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Teaching pack: Cutaneous squamous cell carcinoma

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9 slides generated from the cancer page, with a quiz from the open benchmark and speaker notes that cite the sources. Arrow keys move between slides; Print gives one slide per page.

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  1. Teaching pack · Cancer · skin

    Cutaneous squamous cell carcinoma

    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.

    Teaching pack: Cutaneous squamous cell carcinoma · OnCo, CC BY 4.0 · not medical advice1 / 9
  2. What it is

    In two paragraphs

    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.

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  3. Standard of care

    What is given today, by setting

    SettingApproachGuideline
    Localised low- and high-riskExcision 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
    High-risk after surgery and radiotherapyAdjuvant cemiplimab (C-POST, 2025: reduced locoregional and distant recurrence).not mapped
    Locally advanced or metastaticCemiplimab, pembrolizumab or cosibelimab; neoadjuvant cemiplimab for resectable stage II-IV to shrink surgery (51% pCR).NCCN Category 2A (preferred: cemiplimab, pembrolizumab)
    Immunotherapy-ineligible or refractoryCetuximab ± radiotherapy, platinum-based chemotherapy, capecitabine; trials of intratumoural agents (RP1) and EGFR ADCs.not mapped
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  4. State of the art

    Where the field stands

    • 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.
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  5. History

    How we got here

    1. 1775Percivall Pott links chimney-sweep soot to scrotal SCC
    2. 1938Mohs micrographic surgery introduced
    3. 2011Cetuximab activity in unresectable cSCC (phase 2)
    4. 2018Cemiplimab: first systemic approval for cSCC
    5. 2020Pembrolizumab approved (KEYNOTE-629)
    6. 2022Neoadjuvant cemiplimab: 51% pathological complete response (NEJM)
    7. 2024Cosibelimab approved (December)
    8. 2025C-POST: adjuvant cemiplimab reduces recurrence
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  6. Pipeline

    What is coming

    • Cemiplimab (product)
    • Cosibelimab (product)
    • Vusolimogene oderparepvec (product)
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  7. Open problems

    What nobody has solved

    • 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.
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  8. Quiz

    Check understanding

    1. What is the standard treatment for stage II-III triple-negative breast cancer today?
      Answer
      Neoadjuvant pembrolizumab with carboplatin/paclitaxel then anthracycline chemotherapy, surgery, and adjuvant pembrolizumab (KEYNOTE-522); adjuvant olaparib for germline BRCA carriers with residual disease (OlympiA); capecitabine for residual disease without BRCA.
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  9. Sources

    Read the primary sources

    • NCCN Guidelines: Squamous Cell Skin Cancer: https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1465
    • C-POST (NEJM 2025): https://doi.org/10.1056/NEJMoa2502449
    • NCI PDQ: skin cancer: https://www.cancer.gov/types/skin/patient/skin-treatment-pdq
    • Wikipedia: https://en.wikipedia.org/wiki/Squamous-cell_carcinoma_of_the_skin
    • Guideline: https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1465
    • Guideline: https://doi.org/10.1056/NEJMoa2502449
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