The incidence of invasive melanoma is rising, and Dr Darrell Rigel gave us the data we need to contextualize risk for our patients and ensure they receive the most up-to-date treatments. Importantly, in a pooled analysis with data from 2013-2019, 5-year survival rates were significantly worse for African-American patients with localized, regional, and distant melanoma diagnoses giving melanoma the largest racial disparity in survival difference. This trend is reflected in racial and ethnic minorities across other skin cancers and deserves clinical attention.  However, the past decade has also seen advances in targeted therapies and immune checkpoint inhibitors, which likely account for demonstrated improvement in malignant melanoma survival in Italy between 2003 and 2017. 

Dr Rigel covered who is at risk, especially those subjected to childhood sunburns and frequent sunburns. A less obvious connection was found between those with a family history of melanoma and Parkinson’s disease after following 131,342 patients for many decades. Alcohol consumption also may be a risk factor. While risk factors may provide clinical indication that more information about a lesion is required, the diagnosis of malignant melanoma is not always straightforward and has been quoted to be as low as 65% accurate. Genomics has become an increasingly important tool alongside pathologic findings as atypical genomic data in markers such as PRAME and TERT reflect cellular atypia. Genomic data can further be harnessed to identify patients who are at a higher risk for developing metastatic disease and would benefit from sentinel lymph node biopsies. Dr Rigel walked us through how to understand results from DecisionDx and emphasized the importance of using genomics to optimize clinical care. 

The last portion of the presentation focused on what happens after diagnosis. In one study, over 3500 patients with sentinel lymph node metastases were randomized to get either immediate dissection or nodal observation with ultrasonography, and melanoma-specific survival at 3 years was similar between groups. Histopathologic regression in patients with metastatic melanoma getting sentinel lymph node biopsies or with metastases on immune checkpoint inhibitors was associated with better survival as was treatment with 2 complimentary immune checkpoint inhibitors, specifically adding relatlimab, a lymphocyte-activation gene 3 inhibitor, to nivolumab, the PD-1 inhibitor. One RCT comparing neoadjuvant-adjuvant and adjuvant-only pembrolizumab in advanced-stage metastatic melanoma demonstrated significantly longer overall survival in those who were treated with the PD1 inhibitor before and after surgery. Other factors that may impact survival are beta-blocker use, statin use, and estrogen levels. He concluded by discussing some exciting innovations like an mRNA vaccine for melanoma for those at high risk of recurrence, which was studied in a Phase 2b trial.