Melanoma treatment depends on how deep the tumor has grown and whether it has spread. Early-stage melanoma is curable with surgery alone in the vast majority of cases, with a five-year survival rate above 99% for localized disease. When melanoma reaches nearby lymph nodes, that rate drops to about 76%, and for melanoma that has spread to distant organs, it’s around 35%. The good news: treatment options have expanded dramatically in recent years, and outcomes at every stage continue to improve.
Surgery: The First-Line Treatment
Nearly every melanoma diagnosis begins with surgery. The initial step is usually a biopsy to confirm the diagnosis and measure the tumor’s depth (called Breslow thickness). Once confirmed, a wider excision removes additional tissue around the original site to ensure no cancer cells remain at the edges. The size of that margin depends on how deep the melanoma goes. For melanoma in situ, which hasn’t grown beyond the top layer of skin, surgeons typically remove 5 millimeters to 1 centimeter of surrounding tissue. Deeper tumors require wider margins.
For thin melanomas under 0.8 millimeters that aren’t ulcerated, surgery alone is usually sufficient. The risk that cancer has reached the lymph nodes is less than 5%, so no further procedures are needed. When the tumor is between 0.8 and 1.0 millimeters, or thinner but ulcerated, the risk climbs to 5 to 10%, and your surgeon will likely discuss a sentinel lymph node biopsy. This procedure identifies the first lymph node where cancer would drain and checks it for melanoma cells. For tumors thicker than 1.0 millimeter, sentinel node biopsy is standard practice because the risk of spread exceeds 10%.
Immunotherapy for Advanced Melanoma
Immunotherapy has transformed the treatment of melanoma that can’t be fully removed with surgery or has spread beyond the original site. These drugs work by releasing the brakes on your immune system so it can recognize and attack cancer cells more effectively.
The backbone of immunotherapy is a class of drugs called checkpoint inhibitors. The most widely used approach blocks a protein called PD-1 on immune cells, which cancer exploits to hide from the immune system. A combination of two checkpoint inhibitors, one targeting PD-1 and another targeting a different brake called CTLA-4, is a standard first-line treatment for inoperable or metastatic melanoma. This combination is particularly effective for melanoma that has spread to the brain, where it outperforms either drug alone.
A newer combination pairs a PD-1 blocker with a drug targeting a third checkpoint protein called LAG-3. This became the first FDA-approved therapy to block LAG-3 and offers another option for patients with untreated advanced melanoma.
What Side Effects to Expect
Because checkpoint inhibitors supercharge the immune system, they can trigger inflammation in healthy organs. The most commonly affected systems are the endocrine glands (thyroid, pituitary, adrenal), followed by the nervous system, kidneys, and blood cells. These immune-related side effects range from mild and manageable, like thyroid changes that require hormone replacement, to severe reactions that need prompt treatment. Your oncology team will monitor bloodwork regularly to catch problems early. Combination immunotherapy causes more frequent and more severe side effects than single-agent treatment, which is an important factor in choosing a regimen.
Targeted Therapy for BRAF-Mutant Melanoma
Nearly half of all advanced melanomas carry a specific genetic mutation in a gene called BRAF. If your tumor tests positive for this mutation, you’re a candidate for targeted therapy: pills that directly block the abnormal signaling pathway driving your cancer’s growth.
These drugs come in pairs. One blocks the BRAF protein itself, and the other blocks a downstream protein called MEK. Using both together works better and longer than either alone, because the cancer has a harder time finding workarounds. Three BRAF/MEK combinations are available, and they produce similar response rates and survival outcomes. Targeted therapy tends to shrink tumors quickly, which makes it especially useful when rapid symptom relief is needed. The trade-off is that most patients eventually develop resistance, which is why immunotherapy is often preferred as a first-line option when speed isn’t critical.
Treatment Before and After Surgery
For melanoma that has spread to nearby lymph nodes (stage III), surgery alone carries a significant risk of recurrence. Additional treatment, given either before or after the operation, substantially reduces that risk.
Adjuvant therapy, given after surgery, has strong evidence behind it. PD-1 checkpoint inhibitors given for about a year after surgery improve recurrence-free survival meaningfully. In clinical trials, roughly 60% of patients receiving adjuvant PD-1 therapy remained recurrence-free at three and a half years, compared to about 41% with placebo. For patients with BRAF-mutant melanoma, adjuvant BRAF/MEK inhibitor therapy for 12 months showed similarly strong results: 58% remained recurrence-free after nearly five years of follow-up, compared to 39% with placebo.
Neoadjuvant therapy, given before surgery, is gaining momentum. The idea is to shrink the tumor first, making surgery easier while also giving doctors a window into how well the treatment works for your specific cancer. Combination immunotherapy before surgery has shown pathological response rates around 77 to 80%, meaning the tumor shrinks substantially or disappears entirely from the lymph nodes. In one trial, patients who received neoadjuvant immunotherapy had an estimated three-year recurrence-free survival of 80%, compared to 60% for those who received treatment only after surgery. Neoadjuvant BRAF/MEK therapy has also demonstrated strong results, with 86% of patients showing a pathological response before lymph node surgery.
TIL Therapy: A Newer Option
For patients whose melanoma has progressed through both immunotherapy and, if applicable, targeted therapy, a cell-based treatment called TIL therapy (tumor-infiltrating lymphocyte therapy) became available through FDA accelerated approval. The process involves extracting immune cells that have already infiltrated your tumor, growing billions of them in a lab, and infusing them back into your body. It’s reserved for adults with unresectable or metastatic melanoma who have already tried a PD-1 blocker and, for BRAF-positive patients, a BRAF inhibitor. The treatment requires a hospital stay and is only available at specialized centers, but it represents a meaningful option for patients who have exhausted standard therapies.
Radiation for Brain Metastases
Melanoma has a particular tendency to spread to the brain. When it does, highly focused radiation called stereotactic radiosurgery is a standard treatment. This technique delivers precise, high-dose radiation to individual brain tumors while largely sparing surrounding tissue. It can be used alone or alongside immunotherapy and targeted therapy. Broader whole-brain radiation is sometimes used after surgery or radiosurgery to reduce the chance of new tumors forming elsewhere in the brain, or to relieve symptoms when multiple sites are affected.
How Treatment Decisions Are Made
Your treatment plan depends on several intersecting factors: the stage at diagnosis, whether your tumor carries the BRAF mutation, the location and number of metastases, and your overall health. Early-stage melanoma typically needs only surgery. Stage III melanoma usually involves surgery plus adjuvant or neoadjuvant systemic therapy. Stage IV melanoma is treated with immunotherapy, targeted therapy, or both, with radiation added as needed for brain or bone involvement.
Tumor genetic testing is essential for anyone with advanced melanoma. Knowing your BRAF status determines whether targeted therapy is an option, and it influences the sequencing of treatments. Most oncologists currently favor starting with immunotherapy for BRAF-positive patients unless the disease burden demands the rapid response that targeted therapy provides. For BRAF-negative patients, checkpoint inhibitors are the primary systemic treatment. The choice between single-agent and combination immunotherapy often comes down to balancing effectiveness against side-effect risk, a conversation worth having in detail with your oncologist.