Gestational Trophoblastic Neoplasia Following Hydatidiform Mole and Non-Molar Pregnancy: Clinical and Prognostic Features from a 40-Year Cohort Study at a Reference Center in Southern Brazil

Background: Gestational trophoblastic neoplasia (GTN) is rare but highly curable. This study compared clinical characteristics and outcomes between molar and non-molar disease. Methods: This retrospective cohort included 550 patients at a Brazilian reference center (1985–2025). Survival was assessed using Kaplan–Meier methods. Multivariable analyses included Poisson and Cox regression models. Results: Molar GTN comprised 86% of cases. Non-molar GTN (14%) presented with more advanced FIGO stages, higher WHO risk scores, and more metastases (p < 0.001). Overall five-year disease-specific survival (DSS) was 97.4% (95% CI 95.9–98.9) and progression-free survival (PFS) was 92.4% (95% CI 90.1–94.7). Non-molar disease had lower DSS (84.4% vs. 99.8%; p < 0.001) and PFS (85.3% vs. 93.5%; p = 0.049) in unadjusted analyses. However, after multivariable adjustment, GTN type was not independently associated with DSS (HR 9.41; 95% CI 0.70–127; p = 0.092) or PFS (HR 1.61; 95% CI 0.57–4.60; p = 0.372). Non-molar patients had a lower likelihood of subsequent pregnancy (RR 0.60; 95% CI 0.36–1.00; p = 0.049). Conclusions: Although non-molar GTN presents with more aggressive clinical features, survival outcomes appear to be primarily driven by baseline disease severity rather than GTN subtype itself.