Assessment of the 31-Gene Expression Profile Test by Dermatologists: A Cross-Sectional Survey from National Dermatology Conferences

Background: The 31-gene expression profile (31-GEP) test uses 31 genetic markers obtained from the initial biopsy of a melanoma to assess melanoma-specific survival and sentinel lymph node positivity. Objective: To assess the professional understanding, opinions, and clinical usage of the 31-GEP test by dermatologists. Methods: Data from 589 unique dermatologists were collected during 2 virtual, nation-wide dermatology conferences via an 18-question survey on practice demographics and their clinical use and opinion of the 31-GEP test. Results: Participants reported that integrating the 31-GEP test may benefit patients by increasing knowledge and understanding (72.5%), personalizing treatment options (58.8%), and easing uncertainty about the future (59.7%). Benefits of using the 31-GEP test included identifying true negative patients in high-risk populations (65.6%) as well as true positives in low-risk populations (70.6%).A majority of participants also noted that if a patient received a 31-GEP Class 2B result, they would escalate subsequent management even if the lesions were classified as T1 (61.4%) or AJCC8 Stage I (59.0%). 84.9% of participants were somewhat to very likely to use 31-GEP testing for patient management or recommend this test to a colleague. Limitations: Potential respondent-selection and recall bias. Conclusion: Dermatologists are increasingly integrating the 31-GEP test into their melanoma clinical management decisions. As the 31-GEP test becomes more prevalent in practice, patients may benefit from decreased anxiety and uncertainty from enhanced prognosis, decreased need for unwarranted procedures such as sentinel lymph node biopsy and optimized allocation of healthcare resources.

The 31-gene expression profile test (31-GEP) (DecisionDx-Melanoma, Castle Biosciences, Inc., Friendswood, TX) analyses tissue collected from the initial diagnostic biopsy of a melanoma with an array of 31 genetic markers to assess prognosis. Prior studies have validated its ability to determine the risk of local/distant recurrence and sentinel lymph node positivity to assist in clinical decisionmaking. [1][2][3] The 31-GEP test is reimbursable under Medicare, certified by the Clinical Laboratory Improvement Amendments (CLIA), and was ordered over 16,000 times during 2019. 1,4 Given the increasingly widespread use of 31-GEP, the purpose of this study was to assess the professional understanding, opinions, and clinical usage of the 31-GEP test by dermatologists.
The survey was available electronically via a website link during 2 national Dermatology conferences from October 29, 2020 to November 1, 2020 and January 16-24, 2021. Participants were asked to complete an 18 question survey regarding practice demographics, factors considered prior to ordering 31-GEP, their integration of 31-GEP results into clinical management, and their opinions on the usefulness of the test. IRB approval was obtained. Participants were compensated for their participation. Any duplicates were removed prior to data analysis.
After removing non-US respondents, 589 participants were eligible for the final Study participants reported that benefits of using the 31-GEP test included identifying true negative patients in high-risk populations (65.9%) as well as true positives in low-risk populations (70.1%). Additional benefits included using test results to determine referrals/follow-up frequency (36.3%) and informing discussion regarding potential sentinel lymph node biopsy (SLNBx) (36.0%). A majority reported Breslow thickness ≥ 0.8mm (68.6%) and patient age/sex/history (55.7%) were factored into their decision to order the test. A majority of participants also noted that if a patient received a 31-GEP Class 2B result (which has previously been found to carry increased risk for recurrence within 5 years 1 ), they would escalate subsequent management even if the lesions were classified as T1 (61.0%) or AJCC8 Stage I (58.7%).
Respondents believed potential false positive Class 2B results (i.e. patients at high risk of recurrence within 5 years that do not develop recurrence/metastasis) may be due to prompt/early intervention (71.3%), surgical excision prior to metastatic event (66.0%), or host immune response (71.5%) with a minority (31.2%) believing the result was an intrinsic error with the 31-GEP test. Going forward, 84.9% of participants were somewhat to very likely to use 31-GEP testing for patient management or recommend this test to a colleague and 66.0% would recommend a friend or family member receive the test as part of their care.
Our findings suggest that a majority of Dermatologists not only positively view 31-GEP testing, but are also incorporating it into management of their melanoma patients. Participants noted that having 31-GEP Class results had psychosocial benefits by aiding the physician-patient counseling, reducing anxiety and increasing confidence in the care plan. Given the test is reimbursable under Medicare, this may also ameliorate some patient concerns regarding the potential cost of the test.
From a clinical perspective, the way the studied Dermatologists report using 31-GEP testing largely follows published appropriateuse criteria for the 31-GEP test. 6 Prior studies have determined the usage of the 31-GEP test with the strongest support in the literature was in informing discussions regarding the need for SLNBx (A-Strength SORT recommendation 7 ) with additional recommendation for facilitating management decisions of T1 and T2 melanomas and length of follow-up, 6 which is consistent with our results. Participants also reported confidence in the test with a minority   (1), "something else" currently not understood (1), imperfect predictive value of gene profile (1) attributing potential false-positives to intrinsic test errors and nearly 90% positively viewing, using, or recommending the test. . Limitations of this study include potential respondent-selection bias and the retrospective nature of the study. However, the method of questionnaire delivery (i.e. during a nation-wide virtual conference) potentially minimized regional bias and the studied sample population has a relatively uniform distribution of practice experience.

DISCUSSION
Dermatologists are increasingly integrating the 31-GEP test into their melanoma clinical management decisions. As the 31-GEP test becomes increasingly prevalent in practice, patients may benefit from decreased anxiety and uncertainty from enhanced prognosis, decreased need for potentially unnecessary procedures such as SLNBx and optimized allocation of healthcare resources. Future studies will be needed to determine the impact that the 31-GEP test will have on Dermatology practices and patient outcomes when fully integrated into current melanoma clinical management algorithms. Funding: This study was funded in part by an unrestricted educational grant from Castle Biosciences, Inc.

Skin Cancer Prevention Working Group:
The Skin Cancer Prevention Working Group is a multi-center collaboration of experts dedicated to the prevention of skin cancer. The Working Group consists of clinical and research specialists that have spent years investigating and understanding the diagnosis and management of melanoma and nonmelanoma skin cancer.
The mission of the Working Group is to cultivate and analyze evidence-based research to better understand skin cancer pathophysiology, treatment, and prevention in order to be leaders in skin health education.