Gestational Trophoblastic Disease
Gestational trophoblastic disease arises from placental tissue and is unusual in oncology for being highly curable even in advanced stages, with hCG serving as an exceptionally sensitive marker of disease activity.
Disease categories
Major disease categories
- Complete and partial hydatidiform mole
- Invasive mole
- Choriocarcinoma
- Placental site trophoblastic tumour
- Epithelioid trophoblastic tumour
Molecular
Molecular considerations
Genotyping can distinguish complete from partial mole and can establish whether a tumour is gestational in origin, which materially changes management discussion.
Markers commonly discussed in gestational trophoblastic disease
- hCG
- p57 immunohistochemistry
- Genotyping / ploidy
Not exhaustive, and not every marker is assessed in every patient. Which of these is relevant depends on the individual case and should be discussed with the treating team.
Testing
Genomic testing considerations
Molecular genotyping has a defined diagnostic role in this disease, which is unusual.
Germline
Germline considerations
Recurrent molar pregnancy raises the question of familial biparental hydatidiform mole associated with NLRP7 and KHDC3L.
Molecular monitoring
ctDNA and liquid biopsy considerations
hCG is already a highly sensitive circulating marker, so ctDNA adds little in most situations.
Single-cell & computation
Single-cell and algorithmic approaches
Single-cell analysis in gynaecological cancer is applied to clonal structure at relapse, where the question is whether resistant disease was present from the outset or emerged under treatment. Single-cell DNA sequencing can identify reversion events in a subpopulation before they are detectable in bulk. Algorithmic work includes homologous recombination deficiency scoring from sequencing data, mutational signature analysis, and molecular classification pipelines.
Decisions
Treatment decision questions
Questions worth raising with a treating team when a decision is being made:
- Is hCG being monitored on a defined schedule?
- Has genotyping been performed where the diagnosis is uncertain?
- Has care at a specialist trophoblastic disease centre been considered?
Resistance
Resistance and recurrence questions
- Is hCG plateauing or rising, and has that been acted on?
Trials
Clinical trial considerations
Relevant chiefly in the small number of drug-resistant cases.
When a precision oncology review may help
A review is most useful where the standard pathway has been exhausted or where the picture is more complicated than a protocol accounts for — rare presentations, treatment resistance, complex or apparently contradictory molecular findings, or a decision between several defensible options.
The output is a structured analysis and a set of questions for the treating team. It is not treatment, and it does not replace the treating oncologist.