The first 60 days: 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. Below, week by week, is what OnCo's record of Melanoma says about the first two months: the order is typical, the timing is yours to ask about. Sections appear only where the record has something to say. Orientation, not medical advice.
What happens now
Staging tests establish exactly what and where the cancer is. Everything else follows from the answers.
Dermoscopy, total-body photography for high-risk patients, excisional biopsy with Breslow thickness and ulceration reported; AI decision support emerging.
- Excision biopsy with Breslow depth and ulceration, sentinel node biopsy or ultrasound of a palpable node, PET-CT and brain MRI for stage III, BRAF testing.
Ask which of these were tested and what the results were; see the report reader for what each value means.
These specialties appear in the standard of care for this cancer. In most centres they meet weekly as a tumour board to agree each plan; you can ask when yours was discussed and what was decided.
- PathologistNamed in the standard of care for: Screening and diagnosis, Stage I-II primary.
- RadiologistNamed in the standard of care for: Stage I-II primary.
- SurgeonNamed in the standard of care for: Stage II-III, Screening and diagnosis, Stage I-II primary, Resectable stage III (macroscopic nodes).
- Medical oncologistNamed in the standard of care for: Stage II-III, Metastatic first line, After PD-1, Stage IIB-IIC (thick or ulcerated, node-negative) and 7 more.
- Clinical oncologist (radiotherapy)Named in the standard of care for: Brain metastases.
- Transplant and cell therapy teamNamed in the standard of care for: After PD-1, After anti-PD-1 failure, Metastatic uveal melanoma (HLA-A*02:01-positive).
A second opinion from a centre that treats many similar cases is normal, not rude; the standard of care tells you what to compare it against.
Each row is a setting from the standard of care, in the order it usually arises. Not all will apply to you; your stage and biomarkers decide which do. The guideline grade, where recorded, says how strong the evidence is.
Adjuvant pembrolizumab/nivolumab; neoadjuvant IO for resectable stage III.
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).
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.
Nivolumab or pembrolizumab for one year; dabrafenib-trametinib for BRAF V600 (COMBI-AD, 10-year RFS 48%); relatlimab adds nothing (RELATIVITY-098).
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.
Nivolumab-ipilimumab or nivolumab-relatlimab; BRAF/MEK if rapid control needed.
Lifileucel, RP1 + nivolumab, ipilimumab-based, trials; tebentafusp (uveal).
Adjuvant pembrolizumab or nivolumab for one year (KEYNOTE-716, CheckMate 76K); discuss modest absolute benefit and irAE risk; ctDNA-guided trials.
BRAF + MEK doublet: encorafenib-binimetinib, dabrafenib-trametinib, or vemurafenib-cobimetinib; triplet with atezolizumab is approved but little used.
Lifileucel TIL therapy (accelerated approval 2024), RP1 oncolytic virus + nivolumab (2026), ipilimumab-based rechallenge, brenetafusp trials; clinical trials strongly encouraged.
Tebentafusp (OS benefit, IMCgp100-202); liver-directed therapy for hepatic-dominant disease; ipilimumab-nivolumab has modest activity.
Nivolumab + ipilimumab for asymptomatic disease (~50% intracranial response, CheckMate 204); stereotactic radiosurgery; BRAF/MEK for symptomatic BRAF-mutant disease.
- Surgery first or immunotherapy first?
- Major pathological response at surgery?
Generated from this cancer's standard of care, biomarkers and open problems. Take the group that matches where you are. To tick, add your own and print, open the one-page appointment sheet.
Newly diagnosed
- What is my exact diagnosis, stage, and grade, and which tests established them?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?These results decide eligibility for targeted therapy, immunotherapy, and trials.
- Which subtype is my cancer, and does that change the recommended treatment?Recognised subtypes for this cancer include Superficial spreading, Nodular, Lentigo maligna.
- Is germline (inherited) genetic testing recommended for me or my family?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?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?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?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?Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of CheckMate 067 apply to someone like me?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?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?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?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?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?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?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?Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of KEYNOTE-716 apply to someone like me?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?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?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?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?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?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?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?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?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?Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of COLUMBUS apply to someone like me?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?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?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?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?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?Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of IMCgp100-202 apply to someone like me?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?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?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?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?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?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?Open problems are where trials and second opinions matter most.
- I read that “Uveal and mucosal subtypes”. How does that affect my plan?Open problems are where trials and second opinions matter most.
Trials open now for this cancer in OnCo, largest phase first. Joining a trial is a decision like any other: ask what the comparison arm is, whether a placebo is used, and what happens if you leave. The cancer page searches ClinicalTrials.gov live for more.
- A Clinical Study of BCD-217 (Nurulimab + Prolgolimab) Followed by Anti-PD-1 Compared to Anti-PD-1 Monotherapy as First-Line Treatment in Subjects With Unresectable/Metastatic MelanomaPhase 3 · active · NCT05732805A Double-Blind Placebo-Controlled Comparative Randomized Clinical Study of the Efficacy and Safety of BCD-217 (Nurulimab + Prolgolimab) Followed by Anti-PD-1 Compared to Anti-PD-1 Monotherapy as First-Line Treatment in Subjects With Unresectable/Metastatic Melanoma
- A Clinical Trial of Three Study Medicines (Encorafenib, Binimetinib, and Pembrolizumab) in Patients With Advanced or Metastatic MelanomaPhase 3 · active · NCT04657991A PHASE 3, RANDOMIZED, DOUBLE-BLIND STUDY OF ENCORAFENIB AND BINIMETINIB PLUS PEMBROLIZUMAB VERSUS PLACEBO PLUS PEMBROLIZUMAB IN PARTICIPANTS WITH BRAF V600E/K MUTATION-POSITIVE METASTATIC OR UNRESECTABLE LOCALLY ADVANCED MELANOMA
- A Study of Neoadjuvant Therapy With BCD-217 (Nurulimab + Prolgolimab) in Patients With Resectable Stage III Skin MelanomaPhase 3 · active · NCT05751928A Randomized Study of the Efficacy and Safety of Neoadjuvant Therapy With BCD-217 (Nurulimab + Prolgolimab) Versus Standard Adjuvant Therapy With Pembrolizumab in Patients With Resectable Stage III Skin Melanoma
- A Study of Subcutaneous Nivolumab + Relatlimab Fixed-dose Combination (FDC) in Previously Untreated Metastatic or Unresectable MelanomaPhase 3 · active · NCT05625399A Phase 3, Randomized, Open-label, Study of Subcutaneous Nivolumab + Relatlimab Fixed-dose Combination Versus Intravenous Nivolumab + Relatlimab Fixed-dose Combination in Participants With Previously Untreated Metastatic or Unresectable Melanoma
- A Study to Assess Naporafenib (ERAS-254) Administered With Trametinib in Patients With NRAS-mutant Melanoma (SEACRAFT-2)Phase 3 · active · NCT06346067A Randomized, Open-label Phase III Study in Patients With Previously Treated Unresectable or Metastatic NRAS Mutant Cutaneous Melanoma Comparing the Combination of Naporafenib + Trametinib to Physician's Choice of Therapy (Dacarbazine, Temozolomide or Trametinib Monotherapy) With a Dose Optimization lead-in [SEACRAFT-2]
Much of what helps in the first weeks is free if you know to ask: testing, helplines, rides and lodging, second opinions, trial travel.
- Melanoma: the full pageThe 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.
- One-page appointment sheetYour questions, the words you may hear, what to bring, and space for the answers. Print it.
- Treatment journey: Stage III (node-positive)Surgery to remove the melanoma and the involved nodes, then a year of immunotherapy infusions every few weeks, or immunotherapy for six weeks before surgery, followed by scans for five years.
- Guidelines comparedNCCN, ESMO and NICE side by side for this cancer.
- Treatment sequencingWhich treatment tends to follow which, line by line.
- NavigatorStandard of care for your stage, what you have tried, and trials near you.
- Major pathological response (MPR): When, after pre-surgery treatment, the removed tumour contains little or no living cancer: 10% or less viable cells.
- Breslow thickness: How deep a melanoma has grown into the skin, in millimetres.
- Ulceration (melanoma): Loss of the skin surface over a melanoma under the microscope; a sign of aggressive biology that raises the stage.
- Immune surveillance and cancer immunoediting: The immune system patrols for cells that have turned malignant and destroys most of them; the tumours we see are the ones that learned to hide.
- Bioelectric theory of cancer (Levin): Cells hold a voltage across their membranes, and tissues share these voltages as patterns that guide growth and regeneration.
- Wide local excision: Cutting out a tumour together with a measured rim of normal-looking tissue around it, so that microscopic spread at the edge is removed too.
- Cancer vaccines and oncolytic viruses: Cancer vaccines teach the immune system to recognise proteins on tumour cells; oncolytic viruses infect and burst cancer cells while raising the alarm to immunity.
- Fixed-duration vs continuous therapy: Whether a drug is taken for a set period (say 12 months) and then stopped even though it is still working, or continued indefinitely until it fails.
- HLA-A*02:01 restriction: Some T-cell-receptor drugs only work in people with a particular immune 'tissue type'.
- Liver-directed therapy (TACE, TARE, HAI, ablation): The set of treatments aimed only at tumours in the liver, delivered through its artery or by needle, used when the liver is the main or only site of disease: chemoembolisation, radioactive beads, ablation and infusion pumps.
Every term links to the glossary.