Treatments and outcomes in high‐risk gestational trophoblastic neoplasia: A systematic review and meta‐analysis

Abstract

AbstractBackgroundHigh‐risk gestational trophoblastic neoplasia (GTN) is rare and treated with diverse approaches. Limited published institutional data has yet to be systematically reviewed.ObjectivesTo compile global high‐risk GTN (prognostic score ≥7) cohorts to summarise treatments and outcomes by disease characteristics and primary chemotherapy.Search StrategyMEDLINE, Embase, Scopus, ClinicalTrials.gov and Cochrane were searched through March 2021.Selection CriteriaFull‐text manuscripts reporting mortality among ≥10 high‐risk GTN patients.Data Collection and AnalysisBinomial proportions were summed, and random‐effects meta‐analyses performed.Main ResultsFrom 1137 records, we included 35 studies, representing 20 countries. Among 2276 unique high‐risk GTN patients, 99.7% received chemotherapy, 35.8% surgery and 4.9% radiation. Mortality was 10.9% (243/2236; meta‐analysis: 10%, 95% confidence interval [CI] 7–12%) and likelihood of complete response to primary chemotherapy was 79.7% (1506/1890; meta‐analysis: 78%, 95% CI: 74–83%). Across 24 reporting studies, modern preferred chemotherapy (EMA/CO or EMA/EP) was associated with lower mortality (overall: 8.8 versus 9.5%; comparative meta‐analysis: 8.1 versus 12.4%, OR 0.42, 95% CI: 0.20–0.90%, 14 studies) and higher likelihood of complete response (overall: 76.6 versus 72.8%; comparative meta‐analysis: 75.9 versus 60.7%, OR 2.98, 95% CI: 1.06–8.35%, 14 studies), though studies focused on non‐preferred regimens reported comparable outcomes. Mortality was increased for ultra‐high‐risk disease (30 versus 7.5% high‐risk; meta‐analysis OR 7.44, 95% CI: 4.29–12.9%) and disease following term delivery (20.8 versus 7.3% following molar pregnancy; meta‐analysis OR 2.64, 95% CI: 1.10–6.31%). Relapse rate estimates ranged from 3 to 6%.ConclusionsHigh‐risk GTN is responsive to several chemotherapy regimens, with EMA/CO or EMA/EP associated with improved outcomes. Mortality is increased in patients with ultra‐high‐risk, relapsed and post‐term pregnancy disease.