Melanoma is a type of skin cancer that develops when pigment-producing cells called melanocytes mutate and begin to multiply uncontrollably. Melanoma can occur anywhere on the body, but is most commonly found on areas exposed to the sun, such as the face, neck, arms, and legs. While melanoma accounts for only about 1% of skin cancers, it is far more dangerous than common skin cancers because of its ability to spread to other parts of the body if not caught and treated early.
When first diagnosed, melanoma is categorized into stages based on how far the cancer has advanced. The earliest stages, Stage 0 and Stage I, reflect melanoma tumors that are limited to the outermost skin layer and have not spread to lymph nodes or distant sites. More advanced melanoma refers to Stage II, III, and IV disease, where the cancer has grown thicker and/or wider and has spread to lymph nodes or other organs beyond the skin. Specifically, advanced melanoma indicates:
Stage II Melanoma
Stage II melanomas are divided into Stage IIA, Stage IIB, and Stage IIC. In Stage IIA, the tumor is between 1-2 mm thick and may be ulcerated or have spread to a tiny area of nearby skin. Stage IIB describes a tumor between 2-4 mm thick with ulceration or spread to nearby skin. Stage IIC refers to a tumor greater than 4 mm thick with ulceration or spread to nearby skin. Lymph nodes are still negative for cancer at this stage.
Stage III Melanoma
Stage III indicates that the primary tumor has spread to nearby lymph nodes or lymphatic channels. It is divided into Stage IIIA, IIIB, and IIIC. In Stage IIIA, the cancer has spread to 1-3 lymph node regions near the tumor, but the nodes are not enlarged and the cancer is found only when they are viewed under a microscope. Stage IIIB refers to cancer having spread to a single lymph node that is enlarged due to the melanoma cells. Stage IIIC means that melanoma has spread to 2 or more lymph nodes or into lymph channels connecting nodes.
Stage IV Melanoma
Stage IV is the most advanced stage of melanoma in which the cancer has spread beyond the original area of skin and nearby lymph nodes to distant lymph nodes or organs such as the lungs, liver, bones, brain, or gastrointestinal tract. Stage IV is sometimes referred to as metastatic or advanced metastatic melanoma to distinguish it from earlier stages where metastases have not yet occurred.
Detecting melanoma in its earlier stages offers the best chance for successful treatment and positive outcomes. By Stage IV, the cancer is more difficult to control and survival rates are lower. However, treatments have improved greatly in recent years, providing new hope for patients diagnosed with advanced melanoma.
What Does Advanced Melanoma Look Like?
In its earliest stages, melanoma often presents as an unusual mole or other skin growth that exhibits signs of melanoma such as asymmetry, irregular borders, uneven color, and a larger diameter than 6 mm (about the size of a pencil eraser). The abnormality may also be a new spot or one that has recently changed in size, shape, or color.
As melanoma advances and the tumor grows thicker, it may take on a more nodular appearance, growing vertically down into the skin rather than spreading across the surface. The tumor may break open and ulcerate with areas of bleeding and crusting.
Advanced melanoma can also sometimes present as a flat, slowly enlarging patch on the skin that lacks the distinct tumor mass seen in earlier stages. This form, called lentigo maligna melanoma, accounts for 4-15% of melanomas.
For melanomas on the hands and feet, advanced cases may cause swelling, pain, or bleeding in the fingers and toes. Thick, ulcerated tumors can also develop on the soles, palms, or under or around nails.
As melanoma spreads to other organs, symptoms specific to the site of metastasis may occur:
– Lung metastases can cause shortness of breath, coughing, or blood in phlegm
– Liver metastases may cause abdominal swelling, nausea, weakness, or jaundice
– Brain metastases can lead to headaches, seizures, balance problems, or personality changes
– Bone metastases may produce bone pain or fractures
Diagnosing Advanced Melanoma
To diagnose advanced melanoma, doctors will first perform a physical exam to check all areas of skin and lymph nodes for any suspicious growths or changes.
They will closely inspect the primary tumor site for characteristics of melanoma, and determine the thickness of the tumor by measuring with a ruler. Thicknesses greater than 4 mm are more likely to represent advanced disease. Doctors will also note if the tumor is ulcerated or bleeding.
Cell samples will be taken through a biopsy of the abnormal skin and examined under a microscope to confirm melanoma. A sentinel lymph node biopsy may be done to check for cancer spread to lymph nodes near the tumor.
If melanoma has potentially spread beyond the skin, additional tests will be needed to stage the disease:
Imaging Tests
– CT or CAT scan: This special X-ray creates cross-sectional images of the body to spot tumors in organs like the lungs, liver, or bones. IV contrast dye may be used to make the images clearer.
– PET scan: For this test, you receive an injection of a radioactive glucose solution that accumulates in cancerous areas throughout the body. A scanner detects the radioactivity to highlight metastases.
– MRI: Using radio waves and strong magnets, an MRI generates detailed images of internal organs and tissues. MRIs are helpful for finding brain metastases.
– Ultrasound: High-frequency sound waves are used to produce images of internal structures. Ultrasound may be used to look at skin, lymph node, or abdominal tumors.
Blood Tests
– LDH: A blood enzyme level called lactate dehydrogenase (LDH) can be elevated in advanced melanoma, indicating metastases.
– Liver function tests: Abnormal liver enzyme levels may signify liver metastases.
Once all imaging and blood work is complete, your doctor can assign a formal stage based on how far the cancer has demonstrably spread. This accurate staging is important for deciding on the best treatment options.
Treatment for Advanced Melanoma
Treatment for advanced melanoma focuses on controlling and destroying the cancer wherever it has spread in the body. Common treatments include:
Immunotherapy
Immunotherapy drugs boost the body’s immune system to better recognize and target cancer cells. They have revolutionized the treatment of advanced melanoma in the past decade. Types of immunotherapies used include:
– Immune checkpoint inhibitors: These drugs block proteins on immune T cells or cancer cells that shut down an immune response. This enables T cells to activate and attack the melanoma. Examples are nivolumab, pembrolizumab, and ipilimumab.
– Interleukins: Interleukins are proteins that stimulate white blood cell growth and activity. High dose interleukin-2 can sometimes eliminate melanoma in a small percentage of patients.
– Adoptive cell therapy: Immune cells are removed from your blood, multiplied in a lab, and then infused back into your blood.
Targeted Therapy
Targeted drugs and monoclonal antibodies attack specific molecules or genes that allow melanoma tumors to grow. These include:
– BRAF inhibitors: Vemurafenib, dabrafenib, and encorafenib target mutations in the BRAF gene commonly seen in melanomas.
– MEK inhibitors: Like trametinib and cobimetinib, these block the mutated MEK gene downstream of BRAF.
– KIT inhibitors: For melanomas with KIT mutations, drugs like imatinib mesylate may be used.
Chemotherapy
Cytotoxic chemotherapy drugs kill rapidly dividing cancer cells. Traditional chemo is less often used alone today due to immunotherapy advances, but may be given along with other drugs.
Radiation
Radiation directs high-energy beams to destroy cancer cells and shrink tumors. It may be used locally to treat limited metastases.
Surgery
Surgery to remove lymph nodes, metastatic growths, and primary tumors still has an important role in the treatment of advanced melanoma. Removing visible disease can work well with other therapies.
Depending on the specifics of an individual’s case, medical oncologists may recommend combining surgery, systemic therapies, and radiation as appropriate. Clinical trials for experimental new treatments are another option that may benefit some patients.
Prognosis and Survival Rates for Advanced Melanoma
The prognosis for advanced melanoma varies considerably based on the stage, number and location of metastases, tumor biology features, and other patient factors.
Overall 5-year survival statistics by disease stage are:
– Stage I: Over 90%
– Stage II: Over 60%
– Stage III: Around 40-70%
– Stage IV: 15-20%
However, these statistics reflect older outcomes data. In recent years, survival for advanced melanoma has improved dramatically thanks to advances in treatments like immunotherapy. Longer-term survival data is still pending, but 2-year survival rates today are estimated around:
– Stage III: 65%
– Stage IV: 30-50%
Site of distant spread also affects outlook. For example, 5-year survival is:
– Skin, distant lymph nodes, or subcutaneous tissue: Around 35%
– Lung metastases: 20%
– Brain metastases: 7%
– Liver metastases: Less than 10%
Younger, healthier patients typically achieve better results. Those with few metastases in early Stage IV may hope for long-term remissions or cure with proactive treatment regimens. However, patients with extensive Stage IV disease and multiple affected organs continue to face low survival odds.
Conclusion
Advanced melanoma refers to higher stage II, III and IV cancers where the tumor has grown to an invasive depth, spread to lymph nodes, or metastasized to distant organs. While advanced melanoma historically had a grave prognosis, newly developed treatments provide significantly improved outcomes and management of the disease for many patients. Identifying and treating advanced melanomas as early as possible remains key for maximizing survival. With a comprehensive approach involving surgery, immunotherapy, targeted drugs, chemotherapy, and radiation, even some patients with metastases are experiencing long-term remissions today. Continued research brings hope that advanced melanoma may one day become a largely curable diagnosis.
