# Merkel cell carcinoma

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

## TL;DR

Merkel cell carcinoma is a rare, fast-growing skin cancer, usually caused by a common virus (Merkel cell polyomavirus) or by sun damage. It was almost untreatable once it spread; PD-1/PD-L1 immunotherapy now gives lasting responses in about half of patients.

## Summary

Merkel cell carcinoma (MCC) is a neuroendocrine skin cancer of older, fair-skinned and immunosuppressed people. About 80% of cases in the Northern Hemisphere are driven by clonally integrated Merkel cell polyomavirus (MCPyV, discovered 2008); the remainder are UV-induced with a very high tumour mutational burden. Both forms are immunogenic, which explains why MCC responded to checkpoint blockade when chemotherapy gave only brief responses.

Localised disease is treated with wide excision, sentinel node biopsy and adjuvant radiotherapy; the STAMP and ADMEC-O trials tested adjuvant PD-1 blockade, with ADMEC-O (nivolumab) showing a disease-free survival benefit in 2023. Metastatic disease is treated first line with avelumab (JAVELIN Merkel 200, first approval 2017), pembrolizumab (KEYNOTE-017, 2018) or retifanlimab (POD1UM-201, 2023); durable responses occur in about half, and chemotherapy is reserved for immunotherapy failure. Circulating MCPyV oncoprotein antibodies (AMERK) allow surveillance in seropositive patients.

Unsolved: primary and acquired immunotherapy resistance (about half of patients), immunosuppressed patients (transplant, CLL) who cannot receive checkpoint blockade safely, and the adjuvant standard.

## Fields

- Kind: Cancer
- Last checked: 2026-09-08
- Tags: gap-fill; skin; rare
- Group: skin
- Burden: Merkel cell carcinoma causes about 3,000 cases per year in the US and rising; median age is ~75; it is roughly 40 times rarer than melanoma and more likely to spread stage for stage, which is why immunotherapy's durable responses mattered so much.
- Subtypes: Virus-positive MCC (MCPyV, ~80%); Virus-negative UV-driven MCC (high TMB, RB1/TP53 mutations); MCC in immunosuppressed patients (transplant, CLL, HIV)
- Biomarkers: CK20 perinuclear dot staining; TTF-1 negative; MCPyV large T antigen (IHC/PCR); MCPyV oncoprotein antibody titre (surveillance); Sentinel lymph node status; PD-L1 (not required for treatment); Tumour mutational burden (virus-negative)

## 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/merkel-cell-carcinoma/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/merkel-cell-carcinoma/#overview [4 state-of-the-art points]
- What it is (on the hub): Anatomy, the subtypes and how they differ, how it is staged, and where advanced disease spreads. https://onco.cc/cancers/merkel-cell-carcinoma/#what-it-is [3 subtypes]
- Finding it (on the hub): How it shows itself, how it is confirmed, what screening exists, and the biomarkers clinicians test for. https://onco.cc/cancers/merkel-cell-carcinoma/#finding-it [6 biomarkers]
- Treating it (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/merkel-cell-carcinoma/#treating-it [4 settings, 1 regimen, 4 decisions with options]
- Evidence (on the hub): Trials recruiting now, the landmark trials, the key papers and what they mean, the latest literature, and the milestones year by year. https://onco.cc/cancers/merkel-cell-carcinoma/#evidence [11 trials, 6 milestones]
- The science (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/merkel-cell-carcinoma/#science [3 targets, 3 pathways]
- Where you are (own page): Cases by country, the UK and NHS pathway and other country lenses, and the expert centres with trials on record. https://onco.cc/cancers/merkel-cell-carcinoma/where-you-are/ [1 centre]
- Living with it (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/merkel-cell-carcinoma/#living-with-it [17 questions, 5 red cards]
- What is coming (own page): Everything in development, the open problems and what is being done about them, the roadmaps, and what changed on this record. https://onco.cc/cancers/merkel-cell-carcinoma/coming/ [7 medicines, 11 trials, 4 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/merkel-cell-carcinoma/data/ [52 connected records]

## Standard of care

- Localised (stage I-II): Wide local excision with sentinel node biopsy; adjuvant radiotherapy to the primary site (and nodal basin if node-positive); adjuvant nivolumab supported by ADMEC-O in selected patients. ([Sentinel lymph node biopsy](https://onco.cc/technologies/sentinel-node/), [IMRT / IGRT (modern external beam)](https://onco.cc/technologies/imrt-igrt/), [Nivolumab](https://onco.cc/drugs/nivolumab/))
- Regional nodal disease (stage III): Lymphadenectomy and/or nodal radiotherapy; neoadjuvant nivolumab (CheckMate 358) produced pathological complete responses in about half. ([Nivolumab](https://onco.cc/drugs/nivolumab/), [IMRT / IGRT (modern external beam)](https://onco.cc/technologies/imrt-igrt/))
- Metastatic, first line: Avelumab, pembrolizumab or retifanlimab; ~50% response with most responses durable. ([Avelumab](https://onco.cc/drugs/avelumab/), [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/), [Retifanlimab](https://onco.cc/drugs/retifanlimab/))
- Immunotherapy-refractory: Platinum-etoposide chemotherapy (brief responses), radiotherapy, clinical trials (ipilimumab-nivolumab, T-VEC, adoptive T cells). ([Platinum + etoposide (EP / CE)](https://onco.cc/drugs/platinum-etoposide/), [Ipilimumab](https://onco.cc/drugs/ipilimumab/), [Talimogene laherparepvec](https://onco.cc/drugs/talimogene-laherparepvec/))

## State of the art

- Three approved PD-1/PD-L1 antibodies; about half of metastatic patients respond and most responders stay in remission for years.
- Virus-driven biology makes MCPyV antigens an appealing target for vaccines and TCR-T.
- Adjuvant immunotherapy has its first positive trial (ADMEC-O) and is entering guidelines.
- Serologic surveillance (MCPyV oncoprotein antibodies) reduces imaging in seropositive patients.

## Open problems

- Half of patients do not respond to PD-1 blockade and have no effective second line.
- Immunosuppressed patients: high incidence, poor outcomes, contraindications to immunotherapy.
- No validated adjuvant standard yet despite ADMEC-O.
- Rarity limits trial size; registries (e.g. Seattle) carry much of the evidence.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Merkel-cell_carcinoma
- NCCN Guidelines: Merkel Cell Carcinoma: https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1444
- Merkelcell.org (UW/Fred Hutch): https://merkelcell.org/
- NCI PDQ: Merkel cell carcinoma: https://www.cancer.gov/types/skin/patient/merkel-cell-treatment-pdq

## Connected records

- cancers: [Advanced cutaneous squamous cell carcinoma](https://onco.cc/cancers/advanced-cutaneous-scc/), [Basal cell carcinoma](https://onco.cc/cancers/basal-cell-carcinoma/), [Cutaneous squamous cell carcinoma](https://onco.cc/cancers/cutaneous-scc/), [Locally advanced and metastatic basal cell carcinoma](https://onco.cc/cancers/locally-advanced-bcc/), [Melanoma](https://onco.cc/cancers/melanoma/), [Skin cancer (all types)](https://onco.cc/cancers/skin-cancer/)
- technologies: [Electron beam therapy systems (linac electrons, total skin electron units, mobile electron IORT)](https://onco.cc/technologies/electron-beam-therapy-systems/), [Gamma probes, handheld gamma cameras and dose calibrators](https://onco.cc/technologies/gamma-probes-dose-calibrators/), [Immune checkpoint inhibitors](https://onco.cc/technologies/checkpoint-inhibitor/), [IMRT / IGRT (modern external beam)](https://onco.cc/technologies/imrt-igrt/), [Oncolytic viruses](https://onco.cc/technologies/oncolytic-virus/), [Sentinel lymph node biopsy](https://onco.cc/technologies/sentinel-node/), [TCR-T cell therapy](https://onco.cc/technologies/tcr-t/)
- targets: [CTLA-4](https://onco.cc/targets/ctla4/), [PD-1](https://onco.cc/targets/pd1/), [PD-L1](https://onco.cc/targets/pdl1/)
- drugs: [Avelumab](https://onco.cc/drugs/avelumab/), [Ipilimumab](https://onco.cc/drugs/ipilimumab/), [Nivolumab](https://onco.cc/drugs/nivolumab/), [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/), [Platinum + etoposide (EP / CE)](https://onco.cc/drugs/platinum-etoposide/), [Retifanlimab](https://onco.cc/drugs/retifanlimab/), [Talimogene laherparepvec](https://onco.cc/drugs/talimogene-laherparepvec/)
- companies: [Bristol Myers Squibb](https://onco.cc/companies/bms/), [Incyte](https://onco.cc/companies/incyte/), [Merck & Co. (MSD)](https://onco.cc/companies/merck/), [Merck KGaA (EMD Serono)](https://onco.cc/companies/merck-kgaa/), [Neonc Technologies](https://onco.cc/companies/neonc-technologies/), [Pfizer (incl. Seagen)](https://onco.cc/companies/pfizer/)
- pathways: [Oncogenic viruses](https://onco.cc/pathways/oncogenic-viruses/), [p53 / RB / cell-cycle checkpoint](https://onco.cc/pathways/p53-cell-cycle/), [PD-1 / PD-L1 immune checkpoint & T-cell activation](https://onco.cc/pathways/pd1-checkpoint/)
- terms: [Immune-related adverse events (irAEs)](https://onco.cc/terms/irae/), [Merkel cell polyomavirus (MCPyV) status](https://onco.cc/terms/mcpyv-status/), [Rare cancers](https://onco.cc/terms/rare-cancers/), [Tumour mutational burden (TMB)](https://onco.cc/terms/tmb/)
- trials: [A Study of Pembrolizumab in Japanese Pediatric Participants With Solid Tumors or Lymphomas and Japanese Adult Participants With Merkel Cell Carcinoma (MK-3475-G21/KEYNOTE-G21)](https://onco.cc/trials/nct07302347/), [A Study to Investigate Safety of AZD6750 in Adult Participants With Select Advanced or Metastatic Solid Tumors](https://onco.cc/trials/nct07115043/), [BOXR1030 T Cells in Subjects With Advanced GPC3-Positive Solid Tumors](https://onco.cc/trials/nct05120271/), [CheckMate 358](https://onco.cc/trials/checkmate-358/), [JAVELIN Merkel 200](https://onco.cc/trials/javelin-merkel-200/), [KEYNOTE-017 (Cancer Immunotherapy Trials Network 09)](https://onco.cc/trials/keynote-017/), [Placebo-Controlled Trial of IFx-Hu2.0 Followed By Pembrolizumab In Checkpoint Inhibitor Naïve Participants With Advanced Or Metastatic Merkel Cell Car](https://onco.cc/trials/nct06947928/), [QUILT-3.055: A Study of Combination Immunotherapies in Patients Who Have Previously Received Treatment With Immune Checkpoint Inhibitors](https://onco.cc/trials/nct03228667/), [Safety and Efficacy of NEO212 in Patients With Astrocytoma IDH-mutant, Glioblastoma IDH-wildtype or Brain Metastasis](https://onco.cc/trials/nct06047379/), [STAMP (EA6174)](https://onco.cc/trials/stamp-merkel/), [Study to Investigate the Efficacy and Safety of RP1 in Adult Patients With Organ Transplants and Advanced Skin Malignancies](https://onco.cc/trials/nct04349436/)
- people: [Dirk Schadendorf](https://onco.cc/people/dirk-schadendorf/), [Howard L. Kaufman](https://onco.cc/people/howard-kaufman/), [Reinhard Dummer](https://onco.cc/people/reinhard-dummer/), [Sandra P. D'Angelo](https://onco.cc/people/sandra-dangelo/), [Shailender Bhatia](https://onco.cc/people/shailender-bhatia/)
- institutions: [UPMC Hillman Cancer Center](https://onco.cc/institutions/upmc-hillman/)
- journals: [Tumour virus research](https://onco.cc/journals/tumour-virus-research/)

---
JSON: https://onco.cc/api/v1/entities/merkel-cell-carcinoma.json