Prospective, Multicenter Clinical Impact Evaluation of a 31-Gene Expression Profile Test for Management of Melanoma Patients

Abstract

Objective: A 31-gene expression profile (GEP) test that has been clinically validated identifies melanoma patients with low (Class 1) or high (Class 2) risk of metastasis based on primary tumor biology. This study aimed to prospectively evaluate the test impact on clinical management of melanoma patients.Methods: Physicians at 16 dermatology, surgical or medical oncology centers examined patients to assess clinical features of the primary melanoma. Recommendations for clinical follow-up and surveillance were collected. Following consent of the patient and performance of the GEP test, recommendations for management were again collected, and pre- and post-test recommendations were assessed to determine changes in management resulting from the addition of GEP testing to traditional clinicopathologic risk factors. Results: Post-test management plans changed for 49% (122 of 247) of cases in the study when compared to pre-test plans. Thirty-six percent (66 of 181) of Class 1 cases had a management change, compared to 85% (56 of 66) of Class 2 cases. GEP class was a significant factor for change in care during the study (p<0.001), with Class 1 accounting for 91% (39 of 43) of cases with decreased management intensity, and Class 2 accounting for 72% (49 of 68) of cases with increases.Conclusions: The reported study show that the 31-gene GEP test improves net health outcomes in the management of cutaneous melanoma. Physicians used test results to guide risk-appropriate changes that match the biological risk of the tumor, including directing more frequent and intense surveillance to high-risk, Class 2 patients.

Early outcome of a 31‐gene expression profile test in 86 AJCC stage IB‐II melanoma patients. A prospective multicentre cohort study

“…15 Subsequent studies have analysed the use of the 31-GEP test in combination with the AJCC stage system and found that this approach improves the identification of patients at risk of relapse. 18,19 In this report, we also combined GEP with the AJCC score confirming that patients with higher AJCC (IIB-IIC) staging and Class 2 GEP are at a greater risk of relapse. Nevertheless, two patients with a low-risk AJCC stage and a Class 2 GEP metastasized.…”

“…14 Recently, new prognostic tests based on genetic profiling signatures have been developed to better identify those patients who are at a higher risk of developing metastasis leading to death. [15][16][17][18][19][20] A gene expression profile (GEP) test (DecisionDx-Melanoma, Castle Biosciences, Inc., Friendswood, TX, USA) evaluates 31 genes of primary cutaneous melanoma tumours and based on the expression of these genes (genetic signature) it classifies patients into two groups of risk of relapse, low (class 1) or high (class 2). This test has been validated in several historical cohorts showing that its prognostic ability is independent from the clinical and pathological features of the tumour.…”

“…This test has been validated in several historical cohorts showing that its prognostic ability is independent from the clinical and pathological features of the tumour. [15][16][17][18][19][20][21][22][23][24] However, this test has never before been evaluated in a prospective multicentre cohort.…”

Response to: “Use of a prognostic gene expression profile test for T1 cutaneous melanoma: Will it help or harm patients?”

“…Previous studies have shown that a 31-GEP class 1 result provides reassurance of a low-risk tumor, leading to reduced intensity of patient follow-up and referral patterns. [3][4][5] One could argue that patients who have a negative sentinel lymph node biopsy result but experience metastasis are also harmed by an incorrect result; notably, these patients constitute the majority of those who die of melanoma. 6 In their model for 31-GEP clinical value based on test accuracy metrics, Marchetti et al 2 have not only overestimated the incidence of a class 2 result in T1 tumors but have also failed to account for the 31-GEP subclasses 1A (lowest risk), 1B, 2A, and 2B (highest risk).…”

“…Distinguishing class 1A tumors with a higher than 95% negative predictive value (99% in Greenhaw et al 3 ) and class 2B tumors with a 40% positive predictive value for recurrence is impactful for patients. 4,5 Clinicopathologic features do not identify all thin melanomas that will recur. The multivariate analysis described in Gastman et al 7 ( Supplementary Table III [available at http://www.jaad.org]) emphasizes the value of molecular subclassification in the context of these factors; the 31-GEP class 2B result was the only feature independently associated with recurrence risk for T1 tumors.…”