Prospective validation of the prognostic 31‐gene expression profiling test in primary cutaneous melanoma

Abstract

Background Gene expression profiling (GEP) has been integrated into cancer treatment decision‐making in multiple neoplasms. We prospectively evaluated the prognostic utility of the 31‐GEP test (DecisionDx‐Melanoma, Castle Biosciences, Inc) in cutaneous melanoma (CM) patients undergoing sentinel node biopsy (SNB). Methods One hundred fifty‐nine patients (age 26‐88) diagnosed with melanoma between 01/2013 and 8/2015 underwent SNB and concurrent GEP testing. GEP results were reported as low‐risk Class 1 (subclasses 1A and 1B) or high‐risk Class 2 (subclasses 2A and 2B). Statistical analyses were performed with chi‐square analysis, t tests, log‐rank tests, and Cox proportional hazard models. Recurrence‐free survival (RFS) and distant metastasis‐free survival (DMFS) were estimated using Kaplan‐Meier method. Results Median follow‐up was 44.9 months for event‐free cases. Median Breslow thickness was 1.4 mm (0.2‐15.0 mm). There were 117 Class 1 and 42 Class 2 patients. Gender, age, Breslow thickness, ulceration, SNB positivity, and AJCC stage were significantly associated with GEP classification ( P < 0.05 for all). Recurrence and distant metastasis rates were 5% and 1% for Class 1 patients compared with 55% and 36% for Class 2 patients. Sensitivities of Class 2 and SNB for recurrence were 79% and 34%, respectively. Of 10 SNB‐positive/Class 2 patients, 9 recurred. By multivariate analysis, only SNB result and GEP class were statistically associated with both RFS ( P = 0.008 and 0.0001) and DMFS ( P = 0.019 and 0.001). Conclusions Gene expression profiling Class 2 result and SNB positivity were independently associated with recurrence and distant metastasis in primary CM patients. GEP testing may have additive prognostic utility in initial staging work‐up of these patients.

Recurrence patterns in patients with Stage II melanoma: The evolving role of routine imaging for surveillance

“…27,28 Determining which patients benefit from routine imaging surveillance to improve timing of systemic therapy administration will continue to be refined as genetic profiling and identification of liquid biomarkers improves. 29,30 This study had three main limitations. First, while physicians followed NCCN guidelines for timing of clinical follow-up, practices regarding routine imaging surveillance was variable.…”

“…Two ongoing randomized clinical trials will help to address early adjuvant treatment of higher risk Stage II patients 27,28 . Determining which patients benefit from routine imaging surveillance to improve timing of systemic therapy administration will continue to be refined as genetic profiling and identification of liquid biomarkers improves 29,30 …”

Prognostic Gene Expression Profiling in Melanoma: Necessary Steps to Incorporate into Clinical Practice

“…The 31-GEP test further stratified patients with negative SLNB for distant metastatic risk. Similarly, two recent prospective studies (consisting primarily of AJCC stage I/II patients) found GEP class to be the strongest predictor of both local recurrence and distant metastasis [8,9]. Finally, in a study of 1421 prospectively tested T1/T2 tumor stage patients – most undergoing SLNB – from 26 centers, GEP class was a significant predictor of SLNB-positivity [10].…”

Integration of a 31-Gene Expression Profile Into Clinical Decision-Making in the Treatment of Cutaneous Melanoma

“…5 A recent study by Zager et al 9 suggested the use of the 31-GEP in addition to SLNB in clinical decision-making to further increase the detection if patients at-risk for distant metastasis. 9 This finding was echoed in a prospective validation study by Keller et al 10 which showed that Class 2 31-GEP results and SLNB were independent risk factors for recurrence and distant metastasis. 10 In another study by Vetto et al 6 , it was suggested that the 31-GEP could be used to stratify patients’ risk of SLNB positivity allowing for the option to forgo SLNB in patients with Breslow thickness ≤2.0 mm and age ≥55 years.…”

“…The 31-GEP seeks to identify those T1 and T2 tumors with genetic signatures that are likely to behave in either low-risk or high-risk manners with regard to recurrence, distant metastasis, and mortality. 6,8-11 This test stratified patients into 4 groups: Class 1A (considered low risk of metastasis or recurrence), Classes 1B and 2A (intermediate risk), and Class 2B (high risk). When these groups are further broken down by patient age, it becomes apparent that patients >55 years of age whose tumors are Class 1A have <5% incidence of SLNB positivity.…”