Gestational trophoblastic disease (GTD) is an uncommon group of conditions associated with pregnancy and defined by abnormal trophoblastic proliferation. Arising from an abnormal placenta, it occurs in about 1:1000 pregnancies in Australia but wide variations exist in the reported incidence due to ethnic variations, issues with data capture and a lack of registries.
GTD typically presents in the first trimester with irregular vaginal bleeding and can be suspected on ultrasound but confirmation requires histopathological evaluation of the products of conception and ancillary testing. Most molar pregnancies resolve without treatment after uterine evacuation (D&C), but occasionally the disease persists and progresses into cancer requiring chemotherapy or further surgical intervention.
Histologically, there is a spectrum of disease from premalignant partial (PHM) and complete hydatiform moles (CHM) to malignant conditions of invasive mole, choriocarcinoma, placental site trophoblastic tumour (PSTT) and epithelioid trophoblastic tumour (ETT), collectively known as gestational trophoblastic neoplasia (GTN)
More recently the GTD spectrum has been expanded to include atypical placental site nodules (APSN) as 10-15% may coexist with or develop into PSTT/ETT. Each have unique management depending on fertility wishes.
All cases are made complex by the need for intense monitoring with the hCG tumour assay, potential for malignancy and the occurrence of disease in young patients where future pregnancy is often desired.
In low risk GTN requiring single agent chemotherapy, overall survival approaches 100% and even in high risk GTN treated with multimodal chemotherapy and sometimes surgery for excision of resistant foci of disease and radiotherapy for brain metastases, survival rate is approximately 90%.
Rare diseases such as GTD should have centralised care through state or national-based registries and services. This allows for expert pathology review, clear surveillance pathways, the removal of inconsistent treatment decisions and, most importantly, improved patient survival and patient reported outcomes.
The Western Australian Trophoblastic Centre (WATC) is a state-wide service established in January 2023 by Western Australian Gynaecologic Cancer Service and allows centralised and specialised care to both new and existing, public and private patients with trophoblastic disease.
There is a registry only option for clinicians who wish to continue to manage and follow-up their own patients but can re-refer if escalation of care is required. The service provides full medical, nursing, psychological care and support.
The dedicated GTD nurse is pivotal to the service in the provision of support through diagnosis, monitoring, treatment and beyond. There is a weekly multidisciplinary case conference where all patients on hCG monitoring and chemotherapy are discussed, and once weekly afternoon multidisciplinary clinic.
Psychological support is an integral component of the service. These patients are not only coping with pregnancy loss and its associated grief, but anxiety around fear of recurrence and potential cancer, chemotherapy and loss of future fertility and not surprisingly often require more psychological support in their subsequent pregnancy.
There is a specific second daily clinic for intramuscular methotrexate administration for low-risk GTN including on Saturdays. Logistically methotrexate works well as it avoids the fortnightly day admission for intravenous Actinomycin D with a medical oncologist but patients are given the choice of regimen given both are equally effective.
The WATC has been well supported nationally (QTC and Victorian HyMol) and internationally (Charring Cross and Sheffield) since inception by established trophoblastic centres.
So far, WATC has received approximately 200 new and existing referrals for patients aged 17-53 years (median 31 years). The histology of the referrals includes:
- 108 PHM of which two were ectopic in the fallopian tube or caesarean scar. Two had recurrent partial moles after hCG normalisation. Approximately 25% of partial moles were subsequently non-molar chromosomally abnormal miscarriages on FISH and could be discharged from WATC care
- 72 CHM (two with coexistent viable twin)
- Four APSN
- One new choriocarcinoma, five pre-existing
- One pre-existing ETT and one pre-existing PSTT
10% of referrals are for registry only and the remainder for WATC care.
Nine patients required a hysterectomy (6 CHM, 2 APSN, 1 GTN). All had completed childbearing; 14 patients developed low risk GTN (all complete moles) and required single agent chemotherapy for which approximately 30% had to change to Actinomycin D (consistent with known methotrexate resistance). Two patients required multi-agent EMACO chemotherapy for high risk GTN (one complete mole and one choriocarcinoma). The complete mole had a subsequent hysterectomy on completion of chemotherapy for persistent disease and is now in remission. The choriocarcinoma returned overseas for treatment. For further information contact watc@health.wa.gov.au
Key messages
- Centralised care is crucial to the management of rare diseases such as GTD
- Management of GTD by expert centres results in better patient survival and patent reported outcomes
- Long-term psychological support and management of patient anxiety is critical.
ED: *WA Gynaecologic Cancer Service
Author competing interests – nil