Teaching pack: Gestational trophoblastic neoplasia

Gestational trophoblastic neoplasia (GTN) follows a molar pregnancy (complete or partial hydatidiform mole) or, less often, any pregnancy, and includes invasive mole, choriocarcinoma, placental-site and epithelioid trophoblastic tumours. Serum hCG tracks disease burden with unique precision, so diagnosis is usually made from a plateau or rise in hCG after molar evacuation without histology. The FIGO 2000 prognostic score separates low-risk (single-agent methotrexate or actinomycin D) from high-risk disease (multi-agent EMA-CO), with ultra-high-risk patients started on low-dose induction etoposide-cisplatin to prevent early death.

GTN is highly immunogenic (paternal antigens, PD-L1 expression), and PD-1 blockade produced durable complete remissions in chemotherapy-resistant disease (pembrolizumab, Ghorani 2017; avelumab TROPHIMMUN 2020), now in guidelines. Placental-site and epithelioid tumours are chemo-resistant and treated by hysterectomy. Outcomes depend on centralised care with hCG registries (Charing Cross, Sheffield, Brewer).

• The only cancer routinely diagnosed and monitored by a hormone alone, with near-universal cure.
• Immunotherapy cures a majority of drug-resistant cases; trials (TROPHAMET, TROPHIMMUN) now test it earlier to avoid chemotherapy.
• Centralised registries remain the model for how rare cancers should be managed.

1. 1956Methotrexate cures metastatic choriocarcinoma (Li, Hertz, Spencer)
2. 1973Charing Cross hCG surveillance service established
3. 1979EMA-CO introduced by Bagshawe for high-risk disease
4. 2000FIGO 2000 staging and prognostic score
5. 2017Pembrolizumab cures chemoresistant GTN (Ghorani, Lancet)
6. 2020TROPHIMMUN: avelumab in methotrexate-resistant low-risk GTN

• Pembrolizumab (treatment)
• Avelumab (treatment)

• TROPHIMMUN (phase 2, n=24): hCG normalisation, cohort A (resistance to single-agent chemotherapy): 53.3%

• Late diagnosis where hCG surveillance after molar pregnancy is absent (much of the world).
• Fertility and psychological burden of a pregnancy-related cancer.
• PSTT/ETT chemo-resistance.
• Cumulative etoposide exposure and second cancers.

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.

• NCCN Guidelines: GTN: https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1489
• NCI PDQ: GTD: https://www.cancer.gov/types/gestational-trophoblastic/patient/gtd-treatment-pdq
• Wikipedia: https://en.wikipedia.org/wiki/Gestational_trophoblastic_disease
• Guideline: https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1489