Treatment of malignant germ cell tumors of the ovary
- David M Gershenson, MD
David M Gershenson, MD
- J Taylor Wharton MD Distinguished Chair in Gynecologic Oncology
- Professor of Gynecologic Oncology
- The University of Texas MD Anderson Cancer Center
- Section Editors
- Barbara Goff, MD
Barbara Goff, MD
- Section Editor — Gynecologic Oncology
- Professor of Gynecologic Oncology
- University of Washington
- Alberto S Pappo, MD
Alberto S Pappo, MD
- Section Editor — Pediatric Oncology
- Head of Solid Malignancies Program
- St. Jude Children's Research Hospital
- Don S Dizon, MD, FACP
Don S Dizon, MD, FACP
- Section Editor – Gynecologic Oncology
- Clinical Co-Director, Gynecologic Oncology
- Founder and Director, The Oncology Sexual Health Clinic
- Massachusetts General Hospital Cancer Center
- Associate Professor of Medicine
- Harvard Medical School
- Deputy Editors
- Sadhna R Vora, MD
Sadhna R Vora, MD
- Deputy Editor — Oncology
- Instructor in Medicine
- Harvard Medical School
- Sandy J Falk, MD, FACOG
Sandy J Falk, MD, FACOG
- Senior Deputy Editor — UpToDate
- Deputy Editor — Obstetrics, Gynecology and Women's Health
- Clinical Instructor of Obstetrics, Gynecology and Reproductive Biology
- Harvard Medical School
Ovarian germ cell tumors (OGCTs) are derived from primordial germ cells of the ovary (figure 1). They may be benign or malignant. Malignant germ cell cancers of the ovary include dysgerminomas and nondysgerminomas, which include immature teratomas, embryonal cell carcinoma, yolk sac tumors, primary ovarian (nongestational) choriocarcinomas, polyembryoma, and mixed germ cell tumors . In contrast to epithelial ovarian cancer (EOC), they constitute a rare form of ovarian malignancy. (See "Overview of epithelial carcinoma of the ovary, fallopian tube, and peritoneum".)
Dysgerminomas differ from other malignant OGCTs in several ways: they are more likely to be localized to the ovary at diagnosis (approximately two-thirds of cases are stage IA, (table 1)), bilateral ovarian involvement is more common (10 to 15 percent), they are more likely to spread in a predictable fashion, and they are more sensitive to radiation therapy (RT).
The management of malignant OGCTs will be reviewed here. Pathology and clinical manifestations of these neoplasms, as well as the treatment of benign OGCTs, are reviewed separately. (See "Ovarian germ cell tumors: Pathology, clinical manifestations, and diagnosis".)
In general, the treatment principles for all types of malignant ovarian germ cell tumors (OGCTs) are similar to those that guide the management of the more common epithelial ovarian cancer (EOC), with some exceptions:
●Many OGCTs produce tumor products (alpha fetoprotein [AFP], human chorionic gonadotropin [hCG], lactate dehydrogenase [LDH]) that can be measured in the serum. The presence of these markers provides a highly sensitive and specific indicator of the presence of certain histologic components (table 2). Testing for serum tumor markers prior to definitive treatment can provide a diagnostic clue to the presence of an OGCT. In a child, teen, or young woman, the tumor marker results may help with surgical planning, resulting in the preservation of fertility potential. Furthermore, serial assay of these tumor markers is useful for monitoring the response to chemotherapy and for subsequent posttreatment follow-up. (See "Epithelial carcinoma of the ovary, fallopian tube, and peritoneum: Clinical features and diagnosis".)
- Blaustein's Pathology of the Female Genital Tract, 4th, Blaustein A, Kurman RJ (Eds), Springer-Verlag, 1987.
- Shim SH, Kim DY, Lee SW, et al. Laparoscopic management of early-stage malignant nonepithelial ovarian tumors: surgical and survival outcomes. Int J Gynecol Cancer 2013; 23:249.
- Kumar S, Shah JP, Bryant CS, et al. The prevalence and prognostic impact of lymph node metastasis in malignant germ cell tumors of the ovary. Gynecol Oncol 2008; 110:125.
- Slayton RE, Park RC, Silverberg SG, et al. Vincristine, dactinomycin, and cyclophosphamide in the treatment of malignant germ cell tumors of the ovary. A Gynecologic Oncology Group Study (a final report). Cancer 1985; 56:243.
- Williams SD, Blessing JA, Moore DH, 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.
- Bafna UD, Umadevi K, Kumaran C, et al. Germ cell tumors of the ovary: is there a role for aggressive cytoreductive surgery for nondysgerminomatous tumors? Int J Gynecol Cancer 2001; 11:300.
- Gershenson DM, Morris M, Cangir A, et al. Treatment of malignant germ cell tumors of the ovary with bleomycin, etoposide, and cisplatin. J Clin Oncol 1990; 8:715.
- Dimopoulos MA, Papadopoulou M, Andreopoulou E, et al. Favorable outcome of ovarian germ cell malignancies treated with cisplatin or carboplatin-based chemotherapy: a Hellenic Cooperative Oncology Group study. Gynecol Oncol 1998; 70:70.
- Mann JR, Raafat F, Robinson K, 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.
- Williams SD. Ovarian germ cell tumors: an update. Semin Oncol 1998; 25:407.
- Segelov E, Campbell J, Ng M, et al. Cisplatin-based chemotherapy for ovarian germ cell malignancies: the Australian experience. J Clin Oncol 1994; 12:378.
- Rescorla F, Billmire D, Vinocur C, et al. The effect of neoadjuvant chemotherapy and surgery in children with malignant germ cell tumors of the genital region: a pediatric intergroup trial. J Pediatr Surg 2003; 38:910.
- Talukdar S, Kumar S, Bhatla N, et al. Neo-adjuvant chemotherapy in the treatment of advanced malignant germ cell tumors of ovary. Gynecol Oncol 2014; 132:28.
- Williams S, Blessing JA, Liao SY, 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.
- Culine S, Lhomme C, Kattan J, et al. Cisplatin-based chemotherapy in the management of germ cell tumors of the ovary: The Institut Gustave Roussy Experience. Gynecol Oncol 1997; 64:160.
- Gershenson DM, Kavanagh JJ, Copeland LJ, et al. Treatment of malignant nondysgerminomatous germ cell tumors of the ovary with vinblastine, bleomycin, and cisplatin. Cancer 1986; 57:1731.
- Carlson RW, Sikic BI, Turbow MM, Ballon SC. Combination cisplatin, vinblastine, and bleomycin chemotherapy (PVB) for malignant germ-cell tumors of the ovary. J Clin Oncol 1983; 1:645.
- Taylor MH, Depetrillo AD, Turner AR. Vinblastine, bleomycin, and cisplatin in malignant germ cell tumors of the ovary. Cancer 1985; 56:1341.
- Mayordomo JI, Paz-Ares L, Rivera F, et al. Ovarian and extragonadal malignant germ-cell tumors in females: a single-institution experience with 43 patients. Ann Oncol 1994; 5:225.
- Tewari K, Cappuccini F, Disaia PJ, et al. Malignant germ cell tumors of the ovary. Obstet Gynecol 2000; 95:128.
- Smith JP, Rutledge F. Advances in chemotherapy for gynecologic cancer. Cancer 1975; 36:669.
- Murugaesu N, Schmid P, Dancey G, et al. Malignant ovarian germ cell tumors: identification of novel prognostic markers and long-term outcome after multimodality treatment. J Clin Oncol 2006; 24:4862.
- Rogers PC, Olson TA, Cullen JW, 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.
- Culine S, Lhomme C, Kattan J, et al. Cisplatin-based chemotherapy in dysgerminoma of the ovary: thirteen-year experience at the Institut Gustave Roussy. Gynecol Oncol 1995; 58:344.
- Brewer M, Gershenson DM, Herzog CE, et al. Outcome and reproductive function after chemotherapy for ovarian dysgerminoma. J Clin Oncol 1999; 17:2670.
- Williams SD, Kauderer J, Burnett AF, et al. Adjuvant therapy of completely resected dysgerminoma with carboplatin and etoposide: a trial of the Gynecologic Oncology Group. Gynecol Oncol 2004; 95:496.
- Park JY, Kim DY, Suh DS, 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.
- Patterson DM, Murugaesu N, Holden L, et al. A review of the close surveillance policy for stage I female germ cell tumors of the ovary and other sites. Int J Gynecol Cancer 2008; 18:43.
- Billmire DF, Cullen JW, Rescorla FJ, 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.
- Mangili G, Scarfone G, Gadducci A, et al. Is adjuvant chemotherapy indicated in stage I pure immature ovarian teratoma (IT)? A multicentre Italian trial in ovarian cancer (MITO-9). Gynecol Oncol 2010; 119:48.
- Stambaugh MD. Ovary. In: Principles and Practice of Radiation Oncology, 4th, Perez CA, Brady LW, Halperin CA, Schmidt-Ullrich RK (Eds), Lippincott, Williams and Wilkins, Philadelphia 1997. p.1948.
- Gershenson DM, Del Junco G, Copeland LJ, Rutledge FN. Mixed germ cell tumors of the ovary. Obstet Gynecol 1984; 64:200.
- Gershenson DM, Del Junco G, Herson J, Rutledge FN. Endodermal sinus tumor of the ovary: the M. D. Anderson experience. Obstet Gynecol 1983; 61:194.
- Krepart G, Smith JP, Rutledge F, Delclos L. The treatment for dysgerminoma of the ovary. Cancer 1978; 41:986.
- De Palo G, Lattuada A, Kenda R, et al. Germ cell tumors of the ovary: the experience of the National Cancer Institute of Milan. I. Dysgerminoma. Int J Radiat Oncol Biol Phys 1987; 13:853.
- Teinturier C, Gelez J, Flamant F, et al. Pure dysgerminoma of the ovary in childhood: treatment results and sequelae. Med Pediatr Oncol 1994; 23:1.
- Hale GA, Marina NM, Jones-Wallace D, et al. Late effects of treatment for germ cell tumors during childhood and adolescence. J Pediatr Hematol Oncol 1999; 21:115.
- National Comprehensive Cancer Network (NCCN). NCCN Clinical practice guidelines in oncology. http://www.nccn.org/professionals/physician_gls/f_guidelines.asp (Accessed on February 27, 2016).
- Lai CH, Chang TC, Hsueh S, et al. Outcome and prognostic factors in ovarian germ cell malignancies. Gynecol Oncol 2005; 96:784.
- Lu KH, Gershenson DM. Update on the management of ovarian germ cell tumors. J Reprod Med 2005; 50:417.
- Maltaris T, Boehm D, Dittrich R, et al. Reproduction beyond cancer: a message of hope for young women. Gynecol Oncol 2006; 103:1109.
- Gershenson DM, Miller AM, Champion VL, 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.
- Tangir J, Zelterman D, Ma W, Schwartz PE. Reproductive function after conservative surgery and chemotherapy for malignant germ cell tumors of the ovary. Obstet Gynecol 2003; 101:251.
- Low JJ, Perrin LC, Crandon AJ, Hacker NF. Conservative surgery to preserve ovarian function in patients with malignant ovarian germ cell tumors. A review of 74 cases. Cancer 2000; 89:391.
- Zanetta G, Bonazzi C, Cantù M, et al. Survival and reproductive function after treatment of malignant germ cell ovarian tumors. J Clin Oncol 2001; 19:1015.
- Peccatori F, Bonazzi C, Chiari S, et al. Surgical management of malignant ovarian germ-cell tumors: 10 years' experience of 129 patients. Obstet Gynecol 1995; 86:367.
- Billmire D, Vinocur C, Rescorla F, 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; 39:424.
- Zanagnolo V, Sartori E, Galleri G, et al. Clinical review of 55 cases of malignant ovarian germ cell tumors. Eur J Gynaecol Oncol 2004; 25:315.
- Gordon A, Lipton D, Woodruff JD. Dysgerminoma: a review of 158 cases from the Emil Novak Ovarian Tumor Registry. Obstet Gynecol 1981; 58:497.
- Lopes LF, Macedo CR, Pontes EM, et al. Cisplatin and etoposide in childhood germ cell tumor: brazilian pediatric oncology society protocol GCT-91. J Clin Oncol 2009; 27:1297.
- Mitchell PL, Al-Nasiri N, A'Hern R, et al. Treatment of nondysgerminomatous ovarian germ cell tumors: an analysis of 69 cases. Cancer 1999; 85:2232.
- Mayordomo JI, Paz-Ares L, Diaz-Puente MT, et al. Prognostic factors for women with ovarian germ cell tumors. J Clin Oncol 1994; 12:1737.
- Salani R, Backes FJ, Fung MF, et al. Posttreatment surveillance and diagnosis of recurrence in women with gynecologic malignancies: Society of Gynecologic Oncologists recommendations. Am J Obstet Gynecol 2011; 204:466.
- Byrne J, Fears TR, Gail MH, et al. Early menopause in long-term survivors of cancer during adolescence. Am J Obstet Gynecol 1992; 166:788.
- Sklar CA, Mertens AC, Mitby P, et al. Premature menopause in survivors of childhood cancer: a report from the childhood cancer survivor study. J Natl Cancer Inst 2006; 98:890.
- Travis LB, Andersson M, Gospodarowicz M, et al. Treatment-associated leukemia following testicular cancer. J Natl Cancer Inst 2000; 92:1165.
- Pedersen-Bjergaard J, Daugaard G, Hansen SW, et al. Increased risk of myelodysplasia and leukaemia after etoposide, cisplatin, and bleomycin for germ-cell tumours. Lancet 1991; 338:359.
- Matei D, Miller AM, Monahan P, 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.
- Abdul Razak AR, Li L, Bryant A, Diaz-Padilla I. Chemotherapy for malignant germ cell ovarian cancer in adult patients with early stage, advanced and recurrent disease. Cochrane Database Syst Rev 2011; :CD007584.
- Mandanas RA, Saez RA, Epstein RB, et al. Long-term results of autologous marrow transplantation for relapsed or refractory male or female germ cell tumors. Bone Marrow Transplant 1998; 21:569.
- Theodore C, Chevreau C, Yataqhene Y, et al. A phase II multicenter study of oxaliplatin in combination with paclitaxel in poor prognosis patients who failed cisplatin-based chemotherapy for germ-cell tumors. Ann Oncol 2008; 19:1465.
- Williams SD, Blessing JA, DiSaia PJ, et al. Second-look laparotomy in ovarian germ cell tumors: the gynecologic oncology group experience. Gynecol Oncol 1994; 52:287.
- Munkarah A, Gershenson DM, Levenback C, et al. Salvage surgery for chemorefractory ovarian germ cell tumors. Gynecol Oncol 1994; 55:217.
- Li J, Yang W, Wu X. Prognostic factors and role of salvage surgery in chemorefractory ovarian germ cell malignancies: a study in Chinese patients. Gynecol Oncol 2007; 105:769.
- Rodriguez-Galindo C, Krailo M, Frazier L, et al. Children's Oncology Group's 2013 blueprint for research: rare tumors. Pediatr Blood Cancer 2013; 60:1016.
- Stern JW, Bunin N. Prospective study of carboplatin-based chemotherapy for pediatric germ cell tumors. Med Pediatr Oncol 2002; 39:163.
- Novak ER, Lambrou CD, Woodruff JD. Ovarian tumors in pregnancy. An ovarian tumor registry review. Obstet Gynecol 1975; 46:401.
- SURGICAL STAGING AND PRIMARY CYTOREDUCTION
- Staging system
- Staging procedure
- - Lymphadenectomy
- Initial cytoreduction for advanced disease
- ADJUVANT TREATMENT
- Platinum-based therapy
- - Bleomycin, etoposide, and cisplatin
- Dose and schedule
- - Nondysgerminomas
- - Dysgerminomas
- Substitution of cisplatin with carboplatin
- Surveillance as an alternative option
- Radiation therapy
- TREATMENT OF DE NOVO STAGE IV DISEASE
- FERTILITY PRESERVATION
- Fertility-sparing surgery
- Oocyte cryopreservation
- POSTTREATMENT SURVEILLANCE
- POSTTREATMENT ISSUES
- Premature menopause
- Secondary malignancies
- Other issues
- RELAPSED DISEASE
- Role of surgery
- SPECIAL POPULATIONS
- Children and adolescents
- - Primary treatment
- - Treatment after surgery
- Pregnant women
- SUMMARY AND RECOMMENDATIONS