Gestational Trophoblastic Neoplasia After Human Chorionic Gonadotropin Normalization Following Molar Pregnancy: A Systematic Review and Meta-analysis.

OBJECTIVE: To estimate the incidence of gestational trophoblastic neoplasia following complete and partial molar pregnancy after reaching normal human chorionic gonadotropin (hCG) levels to guide evidence-based follow-up recommendations. DATA SOURCES: MEDLINE, EMBASE, Web of Science, POPLINE, Cochrane, and ClinicalTrials.gov were searched from inception to November 2018, using the intersection of "gestational trophoblastic disease," "molar pregnancy," and "human chorionic gonadotropin" themes. METHODS OF STUDY SELECTION: Search results were screened to identify cohort studies of molar pregnancy reporting gestational trophoblastic neoplasia development, with at least 6 months of intended normal hCG follow-up. TABULATION, INTEGRATION, AND
RESULTS: Two reviewers independently identified articles for inclusion. Data were extracted using a standardized form. For meta-analysis, cumulative incidence of gestational trophoblastic neoplasia, with CIs by the Agresti-Coull method, and pooled risk ratios (RRs) comparing complete and partial mole were calculated. Among the 19 eligible studies that reported adequate data for inclusion in the primary meta-analysis, we found low incidence of gestational trophoblastic neoplasia after normal hCG level following both complete mole (64/18,357, 0.35%, 95% CI 0.27-0.45%), and partial mole (5/14,864, 0.03%, 95% CI 0.01-0.08%). There was a significantly higher risk of gestational trophoblastic neoplasia after complete compared with partial molar pregnancy (RR 4.72, 95% CI 1.81-12.3, P=.002). Among gestational trophoblastic neoplasia cases after normal hCG level following complete mole, 89.6% occurred when the time from evacuation to normalization was 56 days or longer, and 60.7% were diagnosed beyond the commonly recommended 6-month surveillance interval. Sensitivity analyses, including those limiting to studies at low risk of bias, did not significantly affect results. We found an overall incidence of gestational trophoblastic neoplasia of 15.7% for complete mole (1,354/8,611, 95% CI 15.0-16.5%) and 3.95% for partial mole (221/5,593, 95% CI 3.47-4.50%).
CONCLUSION: Gestational trophoblastic neoplasia development after normal hCG level following molar pregnancy is rare. Recommendations for frequency and duration of hCG follow-up can be minimized to lessen burden on patients and informed by the type of molar pregnancy and time interval from uterine evacuation to hCG normalization. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42019116414.