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Limited published institutional data has yet to be systematically reviewed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>To compile global high\u2010risk GTN (prognostic score\u2009\u22657) cohorts to summarise treatments and outcomes by disease characteristics and primary chemotherapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Search Strategy<\/jats:title><jats:p>MEDLINE, Embase, Scopus, ClinicalTrials.gov and Cochrane were searched through March 2021.<\/jats:p><\/jats:sec><jats:sec><jats:title>Selection Criteria<\/jats:title><jats:p>Full\u2010text manuscripts reporting mortality among \u226510 high\u2010risk GTN patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Data Collection and Analysis<\/jats:title><jats:p>Binomial proportions were summed, and random\u2010effects meta\u2010analyses performed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Main Results<\/jats:title><jats:p>From 1137 records, we included 35 studies, representing 20 countries. Among 2276 unique high\u2010risk GTN patients, 99.7% received chemotherapy, 35.8% surgery and 4.9% radiation. Mortality was 10.9% (243\/2236; meta\u2010analysis: 10%, 95% confidence interval [CI] 7\u201312%) and likelihood of complete response to primary chemotherapy was 79.7% (1506\/1890; meta\u2010analysis: 78%, 95% CI: 74\u201383%). 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\u2010analysis: 8.1 versus 12.4%, OR 0.42, 95% CI: 0.20\u20130.90%, 14 studies) and higher likelihood of complete response (overall: 76.6 versus 72.8%; comparative meta\u2010analysis: 75.9 versus 60.7%, OR 2.98, 95% CI: 1.06\u20138.35%, 14 studies), though studies focused on non\u2010preferred regimens reported comparable outcomes. Mortality was increased for ultra\u2010high\u2010risk disease (30 versus 7.5% high\u2010risk; meta\u2010analysis OR\u00a07.44, 95% CI: 4.29\u201312.9%) and disease following term delivery (20.8 versus 7.3% following molar pregnancy; meta\u2010analysis OR\u00a02.64, 95% CI: 1.10\u20136.31%). Relapse rate estimates ranged from 3 to 6%.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>High\u2010risk GTN is responsive to several chemotherapy regimens, with EMA\/CO or EMA\/EP associated with improved outcomes. Mortality is increased in patients with ultra\u2010high\u2010risk, relapsed and post\u2010term pregnancy disease.<\/jats:p><\/jats:sec>","DOI":"10.1111\/1471-0528.17374","type":"journal-article","created":{"date-parts":[[2023,1,17]],"date-time":"2023-01-17T15:24:01Z","timestamp":1673969041000},"page":"443-453","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Treatments and outcomes in high\u2010risk gestational trophoblastic neoplasia: A systematic review and meta\u2010analysis"],"prefix":"10.1111","volume":"130","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5296-9575","authenticated-orcid":false,"given":"Benjamin B.","family":"Albright","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology Duke University Medical Center Durham North Carolina 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