Comprehensive Guide to Melanoma Treatment Options

Surgery remains the cornerstone of treatment for melanoma at every stage. It is frequently paired with adjunctive therapies—such as immunotherapy, targeted agents, chemotherapy, or radiation—to eradicate residual disease.

When melanoma is detected before it metastasizes, the prognosis is generally favorable. Ongoing research continues to refine the role of immunotherapy and targeted therapy for tumors that are less responsive to surgery alone.

For advanced disease that is not curable, clinicians often employ palliative modalities—including radiation or chemotherapy—to control symptoms and extend survival.

Below is an overview of the most commonly used melanoma treatments.

Surgery

Wide local excision is the standard surgical approach. The procedure removes the primary tumor together with a margin of normal tissue; larger defects may require skin grafting.

In cosmetically sensitive areas (e.g., the face), Mohs micrographic surgery can be performed. This technique removes thin tissue layers sequentially, examining each under a microscope to ensure clear margins.

Lymph‑node dissection is indicated when there is evidence of nodal involvement. Rarely, amputation may be necessary for tumors that infiltrate deeply into a digit.

When melanoma has metastasized and curative resection is not possible, surgeons may still remove isolated lesions or affected lymph nodes to provide palliation.

Immunotherapy

Immunotherapy agents stimulate the patient’s immune system to recognize and destroy cancer cells.

For many stage II and III melanomas, the checkpoint inhibitor pembrolizumab (Keytruda) is given adjuvantly after surgery to lower recurrence risk. It is administered intravenously every 2–6 weeks.

Other immunotherapies—such as interleukin‑2 (Proleukin) and the topical agent imiquimod (Aldara/Zyclara)—may be used for unresectable stage III disease, stage IV disease, or recurrent melanoma. Imiquimod is applied to the skin 2–5 times per week for roughly three months following excision of early‑stage lesions.

Chemotherapy

Chemotherapy is generally reserved for cases where newer agents have failed or are unavailable. It may be given after surgery to eradicate microscopic disease or as a primary treatment for unresectable stage III, stage IV, or recurrent melanoma.

Common regimens are delivered intravenously; oral temozolomide (Temodar) is an alternative for some patients. Hyperthermic isolated limb perfusion—direct infusion of chemotherapy into an affected arm or leg with a tourniquet—can be employed for limb‑confined disease.

Radiation Therapy

High‑energy X‑rays or other radiation modalities are used in several scenarios:

• Early‑stage melanoma that cannot be surgically removed
• High‑risk disease after surgery to reduce recurrence
• Local or distant recurrence
• Palliative care to alleviate symptoms in incurable disease

Targeted Therapy

Targeted agents inhibit specific molecular pathways driving melanoma growth, offering a more precise alternative to conventional chemotherapy.

Adjuvant therapy after surgery for high‑risk stage III melanoma may include BRAF inhibitors (dabrafenib [Tafinlar]) combined with MEK inhibitors (trametinib [Mekinist]).

For unresectable stage III, stage IV, or recurrent disease, clinicians may use one of the following FDA‑approved combinations:

• dabrafenib + trametinib
• vemurafenib [Zelboraf]
• cobimetinib [Cotellic]
• encorafenib [Braftovi]
• binimetinib [Mektovi]

Emerging Treatments & Clinical Trials

Research is actively exploring novel approaches, including therapeutic vaccines that aim to prime the immune system against melanoma cells.

Current clinical trials are listed on the National Cancer Institute website.

Multidisciplinary care typically involves dermatologists, surgical oncologists, medical oncologists, and radiation oncologists.

Patients whose melanoma is completely resected may require only a single surgery, followed by regular surveillance—usually every 3–12 months, with more frequent visits for aggressive disease.

Chemotherapy cycles last several weeks; the total number of cycles depends on tumor response and tolerability.

Early‑stage melanoma, confined to the skin, is often curable. Long‑term remission is commonly defined as five years without detectable disease, though recurrences most frequently occur within the first five years. A 2019 Australian cohort of 700 high‑risk patients reported a 13.4 % relapse rate within two years.

According to the SEER database, five‑year relative survival rates vary by stage, underscoring the importance of early detection and appropriate multimodal therapy.