Cancer Expert MD

Melanoma is the most serious form of skin cancer, and in sunny places such as Florida it is especially common. In 2011, people whose melanoma had spread lived a median of about six and a half months. Today, half of those treated with combination immunotherapy are alive and free of death from melanoma 10 years later. And in 2026, a personalized mRNA vaccine became the first of its kind to succeed in a phase 3 trial. This article explains the warning signs, the tests every patient needs, the newest treatments, and the integrative evidence.

The Warning Signs

Most melanomas are found as a new or changing spot on the skin. Doctors use the ABCDE rule: Asymmetry, an irregular Border, uneven Color, a Diameter larger than a pencil eraser, and Evolving, meaning any change in size, shape or color. A spot that looks different from all the others on the body deserves a closer look.

The Tests Every Patient Needs

Thickness and ulceration. The depth of the melanoma, called the Breslow thickness, and whether the surface is broken are the most important early predictors of outcome.

Sentinel lymph node biopsy. For thicker melanomas, the first lymph node that drains the area is checked for spread.

BRAF testing. About half of skin melanomas carry a BRAF mutation, which can be treated with targeted pills such as dabrafenib with trametinib, or encorafenib with binimetinib. See our articles on tumor sequencing and liquid biopsy.

2026: A Personalized mRNA Vaccine

Intismeran is an mRNA vaccine made individually for each patient from the unique mutations in his or her own tumor, teaching the immune system to recognize that specific melanoma. In the phase 2b KEYNOTE-942 trial, adding it to pembrolizumab after surgery reduced the risk of recurrence or death by 49 percent at five years.¹

In the phase 3 INTerpath-001 trial of 1,137 patients whose stage IIB to IV melanoma had been completely removed, adding the vaccine to pembrolizumab reduced the risk of recurrence or death by 42 percent compared with pembrolizumab alone, and by 58 percent after the vaccine course was completed. It also reduced the risk of the cancer spreading to distant organs. It is the first personalized cancer vaccine, and the first mRNA cancer treatment, to succeed in a phase 3 trial. The detailed results are being presented this month at the European Society for Medical Oncology Congress, and overall survival is still being measured.²

Immunotherapy Before Surgery

For melanoma that has spread to visible lymph nodes, the Dutch NADINA trial, led by Christian Blank at the Netherlands Cancer Institute in Amsterdam, compared two doses of nivolumab with ipilimumab before surgery against the standard approach of surgery followed by a year of nivolumab. Among 423 patients, 83.7 percent of those treated before surgery were free of cancer events at one year, compared with 57.2 percent. In 59 percent, the response was so strong that no further treatment was needed after surgery.³ The benefit held at two years, and immunotherapy before surgery is now the standard for these patients.

Advanced Melanoma: Long-Term Survival

Combination immunotherapy. In the CheckMate 067 trial of 945 patients, nivolumab with ipilimumab produced a median overall survival of 71.9 months, and 52 percent were alive and free of death from melanoma at 10 years. Patients who were free of progression at three years had a 96 percent chance of being free of death from melanoma at 10 years.⁴

A newer combination. Relatlimab, which blocks a different immune brake called LAG-3, combined with nivolumab (Opdualag) more than doubled the time before the cancer progressed, 10.1 months compared with 4.6 months with nivolumab alone.⁵

TIL therapy. When immunotherapy stops working, immune cells taken from the patient’s own tumor can be multiplied and returned. In a Dutch-Danish trial of 168 patients, TIL therapy more than doubled the time before progression, 7.2 months compared with 3.1 months with ipilimumab.⁶ A version called lifileucel (Amtagvi) is approved in the United States.

See our article on how immunotherapy works.

Integrative Evidence in Melanoma

Vitamin D. In the Belgian ViDMe trial of 436 patients, a large monthly dose of vitamin D after surgery was safe but did not reduce recurrence.⁷ Large monthly doses have generally failed in cancer trials, while daily dosing has shown more benefit. In a Polish study of 200 patients on immunotherapy, those with normal vitamin D levels responded more often, 56 percent compared with 36 percent.⁸ See our article on vitamin D and cancer.

Fiber and gut bacteria. In a study of 128 melanoma patients at MD Anderson Cancer Center, those who ate enough dietary fiber lived longer without progression on immunotherapy, while over-the-counter probiotic supplements did not help.⁹ Antibiotics around the start of immunotherapy have been linked to worse results.

Skin checks for life. People who have had one melanoma are at higher risk of another, so regular full-skin examinations and sun protection continue after treatment.

How Cancer Expert MD Helps

Cancer Expert MD specializes in education and consultation for people with Stage IV and metastatic cancer. Our guide to what to do when treatment stops working explains re-testing and the next steps, and our book, The New Reality of Cancer, covers testing and treatment across all cancers.

Frequently Asked Questions

What is the new melanoma vaccine?

Intismeran is an mRNA vaccine made from the mutations in each patient’s own tumor. Given with pembrolizumab after surgery, it reduced the risk of recurrence or death by 42 percent in a 2026 phase 3 trial.

Should every melanoma be tested for BRAF?

Every melanoma that has spread or is at high risk of returning should be. About half carry a BRAF mutation, which can be treated with targeted pills.

Is immunotherapy before surgery better?

For melanoma in visible lymph nodes, yes. In the Dutch NADINA trial, it kept 83.7 percent of patients free of cancer events at one year, compared with 57.2 percent with surgery first.

Does vitamin D help melanoma?

Large monthly doses did not prevent recurrence in a Belgian trial, but normal vitamin D levels were linked to better responses to immunotherapy in a Polish study.

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More articles on cancer types and all articles.

References

1. Weber JS, Carlino MS, Khattak A, et al. Individualised neoantigen therapy mRNA-4157 (V940) plus pembrolizumab versus pembrolizumab monotherapy in resected melanoma (KEYNOTE-942): a randomised, phase 2b study. The Lancet. 2024;403(10427):632–644; five-year update, ASCO Annual Meeting 2026.
2. Intismeran autogene plus pembrolizumab versus pembrolizumab alone in completely resected stage IIB–IV melanoma: phase 3 INTerpath-001 trial. European Society for Medical Oncology (ESMO) Congress 2026, Presidential Symposium.
3. Blank CU, Lucas MW, Scolyer RA, et al. Neoadjuvant nivolumab and ipilimumab in resectable stage III melanoma (NADINA). New England Journal of Medicine. 2024;391(18):1696–1708.
4. Wolchok JD, Chiarion-Sileni V, Rutkowski P, et al. Final, 10-year outcomes with nivolumab plus ipilimumab in advanced melanoma. New England Journal of Medicine. 2025;392(1):11–22.
5. Tawbi HA, Schadendorf D, Lipson EJ, et al. Relatlimab and nivolumab versus nivolumab in untreated advanced melanoma. New England Journal of Medicine. 2022;386(1):24–34.
6. Rohaan MW, Borch TH, van den Berg JH, et al. Tumor-infiltrating lymphocyte therapy or ipilimumab in advanced melanoma. New England Journal of Medicine. 2022;387(23):2113–2125.
7. De Smedt J, et al. High-dose vitamin D supplementation does not improve outcome in a cutaneous melanoma population: results of a randomized double-blind placebo-controlled study (ViDMe trial). 2024.
8. Galus Ł, Michalak M, Lorenz M, et al. Vitamin D supplementation increases objective response rate and prolongs progression-free time in patients with advanced melanoma undergoing anti–PD-1 therapy. Cancer. 2023;129(13):2047–2055.
9. Spencer CN, McQuade JL, Gopalakrishnan V, et al. Dietary fiber and probiotics influence the gut microbiome and melanoma immunotherapy response. Science. 2021;374(6575):1632–1640.

This article is for education only. It is not medical advice and does not diagnose or treat any condition. Cancer Expert MD has no financial relationship with any laboratory, drug maker, supplement company, clinic or hospital.