Melanoma Treatment by Stage

Melanoma staging starts with a ruler, not a scan. The pathologist measures Breslow thickness, the vertical depth of the tumor in millimeters, and records whether the surface is ulcerated, meaning the skin over the tumor has broken down.

NCI states that Breslow thickness is more reproducible than the older Clark level, more accurately predicts behavior in lesions thicker than 1.5 mm, and should always be reported. If your report gives a Clark level but no Breslow measurement, ask for it.

Those two numbers define the T categories. T1a is under 0.8 mm without ulceration. T1b is under 0.8 mm with ulceration, or 0.8 to 1.0 mm with or without it. T2a is over 1.0 up to 2.0 mm without ulceration. At the far end, T4b is over 4.0 mm with ulceration.

One caution NCI raises directly. In a study of 140 lesions reviewed by experienced dermatopathologists, 37 showed disagreement over whether the lesion was melanoma at all. In another study, 38% of cases had two or more discordant interpretations by expert pathologists. Agreement was highest for Breslow thickness and ulceration and poor for other features. A second pathology opinion is a reasonable request, not a slight. Cancer staging covers how these letters combine.

Wide local excision removes the scar and a rim of normal skin around it. The size of that rim has been tested repeatedly, and the answer is consistent: bigger has not proved better.

A Swedish trial randomized patients with trunk or limb melanomas 0.8 mm to 2 mm thick to margins of 2 cm or 5 cm. It enrolled 989 patients. At a median follow-up of 11 years there was no significant difference in overall survival, and the local recurrence rate was 1% with no significant difference between the arms.

A European trial compared 2 cm with 5 cm in 326 patients with melanomas 2.1 mm or thinner and found the same. The Intergroup Melanoma Surgical Trial compared 2 cm with 4 cm in melanomas 1 mm to 4 mm thick, and at 10 years found no difference in overall survival, disease-specific survival, or local recurrence.

A single-center review of 2,131 patients with 1 mm to 2 mm melanomas compared histological margins of 8 mm and 16 mm, roughly 1 cm and 2 cm clinically, and found no significant difference in 5-year melanoma-specific survival.

If your surgeon proposes a smaller margin than you expected, this evidence is why. Ask what margin is planned and what thickness it is based on.

Sentinel lymph node biopsy maps the first node your tumor drains into and removes it for examination. It is done at the same operation as the wide excision.

Its purpose is staging rather than treatment. A positive sentinel node moves you into stage III and opens the discussion about drug treatment after surgery. NCI notes one exception in the staging rules: a pathological N category is not required for T1 melanomas, where the clinical assessment is used instead.

Thickness drives the offer. Very thin lesions carry low enough node risk that the procedure adds little.

For melanoma that has reached lymph nodes, drug treatment after surgery is standard. NCI cites adjuvant pembrolizumab versus placebo in resected stage III melanoma, and adjuvant dabrafenib plus trametinib in stage III disease carrying a BRAF mutation.

The newer question is sequence. SWOG S1801 enrolled 313 patients with resectable stage IIIB to stage IV melanoma at 90 United States sites. One group had a short course of pembrolizumab by vein before surgery and then continued it afterwards. The other group had surgery first and the whole course afterwards. The total amount of drug was the same in both arms; only the order differed.

At a median follow-up of 15 months, event-free survival was 72% with the drug given first and 49% with surgery first. Toxicity around the operation did not rise.

NCI is careful about what this does and does not mean. Overall survival data were not yet available at the time of that report, and the FDA has not approved this sequence, pending a randomized phase III trial. Treat it as an evolving specialist strategy, offered at some centres and inside trials, rather than a settled regimen — and ask when the status you are being quoted was last checked.

Melanoma is sorted into four genomic subtypes: BRAF-altered, RAS-altered, NF1-altered, and triple wild-type, meaning none of BRAF, NRAS, HRAS, KRAS, or NF1.

Only the BRAF-altered group has FDA-approved targeted therapy. NCI notes that combining a BRAF inhibitor with a MEK inhibitor, such as dabrafenib plus trametinib or encorafenib plus binimetinib, improves outcomes over a BRAF inhibitor alone.

It also states the hard part plainly: virtually all patients eventually develop resistance and relapse. That is why clinical trials remain a live option even when a targeted drug is working. Ask whether your tumor was tested and which subtype it is.

CheckMate 067 compared nivolumab alone, nivolumab plus ipilimumab, and ipilimumab alone. In that population, 31.5% had BRAF variants, 36% had raised LDH, and 58% had M1c disease.

Median progression-free survival was 6.9 months with nivolumab, 11.5 months with the combination, and 2.9 months with ipilimumab alone. At 28 months, overall survival was 59%, 64%, and 45%. With a minimum follow-up of 36 months, the rates were 52%, 58%, and 34%.

Read the design note carefully. NCI states the trial was powered to compare the combination against ipilimumab, and nivolumab against ipilimumab, but was not powered to compare the combination against nivolumab alone. So the gap between 58% and 52% is not a proven difference. That matters, because the combination brings considerably more immune side effects.

Relatlimab, given as a fixed-dose combination with nivolumab, is a further approved option in untreated advanced disease.

Older treatment still appears in some discussions. NCI notes the FDA approved high-dose interleukin-2 in 1998 based on durable complete responses in only 6% to 7% of previously treated patients, and that no phase III trial has ever compared it with other treatments or shown an effect on overall survival.

Every checkpoint inhibitor here works by releasing brakes on the immune system, so the side effects are autoimmune rather than the usual chemotherapy pattern. They can start months after the last dose. Immune-related side effects covers the specific symptoms and how quickly to report them.

If your melanoma turns out to be a different skin cancer entirely, the plan changes. Merkel cell carcinoma is the one that outpaces melanoma for aggressiveness.

• A new lump appears under the skin near an old melanoma scar, or a lymph node becomes firm and fixed.
• A new cough or breathlessness develops, or a headache is worst in the morning or comes with vomiting.
• On immunotherapy, you have 4 or more loose stools a day above your normal, or blood in the stool.
• Your eyes or skin turn yellow, or urine turns dark.
• Your temperature reaches 100.4 degrees F (38 C). MedlinePlus, reviewed October 2024, uses 100.4 F; NCI's infection page, reviewed January 2020, uses 100.5 F. Use the lower, newer figure.

• https://www.cancer.gov/types/skin/hp/melanoma-treatment-pdq
• https://www.cancer.gov/types/skin/patient/melanoma-treatment-pdq
• https://www.cancer.gov/about-cancer/treatment/side-effects/infection
• https://medlineplus.gov/ency/patientinstructions/000913.htm