Does Genetic Testing Influence Outcomes: Early Experience in Melanoma Case Series

Abstract Background: The treatment and prognosis of melanoma have historically been based on histologic stage and Breslow depth; however, due to the increase in surveillance, melanomas are being identified at an earlier stage and lower Breslow depth. Advances in genetic testing, such as Decision Dx ® , mean that melanoma diagnostic decisions and prognosis can now be directed by genetics. The purpose of this project was to assess the influence of a Decision Dx ® high-grade (Class 2A/B) classification on the treatment of melanoma patients at a regional medical center, particularly those not deemed high risk by conventional classification methods, including Breslow depth and Clark level. Materials and Methods: Melanomas that were diagnosed as Decision Dx ® class 2A/B (high risk) at a single institution between 2019 and 2020 were retrospectively evaluated. Patients were stratified by recurrence and sentinel lymph node (SLN) positivity. Results: A total of 97 Decision Dx ® high-risk patients were evaluated, in whom the average Breslow depth was 2.38 (0.45–7.5 mm), and three most common histologic stages were pT2a (19%), pT2b (18%), and pT4b (22%). Overall, 65% had oncology follow-up, 37% received immunotherapy, and 91% were alive. Recurrence was noted in 22% of the patients ( n = 22); there was no significant difference in Breslow depth between those with and without recurrence. Significantly more of those with recurrence had Stage T3a ( P = 0.0390; no recurrence 0%), oncology follow-up (95%; P = 0.0030), and immunotherapy (86%, P = 0.0001) but no difference in survival ( P = 0.3161). Analysis of the patients with SLN biopsy (SLNBx) positivity showed that they were younger (mean: 63.3 years; P = 0.0040); however, no significant differences were found in histologic variables. Oncology follow-up was higher in the patients who were SLNBx positive (90%; P = 0.0126) as was immunotherapy ( P = 0.0001); however, due to the Decision Dx ® high-risk classification, 60% of the SLNBx-negative patients received oncology follow-up. Overall, recurrence and survival rates were not significantly different between cohorts. Conclusion: Although there were no significant differences in survival/recurrence, some patients would not have received additional follow-up based on the initial pathology who eventually developed recurrence. These data emphasize that genetic analysis can change management decisions and allow for more intensive surveillance, and that Decision Dx ® can play an integral role in defining melanoma behavior along with histologic characterization. Larger studies to substantiate these results are warranted.