Gender Disparities and Advances in Cutaneous Melanoma

In this interview, Dr Elliott Campbell explores the increasing melanoma incidence among middle-aged women alongside stable rates in middle-aged men. He delves into mortality disparities, discusses advances in treatment, and offers insights into improved detection and treatment strategies.

Elliott Campbell, MD, FAAD is a dermatologist and micrographic surgery and dermatologic oncology fellow at Mayo Clinic in Rochester, MN.

The Dermatologist: Your study shows a significant increase in the incidence of cutaneous melanoma in middle-aged women over the past few decades. What are some potential hypotheses or factors that might explain the substantial rise specifically among this demographic?

Dr Campbell: There are many different types of melanomas, however, most are believed to have at least a component of ultraviolet exposure as an etiologic factor. This sun exposure accumulates over an individual's lifetime. Our team theorizes that a major driving factor for increased incidence in women is secondary to previous increases in tanning bed use among our female population. It has also been postulated that estrogen and melanomas could be related, however, this connection has never been substantiated.

The Dermatologist: What are some plausible reasons for the stabilization of cutaneous melanoma incidence in middle-aged men in recent years, and how does this pattern differ from the observed trends in middle-aged women?

Dr Campbell: Overall, based on anecdotal reports from our patients, there appears to be an encouraging trend of reduced sun exposure within our population, both in men and women. Our patients commonly recall, "Back when I was young, we would lay out in the sun for hours with tinfoil and baby oil. We didn't know any better." Although we have a long way to go, our population has embraced healthier photoprotective measures. The surge of UV exposure during the tanning bed era, predominantly in women, has likely mitigated the impact of these general photoprotective practices in that subset of the population.

The Dermatologist: Your study identifies male sex as a significant risk factor for mortality due to melanoma. What are some potential biological, behavioral, or social reasons that might explain this gender disparity in melanoma-related deaths?

Dr Campbell: This is a great question. Initially, one might predict that the disparity is due to later-stage presentation with advanced melanomas. However, our study used a multivariate analysis, which accounted for these additional factors, and there was still a statistically significant increase in disease-specific mortality in men. This suggests that there are other factors beyond advanced stage at diagnosis driving this increased mortality. One potential contributing factor is a lack of follow-up surveillance in this population, or noncompliance with recommended long-term management. However, this has not been substantiated and it is difficult to draw any conclusions based on our data. Another consideration is that men die earlier overall. Perhaps treatment limitations due to other comorbidities or pharmacotherapy intolerance might play a role when controlling for age. These data are important to consider when counseling men with a diagnosis of melanoma on surveillance in the future.

The Dermatologist: What are some potential interventions or advancements in melanoma treatment and management that might have contributed to the linear decrease in mortality from cutaneous melanoma over the study period?

Dr Campbell: Our study's evident reduction in mortality over time is profoundly encouraging and has not been observed in some studied populations. This is likely multifactorial, but some of the improvement is almost certainly attributed to the development and implementation of targeted therapy and immunotherapy, both of which have demonstrated significant mortality benefits. Melanoma surgery utilizing comprehensive margin assessment is also contributing. One example of this is Mohs micrographic surgery for specialized site melanomas, including head and neck tumors known for their heightened risk of recurrence and poor outcomes. We would like to think that screening with earlier detection of clinically meaningful and biologically significant tumors is also contributing to the reduction in mortality. There is good evidence that melanomas caught at an earlier stage are associated with significantly improved outcomes.

The Dermatologist: What factors might contribute to the decreased risk of death among individuals with a more recent diagnosis of melanoma, and how can this information guide efforts to enhance early detection and prompt treatment for those at risk for developing melanoma?

Dr Campbell: We have observed a linear reduction in mortality over time. Therefore, being diagnosed more recently pertains to a better prognosis. This information should encourage patients and providers to continue with ongoing efforts. This includes continued surveillance of at least high-risk populations. We now have indications for immunotherapy for high-risk tumors that are still localized to the skin and have not yet metastasized to lymph nodes or more broadly, the use of Mohs micrographic surgery for appropriate tumors, especially in areas where tissue preservation is critical and the risk of recurrence and mortality is higher, such as the head and neck. Furthermore, continued multidisciplinary care is vital for patients with high-risk, advanced-stage melanomas. Metastatic melanoma is no longer as bleak of a diagnosis as it was 15 years ago. We have many pharmacotherapies and surgical options in our arsenal to combat this tumor. I always tell my patients that there is no better time in history to have a melanoma skin cancer.

The Dermatologist: Are there tips or insights you would like to share with your dermatology colleagues about the increasing incidence and decreasing mortality of cutaneous melanoma among middle-aged adults?

Dr Campbell: There are clearly driving factors outside of overdiagnosis that are responsible for the rise of melanoma in our population. If overdiagnosis is the driving factor, as suggested by other authors, this would likely affect both men and women equally, unless, of course, women are increasing their screening over time compared to men, which we do not have data to support. We need to continue to evaluate potential etiologies for this rise in incidence in women, and patients should be encouraged to avoid tanning beds. Men and women should continue to be encouraged to protect against the sun. And lastly, our field should be proud that we are drastically and consistently improving the mortality rate of this prevalent tumor over time. We should continue these efforts through clinical care and research in collaboration with other specialties.

Reference

Campbell EH, Reinhart JP, Crum OM, et al. Increasing incidence and decreasing mortality of cutaneous melanoma in middle-aged adults: An epidemiologic study in Olmsted County, Minnesota. Mayo Clin Proc. 2023;98(5):713-722. doi:10.1016/j.mayocp.2022.10.029