Management of Malignant Ovarian Germ Cell Tumors İbrahim Serdar Serin, MD University of Erciyes, Medical School, Department Of Obstetrics and Gynecology, Division of Gynecological Oncology

Ovarian germ cell tumors (OGCTs) are derived from primordial germ cells of the ovary

Malignant ovarian germ cell tumours (MOGCTs) (MOGCTs) are rare (% 2-3) Early diagnosis and multiagent chemotherapy are associated with high cure rates of 85.6% Relapse with this cancer have poorer outcomes MOGCTs are managed by multidisciplinary teams

MOGCT Most commonly occur in the first two decades of life can appear at any age Immature teratomas50 yr↑(more common) (A review of the Norwegian Cancer registry)

MOGCT-Presentation Pelvic pain (acute and subacute) Menstrual disturbance A pelvic or abdominal mass Ascites

MOGCT- Diagnosis A solid mass on USG examination in younger women may indicate a MOGCT Imaging of the abdomen, pelvis and chest by CT MRI may provide additional information LDH, AFP, HCG etc (TUMOR MARKERS) provides a highly sensitive and specific indicator of the presence of certain histologic components

MOGCT-Diagnosis The tumor marker results may help surgical planning preservation of fertility potential Furthermore, monitoring the response to chemotherapy posttreatment follow-up

MOGCT-Management The staging is the same as for EOC Fertility-sparing surgery should be performed when possible Children and adeloscents with a germ cell tumor (GCT) differs from that for adult women

Staging Peritoneal cytology total extrafascial hysterectomy with BSO pelvic and paraaortic lymph node dissection omentectomy and cytology of the diaphragm biopsy of any areas where metastases are suspected Cytoreduction often is performed when metastases are evident L/T is generally used

Lympadenectomy Nodal involvement is more common with malignant OGCTs Lymph node metastasis dysgerminoma→ 28 % mixed germ cell tumors → 16 % malignant teratoma → 8 % Lymph node involvement was an independent predictor of poor survival with a hazard ratio of 2.9 (95% CI 1.4-5.7). (Kumar S et al. The prevalence and prognostic impact of lymph node metastasis in malignant germ cell tumors of the ovary. Gynecol Oncol 2008; 110:125.)

Cytoreduction risks benefits

Cytoreduction TUMOR VOLUME is one of the most important prognostic factors for outcome The likelihood of disease progression after postoperative VAC was higher in incompletely resected disease (GOG:Slayton RE et al.Cancer 1985; 56:243)

Cytoreduction Upfront surgical debulking→ important More critical for nondysgerminoma tumors NAC should be administered in rare instances (extent of metastatic disease↑, effusions, comorbidities)

Adjuvat Treatment Most women undergo adjuvant CT after surgery EXCEPT  Stage IA, Grade 1 immature teratoma  Stage IA and IB dysgerminoma

Adjuvant Chemotherapy Multiple platinum-based regimens have been used for OGCTs Bleomycin, etoposide, and cisplatin (BEP) Etoposide and carboplatin Etoposide and cisplatin (EP). carboplatin may be a reasonable alternative for women who cannot tolerate cisplatin For most patients, the regimen of choice is BEP

Adjuvant Chemotherapy-Survival Surgery +BEP  95-100 % (early-stage nondysgerminomatous tumors) 75-80 % (advanced disease at presentation ) More favorable for ovarian dysgerminomas regardless of stage at presentation

Adjuvant Chemotherapy -Toxicity Acute- and later-onset pulmonary toxicity → bleomycin Therapy-related myeloid neoplasms →etoposide Long-term renal and neurotoxicity →cisplatin

Adjuvant Chemotherapy -Dysgerminomas BEP 3 courses  completely resected stage I disease 4 courses  more advanced-stage disease

Adjuvant Chemotherapy -Dysgerminomas Brewer M. J Clin Oncol 1999; 17:2670 n:26 (with pure ovarian dysgerminoma) 54 % stage IIIC or IV 96 % disease free after at least 3 courses of BEP

Adjuvant Chemotherapy- Nondysgerminomas Data is limited BEP for three cycles appears to prevent recurrences Especially in well-staged patients

Adjuvant Chemotherapy- Nondysgerminomas Williams S. J Clin Oncol 1994; 12:701 GOG study n=93 Follow-up between 4 and 90 months  91 were alive and free of recurrence 2 pts developed a treatment-related hematologic secondary malignancy

Fertility Preservation Preservation of a normal-appearing uterus and contralateral ovary is an option Occult contralateral ovarian involvement appears to be greatest with dysgerminomas(5-10 %) The ipsilateral fallopian tube is removed 80 % of women will resume normal menstrual function No increase in pregnancy complications

Fertility Preservation Gordon A et al.Dysgerminoma: a review of 158 cases from the Emil Novak Ovarian Tumor Registry. Obstet Gynecol 1981; 58:497. N=98 Stage IA dysgerminoma 9 developed disease in the contralateral ovary Routinely perform a wedge biopsy of a normal-appearing contralateral ovary ? This practice is not universally accepted

Relapsed Disease First two years after completion of therapy Recurrence is usually detected by a rise in serum tumor markers OR The evolution of new disease on radiographic studies

Relapsed Disease Only treated with surgery surgery+BEP Treated with CT(as adjuvant therapy or first-line treatment of stage IV disease)  repeat treatment with a platinum-based regimen DATA is LIMITED!!!

Management in Children and adolescents Differs from that for adult women The optimal approach has not yet been characterized The contemporary pediatric surgical approach  peritoneal cytology,  primary tumor removal,  biopsy or excision of suspicious implants or lymph nodes,  with no further biopsies (Children’s Oncology Group Rare Tumors Disease Committee )

Management in Children and adolescents Surveillance for girls with stage IA malignant OGCTs appears to be reasonable Adjuvant chemotherapy is routinely offered to patients with higher-stage disease BEP recomended

Conclusion MOGCT typically occur in the first 2 decades of life. Initial clinical work up should include USG, CT scans, or both, as well as tumour markers, including AFP, LDH, β-hCG, and Ca-125. Fertility-sparing surgery with USO is the standard surgical approach for MOGCT, along with surgical staging in apparently early disease.

Conclusion The role of aggressive surgical debulking is not well defined in chemo-sensitive tumours. BEP chemotherapy is the regimen of choice in advanced MOGCT After fertility-sparing surgery and BEP chemotherapy, most women will resume their previous baseline menstrual function. Fertility rates approximate those of the normal population, with no significant increase in the risk of early pregnancy loss or teratogenicity

Teşekkürler Kapuzbaşı Şelalesi Yahyalı/Kayseri