Persistent low-level real human chorionic gonadotropin after gestational trophoblastic disease: natural history and predictors of subsequent gestational trophoblastic neoplasia

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Abstract
ObjectiveTo characterize the natural history of persistent low-level real human chorionic gonadotropin (hCG) after gestational trophoblastic disease (GTD) and identify predictors of subsequent gestational trophoblastic neoplasia (GTN).MethodsRetrospective cohort study included patients with persistent low-level real hCG (≤100 IU/L for ≥3 months) during postmolar surveillance or after GTN remission at specialized GTD referral centers in Rio de Janeiro, Brazil, between 2000 and 2022. Clinical characteristics, hCG patterns, and oncologic outcomes were analyzed. Risk differences (RD) and 95% confidence intervals (CI) were calculated to identify factors associated with subsequent GTN.ResultsAmong 7,304 patients with GTD managed during the study period, 72 (0.9%) developed persistent low-level real hCG. Spontaneous hCG normalization occurred in 88.4% (38/43) of patients during postmolar surveillance and 75.9% (22/29) after GTN remission. During postmolar surveillance, vaginal hemorrhage (RD:35.7%, 95%CI:10.6–60.8), preevacuation hCG ≥100,000 IU/L (RD:22.7%, 95%CI:5.2–40.2), and delayed onset of persistent low-level real hCG ≥7 weeks (RD:16.6%, 95%CI:3.3–30.0) were associated with an increased risk of postmolar GTN. Among patients monitored after GTN remission, age ≥34 years (RD:19.1%, 95%CI:11.0–49.1), preevacuation hCG ≥100,000 IU/L (RD:30.4%, 95%CI:11.6–49.2), and delayed onset of persistent low-level real hCG ≥14 weeks (RD:43.8%, 95%CI:19.4–68.1) were associated with relapsed GTN.ConclusionsPersistent low-level real hCG after GTD frequently resolves spontaneously and does not necessarily represent active malignancy. Careful surveillance until fulfillment of FIGO criteria appears to be the most appropriate management strategy, minimizing unnecessary interventions.