In a new editorial, researchers delve into the intricate dynamics of melanoma and aim to illuminate differences in age-related incidence, prognosis and treatment.
In the realm of cancer research, one persistent trend has emerged — the incidence of invasive melanoma rises steadily with advancing age. While this insidious disease remains rare in children and adolescents, it progressively asserts its presence as individuals grow older. The connection between age and melanoma incidence persists around the world, albeit with varying rates in different countries.
Australia has the highest melanoma rates in the world. According to the Melanoma Institute Australia, every 30 minutes an Australian is diagnosed with melanoma and every 6 hours an Australian dies from it. Thankfully, research is making a difference. In the last decade, the 5-year overall survival rate for advanced melanoma has increased from less than 10% to more than 50%. In 2011, melanoma was Australia’s 7th most deadly cancer. In 2021, melanoma was Australia’s 11th most deadly cancer.
In a new editorial paper, researchers John F. Thompson and Gabrielle J. Williams from the Melanoma Institute Australia at The University of Sydney discuss the intricacies of how age influences different varieties of melanoma incidence, prognosis and treatment. On August 17, 2023, their editorial was published in Aging’s Volume 15, Issue 16, entitled, “The effect of age on melanoma incidence and prognosis.”
Understanding Melanoma Subtypes
The researchers point out that while invasive melanoma is at the forefront of discussion, non-invasive “melanoma in situ” (MIS) follows a similar age-related pattern of increase. MIS, often exemplified by lentigo maligna (LM), results from chronic, accumulated exposure to ultraviolet light. The progression from LM to invasive lentigo maligna melanoma (LMM) occurs at an estimated rate of 3.5% per year, with an average transition period of 28.3 years.
Older patients are more prone to another unique subtype known as desmoplastic melanoma, linked to chronic sun exposure and frequently affects the head or neck. While desmoplastic melanomas have a somewhat higher local recurrence rate, the majority of invasive melanomas in elderly patients exhibit features associated with poorer prognosis, including ulceration, higher mitotic rates and increased Breslow thickness.
Melanoma Biopsies & Treatment Options
Patients with high-risk primary melanomas are often recommended for a sentinel lymph node biopsy (SLNB) to assess the presence of metastatic melanoma cells in regional lymph nodes—a pivotal prognostic factor. Strikingly, the likelihood of a positive SLNB result decreases with age. However, as age advances, the risk of death due to melanoma’s spread to distant sites increases, leaving researchers grappling with the mysteries of why these phenomena occur.
Current treatments for SLN-positive melanoma patients include immunotherapy and targeted therapy. Immunotherapy agents like ipilimumab, pembrolizumab and nivolumab have shown promise in treating melanoma. While initial clinical trials excluded the very young and elderly, subsequent non-randomized studies have revealed that these agents are similarly effective in older patients, with comparable adverse event profiles. However, the efficacy of these therapies in children and adolescents remains uncertain.
Targeted therapies focusing on BRAF mutations, including vemurafenib and dabrafenib, have been employed, particularly in younger patients who exhibit a higher prevalence of BRAF positivity. Response rates are significant but often followed by resistance. Interestingly, these therapies appear to exhibit similar efficacy and safety profiles in older patients, offering a glimmer of hope for this demographic.
In older melanoma patients with brain metastases, radiation therapy has historically played a crucial role, offering alternatives to surgical excision. Studies have revealed that both whole-brain radiotherapy and stereotactic radiotherapy are equally effective in patients aged 70-90 as in younger groups. With the advent of immunotherapy and targeted therapies, combining localized radiation with systemic treatment is becoming an option, particularly in older patients, offering the potential for similar benefits as seen in younger cohorts.
Conclusions & Future Directions
The data presented in this editorial underscore a stark reality — melanoma’s impact escalates with age. Patterns of the disease differ significantly in older age groups, with increasing rates of metastasis and death. However, standard forms of melanoma management, including surgery, radiation therapy and newer systemic therapies, have proven to be as effective and safe in older patients as in their younger counterparts. This knowledge serves as a beacon of hope, offering solace and potential avenues for treatment in the face of this disease.
In closing, the critical role of research and continued investigation cannot be overstated. Further exploration of age-related nuances in melanoma will undoubtedly uncover new insights and lead to more tailored and effective treatments for all patients, regardless of their age.
Click here to read the full editorial published in Aging.
Aging is an open-access, traditional, peer-reviewed journal that has published high-impact papers in all fields of aging research since 2009. All papers are available to readers (at no cost and free of subscription barriers) in bi-monthly issues at Aging-US.com.
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