Melanoma: A growing problem, but there is hope
Introduction
In the realm of cancer, melanoma emerges as a formidable adversary, lurking in the shadows of the skin and often striking when least expected. This insidious foe arises from the malignant transformation of melanocytes, cells originating from the neural crest. While its primary domain is the skin, melanoma can silently appear in unexpected locations, including the gastrointestinal tract and even the brain. The intricacies of melanoma are of paramount importance, given the stark contrast in survival rates, a staggering 97% for stage 0 patients compared to a grim 10% for those grappling with stage IV disease.
In recent years, a chilling reality has swept across the globe, the incidence of malignant melanoma is rapidly surging, outpacing the rise of almost every other form of cancer. While melanoma doesn't discriminate, it does exhibit certain preferences, predominantly affecting individuals with fair complexions, particularly among those of White ethnicity. Statistics reveal that melanoma now ranks as the fifth most common cancer among men and the seventh among women, accounting for 5% of all new cancer cases.
Factors Raising the Stakes
Family History
For some, the risk of melanoma is genetically written in their DNA. Approximately 5% to 10% of patients carry a family history that increases their risk by a significant 2.2-fold if they have at least one affected relative.
Personal Characteristics
Individuals with blue eyes, fair or red hair, and pale skin are at a higher risk, prone to sunburns and freckles, with a strong link to melanoma. Additionally, having a greater number of benign or dysplastic melanocytic nevi (moles) increases the risk more than their size. Immunosuppressive states, common in transplant patients or those with blood cancers, also elevate the risk.
Sun Exposure Over a Lifetime
Prolonged exposure to high UVB and UVA radiation increases the risk of melanoma. Surprisingly, excessive sunscreen use may raise the risk due to its focus on UVB, leaving people exposed to UVA. Low latitudes, a history of severe sunburns, and tanning bed use also increase the risk.
Atypical Mole Syndrome
Atypical multiple mole melanoma can significantly elevate the risk of melanoma. Over a decade, there's a striking 10.7% risk of developing melanoma for those with this syndrome compared to a mere 0.62% in unaffected individuals. The risk escalates further when more family members are affected, with nearly a 100% risk if two or more relatives have dysplastic nevi and melanoma.
Socioeconomic Status
It's not just genetic and environmental factors; socioeconomic status also plays a role. Lower socioeconomic status can be linked to more advanced disease at the time of detection. Newly-diagnosed patients with lower socioeconomic status often have a diminished perception of melanoma risk and limited knowledge about the disease.
The Four Main Types of Skin Melanoma
Superficial spreading melanoma is the most common type, accounting for approximately 70% of melanomas in the UK. It tends to favour those with fair skin and freckles. In women, it frequently appears on the legs, while in men, it tends to manifest on the chest and back.
Following closely behind is nodular melanoma, known for its rapid development. It can grow alarmingly fast, delving deeper into the layers of the skin compared to other melanoma types. It often appears on previously normal skin, typically on the chest, back, head, or neck.
Although less common, comprising about 10% of melanomas, lentigo maligna melanoma is intriguing in its own right. Typically found in older individuals who've experienced years of sun exposure, it commonly resides on areas with substantial sun exposure, like the face and neck. In its early stages, lentigo maligna melanoma spreads sideways within the surface layers of the skin, resembling a freckle but larger, darker, and more conspicuous.
Acral Melanoma is the rarest of them all. Acral melanoma shirks the sun exposure connection. It often lurks on the palms of the hands, the soles of the feet, or even beneath fingernails or toenails. Surprisingly, it prefers people with black or brown skin, and its emergence doesn't seem to be influenced by sun exposure.
Early Detection and Symptoms
To detect melanoma early, remember the "ABCDE" criteria:
- A - Asymmetrical Shape: Melanomas often have an uneven shape, with one half looking different from the other. In contrast, normal moles have an even shape with symmetrical halves.
- B - Border Irregularity: Pay attention to the edges of the mole. Melanomas often have irregular, blurred, or jagged borders, while normal moles have smooth and regular borders.
- C - Colour Variation: Melanomas display an uneven mix of colours, with different shades of black, brown, and pink. In contrast, normal moles typically have a consistent and even colour.
- D - Diameter Size: Most melanomas are larger than 6mm in width, roughly the size of the eraser at the end of a pencil. If a mole appears significantly larger than that, it could be cause for concern.
- E - Evolution: Melanomas undergo changes in size, shape, or colour. Other warning signs might include bleeding, itching, or the development of a crust. In contrast, normal moles usually remain stable in size, shape, and colour.
Treatment Options for Melanoma
Melanoma's primary treatment involves surgical excision, encompassing the removal of adjacent healthy tissue. When the tumour exceeds a thickness of >0.8 mm or presents with ulceration, clinicians may opt for a sentinel lymph node biopsy. Should melanoma cells be detected, the nearby lymph nodes may necessitate removal. Nevertheless, surgical intervention for metastatic tumours, while considered, does not offer a curative solution and often mandates supplementary therapies.
Historically, metastatic melanoma was addressed with chemotherapy, rooted in early experiments conducted by chemist Paul Ehrlich. During the 1940s, researchers such as Alfred Gilman and Louis Goodman developed nitrogen mustard compounds. However, the inaugural FDA-approved melanoma chemotherapeutic, dacarbazine (in 1975), exhibited limited efficacy alongside notable toxicity concerns.
BRAF inhibitors, specifically vemurafenib and dabrafenib, gained approval in 2011 and 2013 for the treatment of BRAF-mutated melanomas. The issue of resistance underscores the need for ongoing research to refine drug combinations.
Melanoma attracts the attention of the immune system owing to its plethora of tumour antigens. Successful outcomes have been observed with immune checkpoint inhibitors like anti-PD-1 and anti-CTLA-4 antibodies (ipilimumab, nivolumab, pembrolizumab), leading to enduring remissions in selected patients.
Immunotherapy has transformed melanoma treatment, markedly elevating survival rates for stage IV disease from a mere six months to an impressive six years. Progress in comprehending the tumour microenvironment and the immune system has laid the foundation for ground-breaking therapies.
Paving the Way Forward with Clinical Trials
Clinical trials play a pivotal role in the battle against melanoma, the deadliest skin cancer. They offer hope by evaluating new drugs, treatments, and approaches, potentially enhancing options for patients. Successful trials can establish new treatments that benefit all melanoma patients. Participants gain access to advanced treatments, especially crucial for those with advanced melanoma. Trials also identify biomarkers for personalised therapy, optimising treatment plans. They provide valuable data for melanoma research and, in some cases, improve survival rates, offering hope and longer lives. Importantly, they also focus on early detection and prevention, reducing melanoma's impact on individuals and communities.
In the relentless quest to conquer melanoma, knowledge, early detection, and innovative treatments serve as our most powerful allies. As the battle against this formidable adversary rages on, scientists and healthcare professionals continue to push the boundaries of what's possible, offering hope to countless individuals affected by this enigmatic disease.
Author
Koddus Ali
Publications Manager & Principal Medical Writer