Health Care Professionals

DecisionDx-Melanoma Summary

  • The DecisionDx-Melanoma gene expression profile test is being widely used to determine metastatic risk in Stage I and II cutaneous melanoma patients
  • Validated as an accurate, independent predictor of a patient’s metastatic risk
  • Found in published study to enhance the accuracy of sentinel lymph node biopsy in predicting metastasis
  • Independent of Breslow’s thickness, ulceration status and mitotic rate; AJCC stage, and Sentinel Lymph Node Biopsy status
  • Performed on formalin-fixed, paraffin embedded primary tumor tissue from either biopsy or excision

In patients with cutaneous melanoma (CM), there is wide variability in metastatic rates within and across TNM stage groupings. For instance, while Stage I melanomas are considered low risk as a group, some tumors are actually at high risk for metastasis. A more objective means of predicting metastatic risk, based on an individual’s specific tumor biology, may add significant value to the comprehensive baseline evaluation and determination of the initial surveillance and treatment.

While sentinel lymph node status has been reported as the most accurate prognostic factor (McMasters, 2004) for predicting metastasis, both AJCC staging and MSLT-1 data (below)  reveal that two of three patients who metastasize are SLNB negative. Under the guidelines of the National Comprehensive Cancer Network (NCCN), 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).

*# deceased at 5 years calculated by multiplying the 5-year survival by stage with the 2012 annual incidence of patients diagnosed by stage according to SEER data.

*# deceased at 5 years calculated by multiplying the 5-year survival by stage with the 2012 annual incidence of patients diagnosed by stage according to SEER data.

Gene expression profile assay shown to be more accurate predictor of metastasis than current staging methods

To meet the need for a more objective and accurate tool in cutaneous melanoma, Castle Biosciences developed a quantitative, RT-PCR-based gene expression profile (GEP) test. The assay analyzes the expression of 31 genes within melanomas, and can more accurately predict distant metastases in Stages I and II patients than can current staging factors (AJCC stage, Breslow’s thickness, ulceration status, mitotic rate and sentinel lymph node status).

The DecisionDx-Melanoma™ test completed validation in a prospectively designed, multi-center program, the largest of its kind in cutaneous melanoma. Data from the studies were reported at the 2013 meeting of the American Society of Clinical Oncology (see Clinical Validation). The DecisionDx-Melanoma test was shown to be more accurate than other factors currently used to predict an individual patient’s metastatic risk, such as AJCC stage, Breslow’s thickness and mitotic rate. The GEP test stratified tumors as low risk (Class 1) or high risk (Class 2). Patients with Class 1 tumors were found to have a 5-year metastasis free survival rate of 97%, while those in Class 2 have a 5-year metastasis free survival of 31%.

NOTE: There are several primary articles that have been submitted for publication in appropriate peer-reviewed medical journals. For that reason, until published, this website will only contain summary data of the validation studies.

Study shows DecisionDx-Melanoma test identifies metastatic risk in sentinel lymph node negative patients

In a clinical study published in the Journal of the American Academy of Dermatology in March 2015, researchers found that the DecisionDx-Melanoma gene expression profile (GEP) test for cutaneous melanoma improved the prognostic accuracy of sentinel lymph node biopsy in identifying patients at high risk of metastasis. In patients with a negative sentinel lymph node biopsy, the GEP test identified the majority of melanomas that ultimately progressed over the subsequent 5-year period. (See GEP/SLNB Published Study.)

Primary tumor tissue from 217 Stage I, II, III, or IV cutaneous melanoma patients with documented SLNB results was analyzed using the DecisionDx-Melanoma test under a multicenter, prospectively-planned, archival tissue study protocol. The predictive accuracy of the DecisionDx-Melanoma and SLNB prognostic tools were evaluated individually and in combinationto assess primary endpoints of disease-free survival (DFS), distant metastasis free survival (DMFS), and overall survival (OS).

Independently, the GEP and SLNB tests were shown to stratify patients according to their risk (univariate analysis using Cox proportional hazards p<0.0001 for GEP for all endpoints, SLNB for DFS and DMFS; SLNB for OS p=0.0099).

Table 1

Multivariate analysis found GEP Class to be independent of SLNB status for all endpoints (p<0.0001) and SLNB status to be independent of GEP Class for DFS (p=0.008) and DMFS (p=0.001) but not OS (p=0.11).

Combining the GEP and SLNB tests showed improvements in stratifying patients who were SLNB negative. The SLNB negative group as a whole had a DFS of 55%. Using the GEP test to further stratify those patients resulted in identification of a higher risk (Class 2) sub-group of SLNB negative patients who had a DFS of 35%. Likewise, SLNB negative patients who were predicted to be low risk (Class 1) using the GEP had a DFS of 83%.

Table 2

 In patients with a negative sentinel lymph node biopsy, a result interpreted as a lower risk for metastasis, the GEP test identified the vast  majority of melanomas that ultimately progressed over the subsequent 5-year period. According to study results, the rate of 5-year metastasis-free survival (MFS) was 55% for SLNB- patients compared to 37% for SLNB+ patients. The GEP test results showed improved prognostic accuracy in these same patients with an MFS of 87% for the low-risk (Class 1) patients and 31% for the high risk (Class 2) patients (Gerami et al., 2014).

Potential benefits of new prognostic tool

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 (Bichakjian, 2011, Coit, 2013). 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 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, including identification of high risk patients among those with a negative SLNB result, or for patients who are ineligible for or who decline a SLNB procedure. Patients with Class 2 biology have a significantly higher risk than most Stage III patients and it is thought that they should be considered for similar management to avoid under-treatment relative to their risk.

DecisionDx-Melanoma was discovered and developed by Castle Biosciences Inc. in its CAP-accredited, CLIA-certified laboratory, and is now being widely used. The test can only be ordered by a licensed physician or other appropriate healthcare provider through direct submission of a requisition to Castle (see Order the Test, top right).