cancersCancer

Melanoma

The cancer that proved immunotherapy works: half of advanced patients now live 10 years. Also the first with an approved TIL therapy, an oncolytic virus, and a positive phase 3 personalised vaccine.

Melanoma arises from pigment cells and is the deadliest skin cancer, though most cases are cured by excision when found early. Risk is driven by ultraviolet exposure and fair skin; the tumour carries the highest mutation burden of any common cancer, which is why it became the proving ground for immunotherapy. About half of cutaneous melanomas carry BRAF V600 mutations, a quarter NRAS, and acral and mucosal subtypes carry KIT alterations; uveal melanoma is a distinct disease driven by GNAQ/GNA11 and BAP1.

The treatment revolution began in 2011 with ipilimumab and vemurafenib and accelerated with PD-1 blockade (2014). Nivolumab-ipilimumab now delivers ~50% melanoma-specific survival at ten years in advanced disease (CheckMate 067), pembrolizumab 34% overall survival at ten years (KEYNOTE-006), and nivolumab-relatlimab offers a gentler doublet. For BRAF-mutant disease, DREAMseq settled that immunotherapy should come first. In resectable stage III disease, NADINA and SWOG S1801 moved immunotherapy to before surgery with response-adapted follow-on treatment, and adjuvant PD-1 or BRAF/MEK covers stage IIB-III. After immunotherapy fails, lifileucel TIL therapy (2024) and the oncolytic virus RP1 with nivolumab (2026) are approved; tebentafusp is the first survival-extending drug in metastatic uveal melanoma. Intismeran autogene plus pembrolizumab became the first personalised mRNA vaccine to pass a phase 3 in August 2026.

Open problems: roughly 40% of advanced patients never respond to immunotherapy, and second-line options after PD-1 failure remain limited; LAG-3 blockade failed as adjuvant therapy and with a different PD-1 partner; adjuvant treatment of stage II over-treats most patients; uveal, mucosal, and acral subtypes lag far behind; brain metastases affect up to half of advanced patients; and half the world's population lacks the HLA type required by the T-cell-receptor drugs.

State of the art today

First cell therapy for a solid tumour.
First positive phase 3 personalised vaccine.
About half of patients with advanced melanoma treated with nivolumab-ipilimumab are alive at ten years, and a third of those on pembrolizumab; durable remissions persist off treatment.
Neoadjuvant immunotherapy with response-adapted follow-on treatment (NADINA, SWOG S1801) is the new standard for resectable stage III disease and lets most patients skip a year of adjuvant therapy.
Sequencing is settled for BRAF-mutant disease: immunotherapy first, targeted therapy in reserve.
Post-PD-1 options now exist: TIL therapy, an oncolytic virus with nivolumab, and PRAME-directed T-cell engagers in phase 3.
The first personalised mRNA vaccine to pass a phase 3 (intismeran, August 2026) did so in melanoma.
Completion lymph node dissection has been abandoned after MSLT-II, sparing most stage III patients lymphoedema.

Show survival figures (1)

Averages across everyone diagnosed, often years ago. Your stage, subtype, age, fitness and the treatment you receive matter more than the average, and the numbers are improving quickly.

10-year survival ~50% with IO doublet.

Who it affects

Melanoma causes about 330,000 cases per year, and incidence is rising in fair-skinned populations.

Group

skin

Where the cases are

Cases by country · GLOBOCAN 2022

All countries →

Site: Melanoma of skin. World: 331,722 new cases, 58,667 deaths.

#	Country	New cases	Deaths	Incidence ASR
1	United States of America	101,388	7,368	16.5
2	Germany	21,976	3,303	12.1
3	United Kingdom	19,712	2,626	15.3
4	Australia	16,819	1,393	37.0
5	France (metropolitan)	15,729	2,087	13.5
6	Italy	13,769	2,463	12.7
7	Russian Federation	12,903	3,928	5.3
8	Canada	11,383	1,369	14.5
9	Brazil	9,676	2,273	3.3
10	China	8,789	5,385	0.4

Uveal and mucosal melanoma are not included.

Standard of care

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Stage II-III

Adjuvant pembrolizumab/nivolumab; neoadjuvant IO for resectable stage III.

NCCN Guidelines: Melanoma: Cutaneous

PembrolizumabNivolumabSentinel lymph node biopsy

Metastatic first line

Nivolumab-ipilimumab or nivolumab-relatlimab; BRAF/MEK if rapid control needed.

NCCN Guidelines: Melanoma: Cutaneous

CheckMate 067Relatlimab + nivolumabEncorafenib

After PD-1

Lifileucel, RP1 + nivolumab, ipilimumab-based, trials; tebentafusp (uveal).

NCCN Guidelines: Melanoma: Cutaneous

LifileucelVusolimogene oderparepvecTebentafusp

Screening and diagnosis

Dermoscopy, total-body photography for high-risk patients, excisional biopsy with Breslow thickness and ulceration reported; AI decision support emerging.

Dermoscopy, total-body photography & AI skin analysis Breslow thickness Ulceration (melanoma)

Stage I-II primary

Wide local excision with margins by thickness (1-2 cm); sentinel lymph node biopsy from ~0.8 mm Breslow or with ulceration; nodal ultrasound surveillance rather than completion dissection if positive (MSLT-II).

NCCN · Category 1 for SLNB thresholds

Sentinel lymph node biopsy MSLT-II Ultrasound

Stage IIB-IIC (thick or ulcerated, node-negative)

Adjuvant pembrolizumab or nivolumab for one year (KEYNOTE-716, CheckMate 76K); discuss modest absolute benefit and irAE risk; ctDNA-guided trials.

NCCN · 2AESMO-MCBS · A

KEYNOTE-716PembrolizumabNivolumab

Resectable stage III (macroscopic nodes)

Neoadjuvant ipilimumab + nivolumab (two cycles) then surgery with response-adapted adjuvant therapy (NADINA), or neoadjuvant pembrolizumab (SWOG S1801); alternative adjuvant-only PD-1 or, if BRAF-mutant, dabrafenib-trametinib.

NCCN · Preferred (neoadjuvant IO)

NADINA SWOG S1801 COMBI-AD Major pathological response (MPR)

Stage III after surgery (adjuvant)

Nivolumab or pembrolizumab for one year; dabrafenib-trametinib for BRAF V600 (COMBI-AD, 10-year RFS 48%); relatlimab adds nothing (RELATIVITY-098).

NCCN · 1ESMO-MCBS · A

COMBI-ADDabrafenib + trametinibRELATIVITY-098

Unresectable or metastatic, first line

Nivolumab + ipilimumab (highest long-term survival; ~59% grade 3-4 events) or nivolumab + relatlimab (Opdualag; ~21%) or anti-PD-1 alone; for BRAF-mutant disease, immunotherapy first (DREAMseq) unless rapid control is needed.

NCCN · 1 (preferred)ESMO-MCBS · 4-5

CheckMate 067 RELATIVITY-047 KEYNOTE-006 DREAMseq (ECOG-ACRIN EA6134)Immunotherapy first, then BRAF/MEK (BRAF-mutant melanoma)

BRAF V600-mutant, after immunotherapy or needing rapid response

BRAF + MEK doublet: encorafenib-binimetinib, dabrafenib-trametinib, or vemurafenib-cobimetinib; triplet with atezolizumab is approved but little used.

NCCN · 1

COLUMBUSEncorafenibBinimetinibVemurafenibCobimetinibBRAF inhibitor + MEK inhibitor

After anti-PD-1 failure

Lifileucel TIL therapy (accelerated approval 2024), RP1 oncolytic virus + nivolumab (2026), ipilimumab-based rechallenge, brenetafusp trials; clinical trials strongly encouraged.

NCCN · 2A

LifileucelC-144-01Vusolimogene oderparepvecPRISM-MEL-301Brenetafusp

Metastatic uveal melanoma (HLA-A*02:01-positive)

Tebentafusp (OS benefit, IMCgp100-202); liver-directed therapy for hepatic-dominant disease; ipilimumab-nivolumab has modest activity.

NCCN · 1

TebentafuspIMCgp100-202 HLA-A*02:01 restriction

Brain metastases

Nivolumab + ipilimumab for asymptomatic disease (~50% intracranial response, CheckMate 204); stereotactic radiosurgery; BRAF/MEK for symptomatic BRAF-mutant disease.

NivolumabIpilimumabSBRT / SABR (stereotactic radiotherapy)

Subtypes & biomarkers

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Subtypes

Superficial spreading (most common cutaneous)
Nodular
Lentigo maligna (chronically sun-damaged skin)
Acral lentiginous (palms, soles, nails; KIT/NRAS; not UV-driven)
Mucosal (KIT, low TMB, poor IO response)
Uveal (GNAQ/GNA11, BAP1; HLA-A*02 tebentafusp)
Desmoplastic (very high TMB, IO-sensitive)
BRAF V600-mutant (~50%)
NRAS-mutant (~25%)
Triple wild-type

Biomarkers clinicians test

BRAF V600
NRAS
KIT (acral/mucosal)
PD-L1 (weak)
TMB
HLA-A*02 :01 (tebentafusp)
Breslow thickness and ulceration (staging)
Sentinel node status
BRAF V600E/K (targeted therapy eligibility)
NRAS, KIT (subtype and trial eligibility)
HLA-A*02 :01 (tebentafusp, brenetafusp)
PRAME (diagnostic IHC; TCR target)
LDH (prognostic in stage IV)
ctDNA (investigational for MRD and response)
TMB and interferon signatures (research predictors of IO response)

Target prevalence in this cancer

Target / alteration	Prevalence	Measure	Source
gp100 (PMEL) HLA-A*02:01 required for tebentafusp	>90%	Melanocytic lineage antigen	Wikipedia
LAG-3 RELATIVITY-047 population	75-80%	LAG-3 >=1% on immune cells	Wikipedia
BRAF	45-50%	V600 mutation	cBioPortal (TCGA)
PD-1 Not an expression prevalence	30-40%	Objective response to PD-1 monotherapy (proxy)	Wikipedia
KIT	2-3%	KIT mutation (acral/mucosal enriched)	cBioPortal (TCGA)
CTLA-4	n/a	Immune-cell target; no tumour prevalence	Wikipedia
PRAME	~90%	IHC positivity in cutaneous melanoma	PMC

How common each drug target or alteration is in this cancer. Population-level and approximate; see the target page for detail. Full matrix.

History

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1975Dacarbazine: ~10% response, standard for 35 years
1992High-dose interleukin-2 produces rare durable cures
The first evidence that the immune system alone could eradicate metastatic melanoma.
Cytokines & engineered cytokines
2002BRAF V600E mutations discovered in ~50% of melanomas
Davies et al., Nature.
BRAF
2010Ipilimumab is the first drug to extend survival in metastatic melanoma
Hodi et al., NEJM.
Ipilimumab
2011Ipilimumab and vemurafenib approved
Ipilimumab
2011Ipilimumab and vemurafenib approved
Immunotherapy and targeted therapy arrive in the same year.
VemurafenibIpilimumab
2014PD-1 inhibitors approved
PembrolizumabNivolumab
2014Pembrolizumab and nivolumab approved; first BRAF/MEK combination (dabrafenib-trametinib)
PembrolizumabNivolumabDabrafenib + trametinib
2015T-VEC: first oncolytic virus
Talimogene laherparepvec
2015CheckMate 067 combination and KEYNOTE-006; T-VEC first oncolytic virus; cobimetinib
CheckMate 067 KEYNOTE-006Talimogene laherparepvecCobimetinib
2017COMBI-AD and CheckMate 238 establish adjuvant therapy for stage III; MSLT-II ends completion dissection
COMBI-AD MSLT-II
2018Encorafenib + binimetinib approved (COLUMBUS); Nobel Prize to Allison and Honjo
COLUMBUSEncorafenibBinimetinib
2021DREAMseq sets sequencing; KEYNOTE-716 extends adjuvant IO to stage II; tebentafusp phase 3 positive
DREAMseq (ECOG-ACRIN EA6134)KEYNOTE-716 IMCgp100-202
2022Nivolumab-relatlimab (Opdualag) approved; tebentafusp approved; SWOG S1801 shows neoadjuvant benefit
RELATIVITY-047Relatlimab + nivolumabTebentafuspSWOG S1801
2024Lifileucel: first TIL therapy
Lifileucel
2024NADINA neoadjuvant phase 3; lifileucel first TIL therapy; KEYNOTE-006 ten-year data; COMBI-AD ten-year data
NADINALifileucelC-144-01 KEYNOTE-006 COMBI-AD
2025RELATIVITY-098 adjuvant LAG-3 negative; CheckMate 067 ten-year survival ~50%
RELATIVITY-098 CheckMate 067
2026Intismeran phase 3 positive; RP1 approved
INTerpath-001 (V940-001)Vusolimogene oderparepvec
2026Intismeran autogene phase 3 positive; RP1 approved with nivolumab; fianlimab-cemiplimab phase 3 misses; brenetafusp phase 3 enrolling
INTerpath-001 (V940-001)Intismeran autogeneVusolimogene oderparepvecFianlimab + cemiplimab phase 3 (first-line melanoma)PRISM-MEL-301

Pipeline

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Phase 3Personalised mRNA neoantigen vaccine

Intismeran autogene

ApprovedOncolytic virus (HSV-1)

Vusolimogene oderparepvec · Tudriqev

ApprovedTIL cell therapy

Lifileucel · Amtagvi

ApprovedImmTAC (TCR×CD3 bispecific)

Tebentafusp · Kimmtrak

Phase 3ImmTAC (PRAME TCR × CD3 bispecific)

Brenetafusp

Phase 3Monoclonal antibody (anti-LAG-3)

Fianlimab

INTerpath-001 (V940-001)PRISM-MEL-301 PRAME ctDNA-guided adjuvant therapy in stage II-III melanoma TCR therapeutics for non-HLA-A*02 patients MRD / molecular residual disease testing Dermoscopy, total-body photography & AI skin analysis Neoadjuvant immunotherapy → response-adapted adjuvant Immuno-PET TCR-T cell therapy

Open problems

Primary IO resistance in ~40%.
Uveal and mucosal subtypes.
Brain metastases.
Primary resistance: about 40% of advanced patients never respond to PD-1-based therapy, and predictive biomarkers (PD-L1, TMB, interferon signatures) remain too weak to guide choices.
After PD-1 failure, response rates for approved options are ~30% at best; most patients still die of melanoma.
LAG-3 blockade is not a class effect: it failed as adjuvant therapy and with cemiplimab, so the biology of when it helps is unresolved.
Adjuvant therapy in stage IIB/IIC treats many to benefit few; ctDNA-guided selection is unproven.
Uveal, mucosal, and acral melanomas respond poorly to checkpoint inhibitors and have few targeted options.
Brain metastases occur in up to half of advanced patients; leptomeningeal disease is untreatable.
T-cell-receptor drugs require HLA-A*02:01, excluding most people of African and East Asian ancestry.
Long-term immune toxicity (endocrinopathies, arthritis) in cured patients is under-studied.

Trials

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Recruiting now (live from ClinicalTrials.gov)

Recruiting trials near you · live from ClinicalTrials.gov

Melanoma

condition: Melanoma

Open on ClinicalTrials.gov →

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Landmark trials in OnCo

C-144-01 CheckMate 067 COLUMBUS COMBI-AD DREAMseq (ECOG-ACRIN EA6134)Fianlimab + cemiplimab phase 3 (first-line melanoma)FMT plus pembrolizumab in anti-PD-1-refractory melanoma (Pittsburgh)IMCgp100-202 INTerpath-001 (V940-001)KEYNOTE-006 KEYNOTE-716 MIMic-01: healthy-donor FMT plus anti-PD-1, first-line melanoma MSLT-II NADINA PRISM-MEL-301 RELATIVITY-047 RELATIVITY-098 SWOG S1801

Expert centres

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Where the expertise is

Centres linked to this cancer in OnCo

Johns Hopkins Hospital / Sidney Kimmel Comprehensive Cancer CenterBaltimore, USNewsweek oncology #10NCI comprehensive
via Pembrolizumab
IEO – European Institute of OncologyMilan, ITNewsweek oncology #11
via Sentinel lymph node biopsy
Institut CurieParis, FRNewsweek oncology #21
via this cancer
Vall d'Hebron University Hospital / VHIOBarcelona, ESNewsweek oncology #28
via Encorafenib
Stanford Health Care / Stanford Cancer InstituteStanford, USNewsweek oncology #30NCI comprehensive
via SBRT / SABR (stereotactic radiotherapy)
Netherlands Cancer Institute (NKI-AvL)Amsterdam, NLNewsweek oncology #45
via this cancer, NADINA
Istituto Nazionale Tumori IRCCS Fondazione G. PascaleNaples, IT
via this cancer, Nivolumab, CheckMate 067, Relatlimab + nivolumab +1
West German Cancer Center (WTZ), University Hospital EssenEssen, DE
via this cancer, Nivolumab, CheckMate 067, Ipilimumab
Dartmouth Cancer CenterLebanon, NH, USNCI comprehensive
via this cancer, Nivolumab, Ipilimumab
Lausanne University Hospital (CHUV) / Ludwig Institute LausanneLausanne, CH
via this cancer, TCR-T cell therapy, Pembrolizumab
NCI Center for Cancer Research (intramural programme)Bethesda, MD, US
via this cancer, TCR-T cell therapy, Cytokines & engineered cytokines
Society of Surgical OncologyRosemont, IL, US
via this cancer, MSLT-II, Sentinel lymph node biopsy
SWOG Cancer Research NetworkPortland, OR, US
via this cancer, SWOG S1801, Nivolumab
Aarhus University HospitalAarhus, DK
via this cancer, SBRT / SABR (stereotactic radiotherapy)
Alliance for Clinical Trials in OncologyChicago, IL, US
via Pembrolizumab, Sentinel lymph node biopsy
Cancer Center Clínica Universidad de Navarra / CIMAPamplona, ES
via this cancer, MRD / molecular residual disease testing
Cancer Research UK Manchester InstituteManchester, GB
via this cancer, MRD / molecular residual disease testing
Comprehensive Cancer Center Tübingen-StuttgartTübingen, DE
via this cancer, TCR-T cell therapy
ECOG-ACRIN Cancer Research GroupPhiladelphia, PA, US
via this cancer, DREAMseq (ECOG-ACRIN EA6134)
Hadassah Medical CenterJerusalem, IL
via this cancer, SBRT / SABR (stereotactic radiotherapy)
IUCT Oncopole – Institut Universitaire du Cancer de ToulouseToulouse, FR
via this cancer, MRD / molecular residual disease testing
Kyoto University HospitalKyoto, JP
via this cancer, Nivolumab
Laura and Isaac Perlmutter Cancer Center at NYU Langone HealthNew York, NY, USNCI comprehensive
via this cancer, Nivolumab
Max Delbrück Center for Molecular MedicineBerlin, DE
via this cancer, TCR-T cell therapy
Moffitt Cancer CenterTampa, FL, USNCI comprehensive
via this cancer, Lifileucel
National Cancer Center Hospital EastKashiwa, Chiba, JP
via MRD / molecular residual disease testing, Nivolumab
Olivia Newton-John Cancer Wellness and Research CentreMelbourne, AU
via this cancer, Immuno-PET
Oslo University Hospital – The Norwegian Radium HospitalOslo, NO
via this cancer, TCR-T cell therapy
Oxford Cancer – Oxford University Hospitals and University of OxfordOxford, GB
via this cancer, Tebentafusp
QIMR Berghofer Medical Research InstituteBrisbane, AU
via this cancer, TCR-T cell therapy
University Hospital Zurich / Comprehensive Cancer Center ZurichZurich, CH
via this cancer, Talimogene laherparepvec
University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer CenterBaltimore, MD, USNCI comprehensive
via TCR-T cell therapy, SBRT / SABR (stereotactic radiotherapy)
UPMC Hillman Cancer CenterPittsburgh, PA, USNCI comprehensive
via this cancer, Relatlimab + nivolumab
Wellcome Sanger InstituteHinxton, GB
via this cancer, BRAF
A.C. Camargo Cancer CenterSão Paulo, BR
via this cancer
Advanced Centre for Treatment, Research and Education in CancerNavi Mumbai, IN
via Nivolumab
American Society for Radiation OncologyArlington, VA, US
via SBRT / SABR (stereotactic radiotherapy)
American Society of HematologyWashington, DC, US
via MRD / molecular residual disease testing
Apollo Hospitals (Apollo Cancer Centres)Chennai, IN
via SBRT / SABR (stereotactic radiotherapy)
Atrium Health Wake Forest Baptist Comprehensive Cancer CenterWinston-Salem, NC, USNCI comprehensive
via SBRT / SABR (stereotactic radiotherapy)
Auckland City Hospital / Te Pūriri o Te Ora Cancer and Blood ServiceAuckland, NZ
via this cancer
Australasian Gastro-Intestinal Trials GroupSydney, AU
via MRD / molecular residual disease testing
Canadian Cancer Trials Group (CCTG)Kingston, ON, CA
via SBRT / SABR (stereotactic radiotherapy)
Cancer Council AustraliaSydney, AU
via this cancer
Cancer Research UK Cambridge Centre / CRUK Cambridge InstituteCambridge, GB
via MRD / molecular residual disease testing
Centre Antoine LacassagneNice, FR
via this cancer
Centre hospitalier de l'Université de Montréal (CHUM)Montréal, QC, CA
via this cancer
Centre Léon BérardLyon, FR
via this cancer
Centre Oscar LambretLille, FR
via SBRT / SABR (stereotactic radiotherapy)
Centro Nacional de Investigaciones Oncológicas (CNIO)Madrid, ES
via this cancer
Champalimaud Foundation – Champalimaud Clinical CentreLisbon, PT
via SBRT / SABR (stereotactic radiotherapy)
Children's Cancer and Leukaemia GroupLeicester, GB
via MRD / molecular residual disease testing
Children's Cancer Hospital Egypt 57357Cairo, EG
via MRD / molecular residual disease testing
Chris O'Brien LifehouseSydney, AU
via this cancer
Comprehensive Cancer Center Freiburg (CCCF)Freiburg im Breisgau, DE
via SBRT / SABR (stereotactic radiotherapy)
David H. Koch Institute for Integrative Cancer Research at MITCambridge, MA, USNCI basic
via Cytokines & engineered cytokines
European Hematology AssociationThe Hague, NL
via MRD / molecular residual disease testing
European Society for Radiotherapy and OncologyBrussels, BE
via SBRT / SABR (stereotactic radiotherapy)
European Society of Surgical OncologyBrussels, BE
via Sentinel lymph node biopsy
FDA Oncology Center of ExcellenceSilver Spring, MD, US
via MRD / molecular residual disease testing
Fundación Arturo López PérezSantiago, CL
via SBRT / SABR (stereotactic radiotherapy)
Geneva University Hospitals (HUG)Geneva, CH
via this cancer
German Hodgkin Study GroupCologne, DE
via Nivolumab
Ghent University Hospital / Cancer Research Institute GhentGhent, BE
via this cancer
GIMEMARome, IT
via MRD / molecular residual disease testing
GOG FoundationPhiladelphia, PA, US
via Pembrolizumab
Hacettepe University Cancer InstituteAnkara, TR
via SBRT / SABR (stereotactic radiotherapy)
Harold C. Simmons Comprehensive Cancer Center, UT SouthwesternDallas, TX, USNCI comprehensive
via SBRT / SABR (stereotactic radiotherapy)
HealthCare Global EnterprisesBengaluru, IN
via SBRT / SABR (stereotactic radiotherapy)
Hokkaido University HospitalSapporo, JP
via SBRT / SABR (stereotactic radiotherapy)
Hospital de Amor (Barretos Cancer Hospital)Barretos, BR
via this cancer
Hospital Universitari i Politècnic La FeValencia, ES
via SBRT / SABR (stereotactic radiotherapy)
Hospital Universitario 12 de OctubreMadrid, ES
via MRD / molecular residual disease testing
HOVONRotterdam, NL
via MRD / molecular residual disease testing
Huntsman Cancer Institute, University of UtahSalt Lake City, UT, USNCI comprehensive
via this cancer
INCLIVA Biomedical Research Institute / Hospital Clínico Universitario de ValenciaValencia, ES
via MRD / molecular residual disease testing
Institut Jules BordetBrussels, BE
via Pembrolizumab
Institute of Oncology LjubljanaLjubljana, SI
via this cancer
IRCCS Humanitas Research HospitalRozzano (Milan), IT
via SBRT / SABR (stereotactic radiotherapy)
IRCCS Ospedale San RaffaeleMilan, IT
via TCR-T cell therapy
IRCCS Regina Elena National Cancer InstituteRome, IT
via this cancer
Istituto Oncologico Veneto IRCCSPadua, IT
via this cancer
Keio University HospitalTokyo, JP
via Sentinel lymph node biopsy
Koo Foundation Sun Yat-Sen Cancer CenterTaipei, TW
via SBRT / SABR (stereotactic radiotherapy)
Leeds Cancer Centre, St James's University HospitalLeeds, GB
via this cancer
Leiden University Medical CenterLeiden, NL
via this cancer
Maria Skłodowska-Curie National Research Institute of OncologyWarsaw, PL
via this cancer
Masaryk Memorial Cancer InstituteBrno, CZ
via this cancer
National Cancer Institute (NIH)Bethesda, MD, US
via TCR-T cell therapy
National Institute of Oncology, HungaryBudapest, HU
via this cancer
NSABP FoundationPittsburgh, PA, US
via Sentinel lymph node biopsy
Peking University Cancer HospitalBeijing, CN
via this cancer
Rajiv Gandhi Cancer Institute and Research CentreNew Delhi, IN
via SBRT / SABR (stereotactic radiotherapy)
Rigshospitalet – Copenhagen University HospitalCopenhagen, DK
via this cancer
Rosalind and Morris Goodman Cancer Institute, McGill UniversityMontréal, QC, CA
via this cancer
Rutgers Cancer Institute of New JerseyNew Brunswick, NJ, USNCI comprehensive
via TCR-T cell therapy
Sahlgrenska University Hospital / Sahlgrenska Center for Cancer ResearchGothenburg, SE
via this cancer
Shandong Cancer Hospital and InstituteJinan, CN
via SBRT / SABR (stereotactic radiotherapy)
Sheba Medical CenterRamat Gan, IL
via this cancer
Skåne University Hospital / Lund University Cancer CentreLund, SE
via this cancer
Sunnybrook Odette Cancer CentreToronto, ON, CA
via SBRT / SABR (stereotactic radiotherapy)
Sydney Children's Hospitals Network / Children's Cancer InstituteSydney, AU
via MRD / molecular residual disease testing
Sylvester Comprehensive Cancer Center, University of MiamiMiami, FL, USNCI clinical
via MRD / molecular residual disease testing
The Wistar InstitutePhiladelphia, PA, USNCI basic
via this cancer
TROG Cancer ResearchNewcastle, NSW, AU
via SBRT / SABR (stereotactic radiotherapy)
UCLA Jonsson Comprehensive Cancer CenterLos Angeles, USNCI comprehensive
via this cancer
UMC Utrecht Cancer CenterUtrecht, NL
via SBRT / SABR (stereotactic radiotherapy)
University Cancer Center Mainz (UCT Mainz) / Universitätsmedizin MainzMainz, DE
via this cancer
University of Arizona Cancer CenterTucson, AZ, USNCI comprehensive
via this cancer
UVA Comprehensive Cancer CenterCharlottesville, VA, USNCI comprehensive
via this cancer
UZ Leuven / Leuven Cancer InstituteLeuven, BE
via this cancer
Vanderbilt-Ingram Cancer CenterNashville, TN, USNCI comprehensive
via this cancer
Velindre Cancer CentreCardiff, GB
via SBRT / SABR (stereotactic radiotherapy)
Weizmann Institute of ScienceRehovot, IL
via this cancer

Seeking a second opinion: ask your oncologist for a referral to a high-volume centre; most accept records and pathology by mail or telehealth. In the US, use the NCI's Find a Cancer Center tool or the nonprofit Cancer Commons, which navigates options for advanced cancers at no cost.

Questions to ask

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Bring to your appointment

Questions to ask your oncologist about Melanoma

Generated from this cancer's standard of care, biomarkers, and pipeline · 40 questions

Newly diagnosed

What is my exact diagnosis, stage, and grade, and which tests established them?
Why: Everything else follows from an accurate stage and subtype.
Which biomarkers have been tested on my tumour (for example BRAF V600, NRAS, KIT, PD-L1, TMB), and what were the results?
Why: These results decide eligibility for targeted therapy, immunotherapy, and trials.
Which subtype is my cancer, and does that change the recommended treatment?
Why: Recognised subtypes for this cancer include Superficial spreading, Nodular, Lentigo maligna.
Is germline (inherited) genetic testing recommended for me or my family?
Why: Inherited variants can change treatment and matter for relatives.

Stage II-III

For my situation (stage ii-iii), which of the standard options do you recommend and why?
Why: Guideline options include: Adjuvant pembrolizumab/nivolumab; neoadjuvant IO for resectable stage III.
Am I a candidate for Pembrolizumab, Nivolumab, and what side effects should I expect?
Why: Knowing the expected toxicities helps you plan work, family, and supportive care.

Metastatic first line

For my situation (metastatic first line), which of the standard options do you recommend and why?
Why: Guideline options include: Nivolumab-ipilimumab or nivolumab-relatlimab; BRAF/MEK if rapid control needed.
Am I a candidate for Relatlimab + nivolumab, Encorafenib, and what side effects should I expect?
Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
How do the results of CheckMate 067 apply to someone like me?
Why: Trial populations differ from individual patients; ask how closely you match.

After PD-1

For my situation (after pd-1), which of the standard options do you recommend and why?
Why: Guideline options include: Lifileucel, RP1 + nivolumab, ipilimumab-based, trials; tebentafusp (uveal).
Am I a candidate for Lifileucel, Vusolimogene oderparepvec, Tebentafusp, and what side effects should I expect?
Why: Knowing the expected toxicities helps you plan work, family, and supportive care.

Screening and diagnosis

For my situation (screening and diagnosis), which of the standard options do you recommend and why?
Why: Guideline options include: Dermoscopy, total-body photography for high-risk patients, excisional biopsy with Breslow thickness and ulceration reported; AI decision support emerging.

Stage I-II primary

For my situation (stage i-ii primary), which of the standard options do you recommend and why?
Why: Guideline options include: Wide local excision with margins by thickness (1-2 cm); sentinel lymph node biopsy from ~0.8 mm Breslow or with ulceration; nodal ultrasound surveillance rather than completion dissection if positive (MSLT-II).
How do the results of MSLT-II apply to someone like me?
Why: Trial populations differ from individual patients; ask how closely you match.

Stage IIB-IIC (thick or ulcerated, node-negative)

For my situation (stage iib-iic (thick or ulcerated, node-negative)), which of the standard options do you recommend and why?
Why: Guideline options include: Adjuvant pembrolizumab or nivolumab for one year (KEYNOTE-716, CheckMate 76K); discuss modest absolute benefit and irAE risk; ctDNA-guided trials.
Am I a candidate for Pembrolizumab, Nivolumab, and what side effects should I expect?
Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
How do the results of KEYNOTE-716 apply to someone like me?
Why: Trial populations differ from individual patients; ask how closely you match.

Resectable stage III (macroscopic nodes)

For my situation (resectable stage iii (macroscopic nodes)), which of the standard options do you recommend and why?
Why: Guideline options include: Neoadjuvant ipilimumab + nivolumab (two cycles) then surgery with response-adapted adjuvant therapy (NADINA), or neoadjuvant pembrolizumab (SWOG S1801); alternative adjuvant-only PD-1 or, if BRAF-mutant, dabrafenib-trametinib.
How do the results of NADINA and SWOG S1801 apply to someone like me?
Why: Trial populations differ from individual patients; ask how closely you match.

Stage III after surgery (adjuvant)

For my situation (stage iii after surgery (adjuvant)), which of the standard options do you recommend and why?
Why: Guideline options include: Nivolumab or pembrolizumab for one year; dabrafenib-trametinib for BRAF V600 (COMBI-AD, 10-year RFS 48%); relatlimab adds nothing (RELATIVITY-098).
Am I a candidate for Dabrafenib + trametinib, and what side effects should I expect?
Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
How do the results of COMBI-AD and RELATIVITY-098 apply to someone like me?
Why: Trial populations differ from individual patients; ask how closely you match.

Unresectable or metastatic, first line

For my situation (unresectable or metastatic, first line), which of the standard options do you recommend and why?
Why: Guideline options include: Nivolumab + ipilimumab (highest long-term survival; ~59% grade 3-4 events) or nivolumab + relatlimab (Opdualag; ~21%) or anti-PD-1 alone; for BRAF-mutant disease, immunotherapy first (DREAMseq) unless rapid control is needed.
How do the results of CheckMate 067 and RELATIVITY-047 apply to someone like me?
Why: Trial populations differ from individual patients; ask how closely you match.

BRAF V600-mutant, after immunotherapy or needing rapid response

For my situation (braf v600-mutant, after immunotherapy or needing rapid response), which of the standard options do you recommend and why?
Why: Guideline options include: BRAF + MEK doublet: encorafenib-binimetinib, dabrafenib-trametinib, or vemurafenib-cobimetinib; triplet with atezolizumab is approved but little used.
Am I a candidate for Encorafenib, Binimetinib, Vemurafenib or related drugs, and what side effects should I expect?
Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
How do the results of COLUMBUS apply to someone like me?
Why: Trial populations differ from individual patients; ask how closely you match.

After anti-PD-1 failure

For my situation (after anti-pd-1 failure), which of the standard options do you recommend and why?
Why: Guideline options include: Lifileucel TIL therapy (accelerated approval 2024), RP1 oncolytic virus + nivolumab (2026), ipilimumab-based rechallenge, brenetafusp trials; clinical trials strongly encouraged.
Am I a candidate for Lifileucel, Vusolimogene oderparepvec, Brenetafusp, and what side effects should I expect?
Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
How do the results of C-144-01 and PRISM-MEL-301 apply to someone like me?
Why: Trial populations differ from individual patients; ask how closely you match.

Metastatic uveal melanoma (HLA-A*02:01-positive)

For my situation (metastatic uveal melanoma (hla-a*02:01-positive)), which of the standard options do you recommend and why?
Why: Guideline options include: Tebentafusp (OS benefit, IMCgp100-202); liver-directed therapy for hepatic-dominant disease; ipilimumab-nivolumab has modest activity.
Am I a candidate for Tebentafusp, and what side effects should I expect?
Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
How do the results of IMCgp100-202 apply to someone like me?
Why: Trial populations differ from individual patients; ask how closely you match.

Brain metastases

For my situation (brain metastases), which of the standard options do you recommend and why?
Why: Guideline options include: Nivolumab + ipilimumab for asymptomatic disease (~50% intracranial response, CheckMate 204); stereotactic radiosurgery; BRAF/MEK for symptomatic BRAF-mutant disease.
Am I a candidate for Nivolumab, Ipilimumab, and what side effects should I expect?
Why: Knowing the expected toxicities helps you plan work, family, and supportive care.

Any stage

Are there clinical trials I could join, for example of Intismeran autogene, Vusolimogene oderparepvec, Lifileucel, Tebentafusp?
Why: Trials are how the next standard of care is set; asking early keeps options open.
Would a second opinion at a high-volume centre change anything, and can you help arrange it?
Why: Rare or high-stakes decisions benefit from a centre that treats many similar patients.
What supportive care (symptom control, nutrition, exercise, mental health, financial help) is available from the start?
Why: Supportive care improves quality of life and helps patients complete treatment.
I read that “Primary IO resistance in ~40%”. How does that affect my plan?
Why: Open problems are where trials and second opinions matter most.
I read that “Uveal and mucosal subtypes”. How does that affect my plan?
Why: Open problems are where trials and second opinions matter most.

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Everything relevant

279top

Direct links plus the targets, companies, and technologies of this cancer's products.

technologies

trials

pairings

BRAF inhibitor + MEK inhibitor Caution: LAG-3 blockade outside active disease Immunotherapy first, then BRAF/MEK (BRAF-mutant melanoma)Neoadjuvant immunotherapy → response-adapted adjuvant Oncolytic virus + PD-1 blockade PD-1 failure → TIL therapy Personalised neoantigen vaccine + PD-1 blockade

roadmaps

Immunotherapy roadmap: Coley's toxins → checkpoint inhibitors → engineered immunity

ideas

A multi-cancer platform trial of adaptive (dose-holiday) therapy A ring-fenced metastasis programme with metastasis-specific endpoints A standard platform to get drugs into the brain: focused ultrasound plus shuttle-engineered therapeutics An organotropism atlas that predicts where a cancer will spread Ban commercial sunbeds Biopsy the one lesion that is growing while the others shrink Brain metastases included by default in every solid-tumour trial Build a human model of the barrier that guards the brain fluid Capture diet, fibre and antibiotic exposure in every immunotherapy pivotal trial CD8 PET to stop or switch immunotherapy early ctDNA-guided adjuvant therapy in stage II-III melanoma De-acidify the tumour so T cells can work in it Eradicate dormant cancer cells: a programme to wake and kill or lock asleep disseminated cells Evolution-guided 'adaptive therapy' dosing tested in randomised phase 2 trials Extended-interval immunotherapy: give checkpoint inhibitors every 8-12 weeks once stable Give immunotherapy in the morning Grow immune command posts inside tumours Judge skin cancer AI by the thick melanomas it prevents, not the thin ones it finds Kill drug-tolerant persisters through ferroptosis Let adolescents from age 12 into adult trials when the cancer biology is the same Microbiome transplant as a routine immunotherapy adjunct Oncolytic viruses that make interleukin-12 only inside the tumour Pause a failed drug so the tumour becomes sensitive to it again Personalised cancer vaccines at commodity cost through fully automated manufacturing Personalised vaccines given only when the blood test turns positive Pre-surgery platform trials that test combinations on pathological response in months Protect the gut flora of patients about to start immunotherapy Randomise a cheap antihistamine alongside immunotherapy Randomised trials of stopping immunotherapy after one year versus continuing Select patients for cell therapy by whether their tumour holds reactive T cells Shared splice-derived neoantigens as off-the-shelf vaccine targets Starve the survivors: target the energy pathway drug-tolerant cells switch to Switch drugs at maximum response, not at relapse Take faecal transplant plus immunotherapy to a definitive trial TCR therapeutics for non-HLA-A*02 patients Test a high-fibre diet as an immunotherapy adjunct Test intermittent dosing of targeted drugs to delay resistance, with honest priors Test protein and resistance training during immunotherapy Time immunotherapy to the moment targeted drugs make tumours visible Treat brain metastases as a disease with its own trials programme Treat immunotherapy side-effects without wiping out the response Treat the draining lymph node before removing it Use a blood test at six weeks to decide whether to keep going Use pre-surgery immunotherapy windows as the field's biomarker engine Watch the immune system's response in the blood three weeks in

collections

Melanoma Research Alliance (MRA)

bottlenecks

Acquired resistance to every therapy AI that is built but not validated or deployed Manufacturing cost and time for living and radioactive medicines Metastasis is understood least and studied last No one can predict who responds to immunotherapy Prevention we already have is not deployed Surgery and radiotherapy cure most, get least The brain: barrier and sanctuary Too many combinations to test

key papers

ASCO 2021 guideline: how to recognise and manage the immune-related side effects of checkpoint inhibitors C-144-01: lifileucel, tumour-infiltrating lymphocytes grown from a patient's own tumour, in melanoma after checkpoint inhibitors have failed CheckMate 067 at ten years: half of melanoma patients treated with nivolumab plus ipilimumab were alive a decade later CheckMate 067 at ten years: nivolumab plus ipilimumab produces long-term survival in half of patients with advanced melanoma Hodi 2010: ipilimumab, the first checkpoint inhibitor, extends survival in metastatic melanoma KEYNOTE-942: a personalised mRNA cancer vaccine plus pembrolizumab after melanoma surgery Leach, Krummel and Allison: releasing the CTLA-4 brake makes mice reject tumours NADINA: two doses of ipilimumab plus nivolumab before surgery beat a year of nivolumab after surgery in stage III melanoma RELATIVITY-047: relatlimab plus nivolumab, the first LAG-3 checkpoint combination, in untreated advanced melanoma Rohaas 2022: the first randomised trial of TIL therapy, against ipilimumab, in advanced melanoma Rojas 2023: a personalised mRNA vaccine trained T cells against each patient's pancreatic cancer, and those who responded stayed cancer-free longer Topalian 2012: the first large trial of a PD-1 antibody shows durable responses across melanoma, lung and kidney cancer

Key papers

12top

rctNew England Journal of Medicine 2025changed practice

CheckMate 067 at ten years: half of melanoma patients treated with nivolumab plus ipilimumab were alive a decade later

Before 2011 median survival in metastatic melanoma was under a year; this trial shows that roughly half of patients treated with combination checkpoint blockade are now long-term survivors, effectively cured. It anchors first-line treatment of advanced melanoma and sets the benchmark for every new regimen, including nivolumab-relatlimab. The combination's toxicity means nivolumab alone or newer doublets remain reasonable for some patients.

rctNew England Journal of Medicine 2025changed practice

CheckMate 067 at ten years: nivolumab plus ipilimumab produces long-term survival in half of patients with advanced melanoma

For patients with advanced melanoma, immunotherapy offers a realistic chance of long-term survival and probably cure, and the ten-year data show that patients who are alive and progression-free at three years rarely die of melanoma afterwards. Nivolumab plus ipilimumab gives the best long-term results but at a high price in serious side effects; nivolumab alone or nivolumab plus relatlimab are alternatives for patients at lower risk or with autoimmune concerns. The trial is also a caution about surrogate endpoints: the survival plateau took years to become visible.

rctThe Lancet 2024

KEYNOTE-942: a personalised mRNA cancer vaccine plus pembrolizumab after melanoma surgery

For the first time a randomised trial suggests that a vaccine tailored to an individual's tumour can reduce relapse when combined with immunotherapy, which is a proof of concept for a field that had failed for decades. Nothing changes for patients yet: the trial was small, the confidence interval crossed one, and the phase 3 trial in melanoma (and parallel trials in lung and other cancers) must confirm it. If it does, personalised mRNA vaccines could become a routine adjunct to checkpoint inhibitors after surgery.

rctNew England Journal of Medicine 2024changed practice

NADINA: two doses of ipilimumab plus nivolumab before surgery beat a year of nivolumab after surgery in stage III melanoma

Patients with melanoma that has spread to palpable lymph nodes should now be offered immunotherapy before rather than only after surgery: two cycles of low-dose ipilimumab with nivolumab, then surgery, with the pathology result deciding whether any more treatment is needed. Most patients respond well and are spared a year of adjuvant therapy. Serious side effects are more common than with nivolumab alone, mostly endocrine, and the approach requires close coordination between oncologists, surgeons and pathologists.

translationalNature 2023

Rojas 2023: a personalised mRNA vaccine trained T cells against each patient's pancreatic cancer, and those who responded stayed cancer-free longer

Pancreatic cancer was thought to be immunologically inert because of its low mutation burden; this study showed that with the right vaccine platform its few neoantigens can still be targeted. It is the strongest human evidence so far that personalised cancer vaccines can generate durable, tumour-specific immunity, and it justifies the randomised trials now running in pancreatic cancer and melanoma. Benefit is not yet proven, because responders may simply have had more immunogenic tumours.

rctNew England Journal of Medicine 2022changed practice

RELATIVITY-047: relatlimab plus nivolumab, the first LAG-3 checkpoint combination, in untreated advanced melanoma

Patients with newly diagnosed advanced melanoma have a dual-checkpoint option that improves on nivolumab alone with only a modest increase in serious side effects, making it attractive for those unable to tolerate or unwilling to risk the toxicity of ipilimumab. It did not prove superior survival, and it has not been compared with nivolumab plus ipilimumab, which remains preferred for patients with brain metastases or other high-risk features. LAG-3 is now an established target under study in many other cancers.

rctNew England Journal of Medicine 2022changed practice

Rohaas 2022: the first randomised trial of TIL therapy, against ipilimumab, in advanced melanoma

This trial supplied the randomised proof that was missing for TIL therapy and showed academic centres can run cell-therapy phase 3 trials without industry. It supports TIL as a standard option after checkpoint inhibitor failure in melanoma and underpinned reimbursement in the Netherlands. The comparator, ipilimumab, is itself only modestly effective in this setting, and overall survival did not differ significantly.

guidelineJournal of Clinical Oncology 2021changed practice

ASCO 2021 guideline: how to recognise and manage the immune-related side effects of checkpoint inhibitors

Checkpoint inhibitors are now given to hundreds of thousands of patients a year, many in community clinics and emergency departments, so a common, explicit playbook for their autoimmune side effects saves lives. The guideline standardised when to stop, when to give steroids and when to escalate, and made multidisciplinary toxicity teams routine. It does not remove the judgement needed for rare events or for patients whose cancer is responding.

translationalJournal of Clinical Oncology 2021changed practice

C-144-01: lifileucel, tumour-infiltrating lymphocytes grown from a patient's own tumour, in melanoma after checkpoint inhibitors have failed

Lifileucel proved that Steven Rosenberg's decades-old TIL concept could be industrialised into a licensed product and gave patients with checkpoint-refractory melanoma, who otherwise have few options, a chance of durable remission. It is the first cell therapy approved for any solid tumour. The treatment requires surgery to harvest tumour, hospitalisation for lymphodepletion and IL-2, and specialised centres, so its reach is limited.

translationalNew England Journal of Medicine 2012changed practice

Topalian 2012: the first large trial of a PD-1 antibody shows durable responses across melanoma, lung and kidney cancer

This study is why PD-1 inhibitors were developed across cancers rather than in melanoma alone: unexpected activity in lung cancer, historically thought immune-resistant, changed drug development priorities industry-wide. It also introduced PD-L1 immunohistochemistry as a candidate biomarker and pneumonitis as a signature toxicity. Within five years PD-1 blockade was approved in more than ten cancers.

rctNew England Journal of Medicine 2010changed practice

Hodi 2010: ipilimumab, the first checkpoint inhibitor, extends survival in metastatic melanoma

This paper launched the immunotherapy era. It was the first randomised evidence that taking a brake off the immune system could extend life in a solid cancer, and it introduced clinicians to immune-related adverse events and to responses that arrive late or after apparent progression. Ipilimumab alone has since been superseded by PD-1 antibodies and combinations, but every checkpoint programme traces back to this result.

basicScience 1996

Leach, Krummel and Allison: releasing the CTLA-4 brake makes mice reject tumours

Every checkpoint inhibitor, from ipilimumab to pembrolizumab, rests on this idea: the immune system can already recognise cancer and just needs its brakes released. It changed the goal of immunotherapy from vaccinating against tumours to unleashing existing T cells.