Treatments for Malignant Melanoma

Malignant melanoma is the overachiever of skin cancers: it’s less common than many others, but it can move fast, travel far, and ignore your calendar plans.
The good news? Melanoma treatment has evolved from “we’ll do our best” to “we have a whole playbook,” thanks to better surgery techniques, smarter drugs,
and immune therapies that basically tell your T-cells, “Heywake up. We’ve got a problem.”

This guide breaks down the most effective, current treatment options for malignant melanomaby stage, biology (like BRAF mutations), and real-life decision points.
It’s educational, not a substitute for medical care, and it’s designed to help you understand the “why” behind the plan your melanoma team recommends.

How Doctors Choose a Melanoma Treatment Plan

Melanoma isn’t treated with a one-size-fits-all approach. Your care team looks at:
tumor depth (Breslow thickness), ulceration, lymph node involvement (often via sentinel lymph node biopsy),
whether melanoma has spread (metastatic melanoma), and sometimes the tumor’s genetic markers.

Staging matters (a lot)

Early-stage melanoma is often treated primarily with surgery and can be cured. Higher-risk stage II and stage III melanoma may add
adjuvant therapy (treatment after surgery) or sometimes neoadjuvant therapy (treatment before surgery).
Stage IV melanoma typically relies on systemic therapyimmunotherapy, targeted therapy, and specialized approaches for specific situations (like brain metastases).

Biomarkers can change the menu

Testing for mutationsespecially BRAF V600can open the door to targeted therapy (BRAF/MEK inhibitors). Other less common changes
(like KIT in certain subtypes) may influence drug options. Think of biomarker testing as checking whether your tumor has a “software update” that medicines can exploit.

Surgery: The Foundation for Many Melanoma Treatments

For many people, melanoma treatment starts with surgery. The goal is straightforward: remove the tumor with a safety margin of normal-looking skin
(called wide local excision). The size of the margin depends on the thickness and features of the melanoma.

Sentinel lymph node biopsy

If the melanoma is deeper or has higher-risk features, doctors may recommend a sentinel lymph node biopsy. This helps determine whether
melanoma has started to spread through the lymphatic system. The result can affect staging and whether additional therapy is recommended.

When surgery isn’t the whole story

If melanoma has spread to lymph nodes or other organsor if there’s a high risk of recurrencesurgery may be combined with systemic therapy.
In some cases of limited metastasis, surgery to remove specific metastatic deposits (metastasectomy) can still play a role, often alongside drug therapy.

Adjuvant and Neoadjuvant Therapy: Reducing Recurrence Risk

After successful surgery, some melanomas still have a higher chance of returning. That’s where adjuvant therapy comes indesigned to wipe out
microscopic disease you can’t see on scans.

Adjuvant immunotherapy

For certain stage IIB/IIC and stage III melanomas (and some resected stage IV cases), adjuvant therapy commonly includes PD-1 inhibitors such as
pembrolizumab or nivolumab. These drugs lower recurrence risk for many patients by boosting immune recognition of cancer cells.

Adjuvant targeted therapy (for BRAF-mutant melanoma)

If the melanoma has a BRAF V600 mutation, adjuvant targeted therapy with a BRAF inhibitor plus a MEK inhibitor
(for example, dabrafenib + trametinib) can be an option after surgery in appropriate stages, based on guideline-driven criteria.

Neoadjuvant therapy: treating before surgery

In selected stage III cases (particularly clinically evident lymph node disease), neoadjuvant immunotherapy is increasingly discussed.
The idea is to shrink disease, improve surgical outcomes, and potentially reduce overall treatment burden. This is a fast-moving area of melanoma care,
often guided by major cancer-center protocols and clinical trial evidence.

Immunotherapy: Teaching Your Immune System New Tricks

Immunotherapy has reshaped melanoma outcomes, especially for advanced or metastatic disease. Instead of attacking cancer directly like chemotherapy,
checkpoint inhibitors remove immune “brakes,” letting T-cells do what they were born to do: eliminate threats.

PD-1 inhibitors (pembrolizumab, nivolumab)

PD-1 inhibitors are widely used across melanoma stagesfrom adjuvant treatment to first-line therapy in metastatic melanoma.
They can produce durable responses in a meaningful subset of patients, and their safety profile is often more manageable than older immunotherapies.

Combination immunotherapy (nivolumab + ipilimumab)

Combining a PD-1 inhibitor with a CTLA-4 inhibitor (like ipilimumab) can raise response rates and deepen responses,
but it also increases the chance of serious immune-related side effects. This combination may be considered for fit patients with aggressive disease,
certain metastasis patterns, or where a higher chance of response is worth the extra toxicity risk.

LAG-3 plus PD-1 (nivolumab + relatlimab)

Another option for unresectable or metastatic melanoma is the fixed-dose combination of nivolumab + relatlimab.
It targets PD-1 and LAG-3two immune checkpointsproviding another evidence-based approach in the metastatic setting.

Intralesional immunotherapy and oncolytic virus therapy (T-VEC)

For some patients with accessible tumors in the skin or lymph nodes, treatments injected directly into lesions can be used.
Talimogene laherparepvec (T-VEC) is an example of an oncolytic virus therapy that can stimulate local and systemic immune responses.
Intralesional therapy may be used alone in select situations or paired with systemic immunotherapy in clinical trial settings.

Immune-related side effects: the “over-enthusiastic immune system” problem

Checkpoint inhibitors can cause inflammation in healthy organsskin rash, colitis, hepatitis, thyroid issues, adrenal problems, and more.
Many side effects are treatable, especially when caught early. The golden rule is: report symptoms quickly, because “I’ll just tough it out”
is not a strategy your colon appreciates.

Targeted Therapy: Precision Drugs for BRAF-Mutant Melanoma

About half of cutaneous melanomas may carry a BRAF mutation, most commonly BRAF V600.
When present, targeted therapy can shut down the MAPK growth pathway using a BRAF inhibitor + MEK inhibitor combination.

Common BRAF/MEK combinations

• Dabrafenib + trametinib
• Vemurafenib + cobimetinib
• Encorafenib + binimetinib

Targeted therapy can work quicklyoften helpful when disease is causing symptoms or needs rapid control. The trade-off is that, compared with immunotherapy,
responses may be less durable for some patients, and resistance can develop.
That’s why treatment sequencing (immunotherapy first vs targeted therapy first) is a major discussion point for BRAF-mutant metastatic melanoma.

Side effects of targeted therapy

Targeted therapy side effects may include fever, fatigue, rash, joint pain, photosensitivity (especially with some drugs),
and lab abnormalities. Fever with dabrafenib/trametinib can be significant and sometimes requires treatment interruptions and supportive management.

TIL Therapy: A Cellular Therapy Option After Standard Treatments

For some patients whose metastatic melanoma has progressed after a PD-1 inhibitor (and after BRAF-targeted therapy if BRAF-mutant),
tumor-infiltrating lymphocyte (TIL) therapy is now an FDA-approved option.
The idea is both simple and sci-fi: collect immune cells from the tumor, expand them in a lab, and infuse them back to fight cancer.

TIL therapy is intensive and usually delivered at specialized centers. It can involve lymphodepleting chemotherapy beforehand and high-dose IL-2 afterward,
so patients are carefully selected based on health, disease characteristics, and treatment history.

Radiation Therapy: Targeted Control, Especially for Brain Mets

Radiation therapy is not the mainstay for most early melanoma, but it can be extremely useful:
for symptom relief (palliative radiation), control of specific sites, and treatment of brain metastases.

Stereotactic radiosurgery (SRS)

For melanoma that spreads to the brain, stereotactic radiosurgery can precisely deliver high-dose radiation to tumors while sparing healthy tissue.
SRS is often paired with immunotherapy in modern care plans, and the combination is an active area of clinical research and practice refinement.

Chemotherapy: Less Common, Still Sometimes Useful

Traditional chemotherapy plays a smaller role today because immunotherapy and targeted therapy are generally more effective for many patients.
Still, chemotherapy may be considered when other treatments aren’t working, aren’t tolerated, or aren’t available.
It can also be used in certain clinical situations and clinical trials.

Other Local and Regional Treatments

Isolated limb infusion/perfusion

For melanoma confined mainly to an arm or leg (like in-transit metastases), regional chemotherapy techniques such as isolated limb infusion/perfusion
may be used at specialized centers. These approaches allow high drug doses to the limb while limiting whole-body exposure.

Managing in-transit and satellite lesions

In-transit metastases (tumor deposits between the primary site and lymph nodes) can be managed with surgery, intralesional therapy,
radiation, systemic therapy, or a combinationdepending on how extensive and fast-moving they are.

Clinical Trials: Where Tomorrow’s Treatments Show Up Early

Clinical trials are not “last resort” by default. In melanoma, trials can be especially valuable because the field moves quickly
new combinations, personalized vaccines, next-gen cellular therapies, and novel intratumoral agents are actively being tested.

When to ask about a trial

• New diagnosis of stage III or stage IV melanoma
• High-risk stage II after surgery
• Progression after PD-1 therapy or after BRAF/MEK therapy
• Rare melanoma subtypes or unusual biomarker profiles

If your treatment plan feels like it has only two doors, a trial may add a third doorand sometimes it’s the one with better lighting and snacks.
(Okay, not the snacks. But definitely more options.)

Supportive Care: Treatment Works Better When You Do, Too

Supportive care isn’t “extra.” It’s part of good oncology. It includes:
managing side effects, protecting skin from UV exposure, nutrition support, pain and symptom management,
mental health resources, and practical planning for work and family life during treatment.

Follow-up and surveillance

After treatment, follow-up typically involves skin exams, lymph node checks, and sometimes imaging depending on stage and recurrence risk.
Early detection of recurrence or a new melanoma can change outcomes, so surveillance is a long-term partnershipnot a one-time victory lap.

Real-World Treatment Experiences (A 500-Word Reality Check)

What does treatment for malignant melanoma feel like in day-to-day life? Experiences vary, but there are patterns many patients reportespecially
when moving through surgery, immunotherapy, targeted therapy, or a mix of everything (because melanoma sometimes insists on being a multi-season series).

Surgery is often described as the “most straightforward” part: there’s a clear problem, a clear procedure, and a clear recovery timeline.
People commonly talk about surprise at the size of the excision margin (“I came in for a spot and left with a zip code”) and the emotional jolt of waiting for
pathology results. If a sentinel lymph node biopsy is involved, the anxiety tends to spikebecause lymph nodes feel like the plot twist that changes the story.
Physical recovery can include soreness, limited movement depending on location, and scar care. Emotionally, many patients say the hard part isn’t the incision
it’s the uncertainty.

Immunotherapy can be deceptively normal at first. Infusion days might feel routine: check-in, labs, IV, go home. Many people keep working
and living lifeuntil side effects appear. Fatigue is one of the most common complaints, and it can be weirdly unpredictable: “fine on Tuesday, human slug by Thursday.”
Skin rashes and itching come up often. Some patients develop thyroid changes and realize it because they feel offcold intolerance, weight changes, brain fog.
Others experience diarrhea or abdominal pain that signals immune-related colitis. The key real-world lesson patients repeat is that reporting symptoms early matters.
Waiting it out can turn a manageable issue into an ER visit. Most patients also talk about the psychological weight of “scanxiety”the days before a scan result
arrives. Even when immunotherapy is working, the mind loves to audition for worst-case scenarios.

Targeted therapy often gets the reputation of “it works fast,” and many patients do feel symptom relief quickly when tumors shrink.
But side effects can be loud. Feverespecially with certain BRAF/MEK combinationscan knock people flat, sometimes requiring pauses and restarts.
Joint aches, fatigue, and skin sensitivity are frequent. Patients often learn to become expert-level planners: thermometer by the bed, hydration on autopilot,
sunscreen like it’s a religion, and a calendar that revolves around how their body responds. Some describe targeted therapy as more “daily management” than
immunotherapy’s “watch for weird immune stuff.”

For advanced disease, treatment decisions can feel like a chess match played at high speed. People talk about balancing response rates, long-term durability,
side effect tolerance, and practical life realities (jobs, caregiving, travel distance to specialty centers). Many also describe the value of second opinions
at major melanoma centersnot because their original doctor is wrong, but because melanoma is complex and options can be nuanced.
The strongest throughline: patients feel better when they understand the plan, the goal (cure, long-term control, symptom relief), and the next step if the current one fails.

Conclusion

Treatments for malignant melanoma have never been more effectiveor more personalized. Surgery remains essential for many early and locally advanced cases,
while immunotherapy and targeted therapy drive modern care for high-risk and metastatic melanoma. Newer approaches, including FDA-approved TIL therapy for
previously treated metastatic melanoma, expand options when standard therapies stop working.

The best next move is usually not “find one magic treatment,” but rather: confirm staging, confirm biomarker status (like BRAF),
understand the intent of therapy, and work with a melanoma-experienced team that can tailor the sequence and combination of treatments to your situation.