OnCo
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Cutaneous squamous cell carcinoma

aka cSCC

A very common sun-related skin cancer that is almost always cured by removing it. The small fraction that grows deep or spreads now responds well to PD-1 immunotherapy, which is also given after surgery in high-risk cases.

Cutaneous squamous cell carcinoma (cSCC) arises from UV-damaged keratinocytes and has one of the highest mutational burdens of any cancer (TP53, NOTCH1/2, CDKN2A). Immunosuppression (transplant recipients have 65-100-fold higher risk) and chronic wounds are other causes. Most tumours are cured by excision or Mohs surgery; risk of recurrence and metastasis is stratified by BWH/AJCC-8 staging (depth, perineural invasion, differentiation, immunosuppression), with radiotherapy for high-risk or inoperable disease.

Cemiplimab (EMPOWER-CSCC-1, 2018) was the first systemic therapy approved for advanced cSCC, with ~45-50% response and durable disease control; pembrolizumab (KEYNOTE-629, 2020) and cosibelimab (anti-PD-L1, December 2024) followed. Neoadjuvant cemiplimab produced pathological complete response in 51% of stage II-IV disease (Gross, NEJM 2022), and the C-POST trial (2025) showed adjuvant cemiplimab after surgery and radiotherapy cut recurrence in high-risk patients, leading to an adjuvant approval. EGFR antibodies (cetuximab) and chemotherapy are reserved for immunotherapy-ineligible patients such as organ-transplant recipients.

Open: managing transplant recipients (checkpoint inhibitors cause graft rejection), chemoprevention (nicotinamide, acitretin), and the burden of field cancerisation.

State of the art today

  • PD-1 blockade produces durable responses in about half of advanced cSCC, one of the best response rates of any solid tumour, explained by extreme UV mutational burden.
  • Neoadjuvant cemiplimab (51% pCR) is redefining surgery for large tumours; adjuvant cemiplimab (C-POST) is the first to reduce recurrence after surgery and radiation.
  • Cosibelimab adds an anti-PD-L1 option with a different toxicity profile.
  • Transplant recipients remain the hardest group: immunotherapy risks graft loss; mTOR-inhibitor switching and acitretin are the preventive levers.
Who it affects
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.

  • Second most common skin cancer; over one million cases per year in the US; about 2-5% metastasise, but that is still several thousand deaths a year.
Group
skin

Where the cases are

Cases by country · GLOBOCAN 2022
All countries →

No country-level case numbers. This cancer is not mapped to a GLOBOCAN site.

Standard of care

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Localised low- and high-risk

Excision with margin control or Mohs micrographic surgery; adjuvant radiotherapy for high-risk features (perineural invasion, positive margins); nodal evaluation for very high risk.

NCCN · Category 2A
IMRT / IGRT (modern external beam)Sentinel lymph node biopsy
High-risk after surgery and radiotherapy

Adjuvant cemiplimab (C-POST, 2025: reduced locoregional and distant recurrence).

C-POST (NEJM 2025)
Cemiplimab
Locally advanced or metastatic

Cemiplimab, pembrolizumab or cosibelimab; neoadjuvant cemiplimab for resectable stage II-IV to shrink surgery (51% pCR).

NCCN · Category 2A (preferred: cemiplimab, pembrol…
CemiplimabPembrolizumabCosibelimab
Immunotherapy-ineligible or refractory

Cetuximab ± radiotherapy, platinum-based chemotherapy, capecitabine; trials of intratumoural agents (RP1) and EGFR ADCs.

CetuximabCarboplatinVusolimogene oderparepvec

Subtypes & biomarkers

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Subtypes
Biomarkers clinicians test

Target prevalence in this cancer

History

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  1. 1775Percivall Pott links chimney-sweep soot to scrotal SCC

    First occupational carcinogen described.

  2. 1938Mohs micrographic surgery introduced
  3. 2011Cetuximab activity in unresectable cSCC (phase 2)
    Cetuximab
  4. 2018Cemiplimab: first systemic approval for cSCC

    EMPOWER-CSCC-1 (NEJM 2018).

    Cemiplimab
  5. 2020Pembrolizumab approved (KEYNOTE-629)
    Pembrolizumab
  6. 2022Neoadjuvant cemiplimab: 51% pathological complete response (NEJM)
    Cemiplimab
  7. 2024Cosibelimab approved (December)
    Cosibelimab
  8. 2025C-POST: adjuvant cemiplimab reduces recurrence
    Cemiplimab

Pipeline

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ApprovedMonoclonal antibody (anti-PD-1)
Cemiplimab · Libtayo
Not mapped hereAnti-PD-L1 monoclonal antibody (IgG1, ADCC-competent)
Cosibelimab · Unloxcyt
ApprovedOncolytic virus (HSV-1)
Vusolimogene oderparepvec · Tudriqev

Open problems

  • Organ-transplant recipients: high incidence, no safe immunotherapy.
  • Who needs adjuvant therapy: gene-expression tests vs clinicopathologic staging.
  • Field cancerisation and multiple primaries in the elderly.
  • Access to Mohs surgery and dermatology capacity.

Trials

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Recruiting now (live from ClinicalTrials.gov)

Recruiting trials near you · live from ClinicalTrials.gov
Cutaneous squamous cell carcinoma
condition: Cutaneous squamous cell carcinoma
Open on ClinicalTrials.gov →

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.

Expert centres

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Where the expertise is

Centres linked to this cancer in OnCo

Seeking a second opinion: ask your oncologist for a referral to a high-volume centre; most accept records and pathology by mail or telehealth. In the US, use the NCI's Find a Cancer Center tool or the nonprofit Cancer Commons, which navigates options for advanced cancers at no cost.

Questions to ask

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Bring to your appointment

Questions to ask your oncologist about Cutaneous squamous cell carcinoma

Generated from this cancer's standard of care, biomarkers, and pipeline · 16 questions

Newly diagnosed

  1. What is my exact diagnosis, stage, and grade, and which tests established them?
    Why: Everything else follows from an accurate stage and subtype.
  2. Which biomarkers have been tested on my tumour (for example BWH and AJCC-8 T stage, Perineural invasion, depth beyond fat, differentiation, Immunosuppression status, Gene-expression prognostic test, PD-L1), and what were the results?
    Why: These results decide eligibility for targeted therapy, immunotherapy, and trials.
  3. Which subtype is my cancer, and does that change the recommended treatment?
    Why: Recognised subtypes for this cancer include Low-risk cSCC, High-risk cSCC, Locally advanced unresectable cSCC.
  4. Is germline (inherited) genetic testing recommended for me or my family?
    Why: Inherited variants can change treatment and matter for relatives.

Localised low- and high-risk

  1. For my situation (localised low- and high-risk), which of the standard options do you recommend and why?
    Why: Guideline options include: Excision with margin control or Mohs micrographic surgery; adjuvant radiotherapy for high-risk features (perineural invasion, positive margins); nodal evaluation for very high risk.

High-risk after surgery and radiotherapy

  1. For my situation (high-risk after surgery and radiotherapy), which of the standard options do you recommend and why?
    Why: Guideline options include: Adjuvant cemiplimab (C-POST, 2025: reduced locoregional and distant recurrence).
  2. Am I a candidate for Cemiplimab, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.

Locally advanced or metastatic

  1. For my situation (locally advanced or metastatic), which of the standard options do you recommend and why?
    Why: Guideline options include: Cemiplimab, pembrolizumab or cosibelimab; neoadjuvant cemiplimab for resectable stage II-IV to shrink surgery (51% pCR).
  2. Am I a candidate for Cemiplimab, Pembrolizumab, Cosibelimab, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.

Immunotherapy-ineligible or refractory

  1. For my situation (immunotherapy-ineligible or refractory), which of the standard options do you recommend and why?
    Why: Guideline options include: Cetuximab ± radiotherapy, platinum-based chemotherapy, capecitabine; trials of intratumoural agents (RP1) and EGFR ADCs.
  2. Am I a candidate for Cetuximab, Carboplatin, Vusolimogene oderparepvec, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.

Any stage

  1. Are there clinical trials I could join, for example of Cemiplimab, Cosibelimab, Vusolimogene oderparepvec?
    Why: Trials are how the next standard of care is set; asking early keeps options open.
  2. 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.
  3. 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.
  4. I read that “Organ-transplant recipients: high incidence, no safe immunotherapy”. How does that affect my plan?
    Why: Open problems are where trials and second opinions matter most.
  5. I read that “Who needs adjuvant therapy: gene-expression tests vs clinicopathologic staging”. How does that affect my plan?
    Why: Open problems are where trials and second opinions matter most.

Print this page for your appointment (your browser's print command). These prompts are for discussion; your clinical team knows your case.

Everything relevant

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Direct links plus the targets, companies, and technologies of this cancer's products.

technologies

10
Chemoprevention & risk-reducing surgeryCytotoxic chemotherapyDermoscopy, total-body photography & AI skin analysisElectrochemotherapyImmune checkpoint inhibitorsIMRT / IGRT (modern external beam)Monoclonal antibodiesOncolytic virusesPlatinum agentsSentinel lymph node biopsy

targets

4
EGFRPD-1PD-L1TP53

drugs

6
ApprovedCytotoxic chemotherapy (platinum)
Carboplatin
ApprovedMonoclonal antibody (anti-PD-1)
Cemiplimab · Libtayo
ApprovedMonoclonal antibody (anti-EGFR)
Cetuximab · Erbitux
Not mapped hereAnti-PD-L1 monoclonal antibody (IgG1, ADCC-competent)
Cosibelimab · Unloxcyt
ApprovedMonoclonal antibody (anti-PD-1)
Pembrolizumab · Keytruda / Keytruda Qlex (SC)
ApprovedOncolytic virus (HSV-1)
Vusolimogene oderparepvec · Tudriqev

companies

7
Bristol Myers SquibbEli Lilly (incl. Loxo)Merck & Co. (MSD)RegeneronReplimuneSanofiSummit Therapeutics

institutions

1
University of Arizona Cancer Center

pathways

2
p53 / RB / cell-cycle checkpointPD-1 / PD-L1 immune checkpoint & T-cell activation

terms

3
Immune-related adverse events (irAEs)Pathologic complete response (pCR)Tumour mutational burden (TMB)

Latest papers

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Latest papers · live from Europe PMC
Open in Europe PMC

Query for this cancer: (TITLE:"Cutaneous squamous cell carcinoma" OR ABSTRACT:"Cutaneous squamous cell carcinoma" OR TITLE:"cSCC" OR ABSTRACT:"cSCC") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Cutaneous squamous cell carcinoma, not a curated reading list.

Connected

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Pages like this

not linked directly; found by shared links

technologies

8
Chemoprevention & risk-reducing surgeryDermoscopy, total-body photography & AI skin analysisElectrochemotherapyImmune checkpoint inhibitorsIMRT / IGRT (modern external beam)Monoclonal antibodiesOncolytic virusesSentinel lymph node biopsy

targets

4
EGFRPD-1PD-L1TP53

drugs

6
ApprovedCytotoxic chemotherapy (platinum)
Carboplatin
ApprovedMonoclonal antibody (anti-PD-1)
Cemiplimab · Libtayo
ApprovedMonoclonal antibody (anti-EGFR)
Cetuximab · Erbitux
Not mapped hereAnti-PD-L1 monoclonal antibody (IgG1, ADCC-competent)
Cosibelimab · Unloxcyt
ApprovedMonoclonal antibody (anti-PD-1)
Pembrolizumab · Keytruda / Keytruda Qlex (SC)
ApprovedOncolytic virus (HSV-1)
Vusolimogene oderparepvec · Tudriqev

companies

5
Merck & Co. (MSD)RegeneronReplimuneSanofiSummit Therapeutics

institutions

1
University of Arizona Cancer Center

pathways

2
p53 / RB / cell-cycle checkpointPD-1 / PD-L1 immune checkpoint & T-cell activation

terms

3
Immune-related adverse events (irAEs)Pathologic complete response (pCR)Tumour mutational burden (TMB)