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Teaching pack: Basal cell carcinoma

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8 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

    Basal cell carcinoma

    Basal cell carcinoma is the most common cancer of all, caused by sun exposure and almost never fatal. Nearly all are removed surgically; the rare advanced cases are treated with drugs that block the hedgehog signalling pathway, and with immunotherapy if those fail.

    Teaching pack: Basal cell carcinoma · OnCo, CC BY 4.0 · not medical advice1 / 8
  2. What it is

    In two paragraphs

    Basal cell carcinoma arises from hedgehog-pathway activation in nearly every case, through loss of PTCH1 (~70%) or activating SMO mutations (~10-20%); germline PTCH1 loss causes Gorlin (basal cell nevus) syndrome. Subtypes range from indolent nodular and superficial to infiltrative, morphoeic and basosquamous tumours with higher recurrence risk.

    Treatment is surgical (excision, Mohs for high-risk sites), with curettage, topical imiquimod or 5-fluorouracil, photodynamic therapy and radiotherapy as alternatives for low-risk or inoperable lesions. Vismodegib (ERIVANCE, 2012) and sonidegib (BOLT, 2015) are oral SMO inhibitors for locally advanced or metastatic BCC with ~45-60% response; their class toxicities (muscle spasms, dysgeusia, alopecia, weight loss) cause many to stop, and resistance arises through SMO mutations. Cemiplimab (2021) is approved after hedgehog-inhibitor failure or intolerance. Nicotinamide and sun protection reduce new BCCs in high-risk patients.

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  3. Standard of care

    What is given today, by setting

    SettingApproachGuideline
    Low-riskStandard excision with 4 mm margin, curettage and electrodesiccation, or topical imiquimod / 5-FU / photodynamic therapy for superficial lesions.NCCN Category 2A
    High-risk or recurrentMohs micrographic surgery or excision with complete margin assessment; radiotherapy if surgery not feasible.NCCN Category 2A
    Locally advanced or metastaticVismodegib or sonidegib; cemiplimab after hedgehog-inhibitor failure or intolerance; multidisciplinary review for surgery/radiotherapy after response.NCCN Category 2A
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  4. State of the art

    Where the field stands

    • Hedgehog inhibitors are among the few targeted drugs whose rationale came straight from a developmental-biology pathway and a hereditary syndrome (Gorlin).
    • Cemiplimab gives a second line after hedgehog-inhibitor failure.
    • Neoadjuvant vismodegib can shrink tumours to make surgery less destructive (VISMONEO).
    • Chemoprevention (nicotinamide) reduces new keratinocyte cancers in high-risk patients.
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  5. History

    How we got here

    1. 1996PTCH1 identified as the Gorlin syndrome gene
    2. 2009Vismodegib phase 1 shows responses in advanced BCC (NEJM)
    3. 2012Vismodegib approved (ERIVANCE)
    4. 2015Sonidegib approved (BOLT)
    5. 2015Nicotinamide reduces new keratinocyte cancers (ONTRAC, NEJM)
    6. 2021Cemiplimab approved after hedgehog-inhibitor failure
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  6. Pipeline

    What is coming

    • Cemiplimab (product)
    • Vismodegib (product)
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  7. Open problems

    What nobody has solved

    • Hedgehog-inhibitor tolerability leads most patients to stop within a year.
    • Resistance via SMO mutations has no approved next-in-class agent.
    • Huge volume: dermatology and Mohs capacity, and cost of treating millions of low-risk lesions.
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  8. Sources

    Read the primary sources

    • NCCN Guidelines: Basal Cell Skin Cancer: https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1416
    • ERIVANCE (NEJM 2012): https://doi.org/10.1056/NEJMoa1113713
    • NCI PDQ: skin cancer: https://www.cancer.gov/types/skin/patient/skin-treatment-pdq
    • Wikipedia: https://en.wikipedia.org/wiki/Basal-cell_carcinoma
    • Guideline: https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1416
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