Melanoma is the most severe form of skin cancer, arising from pigment-producing cells called melanocytes. An “advanced” diagnosis signifies that the cancer has progressed beyond its initial site and regional lymph nodes to other parts of the body. This stage requires a shift from localized treatment approaches to systemic therapies. Understanding the extent of this spread is important for determining the best course of action and managing the condition.
Understanding the Stages of Advanced Melanoma
Advanced melanoma is defined by the American Joint Committee on Cancer (AJCC) Staging System, encompassing Stage III and Stage IV disease. Stage III is characterized by regional spread, meaning the melanoma has traveled from the primary tumor site to nearby lymph nodes or to the skin and lymphatic vessels between the primary site and the closest lymph node basin (in-transit or satellite metastases). This stage is considered advanced because the risk of recurrence and further spread is high, even without distant organ involvement. Stage III classification depends on factors like tumor thickness, ulceration, and the number of lymph nodes involved.
Stage IV represents the most advanced form of the disease, defined by metastasis—the spread of cancer cells to distant organs or tissues. Common sites for these distant metastases include the lungs, liver, brain, and bones. The specific site of metastasis and the level of the enzyme lactate dehydrogenase (LDH) in the blood are used to further categorize Stage IV disease. Staging guides treatment decisions and provides an estimate of the overall prognosis.
Recognizing Signs and Diagnostic Procedures
Identifying advanced melanoma involves recognizing specific symptoms related to the site of metastasis. For example, lung involvement might cause a persistent cough or shortness of breath. Brain metastases can lead to severe headaches, seizures, or changes in personality and cognition.
Other general signs include unexplained weight loss, persistent pain, and extreme fatigue not relieved by rest. Swollen, hard, or tender lymph nodes (under the arm, in the groin, or in the neck) can indicate regional spread. Any hard lumps under the skin, especially near the original tumor site, should be promptly evaluated.
Diagnostic procedures determine the exact stage of the melanoma. Imaging tests, such as computed tomography (CT) scans, positron emission tomography (PET) scans, and magnetic resonance imaging (MRI), visualize internal organs and check for distant spread. CT scans of the chest, abdomen, and pelvis help detect metastases in the lungs and liver. MRI is often used to check for spread to the brain.
Biopsies confirm the presence of cancer cells in suspicious areas. A sentinel lymph node biopsy determines if cancer cells have spread to the nearest lymph nodes. If distant lesions are found, a core needle biopsy may be performed on the metastatic site to confirm the diagnosis and gather tissue for molecular testing. Blood tests measuring serum LDH levels are also part of staging, as elevated levels are associated with a more advanced stage.
Current Strategies for Medical Treatment
The treatment landscape for advanced melanoma has been transformed by systemic therapies that focus on harnessing the immune system or targeting specific genetic mutations within cancer cells. These systemic approaches are now the standard of care for Stage III and Stage IV disease, often replacing traditional chemotherapy as the first-line option. Treatment choice is highly individualized, depending on the stage, genetic mutations present, and the patient’s overall health.
Immunotherapy, particularly the use of immune checkpoint inhibitors, has revolutionized patient outcomes. These drugs, such as anti-PD-1 agents like pembrolizumab and nivolumab, work by blocking proteins that normally act as a “brake” preventing the immune system from attacking the tumor. By releasing this brake, these antibodies unleash the body’s T-cells to recognize and destroy malignant cells.
A combination of different checkpoint inhibitors, such as nivolumab and ipilimumab (an anti-CTLA-4 agent), is frequently used and demonstrates improved overall survival compared to single agents. Immunotherapy is often recommended as the initial treatment for patients with unresectable or metastatic melanoma. Newer combinations, like nivolumab plus relatlimab (an anti-LAG-3 inhibitor), enhance the anti-tumor immune response.
Targeted therapy is a primary approach for patients whose melanoma cells harbor specific genetic alterations, most commonly a mutation in the BRAF gene. This mutation is present in about half of all melanomas and causes the cell to grow and divide uncontrollably. Drugs that block the activity of the BRAF protein, along with MEK inhibitors, can slow or stop cancer growth.
These targeted agents, such as the combinations of dabrafenib plus trametinib or encorafenib plus binimetinib, are typically given together. This combination is more effective and helps prevent the cancer from developing resistance. The combination of BRAF and MEK inhibitors can lead to a rapid reduction in tumor size, which benefits patients with a high tumor burden or aggressive disease. Genetic testing of the tumor tissue is mandatory to determine eligibility for this treatment.
While immunotherapy and targeted therapy are primary treatments, others remain relevant in specific contexts. Radiation therapy may be used to treat symptoms at specific sites, such as bone pain or brain metastases, or to shrink tumors before surgery. Traditional chemotherapy is generally reserved for patients who do not respond to or cannot tolerate immunotherapy or targeted therapy, or it may be used in combination regimens.
Supportive Care and Ongoing Monitoring
Management of advanced melanoma includes comprehensive supportive care aimed at improving the patient’s quality of life. Supportive care, sometimes called palliative care, focuses on managing disease symptoms and treatment side effects. It can be used alongside active therapy from the time of diagnosis. This care encompasses physical symptom management (such as pain and fatigue) and psychosocial support.
For patients receiving systemic treatments, managing adverse events, especially immune-related side effects from checkpoint inhibitors, is a continuous process. A holistic approach often includes tailored programs involving exercise, dietary advice, and psychological counseling to address the emotional and physical challenges. Open communication with the healthcare team about any new or worsening symptoms is important for timely intervention.
Ongoing monitoring is required after treatment to check for recurrence or the development of new cancers. This typically involves regular physical examinations, blood tests, and periodic imaging scans to track disease activity. Lifelong surveillance is recommended, with more intensive follow-up during the first few years when the risk of relapse is highest. Patients are encouraged to perform monthly full-body skin checks and adhere to sun protection practices to reduce the risk of developing a second primary melanoma.