Stage IIB and IIC melanoma
Stage IIB and IIC melanomas are thick or ulcerated skin melanomas that have not reached the lymph nodes but still carry a real risk of coming back. A year of pembrolizumab or nivolumab after surgery lowers that risk, though most people in this group would have been cured by surgery alone, so the decision weighs a modest benefit against a year of treatment.
Overview
Stage II melanoma is node-negative disease staged by Breslow thickness and ulceration: IIB is a 2 to 4 millimetre ulcerated or a thicker non-ulcerated primary, IIC a primary over 4 millimetres with ulceration. Sentinel node biopsy defines the stage; if it is negative, treatment was for decades surgery alone with surveillance, since adjuvant interferon added little. Yet relapse and death rates for IIB and IIC exceed those of IIIA, and because stage II is so much commoner than stage III it contributes more melanoma deaths in absolute numbers.
KEYNOTE-716 (2021) randomised 976 patients with resected IIB or IIC disease to a year of pembrolizumab or placebo and improved twelve-month recurrence-free survival from 83.1 to 90.5 percent (hazard ratio 0.65), with distant metastasis-free survival also improved and the benefit sustained at five years; pembrolizumab was approved for this stage in December 2021. CheckMate 76K (2023) found the same with nivolumab (twelve-month recurrence-free survival 89.0 against 79.4 percent, hazard ratio 0.42), approved in October 2023. INTerpath-001 (2026), which included stage IIB and IIC, met its endpoints for intismeran autogene added to pembrolizumab.
The absolute gain is smaller than in stage III, most patients would never have relapsed, and around one in five who receive a PD-1 antibody has an immune side effect that is sometimes permanent, so guidelines list adjuvant therapy as an option to discuss rather than a default. Circulating tumour DNA, gene-expression profiles and the sentinel node itself are being studied to pick out the minority who will relapse, and the adjuvant COLUMBUS-AD trial is testing encorafenib-binimetinib in BRAF-mutant stage II disease.
State of the art
- Adjuvant pembrolizumab and nivolumab lower relapse risk in stage IIB and IIC melanoma, extending immunotherapy to node-negative disease.
- The debate over treating many to help few has made this stage the test bed for circulating tumour DNA and gene-expression selection.
- The first positive phase 3 personalised vaccine trial included this stage.
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.
- 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.
See all on the product pages:NivolumabPembrolizumab·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 II (COLUMBUS-AD adjuvant targeted therapy trial) · Thick nodular melanoma with negative sentinel node
- Keratinocytes (squamous)
- Dermis (invasive; Breslow depth)Stage IIB (T3b, ulcerated 2 to 4 mm, or T4a, over 4 mm without ulceration) · Stage IIC (T4b, ulcerated and over 4 mm) · Stage IIA (not eligible for adjuvant therapy; surveillance) · BRAF V600-mutant stage II (COLUMBUS-AD adjuvant targeted therapy trial) · Thick nodular melanoma with negative sentinel node
- Merkel cells (dermal-epidermal)Stage IIA (not eligible for adjuvant therapy; surveillance) · BRAF V600-mutant stage II (COLUMBUS-AD adjuvant targeted therapy trial)
- 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 III melanoma (after surgery), 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 IIB and IIC melanomas are thick or ulcerated primaries with a negative sentinel node; in the eighth staging edition five-year melanoma-specific survival is about 87 percent for IIB and 82 percent for IIC, worse than stage IIIA, and because stage II is far commoner than stage III it accounts for a large share of melanoma deaths.
Also on OnCo: Symptoms and red flags · Early detection roadmap.
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 with margins set by thickness and sentinel lymph node biopsy for primaries over 0.8 mm or with ulceration.
One year of pembrolizumab (KEYNOTE-716) or nivolumab (CheckMate 76K), or observation after a shared decision about a modest benefit and immune side effects.
Intismeran autogene with pembrolizumab met its endpoints in INTerpath-001, which included stage IIB and IIC; regulatory review pending.
Skin and nodal examination and, for higher-risk disease, imaging at intervals; patient education on self-examination.
Subtypes & biomarkers
top- Stage IIB (T3b, ulcerated 2 to 4 mm, or T4a, over 4 mm without ulceration)
- Stage IIC (T4b, ulcerated and over 4 mm)
- Stage IIA (not eligible for adjuvant therapy; surveillance)
- BRAF V600-mutant stage II (COLUMBUS-AD adjuvant targeted therapy trial)
- Thick nodular melanoma with negative sentinel node
- Breslow thickness
- Ulceration of the primary
- Sentinel lymph node status (must be negative for stage II)
- Mitotic rate
- BRAF V600 mutation (trial eligibility)
- Circulating tumour DNA and gene-expression profiles (under study to select who needs adjuvant therapy)
How often this target appears
- 2017Eighth edition staging shows stage IIB and IIC outcomes worse than IIIA
- 2021KEYNOTE-716: adjuvant pembrolizumab approved for stage IIB and IIC
- 2023CheckMate 76K: adjuvant nivolumab approved for stage IIB and IIC
- 2026INTerpath-001 positive in resected stage IIB to IV melanoma
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 7 changes by month →- 2026-09-17This recordStage IIB and IIC melanomaFacts 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 positive in resected stage IIB to IV melanoma
A milestone in how this cancer is treated.
- 2023MilestoneEffectiveness Study of Nivolumab Compared to Placebo in Prevention of Recurrent Melanoma After Complete Resection of Stage IIB/C MelanomaCheckMate 76K: adjuvant nivolumab approved for stage IIB and IIC
A milestone in how this cancer is treated.
- 2021Trial resultKEYNOTE-716KEYNOTE-716 reported
RFS and DMFS improved; 5-year benefit sustained (ESMO 2025).
- 2021MilestoneKEYNOTE-716KEYNOTE-716: adjuvant pembrolizumab approved for stage IIB and IIC
A milestone in how this cancer is treated.
What is in development for Stage IIB and IIC melanoma, drawn from the whole corpus: 8 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 · 2
Trials under way · 2
- Adjuvant Encorafenib and Binimetinib in High-risk Stage II Melanoma With a BRAF Mutation. · phase 3 · Pierre Fabre Medicament
- Effectiveness Study of Nivolumab Compared to Placebo in Prevention of Recurrent Melanoma After Complete Resection of Stage IIB/C Melanoma · phase 3 · Bristol-Myers Squibb
Trials reported · 2
- INTerpath-001 (V940-001) · phase 3 · 2026 · positive
- KEYNOTE-716 · phase 3 · 2021 · positive
Ideas not yet in a trial · 1
Open problems and what is being done
Roughly four in five patients would have been cured by surgery alone and cannot yet be told apart from the fifth.
No overall survival benefit has yet been shown for adjuvant therapy in stage II.
Permanent endocrine side effects in a minority weigh heavily when the absolute benefit is a few percentage points.
and how the field plans to fix it →What is being done about thisSide effects and quality of lifeAvailable now- Immune checkpoint inhibitorsStandard of care
- Sentinel lymph node biopsyStandard of care
In trialsNothing recorded yet.
Ideas and roadmapsNothing recorded yet.
Also on OnCo: Side effects by symptom · Immune-related side effects · Toxicity compare · 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 | |
Shanghai · hospital | China | none recorded | 0 | 2,872 | 31,534 | - | |
London · hospital | United Kingdom | none recorded | 0 | 2,376 | 28,940 | - | |
Naples · cancer center | Italy | none recorded | 0 | 961 | 15,028 | - | |
Lausanne · hospital | Switzerland | none recorded | 0 | 509 | 9,176 | - | |
Brussels · cancer center | Belgium | none recorded | 0 | 489 | 8,689 | - | |
Montpellier · cancer center | France | 0 | 434 | 7,776 | - | ||
| Spain | none recorded | 0 | 377 | 3,050 | - | ||
Kansas City, KS · cancer center | United States | 0 | 365 | 4,909 | - | ||
New York · consortium | United States | none recorded | 0 | 326 | 10,206 | - | |
Candiolo · cancer center | Italy | none recorded | 0 | 324 | 4,466 | - | |
Lisbon · research institute | Portugal | none recorded | 0 | 294 | 6,851 | - | |
Kyoto · hospital | Japan | none recorded | 0 | 251 | 1,942 | - | |
London · research institute | United Kingdom | none recorded | 0 | 242 | 3,535 | - |
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 IIB and IIC 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 IIB and IIC 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 Breslow thickness, Ulceration of the primary, Sentinel lymph node status, Mitotic rate, BRAF V600 mutation), 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 IIB, Stage IIC, Stage IIA.
- Is germline (inherited) genetic testing recommended for me or my family?Why: Inherited variants can change treatment and matter for relatives.
Diagnosis and surgery
- For my situation (diagnosis and surgery), which of the standard options do you recommend and why?Why: Guideline options include: Wide local excision with margins set by thickness and sentinel lymph node biopsy for primaries over 0.8 mm or with ulceration.
Adjuvant, stage IIB or IIC
- For my situation (adjuvant, stage iib or iic), which of the standard options do you recommend and why?Why: Guideline options include: One year of pembrolizumab (KEYNOTE-716) or nivolumab (CheckMate 76K), or observation after a shared decision about a modest benefit and immune side effects.
- 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 and Effectiveness Study of Nivolumab Compared to Placebo in Prevention of Recurrent Melanoma After Complete Resection of Stage IIB/C Melanoma 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, which included stage IIB and IIC; 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.
Surveillance
- For my situation (surveillance), which of the standard options do you recommend and why?Why: Guideline options include: Skin and nodal examination and, for higher-risk disease, imaging at intervals; patient education on self-examination.
Any stage
- Are there clinical trials I could join, for example of INTerpath-001 (V940-001), Intismeran autogene, Adjuvant Encorafenib and Binimetinib in High-risk Stage II Melanoma With a BRAF Mutation., ctDNA-guided adjuvant therapy in stage II-III melanoma?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 “Roughly four in five patients would have been cured by surgery alone and cannot yet be told apart from the fifth”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
- I read that “No overall survival benefit has yet been shown for adjuvant therapy in stage II”. 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 IIB and IIC 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
6targets
1drugs
3companies
3terms
5trials
4ideas
1people
1Latest papers
topQuery for this cancer: (TITLE:"Stage IIB and IIC melanoma" OR ABSTRACT:"Stage IIB and IIC melanoma" OR TITLE:"High-risk stage II melanoma" OR ABSTRACT:"High-risk stage II melanoma" OR TITLE:"Thick node-negative melanoma" OR ABSTRACT:"Thick node-negative melanoma" OR TITLE:"Stage IIB/IIC melanoma" OR ABSTRACT:"Stage IIB/IIC melanoma") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Stage IIB and IIC melanoma, not a curated reading list.
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