Background
The risk of malignant transformation of molar pregnancies after human chorionic gonadotropin
levels return to normal is low, roughly 0.4%, but may justify an adaptation of monitoring
strategies for certain patients.
Objective
This study aimed to determine the risk of gestational trophoblastic neoplasia after
human chorionic gonadotropin normalization in women with molar pregnancy and identify
risk factors for this type of malignant transformation to optimize follow-up protocols
after human chorionic gonadotropin normalization.
Study Design
This was a retrospective observational national cohort study based at the French National
Center for Trophoblastic Diseases of 7761 patients, treated between 1999 and 2020
for gestational trophoblastic disease, whose human chorionic gonadotropin levels returned
spontaneously to normal.
Results
Among 7761 patients whose human chorionic gonadotropin levels returned to normal,
20 (0.26%) developed gestational trophoblastic neoplasia. The risk of malignant transformation
varied with the type of mole, from 0% (0 of 2592 cases) for histologically proven
partial mole to 0.36% for complete mole (18 of 5045) and 2.1% (2 of 95) for twin molar
pregnancy. The median time to diagnosis of malignant transformation after human chorionic
gonadotropin normalization was 11.4 months (range, 1–34 months). At diagnosis, 16
of 20 patients (80%) had the International Federation of Gynecology and Obstetrics
stage I tumor, and 10 of 20 patients (50%) had a tumor classified as low risk in terms
of the International Federation of Gynecology and Obstetrics score. In 9 of 20 patients
(45%), the most common first-line treatment was combination chemotherapy. A quarter
of these tumors (5 of 20) were histologically proven placental site or epithelioid
trophoblastic tumors. In univariate analysis, the factors significantly associated
with a higher risk of developing gestational trophoblastic neoplasia after the end
of the normal human chorionic gonadotropin monitoring period were age of ≥45 years
(odds ratio, 8.3; 95% confidence interval, 2.0–32.7; P=.004) and time to human chorionic gonadotropin normalization of ≥8 weeks (odds ratio,
7.7; 95% confidence interval, 1.1–335; P=.03). The risk was even higher for human chorionic gonadotropin normalization times
of ≥17 weeks (odds ratio, 19.5; 95% confidence interval, 3.3–206; P<.001).
Conclusion
In this group of patients with gestational trophoblastic disease, none of the those
with pathologically verified partial mole had malignant transformation, supporting
the current recommendation of stopping human chorionic gonadotropin monitoring after
3 successive negative tests. In cases of complete mole or twin molar pregnancy, we proposed
to extend the monitoring period with quarterly human chorionic gonadotropin measurements
for an additional 30 months in patients with the identified risk factors for late
malignant transformation (age, ≥45 years; time to human chorionic gonadotropin normalization,
≥8 weeks).
Key words
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Article info
Publication history
Published online: May 18, 2021
Accepted:
May 11,
2021
Received in revised form:
May 11,
2021
Received:
March 22,
2021
Footnotes
The authors report no conflict of interest.
This study received no specific funding.
Cite this article as: Descargues P, Hajri T, Massardier J, et al. Gestational trophoblastic neoplasia after human chorionic gonadotropin normalization in a retrospective cohort of 7761 patients in France. Am J Obstet Gynecol 2021;225:401.e1-9.
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