Melanoma treatment depends on how deep the cancer has grown and whether it has spread. For early-stage melanoma caught before it reaches the lymph nodes, surgery alone is often curative. For more advanced disease, treatment typically combines surgery with immunotherapy, targeted therapy, or radiation to reduce the chance of recurrence and extend survival.
Surgery Is the Starting Point
Nearly every melanoma diagnosis begins with surgery. The procedure, called wide local excision, removes the tumor along with a margin of healthy skin around it. How much skin the surgeon takes depends on the thickness of the melanoma, measured in millimeters under a microscope (called Breslow thickness):
- Melanoma in situ (hasn’t grown beyond the top skin layer): 0.5 cm margin
- Less than 1.0 mm thick: 1 cm margin
- 1.0 to 2.0 mm thick: 1 to 2 cm margin
- Greater than 2.0 mm thick: 2 cm margin
For very thin melanomas (under 0.8 mm, no ulceration), surgery alone is usually sufficient. Once a melanoma reaches 0.8 mm or shows ulceration, your surgeon will likely recommend a sentinel lymph node biopsy. This procedure removes the first lymph node where cancer would drain to check whether it has started to spread. For melanomas between 1.0 and 4.0 mm, sentinel lymph node biopsy is a standard recommendation. For tumors thicker than 4.0 mm, it’s still often performed, though the decision involves weighing its benefits for your specific situation.
The results of this biopsy shape everything that follows. A negative result (no cancer in the lymph node) is reassuring and may mean no further treatment is needed. A positive result means the cancer has begun to travel, and additional therapy enters the picture.
Immunotherapy for Advanced Melanoma
Immunotherapy has transformed melanoma treatment over the past decade. These drugs work by removing the brakes that cancer puts on your immune system, allowing your T cells to recognize and attack tumor cells. The main drugs used are checkpoint inhibitors, and they fall into two categories.
The first targets a protein called PD-1 on immune cells. Pembrolizumab and nivolumab are the two most widely used PD-1 inhibitors. They’re effective as standalone treatments and are often the first choice for advanced melanoma. The second category targets a different protein called CTLA-4. Ipilimumab was the first drug of this type approved for melanoma.
Combining both types produces stronger results. In the landmark CheckMate 067 trial, patients who received nivolumab plus ipilimumab together had a median overall survival of 71.9 months, nearly six years. That compared to 36.9 months for nivolumab alone and 19.9 months for ipilimumab alone. A newer combination pairs a PD-1 inhibitor with a LAG-3 inhibitor, offering another option for patients with advanced disease.
Immunotherapy isn’t limited to late-stage melanoma. For stage II melanoma with deeper tumors and stage III disease, checkpoint inhibitors are now commonly used as adjuvant therapy (given after surgery) to reduce the risk of the cancer coming back.
Side Effects of Immunotherapy
Because these drugs activate the immune system broadly, they can trigger inflammation in healthy organs. In a real-world study of 792 melanoma patients on adjuvant PD-1 inhibitors, 88% experienced some type of immune-related side effect. Most were mild: skin rashes, fatigue, joint pain, or thyroid problems. Severe side effects occurred in about 15% of patients, and fatal reactions were rare at 0.6%. Your oncology team will monitor bloodwork and symptoms closely throughout treatment to catch and manage these reactions early.
Neoadjuvant Therapy: Treatment Before Surgery
A growing shift in melanoma care involves giving immunotherapy before surgery rather than only after. The logic is straightforward: while the tumor is still in the body, the immune cells living inside it can be activated by the drugs. Once the tumor is removed, those primed immune cells are gone. Clinical trials at MD Anderson Cancer Center found that patients who received immunotherapy before surgery had a significantly lower risk of their cancer returning compared to those who received it only afterward. In some cases, most patients had no active cancer cells left in their tumors by the time they reached surgery. Importantly, giving combination checkpoint inhibitors before surgery did not cause side effects that delayed the operation.
Targeted Therapy for BRAF-Positive Melanoma
About 50% of melanomas carry a specific genetic mutation called BRAF V600. If your tumor tests positive for this mutation, you have an additional treatment option: targeted therapy drugs that block the signals driving cancer cell growth.
These drugs are used in pairs. A BRAF inhibitor is combined with a MEK inhibitor because using both together works better and helps prevent resistance. The three approved pairings are:
- Dabrafenib plus trametinib
- Vemurafenib plus cobimetinib
- Encorafenib plus binimetinib
For patients with BRAF-positive advanced melanoma, doctors have had to decide whether to start with immunotherapy or targeted therapy. Research now suggests that starting with combination immunotherapy (nivolumab plus ipilimumab) tends to produce better long-term outcomes than starting with targeted therapy, though targeted drugs can still play an important role later in treatment or when a rapid response is needed. In some cases, targeted therapy is combined with an additional immunotherapy drug for a three-drug approach.
TIL Therapy: A Newer Option
In 2024, the FDA granted accelerated approval to lifileucel (brand name Amtagvi), the first tumor-infiltrating lymphocyte (TIL) therapy for melanoma. This treatment is designed for adults with advanced melanoma that can’t be surgically removed or has spread, and who have already tried a PD-1 inhibitor (and a BRAF/MEK inhibitor combination if their tumor is BRAF-positive).
The process involves removing a piece of your tumor, extracting the immune cells from within it, growing billions of copies of those cells in a lab, and then infusing them back into your body. It’s a complex, intensive treatment typically reserved for patients who have run out of other options, but it represents a meaningful new avenue for people with hard-to-treat disease.
Radiation Therapy
Radiation is not a primary treatment for melanoma the way it is for some other cancers. Its main role is managing melanoma that has spread to the brain, which happens in a significant portion of advanced cases. Stereotactic radiosurgery (SRS), a highly focused form of radiation, delivers precise doses to brain tumors while sparing surrounding tissue.
Combining SRS with immunotherapy or targeted therapy produces substantially better outcomes than either approach alone. In a systematic review, adding SRS to a PD-1 inhibitor reduced the risk of death by 65% compared to SRS alone. Adding SRS to a combination of checkpoint inhibitors reduced the risk by 59%. Radiation may also be used after lymph node surgery to reduce the chance of local recurrence, or as palliative treatment to relieve symptoms in areas where the cancer is causing pain or other problems.
What Happens After Treatment
Once active treatment ends, follow-up surveillance becomes the priority. For high-risk melanoma (stage IIB and above), guidelines recommend imaging with PET or CT scans for the first five years. Most oncologists schedule these every four to six months during that window. For the first two years, when recurrence risk is highest, imaging may happen as often as every three months. After five years, routine imaging is generally no longer recommended, though regular skin checks and physical exams continue indefinitely.
People who have had one melanoma are at increased risk of developing a second one. Full-body skin exams, both self-performed monthly and conducted by a dermatologist at least annually, remain an important part of long-term care. Catching a recurrence or a new melanoma early, when surgery alone can handle it, makes an enormous difference in outcomes.