Malignant Adult Ovarian Germ Cell Tumors: An International Multicenter Study to Identify Relevant Prognostic Risk Factors for Stage IC and Beyond.

Abstract

Malignant ovarian germ cell tumors (MOGCTs) are rare, aggressive malignancies predominantly affecting young women. Unlike testicular germ cell tumors, prognostic factors are poorly understood, with small studies suggesting advanced stage as an adverse factor. Here, we examine a large international series to identify relevant prognostic factors. We analyzed data from 254 patients with International Federation of Gynecology and Obstetrics stage IC-IV MOGCT, requiring surgery and chemotherapy between 1971 and 2018 at two UK and the Multicenter Italian Trials in Ovarian Cancer centers. The median age was 27 years (IQR, 21-31). Initial treatment was surgery in 87.8% of patients (50.4% fertility sparing, 37.4% nonsparing) or neoadjuvant chemotherapy. Most underwent BEP or POMB/ACE chemotherapy, with 32.5% receiving high-dose chemotherapy (HDCT) at relapse. First-line treatment resulted in a complete response in 84.6% (n = 215) and partial response or stable disease in 7.9% (n = 20), while 4.7% (n = 12) progressed. Overall, 37 patients (14.6%) died of disease. Ten-year progression-free survival and cancer-specific survival (CSS) was 82.8% (95% CI, 77.2 to 87.2) and 83.2% (95% CI, 77.3 to 87.7), respectively. CSS for stage IV disease was 79.4% (95% CI, 69.5 to 86.4). Age ≥35 years (hazard ratio [HR], 2.8 [95% CI, 1.5 to 5.4]; <i>P</i> = .003), stage III/IV disease (HR, 1.4 [95% CI, 1,0.2 to 1.9]; <i>P</i> = .035), and nondysgerminoma histology (HR, 7.3 [95% CI, 1.9 to 64.8]; <i>P</i> = .01) had worse CSS on multivariable analysis. By contrast, CSS of immature grade 2/3 MOGCT mirrored dysgerminomas. HDCT appeared to improve survival in first but not later relapses. Advanced stage (III/IV), age >35 years, and nondysgerminoma (excluding grade 2/3 immature teratomas) are adverse prognostic factors. Stage IV disease can achieve 80% long-term survival rates, and HDCT improves survival in first but not second relapse.