Pocket Oncology (Pocket Notebook Series), 1st Ed.

OVARIAN GERM CELL TUMORS

Anya Litvak and Rachel N. Grisham

Epidemiology: 0.41 per 100000 in the USA; 5% of all ovarian malignancies; 20% of all benign ovarian tumors; usu present at early stage in young women between 10 & 30 y of age; ↑ rate in Asian/Pacific islanders/ Hispanic population > Caucasians; tumors tend to be large at dx (median size = 16 cm)

Risk Factors and Clinical Manifestations

• RF for poor survival: Advanced FIGO stage, nondysgerminoma or grade 2/3 immature teratoma, bulky residual disease after surgery, elevation of both HCG & AFP tumor markers preoperatively (J Clin Oncol 2006;24:4862–4866)

• Sx: Abdominal pain & palpable pelvic abdominal mass (85%), abdominal distension (35%), fever (10–25%), vaginal bleeding from B-HCG/estrogen production (10%), precocious puberty 2/2 to B-HCG production (rare), NMDA receptor encephalitis (rare), hyperthyroidism (2/2 struma ovarii). Can be bilateral in benign cystic teratoma, dysgerminoma, & tumors w/components of dysgerminoma

• Growing teratoma syndrome: Rare complication of immature teratomas 2/2 enlarging teratoma that becomes mature during chemo; needs prompt surgery

Workup and Staging

• W/u: Serum tumor markers: AFP, LDH, HCG; CXR, pelvic US or CT abd/pelvis. Karyotype if dysgenetic gonads are suspected. Use tumor markers to monitor response to Rx & recurrence. R/O pregnancy if B-HCG ↑

• Fertility preservation: Discuss embryo cryopreservation. If not feasible, cryopreservation of oocytes or ovarian tissue an option (experimental)

• Stage I: Confined to ovaries (Stage IA: Single ovary; Stage IB: Both ovaries; Stage IC: Ovarian surface involvement or capsule rupture); Stage II: Extension into other pelvic tissues (Stage IIA: Extension/implants on uterus/tubes; Stage IIB: Extension or implants on other pelvic tissues; Stage IIC other Stage II criteria plus + washings); Stage III: Disease spread beyond pelvis or to lymph nodes but remains in abdomen/pelvis (Stage IIIA:Microscopic peritoneal mets beyond pelvis; Stage IIB: Macroscopic mets beyond pelvis (≤2 cm); Stage IIIC: Peritoneal mets beyond pelvis >2 cm or regional lymph node mets); Stage IV: Distant mets or liver parenchyma involvement

Management: Low Risk Disease (Benign OGCT; Stage IA, Grade 1 Immature Teratoma & Stage IA Dysgerminoma):

• Definitive Surgery: Fertility sparing ovarian cystectomy/salpingooophorectomy if fertility is desired or standard surgical staging (TAH, BSO) & optimal cytoreduction if pt has completed childbearing. May want to bx contralateral ovary if dysgerminoma present (controversial).

Management: All Other Malignant OGCT:

• 1° Surgery: Perform before chemo as pts w/completely resected disease have ↑ oncologic results, although data inconclusive. May be more critical for nondysgerminomas

• Adjuvant Chemotherapy: Standard of care w/3–6 cycles of BEP (bleomycin, etoposide, CIS). Ideally give 7–10 d after surgery; give at full dose Rx even w/myelosuppression as ↑ oncologic benefit (N Engl J Med 1987;316:1435–1440; J Clin Oncol 1994;12:701–706)

• Debulking Surgery after Chemotherapy: Consider if residual disease present after adjuvant chemotherapy w/negative tumor markers. Can prevent Growing Teratoma Syndrome & dedifferentiation of teratoma into active CA (Gynecol Oncol 1994;55:217–223)

• RT: Previously used in dysgerminomas; currently has largely been replaced by platinum-based chemotherapy (J Clin Oncol 1991;9:1950–1955)

Management: Recurrent Malignant OGCT:

• 90% of pts that will recur, recur in first 2 y after Rx completion; if recurs after 2 y, usu slow growing & chemo resistant

• Salvage Chemotherapy: If no prior chemotherapy: BEP; If prior chemotherapy:

VIP (etoposide, ifosfamide, CIS), VeIP (Vinblastine, ifosfamide, CIS), TIP (paclitaxel, ifosfamide, CIS). Palliative options: Paclitaxel, GEM ± CIS, epirubicin + CIS

• High-Dose Chemotherapy w/Stem Cell Rescue: Consider for persistent, refractory, or platinum-resistant disease (J Clin Oncol 2000;18:1173–1180)

Long Term Side Effects of BEP Chemotherapy:

• Renal insufficiency, gonadal dysfunction, neurotoxicity, cardiovascular tox 2/2 to CIS, 2° malignancies 2/2 etoposide (solid tumors, leukemias), & pulm fibrosis 2/2 bleomycin. 80% pts preserve menstrual function after fertility sparing surgery/platinum-based chemotherapy (Obstet Gyn 2003;101(2):251)