# Stage IIB and IIC melanoma

Source: https://onco.cc/cancers/stage-ii-melanoma/  
OnCo record `stage-ii-melanoma` (Cancer). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Summary

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.

## Fields

- Kind: Cancer
- Last checked: 2026-09-17
- Also known as: High-risk stage II melanoma; Thick node-negative melanoma; Stage IIB/IIC melanoma
- Tags: subtype-page
- Group: skin
- Burden: 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.
- Subtypes: 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
- Biomarkers: 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)

## Sections of this record

The page is a hub with ten sections in reading order; large sections have their own page. The same plan as JSON: https://onco.cc/api/v1/cancers/stage-ii-melanoma/sections.json

- Overview (on the hub): The TL;DR, the family this cancer belongs to, the organ, who gets it and what the state of the art is. https://onco.cc/cancers/stage-ii-melanoma/#overview [3 state-of-the-art points]
- Types and stages (on the hub): Anatomy, the subtypes and how they differ, how it is staged, and where advanced disease spreads. https://onco.cc/cancers/stage-ii-melanoma/#what-it-is [5 subtypes]
- Symptoms and diagnosis (on the hub): How this cancer shows itself, how the diagnosis is confirmed, and the biomarkers clinicians test for. https://onco.cc/cancers/stage-ii-melanoma/#finding-it [6 biomarkers]
- Treatment (on the hub): The standard of care by setting, the medicines, surgery and radiotherapy named in it, and the regimens behind them. https://onco.cc/cancers/stage-ii-melanoma/#treating-it [4 settings, 2 decisions with options]
- Trials and papers (on the hub): Trials recruiting now, the landmark trials, the trials held by this cancer's subtypes, the key papers and what they mean, the latest literature, and the milestones year by year. https://onco.cc/cancers/stage-ii-melanoma/#evidence [4 trials, 3 key papers, 4 milestones]
- Biology and targets (on the hub): The molecular landscape: the targets and how often each appears, the pathways, the mechanics stages and the preclinical models. https://onco.cc/cancers/stage-ii-melanoma/#science [1 target]
- Countries and centres (own page): Cases by country, the UK and NHS pathway and other country lenses, the expert centres with trials on record, and the centres named on this cancer's subtypes. https://onco.cc/cancers/stage-ii-melanoma/where-you-are/
- Decisions and support (on the hub): The decisions you may face, the aids that walk through them, the warnings on record, the first sixty days and the questions to ask. https://onco.cc/cancers/stage-ii-melanoma/#living-with-it [17 questions, 3 red cards]
- Pipeline and open problems (own page): Everything in development, the medicines held by this cancer's subtypes, the open problems and what is being done about them, the roadmaps, and what changed on this record. https://onco.cc/cancers/stage-ii-melanoma/coming/ [3 medicines, 4 trials, 1 idea, 3 open problems]
- Data (own page): Every connected record, the notes, the JSON, Markdown and RDF twins, and where the record came from and when it was checked. https://onco.cc/cancers/stage-ii-melanoma/data/ [29 connected records]

## Standard of care

- Diagnosis and surgery: Wide local excision with margins set by thickness and sentinel lymph node biopsy for primaries over 0.8 mm or with ulceration. ([Wide local excision](https://onco.cc/terms/wide-local-excision/), [Sentinel lymph node biopsy](https://onco.cc/technologies/sentinel-node/), [Breslow thickness](https://onco.cc/terms/breslow-thickness/))
- Adjuvant, stage IIB or IIC: One year of pembrolizumab (KEYNOTE-716) or nivolumab (CheckMate 76K), or observation after a shared decision about a modest benefit and immune side effects. ([KEYNOTE-716](https://onco.cc/trials/keynote-716/), [Effectiveness Study of Nivolumab Compared to Placebo in Prevention of Recurrent Melanoma After Complete Resection of Stage IIB/C Melanoma](https://onco.cc/trials/nct04099251/), [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/), [Nivolumab](https://onco.cc/drugs/nivolumab/))
- Adjuvant vaccine (emerging): Intismeran autogene with pembrolizumab met its endpoints in INTerpath-001, which included stage IIB and IIC; regulatory review pending. ([INTerpath-001 (V940-001)](https://onco.cc/trials/interpath-001/), [Intismeran autogene](https://onco.cc/drugs/intismeran-autogene/))
- Surveillance: Skin and nodal examination and, for higher-risk disease, imaging at intervals; patient education on self-examination. ([Skin cancer screening (visual skin examination)](https://onco.cc/technologies/skin-cancer-screening/), [Dermoscopy, total-body photography & AI skin analysis](https://onco.cc/technologies/dermoscopy-ai/))

## 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.

## Open problems

- 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.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Melanoma
- KEYNOTE-716 (Lancet 2022): https://doi.org/10.1016/S0140-6736(22)00562-1
- CheckMate 76K (Nature Medicine 2023): https://doi.org/10.1038/s41591-023-02583-2
- Wikipedia: https://en.wikipedia.org/wiki/Melanoma

## Connected records

- cancers: [Advanced melanoma (unresectable stage III and stage IV)](https://onco.cc/cancers/advanced-melanoma/), [BRAF V600-mutant melanoma](https://onco.cc/cancers/braf-v600-melanoma/), [Melanoma](https://onco.cc/cancers/melanoma/), [Stage III melanoma (after surgery)](https://onco.cc/cancers/stage-iii-melanoma/)
- technologies: [Dermoscopy, total-body photography & AI skin analysis](https://onco.cc/technologies/dermoscopy-ai/), [Immune checkpoint inhibitors](https://onco.cc/technologies/checkpoint-inhibitor/), [Liquid biopsy (ctDNA)](https://onco.cc/technologies/liquid-biopsy/), [Sentinel lymph node biopsy](https://onco.cc/technologies/sentinel-node/), [Skin cancer screening (visual skin examination)](https://onco.cc/technologies/skin-cancer-screening/)
- targets: [PD-1](https://onco.cc/targets/pd1/)
- drugs: [Intismeran autogene](https://onco.cc/drugs/intismeran-autogene/), [Nivolumab](https://onco.cc/drugs/nivolumab/), [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/)
- terms: [Breslow thickness](https://onco.cc/terms/breslow-thickness/), [Circulating tumour DNA (ctDNA)](https://onco.cc/terms/ctdna/), [Neoadjuvant / adjuvant / perioperative](https://onco.cc/terms/neoadjuvant-adjuvant/), [Ulceration (melanoma)](https://onco.cc/terms/ulceration-melanoma/), [Wide local excision](https://onco.cc/terms/wide-local-excision/)
- trials: [Adjuvant Encorafenib and Binimetinib in High-risk Stage II Melanoma With a BRAF Mutation.](https://onco.cc/trials/nct05270044/), [Effectiveness Study of Nivolumab Compared to Placebo in Prevention of Recurrent Melanoma After Complete Resection of Stage IIB/C Melanoma](https://onco.cc/trials/nct04099251/), [INTerpath-001 (V940-001)](https://onco.cc/trials/interpath-001/), [KEYNOTE-716](https://onco.cc/trials/keynote-716/)
- people: [Jason J. Luke](https://onco.cc/people/jason-luke/), [Jeffrey E. Gershenwald](https://onco.cc/people/jeffrey-gershenwald/), [John M. Kirkwood](https://onco.cc/people/john-kirkwood/)
- key papers: [CheckMate 76K: adjuvant nivolumab in resected stage IIB or IIC melanoma](https://onco.cc/key-papers/paper-checkmate-76k-nat-med-2023/), [KEYNOTE-716: adjuvant pembrolizumab versus placebo in completely resected stage IIB or IIC melanoma](https://onco.cc/key-papers/paper-keynote-716-lancet-2022/), [Melanoma staging: evidence-based changes in the AJCC eighth edition cancer staging manual](https://onco.cc/key-papers/paper-ajcc-8-melanoma-gershenwald-ca-2017/)
- ideas: [ctDNA-guided adjuvant therapy in stage II-III melanoma](https://onco.cc/ideas/idea-ctdna-guided-adjuvant-melanoma/)

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JSON: https://onco.cc/api/v1/entities/stage-ii-melanoma.json