31-GEP Test Research Articles

Integrating the melanoma 31-gene expression profile test with clinical and pathologic features can provide personalized precision estimates for sentinel lymph node positivity: an independent performance cohort.

Up to 88% of sentinel lymph node biopsies (SLNBs) are negative. The 31-gene expression profile (31-GEP) test can help identify patients with a low risk of SLN metastasis who can safely forego SLNB. The 31-GEP classifies patients as low (Class 1A), intermediate (Class 1B/2A), or high risk (Class 2B) for recurrence, metastasis, and SLN positivity. The integrated 31-GEP (i31-GEP) combines the 31-GEP risk score with clinicopathologic features using a neural network algorithm to personalize SLN risk prediction. Patients from a single surgical center with 31-GEP results were included (n = 156). An i31-GEP risk prediction < 5% was considered low risk of SLN positivity. Chi-square was used to compare SLN positivity rates between groups. Patients considered low risk by the i31-GEP had a 0% (0/30) SLN positivity rate compared to a 31.9% (30/94, p < 0.001) positivity rate in those with > 10% risk. Using the i31-GEP to guide SLNB decisions could have significantly reduced the number of unnecessary SLNBs by 19.2% (30/156, p < 0.001) for all patients and 33.0% (30/91, p < 0.001) for T1-T2 tumors. Patients with T1-T2 tumors and an i31-GEP-predicted SLN positivity risk > 10% had a similar SLN positivity rate (33.3%) as patients with T3-T4 tumors (31.3%). The i31-GEP identified patients with < 5% risk of SLN positivity who could safely forego SLNB. Combining the 31-GEP with clinicopathologic features for a precise risk estimate can help guide risk-aligned patient care decisions for SLNB to reduce the number of unnecessary SLNBs and increase the SLNB positivity yield if the procedure is performed.

31-GEP (DecisionDx): a review of clinical utility and performance in a Mayo Clinic cohort.

Cutaneous melanoma (CM) is a significant health concern because of its high metastatic potential. Gene Expression Profile (GEP) testing, particularly the 31-GEP test (DecisionDx-Melanoma), has been increasingly used for risk stratification in CM patients. This study aimed to evaluate the clinical utility and performance of the 31-GEP test in a real-world setting. Patients with CM who underwent 31-GEP testing from August 2014 to August 2022 at our institution were identified through searches of electronic health records. The study analyzed the influence of 31-GEP testing on clinical decision-making related to sentinel lymph node biopsy (SLNB), medical oncology referral, and postdiagnosis surveillance. Kaplan-Meier curves and Cox proportional hazard models were used to elucidate the test's performance, focusing on relapse-free survival (RFS) and melanoma-specific survival (MSS). The study included 65 CM patients. Dermatologists ordered more than 80% of 31-GEP tests. In 81.5% of cases, 31-GEP results did not alter standard clinical management. SLNB decisions were unaffected in 92% of patients with pre-SLNB 31-GEP results. Among patients with stage I-IIA melanoma, 25% of those with high-risk 31-GEP results were referred to medical oncology. Contrary to expectations, the rate of nodal metastasis was higher in low-risk than in high-risk 31-GEP cases. Survival analysis showed overlapping RFS and MSS curves between different 31-GEP classes, suggesting limited prognostic value. The 31-GEP test has a limited impact on clinical management decisions and shows limited prognostic value.

The 31-GEP to identify patients with localized cutaneous melanoma at the highest risk of metastasis to the central nervous system.

9530 Background: Cutaneous melanoma (CM) metastasis to the central nervous system (CNS) has a poor prognosis; however, treatment of CNS metastasis while asymptomatic is associated with better outcomes. CNS imaging is not routinely recommended for patients with early-stage CM (i.e., AJCC stage I–II), yet ˜14% of patients with stage II melanoma will develop CNS metastases. The 31-gene expression profile test (31-GEP) identifies patients at a low (Class 1A), intermediate (Class 1B/2A), or high risk (Class 2B) of tumor recurrence and metastasis. We evaluated the association of CNS metastasis with the 31-GEP test result for the purpose of directing CNS-directed imaging to detect metastasis earlier and, thus, improve outcomes. Methods: A retrospective analysis of patients clinically tested with the 31-GEP from 2013-2017. Patients were included in the study if they had clinical or pathological AJCC stage I-II CM (n=1,662). Kaplan-Meier analysis was used to estimate 5-year recurrence-free survival (RFS), and the log-rank test was used to compare survival between groups. Patients with non-CNS metastasis were censored at the time of recurrence. Univariate analysis to identify predictors of CNS metastasis was performed for tumor location, mitotic rate, Breslow thickness, ulceration status, tumor-infiltrating lymphocytes, age, sex, regression, lymphovascular invasion, tumor subtype, and 31-GEP results. Only significant (p&lt;0.01) factors in univariate analysis were included in Cox multivariable analysis. Results: Median follow-up time was 4.6 years (range: 0.02-14.5 years). Patients with a CNS metastasis tended to have thicker tumors (median 1.1 vs. 0.8, p=0.003), higher mitotic rate/mm2 (median 2.5 vs. 1.0, p&lt;0.001) and a higher proportion of males (73% vs. 55%, p=0.03) than patients that did not develop CNS metastasis. Patients with a Class 2B result were significantly more likely to develop CNS metastasis (7.4% [15/202]) relative to patients with a Class 1B/2A (1.7% [5/291]) or Class 1A (0.9% [10/1,169], p&lt;0.001) 31-GEP result. Patients with a Class 2B result had significantly lower 5-year RFS than patients with a Class 1B/2A or Class 1A result (91.6% vs. 98.2% vs. 99.1%, p&lt;0.001) and had shorter times to CNS metastases (1.5 yrs. vs. 4.2 yrs. vs. 3.4 yrs. p&lt;0.001). In multivariable analysis, only the 31-GEP Class 2B (HR=9.42, p&lt;0.001) result was a significant predictor of CNS metastasis; mitotic rate, Breslow thickness, and ulceration were not significantly predictive. Conclusions: Under multivariable analysis, the 31-GEP was the only significant predictor of CNS metastasis, and CNS metastasis occurred early (1.5 yrs). Patients with early-stage I-II CM and a Class 2B result should be considered for CNS imaging to enable asymptomatic detection of CNS metastasis and, thus, improve survival relative to symptomatic CNS metastasis.

Use of the 31-Gene Expression Profile Test to Aid in the Decision of Adjuvant Treatment of Cutaneous Melanoma

Melanoma is the fifth most common cancer in the United States, with over 7,000 deaths annually. Although most patients diagnosed with early-stage (stage I or II) disease have an excellent prognosis, two out of three patients who die from melanoma were initially diagnosed in early stages. Thus, additional methods to identify which patients are at risk of poor outcomes are needed. DecisionDx-Melanoma is a 31-gene expression profile (31-GEP) molecular risk stratification test that predicts an individual’s risk of recurrence or metastasis in patients with cutaneous melanoma (CM). Here, we describe a 61-year-old man who presented with a spot on his upper scalp. A biopsy confirmed malignant melanoma measuring &gt; 3.87 mm, with ulceration and mitotic rate 2 to 3/mm2. CT, PET, and MRI scans did not reveal metastasis. Following wide local excision and sentinel lymph node biopsy, he was diagnosed with stage IIB CM. Due to the presence of high-risk features, 31-GEP testing was ordered, which revealed Class 2B (high-risk) CM. Due to the high-risk 31-GEP result, the patient was treated off-label with nivolumab for 1 year and received follow-up surveillance scans every 3 months for 3 years. At his last follow-up in April 2022, scans continued to show no recurrent or metastatic disease. The patient continues dermatologic screening every 6 months. The 31-GEP test provides valuable additional information to help clinicians make personalized, risk-based treatment and surveillance plans for patients with CM.

The 31-Gene Expression Profile Test Outperforms AJCC in Stratifying Risk of Recurrence in Patients with Stage I Cutaneous Melanoma.

Patients with stage I cutaneous melanoma (CM) are considered at low risk for metastasis or melanoma specific death; however, because the majority of patients are diagnosed with stage I disease, they represent the largest number of melanoma deaths annually. The 31-gene expression profile (31-GEP) test has been prospectively validated to provide prognostic information independent of staging, classifying patients as low (Class 1A), intermediate (Class 1B/2A), or high (Class 2B) risk of poor outcomes. Patients enrolled in previous studies of the 31-GEP were combined and evaluated for recurrence-free (RFS) and melanoma-specific survival (MSS) (n = 1261, "combined"). A second large, unselected real-world cohort (n = 5651) comprising clinically tested patients diagnosed 2013-2018 who were linked to outcomes data from the NCI Surveillance, Epidemiology, and End Results (SEER) Program registries was evaluated for MSS. Combined cohort Class 1A patients had significantly higher RFS than Class 1B/2A or Class 2B patients (97.3%, 88.6%, 77.3%, p < 0.001)-better risk stratification than AJCC8 stage IA (97.5%) versus IB (89.3%). The SEER cohort showed better MSS stratification by the 31-GEP (Class 1A = 98.0%, Class 1B/2A = 97.5%, Class 2B = 92.3%; p < 0.001) than by AJCC8 staging (stage IA = 97.6%, stage IB = 97.9%; p < 0.001). The 31-GEP test significantly improved patient risk stratification, independent of AJCC8 staging in patients with stage I CM. The 31-GEP provided greater separation between high- (Class 2B) and low-risk (Class 1A) groups than seen between AJCC stage IA and IB. These data support integrating the 31-GEP into clinical decision making for more risk-aligned management plans.

Clinical Utility of the 31-Gene Expression Profile Test on the Management of Cutaneous Melanoma by Nurse Practitioners and Physician Assistants.

The 31-gene expression profile (31-GEP) can predict the risk of recurrence and metastasis in cutaneous melanoma (CM). We assessed the viewpoints and use of 31-GEP testing by physician assistants (PAs) and nurse practitioners (NPs) for patients with CM. NPs and PAs (n = 369) completed an 18-question online survey about their viewpoints and use of the 31-GEP risk-stratification test. Most practitioners (n = 334, 90.5%) felt prognostic testing improved patient care and would recommend the 31-GEP to a colleague (n = 333, 90.2%) or a friend or family member (n = 289, 78.3%) who was diagnosed with CM. The 31-GEP test was used by 176 respondents in the preceding 12 months (53%). Among users of the 31-GEP test, 78% stated that the results would impact follow-up schedule and referral, 66% overall treatment decisions, 62% sentinel lymph node biopsy recommendations, and 50% surveillance imaging. In thin tumors (≤ 1 mm), 82% of 31-GEP users and 44% of nonusers stated that the 31-GEP results would impact their treatment plan decisions. The 31-GEP test significantly impacts treatment plans in CM, particularly for thin and stage I melanomas. Importantly, even nonusers stated that 31-GEP test results would impact treatment plans as well as recommendations to a friend or family member.

The Integrated i31-GEP Test Outperforms the MSKCC Nomogram at Predicting SLN Status in Melanoma Patients.

Sentinel lymph node biopsy (SLNB) for patients with cutaneous melanoma is primarily a prognostic procedure that broadly identifies patients who may have disease progression and may warrant additional intervention. However, 88% of patients undergoing SLNB receive a negative result and of those, some will succumb to their disease. One clinical utility of the integrated 31-GEP test, which combines gene expression data with clinicopathologic factors to provide a personalized, precise risk of SLN positivity, is SLNB guidance. This study compared the i31-GEP for SLNB to a nomogram that predicts SLN positivity using only clinicopathologic factors. Patients with T1-T2 tumors and known SLN status (N=465) were analyzed by the i31-GEP for SLNB and a nomogram developed at Memorial Sloan Kettering Cancer Center (MSKCC). A 5% risk threshold was used to conform with national guidelines. In patients with <5% predicted risk, SLN positivity was 2.7% (3/111) for i31-GEP versus 10.0% (11/110, p=0.026) for MSKCC. In each T-category, the i31-GEP maintained a false-negative rate below the 5% risk threshold in those predicted to have a <5% risk, while the MSKCC nomogram did not. Integrating the 31-GEP with traditional factors outperformed a nomogram that uses clinicopathologic factors alone to predict SLN status. Incorporating the i31-GEP into clinical practice could improve identification of patients for SLNB, resulting in better risk-aligned management.

Combining the 31-gene expression profile test for cutaneous melanoma with the American Joint Committee on Cancer staging identifies the highest-risk patients with stage I-II disease

Introduction: Management guidelines for cutaneous melanoma (CM) are based on patients’ recurrence risk by stage. Most newly diagnosed patients (88%) will be categorized as node-negative (stage I-II) and will be considered low-risk. However, because of the size of this group, the small percentage of stage I-II individuals who do die of melanoma account for the majority of melanoma-associated deaths. In collaboration with the Surveillance, Epidemiology, and End Results (SEER) program, we demonstrated, in a large, unselected cohort of clinically tested patients, that the 31-GEP test identifies those individuals with stage I-II disease, who have higher risk of melanoma-specific death and who may benefit from more aggressive management. &#x0D; Methods: SEER registries linked individuals diagnosed with CM between 2013-2018 were linked to data for 31-GEP-tested patients (N=9,207 after exclusions). For this study, analysis focused on the subset reported as node-negative (N=6,301). Patient 5-year melanoma-specific survival (MSS) was estimated using Kaplan-Meier analysis and the log-rank test for patients considered by the 31-GEP to be low-risk (Class 1A), intermediate-risk (Class 1B/2A), or high-risk (Class 2B). Multivariable Cox regression analysis was used to evaluate significant predictors of melanoma-specific death. Notably, at the time of diagnosis, none of the immune checkpoint inhibitor or targeted signal transduction therapies were approved for use in node-negative patients, providing a largely contemporary therapy naïve cohort. &#x0D; Results: Patients with a Class 2B 31-GEP result had significantly lower 5-year MSS than patients with Class 1B/2A or Class 1A results (85.0% vs. 95.6% vs. 97.9%, p&lt;0.001). The 31-GEP Class 2B result (HR=4.08, p&lt;0.001) was the strongest predictor of melanoma-specific death. Breslow thickness (HR=1.16, p=0.002), presence of ulceration (HR=2.10, p=0.006), and age (HR=1.05, p&lt;0.001) were also significant predictors of melanoma-specific death. The 31-GEP had a sensitivity of 78.4% and a negative predictive value (NPV) of 99.4%. Combining the 31-GEP Class result with AJCC staging could increase the sensitivity to 82.0% while maintaining a high NPV (99.4%). &#x0D; Conclusion: In a large, unselected cohort of patients with stage I-II CM, the 31-GEP Class 2B identified patients with a high risk of progression and death from melanoma who should be considered for more aggressive management. Conversely, the high NPV suggests that the 31-GEP reliably identifies patients at low risk of tumor progression who could safely avoid intensive surveillance and intervention.

31-Gene Expression Profile Testing in Cutaneous Melanoma and Survival Outcomes in a Population-Based Analysis: A SEER Collaboration.

The DecisionDx-Melanoma 31-gene expression profile (31-GEP) test is validated to classify cutaneous malignant melanoma (CM) patient risk of recurrence, metastasis, or death as low (class 1A), intermediate (class 1B/2A), or high (class 2B). This study aimed to examine the effect of 31-GEP testing on survival outcomes and confirm the prognostic ability of the 31-GEP at the population level. Patients with stage I-III CM with a clinical 31-GEP result between 2016 and 2018 were linked to data from 17 SEER registries (n = 4,687) following registries' operation procedures for linkages. Melanoma-specific survival (MSS) and overall survival (OS) differences by 31-GEP risk category were examined using Kaplan-Meier analysis and the log-rank test. Crude and adjusted hazard ratios (HRs) were calculated using Cox regression model to evaluate variables associated with survival. 31-GEP tested patients were propensity score-matched to a cohort of non-31-GEP tested patients from the SEER database. Robustness of the effect of 31-GEP testing was assessed using resampling. Patients with a 31-GEP class 1A result had higher 3-year MSS and OS than patients with a class 1B/2A or class 2B result (MSS: 99.7% v 97.1% v 89.6%, P < .001; OS: 96.6% v 90.2% v 79.4%, P < .001). A class 2B result was an independent predictor of MSS (HR, 7.00; 95% CI, 2.70 to 18.00) and OS (HR, 2.39; 95% CI, 1.54 to 3.70). 31-GEP testing was associated with a 29% lower MSS mortality (HR, 0.71; 95% CI, 0.53 to 0.94) and 17% lower overall mortality (HR, 0.83; 95% CI, 0.70 to 0.99) relative to untested patients. In a population-based, clinically tested melanoma cohort, the 31-GEP stratified patients by their risk of dying from melanoma.

Integrating the 31-gene expression profile test into clinical decision-making to guide risk-aligned care decisions for patients with stage I-III cutaneous melanoma: NCI-SEER Analysis.

6601 Background: Cutaneous melanoma (CM) management depends on an estimate of recurrence risk or death. Because of recognized disease risk and drug efficacy, pembrolizumab immunotherapy has been approved for stage IIB-C patients. However, it is a treatment with potential financial and biological toxicities with 16% of patients experiencing severe treatment related adverse events. Improved risk stratification could identify individuals for whom more selective management would be appropriate. In collaboration with the NCI Surveillance, Epidemiology, and End Results (SEER) program, which includes information on patients tested with a 31-gene expression profile (31-GEP) test in an unbiased and unselected manner, we confirm the 31-GEP adds independent prognostic value in patients with stage I-III CM, and investigated whether the 31-GEP could identify stage IIB-C patients who might reasonably avoid adjuvant therapy while also identifying patients with stage I disease who might benefit from more aggressive diagnostic and/or therapeutic intervention. Methods: SEER registries linked CM cases diagnosed 2013-2018 to 31-GEP test results provided by Castle Biosciences (9,207 matched) using a registry trusted third party (honest broker), including subsets of stage IIB-IIC (n=775) and stage I (n=5,651) melanoma. The primary endpoint was melanoma-specific survival (MSS). The 31-GEP risk-groups included Class 1A (low), Classes 1B/2A (intermediate), and Class 2B (high). Each was compared using Kaplan-Meier analysis and the log-rank test. Results: In the overall cohort, patients with a Class 1A result had a significantly higher 5-year MSS than a Class 1B/2A or Class 2B result (97.4% vs. 93.5% vs. 83.3%, p&lt;0.001). In multivariable analysis, a Class 2B result (HR=3.26, p&lt;0.001) and positive lymph node status (HR=3.41, p&lt;0.001) were the strongest predictors of diminished MSS. In stage IIB-C, 18.8% (146/775) of patients received a Class 1A result with an associated 5-year MSS of 89.1% (vs. Class 2B: 76.6%, p=0.001), despite the absence of pembrolizumab approval for the evaluated SEER population. Alternatively, 4.6% (260/5,651) of patients with stage I disease had a Class 2B result, with an associated 5-year MSS of 92.3% (vs. Class 1A: 98.0%, p&lt;0.001). Conclusions: The SEER database allowed a non-biased analysis of a large cohort of patients with stage I-III CM who were tested with the 31-GEP. The 31-GEP identifies patients, including those with stage IIB-C disease, with favorable outcomes and could help physicians and patients decide whether to pursue adjuvant therapy. Moreover, the 31-GEP identities high-risk patients, including those with stage I disease, for whom more aggressive follow-up and early intervention should be considered.

The 31-gene expression profile test informs sentinel lymph node biopsy decisions in patients with cutaneous melanoma: results of a prospective, multicenter study

Background The 31-gene expression profile test (Class 1A: low-risk; 1B/2A: intermediate-risk; 2B: high-risk) is validated to identify patients with cutaneous melanoma who can safely forego sentinel lymph node biopsy (SLNB). The objective of the current study is to quantify SLNB reduction by clinicians using 31-GEP. Methods Patients with T1-T2 tumors eligible for SLNB were seen by surgical oncologists (89.1%), dermatologists (7.8%), and medical oncologists (3.1%). After receiving 31-GEP results but before SLNB, clinicians were asked which clinical and pathological features influenced SLNB decisions (n = 191). The Exact binomial test was used to compare SLNB procedure rates to a contemporary study (78% SLNB baseline rate). Logistic regression modeling (odds ratio [OR], 95% CI) was used to identify features associated with SLNB procedure rates. Results One hundred clinical decisions (52.4%) were influenced by the 31-GEP to forego SLNB and 70% (70/100) were not performed. Of the 30 performed, 0% (0/30) were positive. The 31-GEP influenced sixty-three clinical decisions (33.0%) to perform SLNB, and 92.1% (58/63) were performed. There was a clinically meaningful 29.4% reduction of SLNBs performed in patients with a Class 1A result relative to the baseline rate of 78.0% (p < .01). In patients ≥55 or ≥65-year-old, SLNB reduction was 32.3% (p < .01), 28.3% (p < .01), respectively. Overall, 85.3% of decisions relating to SLNB were influenced by 31-GEP results. Conclusion In this prospective, multicenter study, clinicians demonstrated clinically meaningful use of the 31-GEP test to forego or pursue SLNB in patients with T1-T2 tumors resulting in a significant, risk appropriate decrease in SLNBs.

Incorporating Prognostic Gene Expression Profile Assays into the Management of Cutaneous Melanoma: An Expert Consensus Panel

Background: Cutaneous melanoma (CM) guidelines put forth by the eighth edition of the American Joint Committee on Cancer (AJCC8) and the National Comprehensive Cancer Network (NCCN) do not currently account for lesion genomics when assessing prognosis. Gene Expression Profile (GEP) tests have become a widely adopted tool to help clinicians identify patients at higher risk for metastasis and recurrence.&#x0D; Objective: To review the available literature that has been published since a consensus panel in 2018 on three commercially available GEP tests used in the prognostic assessment of CM and create updated guidelines and consensus statements for their optimal use.&#x0D; Methods: A comprehensive literature search of PubMed and Google Scholar was conducted for relevant English-language original research articles, meta-analyses, and systematic reviews published from 2019 through 2022. A panel of 6 key opinion leaders in dermatology with specialized expertise in diagnosing and managing CM then convened to review the articles and create guidelines. A modified Delphi process was used to approve each statement. The panel assigned each article a level of evidence and each consensus statement a strength of recommendation using Strength of Recommendation Taxonomy (SORT) criteria.&#x0D; Results: The literature search identified 785 articles that met the search criteria. Of these, there were 22 articles that validated the 31-GEP test, 2 that validated the 11-GEP test, and 7 that validated the 8-GEP + CP test. The panel unanimously approved 6 usage guidelines and 5 consensus supporting statements for the appropriate use of these tests.&#x0D; Conclusion: Based on the currently available literature, GEP tests provide valuable information beyond AJCC8 and NCCN guidelines for the prognostic assessment of CM. There are significantly more validation studies supporting the use of the 31-GEP test compared to the 11-GEP test and the 8-GEP + CP test.

Clinical Utility of Dermoscopy and 31-Gene Expression Profiling by Dermatology Providers in Melanoma Management Care.

A 31-gene expression profile (31-GEP) test that predicts metastatic risk in patients with cutaneous malignant melanoma (CMM) has previously been validated and is available for clinical use. The test dichotomizes patients into lower risk and higher risk groups based on differences that correspond to unique genetic expression patterns. Although the impact of such a test on dermatology providers' clinical decision-making has been studied, little is known about whether there exists an association between certain clinical features, such as dermoscopy, and 31-GEP results. In this retrospective analysis of 31-GEP test results ordered by dermatologists, we evaluated the frequency of dermoscopic features, using a modified dermoscopy three-point checklist, in 17 cases (n=17) and compared these findings to other key clinicopathologic features including tumor thickness, ulceration, and mitotic rate to 31-GEP results. Additionally, we evaluated the dermatologist's perspective and incorporation of GEP testing as part of patient discussion on melanoma management. 31-GEP stratified patients into 4 groups; groups 1A and 1B are considered low risk of metastasis or recurrence, while 2A and 2B are considered high risk. Of the 17 cases, we had fifteen group 1A (88.23%), one 1B (5.88%), and one 2B (5.88%) result. Overall frequency of dermoscopic features is as follows; 100% of lesions presented with asymmetry, 47% with round structures, and 70.6% with blue-white color. The average time providers spent explaining and ordering the test was 15 minutes, with a range of 10 to 20 minutes. This study represents our experience and understanding of the dermatologist&rsquo;s role ordering 31-GEP in the care pathway of melanoma patients and we recommend that dermatology providers consider ordering the test for newly diagnosed CMM patients. J Drugs Dermatol. 2022;21(12): doi:10.36849/JDD.6889.

32344 The 31-gene expression profile stratifies recurrence and metastasis risk in patients with cutaneous melanoma

Background: Sentinel node biopsy is a prognostic indicator of melanoma recurrence. We hypothesized that the addition of the primary melanoma molecular signature from the 31-gene expression profile (31-GEP) test could refine the risk of recurrence for patients with a negative, positive, or no sentinel node biopsy, respectively. Materials and methods: Kaplan-Meier, Cox regression, and accuracy metrics were retrospectively analyzed for 438 patients with stage I-III melanoma from 2 surgical oncology centers and 1 dermatology center, consecutively tested with the 31-GEP test. Patients were stratified by the 31-GEP as low-risk (Class 1A), intermediate-risk (Class 1B/2A), and high-risk (Class 2B) of recurrence or metastasis. Results: The 31-GEP significantly stratified patient risk for RFS (P < .001), DMFS (P < .001), and MSS (P < .001), and was a significant, independent predictor of metastatic recurrence (HR 5.38, P = .014). Combining the 31-GEP with sentinel lymph node status identified patients with higher (26.7%; Class 2B/node-positive) or lower (2.0%; Class 1A/node-negative) recurrence risk than if using SLN status alone. Conclusions: The 31-GEP improves prognostic accuracy in stage I-III melanoma.

Attitudes of patients with cutaneous melanoma toward prognostic testing using the 31-gene expression profile test.

Although most patients diagnosed with early-stage cutaneous melanoma (CM) have excellent outcomes, because of the large number diagnosed each year, many will experience recurrence or death. Prognostic testing for CM using the 31-gene expression profile (31-GEP) test can benefit patients by helping guide risk-appropriate treatment and surveillance plans. We sought to evaluate patients' attitudes toward prognostic testing with the 31-GEP and assess whether patients experience decision regret about having 31-GEP testing. A 43-question survey was distributed by the Melanoma Research Foundation in June-August 2021 to CM patients enrolled in their database. Patients were asked questions regarding their decision to undergo 31-GEP testing and the extent to which they experienced decision regret using a validated set of Decision Regret Scale questions. We analyzed responses from patients diagnosed in 2014 or later (n = 120). Of these, 28 had received 31-GEP testing. Most respondents (n = 108, 90%) desired prognostic information when diagnosed. Of those who received 31-GEP testing, most felt the results were useful (n = 22 out of 24) and had regret scores significantly less than neutral regret, regardless of their test results (Class 1: p < 0.001; Class 2: p = 0.036). Further, decision regret scores were not significantly different between patients who received a Class 1 31-GEP result and those who received a Class 2 result (mean Class 1=1.39 and mean Class 2=1.90, p = 0.058). Most newly diagnosed CM patients desired prognostic information about their tumors. Patients who received 31-GEP testing felt it was useful and did not regret their decision to undergo 31-GEP testing.

LB1003 The 31-GEP stratifies risk of recurrence and metastasis in 894 medicare-eligible patients with cutaneous melanoma

Background: The incidence of cutaneous melanoma (CM) is rising, particularly among older patients who generally have worse outcomes than younger patients. The 31-gene expression profile (GEP) test stratifies patient risk of recurrence and metastasis into low (Class 1A), intermediate (Class 1B/2A), and high risk (Class 2B). The study goal was to demonstrate the 31-GEP provides critical risk information for Medicare-eligible patients, allowing providers to identify patients who may benefit from increased surveillance or therapeutic treatment. Methods: Retrospective analysis of patients over 65 years old enrolled in previous studies who received 31-GEP testing (n=894). Recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) were assessed using Kaplan-Meier, log-rank test, and Cox regression multivariable analysis. Results: Patients with a Class 1A 31-GEP result had higher 5-year RFS (93.9% vs. 52.0%, p<0.001) and DMFS (96.3% vs. 64.8%, p<0.001) than patients with a Class 2B result. A Class 2B result was a significant predictor for RFS (HR=4.66, p<0.001) and DMFS (5.34, p<0.001) in multivariable analysis including AJCC 8th edition stage. Stage II (RFS: HR=2.37, p<0.001; DMFS: HR=1.83, p=0.033) and stage III disease (RFS: HR=6.22, p<0.001; DMFS: HR=6.20, p<0.001) were also significant. Older patients with a negative SLNB and a Class 1A 31-GEP result had higher 5-year RFS (88.2% vs. 53.0%, p<0.001) and DMFS (93.0% VS. 69.4%, p<0.001) than those with a Class 2B result. Class 1A patients who did not receive a SLNB had high RFS (98.2%) and DMFS (99.1%). Conclusions: The 31-GEP test stratified risk of recurrence and survival in Medicare-eligible patients and added independent prognostic information to current staging methods. In patients with a potentially large number of comorbidities, identifying those who can forego more extensive therapy is vital.

LB881 Clinical utility of dermoscopy and 31-gene expression profiling by dermatology providers in melanoma management care

A 31-gene expression profile (31-GEP) test that predicts metastatic risk in patients with cutaneous malignant melanoma (CMM) has previously been validated and is available for clinical use. The test dichotomizes patients into lower risk and higher risk groups based on differences that correspond to unique genetic expression pattern. Although the impact of such a test on dermatology provider’s clinical decision-making has been studied, little is known about whether there exists an association between certain clinical features, such as dermoscopy, and 31-GEP results.

Expert Consensus on the Use of Prognostic Gene Expression Profiling Tests for the Management of Cutaneous Melanoma: Consensus from the Skin Cancer Prevention Working Group.

BackgroundPrognostic assessment of cutaneous melanoma relies on historical, clinicopathological, and phenotypic risk factors according to American Joint Committee on Cancer(AJCC) and National Comprehensive Cancer Network (NCCN) guidelines but may not account for a patient’s individual additional genetic risk factors.ObjectiveTo review the available literature regarding commercially available gene expression profile (GEP) tests and their use in the management of cutaneous melanoma.MethodsA literature search was conducted for original, English-language studies or meta-analyses published between 2010 and 2021 on commercially available GEP tests in cutaneous melanoma prognosis, clinical decision-making regarding sentinel lymph node biopsy, and real-world efficacy. After the literature review, the Skin Cancer Prevention Working Group, an expert panel of dermatologists with specialized training in melanoma and non-melanoma skin cancer diagnosis and management, utilized a modified Delphi technique to develop consensus statements regarding prognostic gene expression profile tests. Statements were only adopted with a supermajority vote of > 80%.ResultsThe initial search identified 1064 studies/meta-analyses that met the search criteria. Of these, we included 21 original articles and meta-analyses that studied the 31-GEP test (DecisionDx-Melanoma; Castle Biosciences, Inc.), five original articles that studied the 11-GEP test (Melagenix; NeraCare GmbH), and four original articles that studied the 8-GEP test with clinicopathological factors (Merlin; 8-GEP + CP; SkylineDx B.V.) in this review. Six statements received supermajority approval and were adopted by the panel.ConclusionGEP tests provide additional, reproducible information for dermatologists to consider within the larger framework of the eighth edition of the AJCC and NCCN cutaneous melanoma guidelines when counseling regarding prognosis and when considering a sentinel lymph node biopsy.

Expanded evidence that the 31-gene expression profile test provides clinical utility for melanoma management in a multicenter study

Objective National Comprehensive Cancer Network (NCCN) guidelines for cutaneous melanoma (CM) recommend physicians consider increased surveillance for patients who typically have lower melanoma survival rates (stages IIB-IV as determined by the American Joint Committee on Cancer (AJCC), 8th edition). However, up to 15% of patients identified as having a low recurrence risk (stages I-IIA) experience disease recurrence, and some patients identified as having a high recurrence risk will not experience any recurrence. The 31-gene expression profile test (31-GEP) stratifies patient recurrence risk into low (Class 1) and high (Class 2) and has demonstrated risk-appropriate impact on disease management and clinical decisions. Methods Five-year plans for lab work, frequency of clinical visits, and imaging pre- and post-31-GEP test results were assessed for a cohort of 509 stage I-III patients following an interim subset analysis of 247 patients. Results After receiving 31-GEP results, 50.6% of patients had a change in management plans in at least one of the following categories—clinical visits, lab work, or surveillance imaging. The changes aligned with the risk predicted by the 31-GEP for 76.1% of patients with a Class 1 result and 78.7% of patients with a Class 2 result. A Class 1 31-GEP result was associated with changes toward low-intensity management recommendations, while a Class 2 result was associated with changes toward high-intensity management recommendations. Conclusion The 31-GEP can stratify patient recurrence risk in patients with CM, and clinicians understand and apply the prognostic ability of the 31-GEP test to alter patient management in risk-appropriate directions.

Improved cutaneous melanoma survival stratification through integration of 31-gene expression profile testing with the American Joint Committee on Cancer 8th Edition Staging.

Cutaneous melanoma (CM) survival is assessed using averaged data from the American Joint Committee on Cancer 8th edition (AJCC8). However, subsets of AJCC8 stages I-III have better or worse survival than the predicted average value. The objective of this study was to determine if the 31-gene expression profile (31-GEP) test for CM can further risk-stratify melanoma-specific mortality within each AJCC8 stage. This retrospective multicenter study of 901 archival CM samples obtained from patients with stages I-III CM assessed 31-GEP test predictions of 5-year melanoma-specific survival (MSS) using Kaplan-Meier and Cox proportional hazards. In stage I-III CM population, patients with a Class 2B result had a lower 5-year MSS (77.8%) than patients with a Class 1A result (98.7%) and log-rank testing demonstrated significant stratification of MSS [χ2 (2df, n = 901) = 99.7, P < 0.001). Within each stage, 31-GEP data provided additional risk stratification, including in stage I [χ2 (2df, n = 415) = 11.3, P = 0.004]. Cox regression multivariable analysis showed that the 31-GEP test was a significant predictor of melanoma-specific mortality (MSM) in patients with stage I-III CM [hazard ratio: 6.44 (95% confidence interval: 2.61-15.85), P < 0.001]. This retrospective study focuses on Class 1A versus Class 2B results. Intermediate results (Class 1B/2A) comprised 21.6% of cases with survival rates between Class 1A and 2B, and similar to 5-year MSS AJCC stage values. Data from the 31-GEP test significantly differentiates MSM into lower (Class 1A) and higher risk (Class 2B) groups within each AJCC8 stage. Incorporating 31-GEP results into AJCC8 survival calculations has the potential to more precisely assess survival and enhance management guidance.