Stage III melanoma (after surgery)
Stage III melanoma has spread to nearby lymph nodes but not further, and after surgery a year of immunotherapy, or of targeted pills if the cancer has a BRAF mutation, roughly halves the chance of it coming back. The newest trials show that giving immunotherapy before the operation instead of after works even better and lets most people stop treatment early.
Overview
Stage III melanoma is defined by regional nodal, satellite or in-transit disease and is staged by primary thickness and ulceration together with the number and size of nodal deposits. MSLT-II (2017) showed that removing the whole nodal basin after a positive sentinel node does not improve melanoma-specific survival, so most patients now keep their nodes and are watched with ultrasound. For decades the only adjuvant drug was high-dose interferon alfa, with a small relapse-free benefit and heavy toxicity; adjuvant ipilimumab (EORTC 18071, 2015) improved survival but at the cost of frequent severe immune toxicity.
CheckMate 238 (2017) showed nivolumab beat ipilimumab for recurrence-free survival (70.5 against 60.8 percent at one year) with a third of the serious toxicity, and KEYNOTE-054 (2018) showed pembrolizumab beat placebo (75.4 against 61.0 percent at one year, 55.4 against 38.3 percent at five years). COMBI-AD (2017) showed a year of dabrafenib-trametinib halved relapse risk in BRAF-mutant disease (ten-year relapse-free survival 48 against 32 percent). Adding ipilimumab to nivolumab (CheckMate 915) or relatlimab to nivolumab (RELATIVITY-098) after surgery added nothing, so a year of single-agent anti-PD-1 antibody, or the BRAF-MEK doublet, became the adjuvant standard.
The neoadjuvant trials then changed the timing. SWOG S1801 (2022) moved three of eighteen pembrolizumab doses to before surgery and improved two-year event-free survival from 49 to 72 percent with the same total drug. NADINA (2024) gave two cycles of ipilimumab plus nivolumab before surgery and adjuvant therapy only to poor responders, and cut events by two thirds against adjuvant nivolumab (twelve-month event-free survival 83.7 against 57.2 percent); about six in ten patients had a major pathological response and needed no further treatment. Neoadjuvant immunotherapy is now the preferred approach for macroscopic nodal disease. INTerpath-001 (2026) added the personalised mRNA vaccine intismeran autogene to adjuvant pembrolizumab and met its recurrence-free survival endpoint in resected stage IIB to IV disease, confirming the phase 2b KEYNOTE-942 signal (eighteen-month recurrence-free survival 78.6 against 62.2 percent).
State of the art
- A year of anti-PD-1 antibody or of dabrafenib-trametinib after surgery roughly halves the risk of relapse.
- Neoadjuvant immunotherapy (SWOG S1801, NADINA) beats the same drugs given only after surgery and lets most responders stop treatment early.
- The first positive phase 3 personalised cancer vaccine trial (INTerpath-001) was in this setting.
Red cards
From the labels and guidelines behind the standard of care. Your team's thresholds win.- Emergency services nowHypophysitis or adrenal crisis
Persistent headache with extreme tiredness, nausea, dizziness on standing or low blood pressure. Vomiting, severe weakness or collapse is adrenal crisis.
- Emergency services nowFainting or palpitations
Fainting, near-fainting, or an irregular or racing heartbeat; several kinase inhibitors prolong the QT interval and the labels require ECG and electrolyte monitoring.
- Check before combiningFood and drink: Dabrafenib + trametinib
Dabrafenib: take on an empty stomach. Trametinib: take on an empty stomach; both cause pyrexia.
- Check before combiningFood and drink: Pembrolizumab
No pharmacokinetic interactions expected (antibody). See the irAE guide for toxicity management.
- Good to knowImmune-related endocrinopathies (thyroiditis, hypophysitis)
Immunotherapy can attack hormone-producing glands: most often the thyroid (usually ending in an under-active thyroid needing lifelong tablets), and less often the pituitary (hypophysitis) or adrenal glands, which can be life-threatening if missed.
- Good to knowImmune-mediated colitis and diarrhoea
Inflammation of the bowel caused by immunotherapy releasing the immune system against the gut lining, producing diarrhoea that can be severe. It is the commonest serious side effect of CTLA-4 antibodies and is treated with steroids and, if needed, infliximab.
See all on the product pages:Dabrafenib + trametinibIpilimumabNivolumabPembrolizumab·Printable cards in the navigator
Anatomy and lymph node drainage
- Epidermis (in situ)
- Basal layer (melanocytes, basal cells)
- Keratinocytes (squamous)
- Dermis (invasive; Breslow depth)
- Merkel cells (dermal-epidermal)
- Dermal vessels (Kaposi)
- Acral and mucosal sites
- Nodes: sentinel node in the draining basin
- Nodes: regional basin (axilla, groin, neck)
Each skin cancer comes from a different cell layer: melanocytes and basal cells at the base of the epidermis, keratinocytes above them, Merkel cells and blood vessels in the dermis; depth of invasion decides the risk.
- Epidermis (in situ)
- Basal layer (melanocytes, basal cells)BRAF V600-mutant stage III (adjuvant dabrafenib-trametinib option)
- Keratinocytes (squamous)
- Dermis (invasive; Breslow depth)Stage IIIA (microscopic nodal disease, thin primary) · Stage IIIB and IIIC (clinically detected nodes, satellites or in-transit metastases) · Stage IIID (thick ulcerated primary with matted or numerous nodes) · Resectable macroscopic stage III (neoadjuvant immunotherapy candidates, NADINA) · BRAF V600-mutant stage III (adjuvant dabrafenib-trametinib option)
- Merkel cells (dermal-epidermal)Resectable macroscopic stage III (neoadjuvant immunotherapy candidates, NADINA) · BRAF V600-mutant stage III (adjuvant dabrafenib-trametinib option)
- Dermal vessels (Kaposi)
- Acral and mucosal sites
- sentinel node in the draining basin
- regional basin (axilla, groin, neck)
Same organ: Melanoma, Basal cell carcinoma, Cutaneous squamous cell carcinoma, Merkel cell carcinoma, Kaposi sarcoma, Skin cancer (all types), BRAF V600-mutant melanoma, Stage IIB and IIC melanoma, Advanced melanoma (unresectable stage III and stage IV), Mucosal melanoma, Acral melanoma, Advanced cutaneous squamous cell carcinoma, Locally advanced and metastatic basal cell carcinoma, Dermatofibrosarcoma protuberans
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.
- Stage III means the melanoma has reached the regional lymph nodes or produced satellite or in-transit deposits in the skin; in the eighth edition of the staging system five-year melanoma-specific survival ranges from 93 percent for stage IIIA to 32 percent for stage IIID, so it is the stage where preventing relapse matters most.
Cases by country
No country-level case numbers. This cancer is not mapped to a GLOBOCAN site.
One section per setting: the options named, what each is for, the trials behind them, the recorded trade-offs and the questions to ask.
Wide local excision, no completion lymph node dissection (MSLT-II), nodal ultrasound surveillance, then adjuvant systemic therapy.
Neoadjuvant ipilimumab plus nivolumab for two cycles then surgery, with adjuvant therapy only if the pathological response is poor (NADINA); or neoadjuvant then adjuvant pembrolizumab (SWOG S1801).
One year of nivolumab (CheckMate 238) or pembrolizumab (KEYNOTE-054); dabrafenib-trametinib for one year is the alternative in BRAF V600-mutant disease (COMBI-AD).
Intismeran autogene with pembrolizumab met its endpoints in INTerpath-001 (2026); regulatory review pending.
Excision where feasible; intralesional talimogene laherparepvec or the immunocytokine daromun before surgery; isolated limb perfusion for extensive limb disease.
Subtypes & biomarkers
top- Stage IIIA (microscopic nodal disease, thin primary)
- Stage IIIB and IIIC (clinically detected nodes, satellites or in-transit metastases)
- Stage IIID (thick ulcerated primary with matted or numerous nodes)
- Resectable macroscopic stage III (neoadjuvant immunotherapy candidates, NADINA)
- BRAF V600-mutant stage III (adjuvant dabrafenib-trametinib option)
- Sentinel node-positive with no palpable disease (observation of the basin after MSLT-II)
- Sentinel node status and nodal tumour burden
- Breslow thickness and ulceration of the primary
- BRAF V600 mutation (adjuvant targeted therapy option)
- Pathological response after neoadjuvant immunotherapy (major pathological response guides omission of adjuvant therapy)
- Circulating tumour DNA after surgery (trials of adjuvant selection)
- Interferon-gamma gene signature (exploratory predictor in NADINA)
How often this target appears
- 1996ECOG 1684: high-dose interferon alfa becomes the first adjuvant therapy
- 2015EORTC 18071: adjuvant ipilimumab improves relapse-free and overall survival at high toxicity
- 2017MSLT-II: completion lymph node dissection abandoned; CheckMate 238 and COMBI-AD set adjuvant nivolumab and dabrafenib-trametinib
- 2018KEYNOTE-054: adjuvant pembrolizumab beats placebo
- 2022SWOG S1801: three doses before surgery beat the same drug given only after
- 2023KEYNOTE-942: intismeran autogene plus pembrolizumab lowers relapse in phase 2b
- 2024NADINA: neoadjuvant ipilimumab plus nivolumab cuts events by two thirds
- 2026INTerpath-001: first positive phase 3 personalised vaccine trial
Dated changes read from the records linked to this cancer: approvals, regulatory steps, reported trials, guideline versions and milestones. Newest first; no date is inferred.
All 17 changes by month →- 2026-09-17This recordStage III melanoma (after surgery)Facts on this page last checked
When this page itself was last checked or edited.
- 2026Trial resultINTerpath-001 (V940-001)INTerpath-001 (V940-001) reported
RFS and DMFS significantly improved (HRs pending presentation).
- 2026MilestoneINTerpath-001 (V940-001)INTerpath-001: first positive phase 3 personalised vaccine trial
A milestone in how this cancer is treated.
- 2025Trial resultRELATIVITY-098RELATIVITY-098 reported
RFS not improved.
- 2024Trial resultNADINANADINA reported
12-month EFS 83.
- 2024MilestoneNADINANADINA: neoadjuvant ipilimumab plus nivolumab cuts events by two thirds
A milestone in how this cancer is treated.
What is in development for Stage III melanoma (after surgery), drawn from the whole corpus: 15 items. Drugs are grouped by the most advanced trial phase they have reached anywhere; approved treatments sit under standard of care. Technologies are the methods being tested for this cancer, trials are the studies recorded here, and ideas are proposals not yet in a trial.
Drugs in phase 3 · 1
Technologies being tested · 1
Trials under way · 5
- SCIB1 and iSCIB1+ in Melanoma Patients Receiving Nivolumab With Ipilimumab or SCIB1 With Pembrolizumab (The SCOPE Study) · phase 2 · Scancell Ltd
- Phase II Trial of Neoadjuvant and Adjuvant IO102-IO103 and Pembrolizumab KEYTRUDA® in Patients With Resectable Tumors · phase 2 · IO Biotech
- Efficacy of Daromun Neoadjuvant Intratumoral Treatment in Clinical Stage IIIB/C/D Melanoma Patients · phase 3 · Philogen S.p.A.
- Neoadjuvant L19IL2/L19TNF- Pivotal Study · phase 3 · Philogen S.p.A.
- Study of Pembrolizumab (MK-3475) Versus Placebo After Complete Resection of High-Risk Stage III Melanoma (MK-3475-054/1325-MG/KEYNOTE-054) · phase 3 · Merck Sharp & Dohme LLC
Trials reported · 7
- INTerpath-001 (V940-001) · phase 3 · 2026 · positive
- RELATIVITY-098 · phase 3 · 2025 · negative
- CheckMate 238 · phase 3 · 2017 · positive
- COMBI-AD · phase 3 · 2017 · positive
- MSLT-II · phase 3 · 2017 · positive
- NADINA · phase 3 · 2024 · positive
- SWOG S1801 · phase 2 · 2022 · positive
Ideas not yet in a trial · 1
Open problems and what is being done
Most stage IIIA patients would never have relapsed, so a year of immunotherapy with lifelong endocrine side effects in some is given to many who do not need it.
and how the field plans to fix it →What is being done about thisRecurrence and residual diseaseAvailable nowNothing recorded yet.
In trials- CheckMate 238Positive
- COMBI-ADPositive
- NADINAPositive
- Personalised neoantigen (mRNA) vaccinesPhase 3
Ideas and roadmapsBackground: Neoadjuvant / adjuvant / perioperative. Also on OnCo: Treatment journeys · Survivorship planner.
No biomarker yet tells who can safely skip adjuvant therapy; circulating tumour DNA trials are testing this.
Overall survival gains from adjuvant PD-1 blockade are small because relapsing patients receive the same drugs later.
and how the field plans to fix it →What is being done about thisRecurrence and residual diseaseAvailable nowNothing recorded yet.
In trials- CheckMate 238Positive
- COMBI-ADPositive
- NADINAPositive
- Personalised neoantigen (mRNA) vaccinesPhase 3
Ideas and roadmapsBackground: Neoadjuvant / adjuvant / perioperative. Also on OnCo: Treatment journeys · Survivorship planner.
Trials
topTrials recruiting now
Country and place are remembered in this browser only. A postcode is sent to OpenStreetMap's Nominatim service to find coordinates when you press the button; nothing else leaves your device.
Landmark trials
Expert centres
topExpert centres
Baltimore · cancer center | United States | 0 | 2,955 | 41,449 | #10 | ||
Milan · cancer center | Italy | none recorded | 0 | 1,246 | 21,746 | #11 | |
Amsterdam · cancer center | Netherlands | none recorded | 1 | 1,451 | 25,873 | #45 | |
Rosemont, IL · consortium | United States | none recorded | 1 | 49 | 750 | - | |
Portland, OR · consortium | United States | none recorded | 1 | 42 | 1,880 | none recorded | - |
Philadelphia · cancer center | United States | 0 | 3,148 | 54,267 | - | ||
St. Louis, MO · cancer center | United States | 0 | 1,950 | 25,697 | - | ||
Naples · cancer center | Italy | none recorded | 0 | 961 | 15,028 | - | |
Zurich · hospital | Switzerland | none recorded | 0 | 835 | 10,668 | - | |
Lausanne · hospital | Switzerland | none recorded | 0 | 509 | 9,176 | - | |
Brussels · cancer center | Belgium | none recorded | 0 | 489 | 8,689 | - | |
Mainz · university | Germany | none recorded | 0 | 483 | 5,527 | - | |
Tübingen · cancer center | Germany | none recorded | 0 | 435 | 4,909 | - | |
Houston · research institute | United States | FCCT directory | 0 | 411 | 6,335 | - | |
Kyoto · hospital | Japan | none recorded | 0 | 251 | 1,942 | - |
These are the things we can measure; they are not a ranking of quality. Each column is a field on the institution record or a count over what OnCo has linked; a centre that treats many patients with Stage III melanoma but is thinly recorded here will look small.
Not known: OnCo holds no case-volume or outcome figures for centres, so none are shown. Where a national audit or registry publishes them, the centre's page links to it. Default order: Newsweek rank, then trials for this cancer, then research output.
Questions to ask
topQuestions to ask your oncologist about Stage III melanoma
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 Sentinel node status and nodal tumour burden, Breslow thickness and ulceration of the primary, BRAF V600 mutation, Pathological response after neoadjuvant immunotherapy, Circulating tumour DNA after surgery), 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 Stage IIIA, Stage IIIB and IIIC, Stage IIID.
- Is germline (inherited) genetic testing recommended for me or my family?Why: Inherited variants can change treatment and matter for relatives.
Positive sentinel node, no palpable disease
- For my situation (positive sentinel node, no palpable disease), which of the standard options do you recommend and why?Why: Guideline options include: Wide local excision, no completion lymph node dissection (MSLT-II), nodal ultrasound surveillance, then adjuvant systemic therapy.
- How do the results of MSLT-II apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
Resectable macroscopic nodal disease
- For my situation (resectable macroscopic nodal disease), which of the standard options do you recommend and why?Why: Guideline options include: Neoadjuvant ipilimumab plus nivolumab for two cycles then surgery, with adjuvant therapy only if the pathological response is poor (NADINA); or neoadjuvant then adjuvant pembrolizumab (SWOG S1801).
- Am I a candidate for Nivolumab, Ipilimumab, Pembrolizumab, 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 NADINA and SWOG S1801 apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
Adjuvant, after upfront surgery
- For my situation (adjuvant, after upfront surgery), which of the standard options do you recommend and why?Why: Guideline options include: One year of nivolumab (CheckMate 238) or pembrolizumab (KEYNOTE-054); dabrafenib-trametinib for one year is the alternative in BRAF V600-mutant disease (COMBI-AD).
- Am I a candidate for Nivolumab, Pembrolizumab, 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 CheckMate 238 and Study of Pembrolizumab (MK-3475) Versus Placebo After Complete Resection of High-Risk Stage III Melanoma (MK-3475-054/1325-MG/KEYNOTE-054) apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
Adjuvant vaccine (emerging)
- For my situation (adjuvant vaccine (emerging)), which of the standard options do you recommend and why?Why: Guideline options include: Intismeran autogene with pembrolizumab met its endpoints in INTerpath-001 (2026); regulatory review pending.
- Am I a candidate for Intismeran autogene, 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 INTerpath-001 (V940-001) apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
In-transit disease
- For my situation (in-transit disease), which of the standard options do you recommend and why?Why: Guideline options include: Excision where feasible; intralesional talimogene laherparepvec or the immunocytokine daromun before surgery; isolated limb perfusion for extensive limb disease.
- Am I a candidate for Talimogene laherparepvec, 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 Neoadjuvant L19IL2/L19TNF- Pivotal Study and Efficacy of Daromun Neoadjuvant Intratumoral Treatment in Clinical Stage IIIB/C/D Melanoma Patients apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
Any stage
- Are there clinical trials I could join, for example of INTerpath-001 (V940-001), Intismeran autogene, ctDNA-guided adjuvant therapy in stage II-III melanoma, SCIB1 and iSCIB1+ in Melanoma Patients Receiving Nivolumab With Ipilimumab or SCIB1 With Pembrolizumab (The SCOPE Study)?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 “Most stage IIIA patients would never have relapsed, so a year of immunotherapy with lifelong endocrine side effects in some is given to many who do not need it”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
- I read that “No biomarker yet tells who can safely skip adjuvant therapy; circulating tumour DNA trials are testing this”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
Newly diagnosed? Read the first 60 days with Stage III melanoma, then print the one-page appointment sheet with room for the answers.
Print this page for your appointment (your browser's print command). These prompts are for discussion; your clinical team knows your case.
Direct links plus the targets, companies, and technologies of this cancer's products.
technologies
8targets
4drugs
9companies
5terms
6trials
12ideas
1people
5Latest papers
topQuery for this cancer: (TITLE:"Stage III melanoma" OR ABSTRACT:"Stage III melanoma" OR TITLE:"after surgery" OR ABSTRACT:"after surgery" OR TITLE:"Resected stage III melanoma" OR ABSTRACT:"Resected stage III melanoma" OR TITLE:"Node-positive melanoma" OR ABSTRACT:"Node-positive melanoma" OR TITLE:"Regional melanoma" OR ABSTRACT:"Regional melanoma" OR TITLE:"Adjuvant melanoma setting" OR ABSTRACT:"Adjuvant melanoma setting") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Stage III melanoma (after surgery), not a curated reading list.
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