Contemporary management of ovarian germ cell tumors and remaining controversies


      • Ovarian GCTs are rare tumors of the ovary with favorable outcomes.
      • Risk classification systems for ovarian and pediatric GCT have been proposed to refine post-operative management.
      • GYN, pediatric, and medical oncologist collaboration is needed to prospectively evaluate clinical decisions.


      Ovarian germ cell tumors (GCTs) are rare in adults, but are more common in adolescents and young adults. Contemporary management of ovarian GCTs is evolving as collaboration among pediatric, medical, and gynecologic oncologists increases, and studies increasingly incorporate female adult patients. Despite an improved understanding of ovarian GCT, many questions remain. Areas of continued controversy include which stage I ovarian GCTs and immature teratomas can be observed without adjuvant therapy, appropriate risk classification for ovarian GCT, surveillance strategies, and optimal therapy for recurrence. These topics as well as active areas of clinical investigation are discussed.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Gynecologic Oncology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Siegel R.L.
        • Miller K.D.
        • Jemal A.
        Cancer statistics, 2019.
        CA Cancer J. Clin. 2019; 69: 7-34
        • Poynter J.N.
        • et al.
        Incidence of intracranial germ cell tumors by race in the United States, 1992–2010.
        J. Neuro-Oncol. 2014; 120: 381-388
        • Prat J.
        • et al.
        Germ cell tumours.
        in: Kurman R.J. WHO Classification of Tumors of Female Reproductive Organs. International Agency for Research on Cancer (IARC), Sant-Ismier, France2014
        • Kraggerud S.M.
        • et al.
        Molecular characteristics of malignant ovarian germ cell tumors and comparison with testicular counterparts: implications for pathogenesis.
        Endocr. Rev. 2013; 34: 339-376
        • Filippou P.
        • Ferguson J.E.
        • Nielsen M.E.
        Epidemiology of prostate and testicular cancer.
        Semin. Interv. Radiol. 2016; 33: 182-185
        • Smith H.O.
        • et al.
        Incidence and survival rates for female malignant germ cell tumors.
        Obstet. Gynecol. 2006; 107: 1075-1085
        • Collinson K.
        • et al.
        Age-related biological features of germ cell tumors.
        Genes Chromosom. Cancer. 2014; 53: 215-227
        • Berney D.M.
        • et al.
        Ovarian germ cell tumour classification: views from the testis.
        Histopathology. 2020; 76: 25-36
        • Ulbright T.M.
        Germ cell tumors of the gonads: a selective review emphasizing problems in differential diagnosis, newly appreciated, and controversial issues.
        Mod. Pathol. 2005; 18: S61-S79
        • Oosterhuis J.W.
        • Looijenga L.H.J.
        Human germ cell tumours from a developmental perspective.
        Nat. Rev. Cancer. 2019; 19: 522-537
        • Frazier A.L.
        • et al.
        Revised risk classification for pediatric extracranial germ cell tumors based on 25 years of clinical trial data from the United Kingdom and United States.
        J. Clin. Oncol. 2015; 33: 195-201
        • Frazier A.
        • et al.
        Validation of the MaGIC pediatric germ cell tumour risk stratification.
        Eur. Urol. Suppl. 2019; 18: 20
        • Meisel J.L.
        • et al.
        Development of a risk stratification system to guide treatment for female germ cell tumors.
        Gynecol. Oncol. 2015; 138: 566-572
        • Mangili G.
        • et al.
        Outcome and risk factors for recurrence in malignant ovarian germ cell tumors: a MITO-9 retrospective study.
        Int. J. Gynecol. Cancer. 2011; 21: 1414-1421
        • Newton C.
        • et al.
        A multicentre retrospective cohort study of ovarian germ cell tumours: evidence for chemotherapy de-escalation and alignment of paediatric and adult practice.
        Eur. J. Cancer. 2019; 113: 19-27
        • Euscher E.D.
        Germ cell tumors of the female genital tract.
        Surg Pathol Clin. 2019; 12: 621-649
        • Brown J.
        • et al.
        Gynecologic Cancer Intergroup (GCIG) consensus review for ovarian germ cell tumors.
        Int. J. Gynecol. Cancer. 2014; 24: S48-S54
        • Gershenson D.M.
        • Frazier A.L.
        Conundrums in the management of malignant ovarian germ cell tumors: toward lessening acute morbidity and late effects of treatment.
        Gynecol. Oncol. 2016; 143: 428-432
        • Mangili G.
        • et al.
        The role of staging and adjuvant chemotherapy in stage I malignant ovarian germ cell tumors (MOGTs): the MITO-9 study.
        Ann. Oncol. 2017; 28: 333-338
        • Mahdi H.
        • et al.
        Prognostic impact of lymphadenectomy in clinically early stage malignant germ cell tumour of the ovary.
        Br. J. Cancer. 2011; 105: 493-497
        • Rogers P.C.
        • et al.
        Treatment of children and adolescents with stage II testicular and stages I and II ovarian malignant germ cell tumors: a Pediatric Intergroup Study—Pediatric Oncology Group 9048 and Children’s Cancer Group 8891.
        J. Clin. Oncol. 2004; 22: 3563-3569
        • Billmire D.
        • et al.
        Outcome and staging evaluation in malignant germ cell tumors of the ovary in children and adolescents: an intergroup study.
        J. Pediatr. Surg. 2004; 39 (discussion 424-9): 424-429
        • Gershenson D.M.
        Management of ovarian germ cell tumors.
        J. Clin. Oncol. 2007; 25: 2938-2943
        • Johansen G.
        • et al.
        Fertility-sparing surgery for treatment of non-epithelial ovarian cancer: oncological and reproductive outcomes in a prospective nationwide population-based cohort study.
        Gynecol. Oncol. 2019; 155: 287-293
        • Park J.Y.
        • et al.
        Outcomes of surgery alone and surveillance strategy in young women with stage I malignant ovarian germ cell tumors.
        Int. J. Gynecol. Cancer. 2016; 26: 859-864
        • Pawinski A.
        • et al.
        PVB chemotherapy in patients with recurrent or advanced dysgerminoma: a phase II study of the EORTC Gynaecological Cancer Cooperative Group.
        Clin Oncol (R Coll Radiol). 1998; 10: 301-305
        • Williams S.D.
        • et al.
        Chemotherapy of advanced dysgerminoma: trials of the Gynecologic Oncology Group.
        J. Clin. Oncol. 1991; 9: 1950-1955
        • Williams S.D.
        • et al.
        Adjuvant therapy of completely resected dysgerminoma with carboplatin and etoposide: a trial of the Gynecologic Oncology Group.
        Gynecol. Oncol. 2004; 95: 496-499
        • Shah R.
        • et al.
        Is carboplatin-based chemotherapy as effective as cisplatin-based chemotherapy in the treatment of advanced-stage dysgerminoma in children, adolescents and young adults?.
        Gynecol. Oncol. 2018; 150: 253-260
        • Simone C.G.
        • Markham M.J.
        • Dizon D.S.
        Chemotherapy in ovarian germ cell tumors: a systematic review.
        Gynecol. Oncol. 2016; 141: 602-607
        • Williams S.D.
        • et al.
        Cisplatin, vinblastine, and bleomycin in advanced and recurrent ovarian germ-cell tumors. A trial of the Gynecologic Oncology Group.
        Ann. Intern. Med. 1989; 111: 22-27
        • Williams S.
        • et al.
        Adjuvant therapy of ovarian germ cell tumors with cisplatin, etoposide, and bleomycin: a trial of the Gynecologic Oncology Group.
        J. Clin. Oncol. 1994; 12: 701-706
        • Billmire D.F.
        • et al.
        Surveillance after initial surgery for pediatric and adolescent girls with stage I ovarian germ cell tumors: report from the Children’s Oncology Group.
        J. Clin. Oncol. 2014; 32: 465-470
        • Mann J.R.
        • et al.
        The United Kingdom Children’s Cancer Study Group’s second germ cell tumor study: carboplatin, etoposide, and bleomycin are effective treatment for children with malignant extracranial germ cell tumors, with acceptable toxicity.
        J. Clin. Oncol. 2000; 18: 3809-3818
        • Frazier A.L.
        • et al.
        Comparison of carboplatin versus cisplatin in the treatment of paediatric extracranial malignant germ cell tumours: a report of the Malignant Germ Cell International Consortium.
        Eur. J. Cancer. 2018; 98: 30-37
        • Shaikh F.
        • et al.
        Is there a role for carboplatin in the treatment of malignant germ cell tumors? A systematic review of adult and pediatric trials.
        Pediatr. Blood Cancer. 2013; 60: 587-592
        • Marina N.M.
        • et al.
        Complete surgical excision is effective treatment for children with immature teratomas with or without malignant elements: a Pediatric Oncology Group/Children’s Cancer Group Intergroup Study.
        J. Clin. Oncol. 1999; 17: 2137-2143
        • Norris H.J.
        • Zirkin H.J.
        • Benson W.L.
        Immature (malignant) teratoma of the ovary: a clinical and pathologic study of 58 cases.
        Cancer. 1976; 37: 2359-2372
        • Gershenson D.M.
        • et al.
        Immature teratoma of the ovary.
        Obstet. Gynecol. 1986; 68: 624-629
        • Pashankar F.
        • et al.
        Is adjuvant chemotherapy indicated in ovarian immature teratomas? A combined data analysis from the Malignant Germ Cell Tumor International Collaborative.
        Cancer. 2016; 122: 230-237
        • Palmer R.D.
        • et al.
        Malignant germ cell tumors display common microRNA profiles resulting in global changes in expression of messenger RNA targets.
        Cancer Res. 2010; 70: 2911-2923
        • Nappi L.
        • et al.
        Developing a highly specific biomarker for germ cell malignancies: plasma miR371 expression across the germ cell malignancy spectrum.
        J. Clin. Oncol. 2019; 37: 3090-3098
        • Matei D.
        • et al.
        Chronic physical effects and health care utilization in long-term ovarian germ cell tumor survivors: a Gynecologic Oncology Group study.
        J. Clin. Oncol. 2009; 27: 4142-4149
        • Fung C.
        • et al.
        Testicular cancer survivorship.
        J. Natl. Compr. Cancer Netw. 2019; 17: 1557-1568
        • Fosså S.D.
        • et al.
        Increased mortality rates in young and middle-aged patients with malignant germ cell tumours.
        Br. J. Cancer. 2004; 90: 607-612
        • Solheim O.
        • et al.
        Malignant ovarian germ cell tumors: presentation, survival and second cancer in a population based Norwegian cohort (1953–2009).
        Gynecol. Oncol. 2013; 131: 330-335
        • Solheim O.
        • et al.
        Prognostic factors in malignant ovarian germ cell tumours (The Surveillance, Epidemiology and End Results experience 1978–2010).
        Eur. J. Cancer. 2014; 50: 1942-1950
        • Gadducci A.
        • Lanfredini N.
        • Tana R.
        Menstrual function and childbearing potential after fertility-sparing surgery and platinum-based chemotherapy for malignant ovarian germ cell tumours.
        Gynecol. Endocrinol. 2014; 30: 467-471
        • Gershenson D.M.
        Menstrual and reproductive function after treatment with combination chemotherapy for malignant ovarian germ cell tumors.
        J. Clin. Oncol. 1988; 6: 270-275
        • Gershenson D.M.
        • et al.
        Reproductive and sexual function after platinum-based chemotherapy in long-term ovarian germ cell tumor survivors: a Gynecologic Oncology Group Study.
        J. Clin. Oncol. 2007; 25: 2792-2797
        • de La Motte Rouge T.
        • et al.
        Survival and reproductive function of 52 women treated with surgery and bleomycin, etoposide, cisplatin (BEP) chemotherapy for ovarian yolk sac tumor.
        Ann. Oncol. 2008; 19: 1435-1441
        • Lorch A.
        • et al.
        Conventional-dose versus high-dose chemotherapy as first salvage treatment in male patients with metastatic germ cell tumors: evidence from a large international database.
        J. Clin. Oncol. 2011; 29: 2178-2184
        • Reddy Ammakkanavar N.
        • et al.
        High-dose chemotherapy for recurrent ovarian germ cell tumors.
        J. Clin. Oncol. 2015; 33: 226-227
        • De Giorgi U.
        • et al.
        High-dose chemotherapy for adult-type ovarian granulosa cell tumors: a retrospective study of the European Society for Blood and Marrow Transplantation.
        Int. J. Gynecol. Cancer. 2017; 27: 248-251
        • Mego M.
        • et al.
        Phase II study of everolimus in refractory testicular germ cell tumors.
        Urol. Oncol. 2016; 34 (p. 122.e17-22)
        • Fenner M.
        • et al.
        Everolimus in patients with multiply relapsed or cisplatin refractory germ cell tumors: results of a phase II, single-arm, open-label multicenter trial (RADIT) of the German Testicular Cancer Study Group.
        J. Cancer Res. Clin. Oncol. 2019; 145: 717-723
        • Einhorn L.H.
        • et al.
        Phase II study of imatinib mesylate in chemotherapy refractory germ cell tumors expressing KIT.
        Am. J. Clin. Oncol. 2006; 29: 12-13
        • Feldman D.R.
        • et al.
        Phase II trial of sunitinib in patients with relapsed or refractory germ cell tumors.
        Investig. New Drugs. 2010; 28: 523-528
        • Necchi A.
        • et al.
        Pazopanib in advanced germ cell tumors after chemotherapy failure: results of the open-label, single-arm, phase 2 Pazotest trial.
        Ann. Oncol. 2017; 28: 1346-1351
        • Necchi A.
        • et al.
        Brentuximab vedotin in CD30-expressing germ cell tumors after chemotherapy failure.
        Clin Genitourin Cancer. 2016; 14 (p. 261-264.e4)
        • Adra N.
        • et al.
        Phase II trial of pembrolizumab in patients with platinum refractory germ-cell tumors: a Hoosier Cancer Research Network Study GU14-206.
        Ann. Oncol. 2018; 29: 209-214
        • Necchi A.
        • et al.
        An open-label randomized phase 2 study of durvalumab alone or in combination with tremelimumab in patients with advanced germ cell tumors (APACHE): results from the first planned interim analysis.
        Eur. Urol. 2019; 75: 201-203