Real-World Evidence Shows Clinicians Appropriately Use the Prognostic 40-Gene Expression Profile (40-GEP) Test for High-Risk Cutaneous Squamous Cell Carcinoma (cSCC) Patients.

Treatment decisions for patients with cutaneous squamous cell carcinoma (cSCC) are traditionally based upon clinicopathologic risk factors and staging systems. Due to the accuracy limitations of these resources in predicting poor outcomes, there is a clinically significant need for more accurate methods of risk assessment. The 40-gene expression profile (40-GEP) test was developed to augment metastatic risk prediction of high-risk cSCC patients and has been validated in two independent, multi-center studies involving over 1,000 patients. This study substantiates that the 40-GEP is appropriately utilized by clinicians and that the personalized risk-stratification results are impactful in guiding risk-aligned patient management.

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.

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.

BACKGROUND: Prognostic 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. OBJECTIVE: To review the available literature regarding commercially available gene expression profile (GEP) tests and their use in the management of cutaneous melanoma. METHODS: A 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%. RESULTS: The 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. CONCLUSION: GEP 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.

Impact of a prognostic 40-gene expression profiling test on clinical management decisions for high-risk cutaneous squamous cell carcinoma.

Objective: To determine how results from a prognostic 40-gene expression profiling (40-GEP) test would impact clinician management decisions and how their choices would align with a National Comprehensive Cancer Network (NCCN) compliant, risk-directed management plan for high-risk cutaneous squamous cell carcinoma (cSCC).Methods: Clinicians attending a national dermatology conference were presented with 40-GEP test validation data. They were asked to rate clinicopathological features and molecular test results to assess their opinion of how concerning each is to cSCC prognosis. When presented with vignettes describing patients with NCCN-defined high-risk features, clinicians were asked to select a treatment plan using pre-test (no 40-GEP results), then, post-test (40-GEP Class 1, 2A, or 2B results) methodology along with corresponding metastasis rates for each test group.Results: Risk factors deemed of highest concern for metastatic outcomes were a Class 2B 40-GEP result, perineural invasion, immunosuppression, invasion beyond subcutaneous fat, and tumor diameter >1 cm on the scalp. When presented with a 40-GEP result that indicated reduced risk of metastasis (Class 1), clinicians altered their treatment management plan accordingly. Specifically, there was significant reduction in the recommendations for sentinel lymph node biopsy, adjuvant radiation or chemotherapy, follow-up time, and nodal imaging. By comparison, when a 40-GEP result indicated an increased risk of metastasis (Class 2B), significant risk-appropriate increases in management intensity was observed for the aforementioned clinical decisions.Conclusion: Integration of 40-GEP results impacted management decisions in a significant and risk-appropriate manner for high-risk cSCC patient scenarios, while remaining aligned with national guidelines for patient management.

Impact of Gene Expression Profile Testing on the Management of Squamous Cell Carcinoma by Dermatologists

Background: The incidence of cutaneous squamous cell carcinoma (cSCC) is increasing likely due to improved detection and a growing elderly population. Although the prognosis of cSCC is excellent with complete surgical excision, many patients who go on to develop metastasis are initially classified as low-risk. The most commonly used staging systems, American Joint Committee on Cancer (AJCC) and Brigham Women's Hospital (BWH), have low sensitivity and low positive predictive value for predicting metastasis. A gene expression profile test (cSCC-GEP) is in development to identify patients with cSCC at high risk for metastasis and death. Objective: To determine the impact of cSCC-GEP test results on management decisions made by dermatologists for cSCC patients. Design, Setting, and Participants: 402 dermatologists attending a national dermatology conference completed an online survey designed to determine the impact of cSCC-GEP test results on management decisions in a variety of clinical situations. Participants answered a series of questions related to three cSCC patient vignettes, each featuring different patient and lesion characteristics. Main Outcomes and Measures: Proportion of dermatologists who would recommend radiation, chemotherapy/immunotherapy, or sentinel lymph node biopsy (SLNBx) for each patient vignette (without cSCC-GEP results, with a lower risk result, or with a higher risk result). The effect of the test results on the follow-up intervals recommended by dermatologists was also examined. Results: In the majority of vignettes, a lower risk cSCC-GEP test result led to a statistically significant decrease in the proportion of dermatologists who would recommend radiation, chemotherapy/immunotherapy, SLNBx, or quarterly follow-up. Conversely, a higher risk cSCC-GEP result significantly altered management toward increased intensity (more recommendations for radiation, chemotherapy/immunotherapy, SLNBx, or quarterly follow-up) in all vignettes. Conclusions and Relevance: The results of a cSCC-GEP test appear to significantly impact decisions made by dermatologists regarding subsequent management, SLNBx, and follow-up intervals for patients with cSCC. J Drugs Dermatol. 2019;18(10):980-984.