Disease Stage/Age Among Adverse Prognostic Factors for Ovarian Germ Cell Tumors

In an international multicenter study of 254 patients with stage IC/M to IV malignant ovarian germ cell tumors (MOGCTs), researchers identified age of 35 years or older, advanced FIGO stage, and nondysgerminoma histology as independent predictors of worse cancer-specific survival (CSS), according to findings published in the Journal of Clinical Oncology. The analysis also found that grade 2/3 immature teratomas carried a prognosis mirroring dysgerminomas, and that high-dose chemotherapy (HDCT) improved survival when used at first relapse but not at subsequent relapses.

What were the key prognostic factors for survival?

On multivariable analysis, age of 35 years or older was associated with worse CSS (HR, 2.8; 95% CI, 1.4 to 5.4; P = .003), as was advanced FIGO stage III/IV disease (HR, 1.4; 95% CI, 1.02 to 1.9; P = .035). Nondysgerminoma histology, excluding grade 2/3 immature teratomas, was also linked with worse CSS compared with dysgerminoma (HR, 4.8; 95% CI, 1.7 to 16.9; P = .001) and compared with immature teratoma (HR, 7.3; 95% CI, 1.9 to 64.8; P = .001). No significant difference in CSS was observed between patients treated with cisplatin, vincristine, methotrexate, and bleomycin/actinomycin D, cyclophosphamide, and etoposide (POMB/ACE) vs bleomycin, etoposide, and cisplatin (BEP) chemotherapy, nor between those who underwent fertility-sparing vs nonfertility-sparing surgery.

How did survival outcomes differ by histology and stage?

The 10-year estimated CSS for dysgerminoma and grade 2/3 immature teratoma was 94.7% (95% CI, 84.4%-98.3%) and 97.5% (95% CI, 83.4%-99.6%), respectively. Other histologic subtypes had significantly lower CSS (P <.001), including 77.8% (95% CI, 61.4%-87.9%) for mixed MOGCTs, 71.7% (95% CI, 58.4%-81.4%) for yolk sac tumor, 50.0% (95% CI, 5.9%-84.5%) for choriocarcinoma, and 33.3% (95% CI, 1.0%-77.4%) for embryonal carcinoma. By FIGO stage, 10-year estimated CSS was 92.3% (95% CI, 82.1%-96.8%) for stage IC/M, 79.5% (95% CI, 56.2%-91.3%) for stage II, 79.4% (95% CI, 69.5%-86.4%) for stage III, and 79.4% (95% CI, 61.5%-89.7%) for stage IV.

How did high-dose chemotherapy affect relapsed disease?

Among patients who relapsed, HDCT significantly improved CSS compared with conventional chemotherapy alone on both univariable and multivariable analysis (HR, 0.16; 95% CI, 0.04 to 0.68; P = .013). The 5-year CSS with HDCT, conventional chemotherapy, and conventional chemotherapy plus surgery was 34.2% (95% CI, 9.9%-60.8%), 25.0% (95% CI, 3.7%-55.8%), and 29.0% (95% CI, 8.2%-54.2%), respectively. Among 10 patients who received HDCT as second-line treatment, 80%, 60%, and 45% remained progression free at 1, 2, and 5 years, respectively. All 3 patients who received HDCT at subsequent relapse died of disease.

What was the study design and patient population?

Investigators analyzed data from patients with stage IC to IV MOGCT, or stage IA/B disease with persisting or rising tumor markers, who received surgery and chemotherapy between 1971 and 2018 at 2 UK centers and the Multicenter Italian Trials in Ovarian Cancer group. The median age at diagnosis was 27 years (IQR, 21-31), and the median follow-up from the end of last treatment was 6.9 years (range, 0.13-41.7). Surgery was the initial treatment in 87.8% of patients, with fertility-sparing surgery performed in 50.4%. First-line chemotherapy consisted of BEP in 48.0% of patients and POMB/ACE in 42.5%. Overall, 84.6% of patients achieved a complete response to first-line treatment, and 14.6% died of disease.

What are the clinical implications of these findings?

The authors noted that unlike testicular germ cell tumors, no universally accepted prognostic classification system exists for MOGCT. The study’s authors partially validated the modified International Germ Cell Cancer Collaborative Group risk stratification system, reproducing good and intermediate prognosis groups but not a distinct poor-prognosis group. Given the poorer prognosis observed with yolk sac tumor, choriocarcinoma, and stage IV disease, the authors suggested HDCT might be investigated as consolidation during first-line treatment in future studies. They also noted that most relapses occurred within 2 years of first-line treatment, though late relapses occurred up to 22 years after diagnosis, underscoring the need for long-term surveillance.

References

Bergamini A, Suyanto S, Savva C, et al. Malignant adult ovarian germ cell tumors: an international multicenter study to identify relevant prognostic risk factors for stage IC and beyond. J Clin Oncol. 2026;44(18):1720-1729. doi:10.1200/JCO-25-00840