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Teaching pack: Testicular germ cell tumours

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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 · genitourinary

    Testicular germ cell tumours

    Testicular germ cell tumours are the most curable adult solid cancer. Cisplatin-based chemotherapy cures the large majority of even widely spread disease; today's research is about giving less treatment to the many while rescuing the few who relapse.

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

    In two paragraphs

    Testicular germ cell tumours (GCTs) are seminomas or non-seminomas (embryonal carcinoma, yolk sac tumour, choriocarcinoma, teratoma, mixed), arising from germ cell neoplasia in situ, almost universally carrying 12p gain (i(12p)). Serum tumour markers (AFP, hCG, LDH) stage and monitor the disease; miR-371a-3p is a more sensitive marker entering practice. The IGCCCG classification (1997, updated 2021) divides metastatic disease into good, intermediate and poor prognosis with 5-year survival of ~95%, ~90% and ~65-70%.

    Orchiectomy is followed by surveillance for most stage I disease; adjuvant carboplatin (seminoma) or one cycle of BEP (non-seminoma) are options for high-risk stage I. Metastatic disease receives BEP ×3 (good risk) or ×4 (intermediate/poor), or EP ×4 when bleomycin is contraindicated; residual masses after chemotherapy in non-seminoma are resected (retroperitoneal lymph node dissection). Relapse is treated with conventional-dose salvage (TIP, VeIP) or high-dose chemotherapy with autologous stem-cell rescue (TI-CE); the TIGER trial directly compares these. Survivorship (cardiovascular risk, second cancers, hypogonadism, infertility, ototoxicity, neuropathy) is a central concern because patients live 50+ years after cure.

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  3. Standard of care

    What is given today, by setting

    SettingApproachGuideline
    Stage I seminomaOrchiectomy then surveillance (preferred); adjuvant carboplatin AUC 7 ×1 or para-aortic radiotherapy for those declining surveillance.NCCN Category 2A (surveillance preferred)
    Stage I non-seminomaSurveillance (relapse ~15-50% by LVI status, all salvageable); or BEP ×1 or nerve-sparing RPLND for high-risk.NCCN Category 2A
    Metastatic, IGCCCG good riskBEP ×3 or EP ×4; post-chemotherapy RPLND for residual non-seminoma masses >1 cm.NCCN Category 1
    Metastatic, intermediate/poor riskBEP ×4 (or VIP if bleomycin contraindicated); early marker-decline assessment to intensify (GETUG-13); brain metastases treated multimodally.NCCN Category 1
    RelapsedTIP or VeIP conventional-dose salvage, or high-dose carboplatin-etoposide with autologous stem-cell rescue (TI-CE); TIGER phase 3 compares the two; late relapse and teratoma need surgery.NCCN Category 2A
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  4. State of the art

    Where the field stands

    • Cure rates above 95% are the benchmark for what chemotherapy can do; the field now works on de-escalation (surveillance for stage I, single-cycle adjuvant therapy) and survivorship.
    • miR-371a-3p promises to replace marker-negative uncertainty with a sensitive blood test for viable disease.
    • High-dose chemotherapy cures a substantial fraction of relapsed patients; TIGER will define its place.
    • Poor-risk disease and platinum-refractory GCT remain the unsolved minority; immunotherapy failed here.
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  5. History

    How we got here

    1. 1960Li and colleagues: actinomycin D, methotrexate and chlorambucil active in GCT
    2. 1974Einhorn introduces cisplatin (PVB)
    3. 1987BEP replaces PVB (Williams, NEJM)
    4. 1989BEP ×3 sufficient for good-risk disease (Einhorn)
    5. 1997IGCCCG prognostic classification
    6. 2005Carboplatin ×1 equals radiotherapy for stage I seminoma (MRC TE19)
    7. 2014Surveillance becomes standard for stage I
    8. 2019miR-371a-3p validated as a serum marker (Dieckmann, JCO)
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  6. Pipeline

    What is coming

    • Autologous stem cell transplant (high-dose therapy) (technology)
    • Carboplatin (product)
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  7. Open problems

    What nobody has solved

    • Platinum-refractory disease has no effective therapy; checkpoint inhibitors were inactive.
    • Late effects of cisplatin (cardiovascular disease, second cancers, hearing loss) in men cured in their 20s.
    • Over-treatment of stage I disease without reliable predictors.
    • Access to high-dose chemotherapy and expert RPLND outside specialist centres.
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  8. Sources

    Read the primary sources

    • NCCN Guidelines: Testicular Cancer: https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1468
    • IGCCCG Update (JCO 2021): https://doi.org/10.1200/JCO.20.03296
    • NCI PDQ: testicular cancer: https://www.cancer.gov/types/testicular/patient/testicular-treatment-pdq
    • Wikipedia: https://en.wikipedia.org/wiki/Testicular_cancer
    • Guideline: https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1468
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