically proven through validation, concordance, reliability and specimen type studies, most of which have been published in peer reviewed journals;
- Technically validated in a CAP accredited / CLIA certified laboratory. In fact, all of the development and validation work was performed under standard operating procedures that are identical to those employed in the clinical application of the test;
- Shown to be independent of and more accurate than current histologic factors used to predict an individual patient’s metastatic risk, including AJCC stage, Breslow’s thickness and mitotic rate;
- By virtue of the completion of the prospectively planned, archival tissue validation study, the test meets the level III of the level of evidence Tumor Marker Utility Grading System (TMUGS).