The most common way to treat melanoma is through surgery to remove the tumor and surrounding tissue. This is typically the first line of treatment for early stage melanomas that have not spread beyond the skin. Other common treatments include immunotherapy, targeted therapy, chemotherapy, and radiation therapy. The specific treatment plan depends on the stage and characteristics of the melanoma.
Surgery
Surgery is the mainstay treatment for melanoma. The goal is to remove the entire tumor along with a margin of healthy tissue to ensure all cancerous cells are eliminated. There are several types of surgery used:
Excisional Surgery
This involves cutting out the tumor and surrounding tissue, including a margin around the tumor. The size of the margin depends on the thickness of the melanoma. Thicker tumors require wider margins to remove any potential spread. Generally margins of 0.5-2 cm are removed.
Mohs Surgery
Also known as microscopically controlled surgery, this technique involves progressively removing thin layers of skin and examining them under a microscope during the procedure until no cancer cells remain. This allows maximal preservation of healthy tissue.
Lymph Node Removal
If the melanoma has spread to nearby lymph nodes, these may be removed during surgery through a procedure called a lymph node dissection. This is done to prevent further spread of cancer cells.
Surgery is highly effective for early stage melanomas confined to the skin. The 5-year survival rate for stage 0-II melanomas treated with surgery alone is over 90%. However, additional treatments are needed if the cancer has spread to lymph nodes or distant organs.
Immunotherapy
Immunotherapy involves using medications to stimulate the body’s own immune system to identify and destroy cancer cells. It has become an increasingly common treatment for melanoma, especially in advanced stages. The main types of immunotherapy drugs used include:
Checkpoint Inhibitors
These work by blocking proteins on immune T cells or cancer cells that shut down immune responses. This releases the “brakes” on the immune system. Examples include ipilimumab, nivolumab, and pembrolizumab.
Interleukin-2
IL-2 is a protein that stimulates growth and activity of T cells. High doses of IL-2 can sometimes eliminate melanoma. However, side effects are severe.
Interferons
Interferons are proteins naturally made by the immune system. Artificial interferon given as an injection can boost anti-cancer activity. Low-dose interferon may be given after surgery to treat high risk melanomas.
Studies show checkpoint inhibitor immunotherapy improves survival in metastatic melanoma. Median overall survival is increased by 4-15 months compared to chemotherapy. Combining immunotherapy drugs together may further enhance outcomes.
Targeted Therapy
Targeted drugs and inhibitors focus on specific mutations, proteins, or pathways that are unique to cancer cells. This allows more precise treatment than chemotherapy. Examples of targeted therapy drugs used for melanoma include:
BRAF inhibitors
About half of melanomas have a mutated BRAF gene. BRAF inhibitors like vemurafenib and dabrafenib specifically block the defective BRAF protein. This can dramatically shrink tumors, though resistance often develops over time.
MEK inhibitors
These inhibitors block MEK proteins involved in cell division and growth. Trametinib and cobimetinib are MEK inhibitors that may be combined with BRAF inhibitors to improve efficacy and delay resistance.
KIT inhibitors
For the subset of melanomas with mutated KIT genes, inhibitors like imatinib which block the KIT protein tend to have high response rates. However, long-term control of disease is uncommon.
In clinical trials, targeted therapy for advanced melanoma patients leads to tumor shrinkage in over half of patients. Median progression-free survival is increased by several months compared to chemotherapy.
Chemotherapy
Chemotherapy uses anti-cancer drugs that target rapidly dividing cells. It is not commonly used as initial treatment for melanoma, but may be an option to treat widespread or recurrent melanoma. Chemotherapy is typically combined with other drugs like immunotherapy to enhance effectiveness. Commonly used chemotherapy drugs for melanoma include:
Dacarbazine
An alkylating agent that damages DNA of cancer cells, dacarbazine is the most common chemotherapy drug for melanoma. Unfortunately, response rates are quite low with a median duration of just 4-6 months.
Temozolomide
An oral chemotherapy drug similar to dacarbazine. It can penetrate the brain and may be used to treat melanoma that has spread to the brain.
Cisplatin, vinblastine, paclitaxel
These are other chemotherapy drugs sometimes combined with dacarbazine or used alone when dacarbazine fails. Multi-drug regimens may improve response rates compared to single agents.
Biochemotherapy
Combining chemotherapy with immunotherapy drugs like IL-2 or interferon may enhance the immune response and effectiveness. However, side effects are increased.
Overall, chemotherapy may provide temporary control of melanoma for some patients. But long-term survival benefit is limited, with 5-year survival rates under 10%. Improved options like immunotherapy have supplanted chemotherapy in most cases.
Radiation Therapy
Radiation is used less commonly for melanoma treatment. The high-energy beams can destroy cancer cells and shrink tumors, but have little impact on widely spread melanoma. Main uses include:
After surgery
Radiation may be given after surgical removal of a melanoma to help eliminate any remaining cancer cells in the surrounding skin or tissue. This lowers the risk of recurrence.
Metastases
For melanoma that has spread in a localized area like a small tumor in the lung or brain, focused radiation targeting just that tumor may be used. This is called stereotactic radiosurgery (SRS).
Symptom relief
Radiation therapy directed at metastases can help provide relief of symptoms like pain or bleeding. However, it does not prolong survival.
While radiation has a limited role in treating melanoma, it can be beneficial in certain situations like adjuvant therapy after surgery or controlling isolated metastases.
Emerging Treatments
With greater understanding of melanoma genetics and immunology, new treatments continue to emerge. Some potential future options include:
Neoadjuvant immunotherapy
Currently, immunotherapy like checkpoint inhibitors is mostly used for advanced melanoma. But studies are underway to evaluate its potential impact as an initial therapy before surgery to shrink tumors and eliminate metastases.
Triple-combination therapies
Using immunotherapy along with dual-targeted therapy like a BRAF plus MEK inhibitor is another approach being studied to enhance effectiveness and delay drug resistance.
Oncolytic virus therapy
Engineered viruses are being designed that can infect and damage melanoma cells directly. Talimogene laherparepvec (T-VEC) was recently approved as an injected oncolytic virus treatment for melanoma.
Cancer vaccines
Vaccines customized to prime the immune system to recognize melanoma cell proteins may improve immune-mediated destruction of cancer. Vaccines are typically combined with other immunotherapies.
Outlook Based on Stage
Melanoma prognosis and survival rates vary substantially based on the stage at diagnosis:
| Stage | 5-year Survival Rate |
|---|---|
| Stage 0 | 97% |
| Stage I | 87-96% |
| Stage II | 61-82% |
| Stage III | 28-75% |
| Stage IV | 7-19% |
For early stage I-II melanomas, surgery alone is typically curative. More advanced stage II-III disease often requires combined approaches like surgery, immunotherapy, targeted therapy, and/or radiation to attempt to achieve long-term survival. However, the prognosis for stage IV melanoma with distant metastases remains poor despite treatment advances. Continued research and progress in melanoma therapies is needed.
Conclusion
Surgery is generally the first line treatment for melanoma, combined with lymph node evaluation and resection if nodes are involved. But a multidisciplinary approach utilizing radiation, systemic therapies like immunotherapy and/or targeted agents is often required, especially when cancer has spread beyond the skin. Treatment selection depends on the specific stage, mutations, and other characteristics of the melanoma. With effective early detection and prompt treatment, melanoma cure rates can be significantly improved. However, advanced melanoma remains a challenge to treat effectively. Further research into new therapies and combinations is warranted to continue improving the outlook for melanoma patients.