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Ovarian Dysgerminomas Treatment & Management

  • Author: Chad M Michener, MD; Chief Editor: Warner K Huh, MD  more...
 
Updated: Apr 15, 2015
 

Medical Care

A preponderance (75-80%) of dysgerminomas present as stage I cancers and, therefore, can be treated by surgical resection alone with a unilateral salpingo-oophorectomy and staging. This is preferred when attempting to preserve fertility; however, diligent follow-up care, with serial pelvic examinations and tumor markers (ie, beta-human chorionic gonadotropin [beta-hCG], alpha-fetoprotein [AFP], lactate dehydrogenase [LDH]) is mandatory if resection is the only treatment modality.

Adjuvant therapy should be reserved for women with stage Ib-IV ovarian dysgerminomas. Platinum-based chemotherapy has become the standard of care for these patients and is generally well tolerated. Radiation therapy has also been administered to patients with stage I-III tumors, with excellent response rates overall. However, this has been mostly abandoned due to high success rates with platinum-based chemotherapy, as well as avoiding long-term complications from radiation, including sterility and early menopause.

Stage Ia dysgerminomas

Typically, the authors do not recommend any adjuvant chemotherapy for stage Ia dysgerminomas. Although 10-15% of stage Ia tumors may recur, essentially all of them are salvaged with chemotherapy. Patients with completely resected stage Ib and Ic tumors should receive 3 cycles of BEP (bleomycin, etoposide, platinum), and those with completely resected stage II-IV tumors should receive 4 cycles of BEP. Patients with bulky residual disease may require additional cycles. However, care should be taken to watch for pulmonary toxicity with bleomycin and the potential for secondary leukemias with high cumulative doses of etoposide; these precautions should be discussed with the patient.

Fertility after chemotherapy

In studies of young women who received platinum-based chemotherapy for ovarian germ cell tumors (GCTs), 62 (87%) of 71 resumed regular menstrual function and 24 of these women delivered 37 children after chemotherapy.[3] In a study by Weinberg et al,[4] 40 women with malignant ovarian GCTs were followed for reproductive outcomes. Twenty-two women underwent fertility-sparing surgery and 16 of these received chemotherapy. The majority of patients (14 of 16) received BEP. Follow-up was available for 14 of the 16 patients. All 14 returned to normal menstrual function. Eight of the 10 women who attempted pregnancy had 11 pregnancies with 14 live births.

Adjuvant chemotherapy regimens

The 4 regimens for chemotherapy are as follows: (1) BEP, which is the preferred regimen; (2) methotrexate, actinomycin D, and chlorambucil (MAC); (3) cisplatin, vincristine, and bleomycin (PVB); and (4) vincristine, actinomycin D, and cyclophosphamide (VAC). Although the efficacy has been analyzed for each protocol, the BEP protocol has been favored in recent years owing to high cure rates with a favorable toxicity profile.

Important to note is that the authors attempt to keep patients on schedule despite bone marrow toxicity that may develop. Given the high cure rates and relatively low rates of neutropenic fever, it is best to continue treatment as scheduled even if blood counts are lower than what is typically considered acceptable to begin a new cycle. Consideration for dose reduction and addition of growth factors should be made on a case-by-case basis and should be used after neutropenic fever.

BEP protocol (generally preferred)

The protocol is as follows[5] :

  • Bleomycin - Maximum 30 U IV per week for 9 weeks; dose at 20 U/m 2
  • Etoposide (ie, VP-16) - 100 mg/m 2 on days 1-5 q3wk for 3 courses; reduced 20% for granulocytic fever or previous radiotherapy
  • Cisplatin - 20 mg/m 2 on days 1-5 q3wk for 3 courses

In 2004, the Gynecologic Oncology Group (GOG) published their experience using carboplatin and etoposide in ovarian dysgerminomas.[6] They followed 39 eligible patients with completely resected stage Ib-III disease for a median follow-up of 7.8 years. There were no disease recurrences, although one patient had an intercurrent death from lung cancer. Although not considered the standard, this regimen may be considered in patients with preexisting renal or neurologic disease.

This regimen is carboplatin t 400 mg/m2 on day 1 and etoposide at 120 mg/m2 on days 1-3 q4wk for 3 cycles.

Antiemetics

Antiemetics that may be used in chemotherapy are as follows:

  • Chlorpromazine - 25-50 mg PO/IM/PR q4h
  • Odansetron 4-8 mg IV/PO prior to chemotherapy
  • Lorazepam 1-2 mg PO/IV q6h
  • Dexamethasone 8 mg IV prior to cisplatin and 4 mg q4h for 2 doses

Radiation therapy

Primary therapy with radiation is reserved for patients who cannot tolerate chemotherapy or surgical resection.

Radiation is used to treat periaortic and pelvic lymph node metastases. Shielding the remaining ovary in an attempt to preserve fertility is not uncommon. Oophoropexy may be used to mechanically hold the remaining ovary away from the radiation field.

Radiation therapy may be used for any dysgerminomas staged Ib-III. The field of exposure extends from T11 to L5, with shielding of the contralateral ovary and the femur head.

The use of radiation in stage Ia cancers is considered precautionary. Most patients present with stage I disease and usually can be treated with simple resection (eg, unilateral salpingo-oophorectomy). Some authors have advocated radiation therapy for stage IA tumors larger than 10 cm. However, owing to the high sensitivity for radiation and platinum-based chemotherapy, the authors do not recommend treating stage Ia tumors with any adjuvant therapy.

De Palo,[7] Freed, and Lawson developed the 3 major radiation therapy protocols. These protocols differ mainly in their treatment of the abdomen for node-positive disease and in prophylactic treatment of the mediastinum.

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Surgical Care

Full surgical staging is recommended for ovarian germ cell tumors (GCTs) to identify women with greater than stage Ia disease. Pattern of spread for ovarian dysgerminomas often follows a lymphatic rather than peritoneal route, with up to 25% of patients having lymphatic involvement. Therefore, complete lymphadenectomy should be performed.

Fertility preservation

Since many women with ovarian dysgerminomas are be in their 20s and 30s, any woman who wishes to maintain fertility should undergo exploratory laparotomy, pelvic washings, unilateral salpingo-oophorectomy, ipsilateral pelvic and bilateral para-aortic lymphadenectomy, omentectomy, and peritoneal biopsies. It is not recommended to leave the ipsilateral tube, owing to the rich lymphovascular connection between the tube and the ovary.

It should be noted that contralateral positive pelvic nodes may be seen in 10-50% of women with positive pelvic lymph nodes at surgery for epithelial ovarian cancers. Although no data exist for dysgerminomas, bilateral pelvic lymphadenectomy should be performed if there is extraovarian pelvic involvement and should be considered in patients in whom disease appears to be confined to the ovary.

Additionally, note that the contralateral ovary may be involved in 5-10% of patients who appear to have stage Ia disease. Historically, a wedge biopsy of the contralateral ovary was recommended to rule out microscopic spread in the contralateral ovary. However, the authors of this article advocate leaving the opposite ovary undisturbed if it is of normal size and appearance. This is suggested for 2 reasons. First, dysgerminomas are highly responsive to both radiation and platinum-based chemotherapy, so adjuvant therapy for advanced-stage disease and treatment of recurrence are typically very successful. Second, performing a biopsy of a normal contralateral ovary may diminish fertility as a result of adhesion formation following the biopsy.

Women who have completed childbearing

These women should undergo exploratory laparotomy, pelvic washings, total abdominal hysterectomy, bilateral salpingo-oophorectomy, ipsilateral pelvic and bilateral para-aortic lymphadenectomy, omentectomy, and peritoneal biopsies.

Women with metastatic disease

Identification of disease extending beyond the ovary at laparotomy should lead to an attempt at complete surgical cytoreduction. Although no prospective data comparing outcomes of surgical debulking in advanced-stage ovarian GCTs are available, evidence suggests that women treated with chemotherapy after optimal surgical cytoreduction have a better prognosis than those with bulky residual or unresectable disease. However, one should bear in mind that these tumors do have an excellent response to platinum-based chemotherapy, so the risk-to-benefit ratio of radical surgical procedures should be considered in this context.

Incompletely staged patients with presumed stage Ia disease

National Comprehensive Cancer Network (NCCN) guidelines suggest checking tumor markers and CT scanning of the chest, abdomen, and pelvis. If results are normal, patients may be observed. If any abnormalities are noted on these tests, laparotomy and complete surgical staging should be performed.

An Italian study of 26 women with ovarian dysgerminomas showed only 19.2% had complete surgical staging. Three of these women (11.5%) suffered recurrence, with 2 having lymph nodes as part of their recurrent disease.[8] All of them were salvaged with chemotherapy with or without surgery. The overall recurrence risk in unstaged women was 20% in this study, which may help in counseling women in this situation.

Laparoscopy

Case reports describe laparoscopic management and staging of ovarian GCTs. However, data on outcome are lacking and should still be considered investigational, as the standard is still laparotomy.

Surgical preparation

Traditionally, patients undergoing surgery for ovarian cancer often undergo a mechanical and/or antibiotic bowel preparation before surgery. This was once felt to be critical in the case of unsuspected gastrointestinal spread requiring bowel resection. However, current data in the colorectal literature suggests that bowel preparation can be safely abandoned.

Second-look surgery

According to current American College of Obstetricians and Gynecologists (ACOG) recommendations, second-look laparotomies are not considered the standard of care for dysgerminomas.[9] . However, second-look surgery should be considered for patients with persistent elevation in tumor markers, especially if associated with abnormal findings on posttreatment imaging.

Management in pregnancy

Most adnexal masses found in pregnancy resolve spontaneously within the first trimester. Two percent of all adnexal masses persisting during pregnancy are malignant (dysgerminomas included). For this reason, a more cautious observational approach is advocated up to 16 weeks' gestation. Moreover, the risk of aborting a viable fetus with surgery in the first trimester approaches 30%.

If surgery is indicated, the ideal intervention time is 16-18 weeks' gestation. General anesthesia should be used. Placement of a higher-than-usual vertical incision is necessary because the ovary becomes an abdominal structure after 16 weeks' gestation.

Frozen sections should be taken at the time of surgery. If the pathology is hyperreactio luteinalis or luteoma, no intervention is indicated and the abdomen should be closed. Since the majority (90%) of dysgerminomas found in pregnancy are unilateral, one should avoid biopsy of the contralateral ovary if this ovary appears normal. Lymphadenectomy may also be limited if the uterus is obstructive to the pelvic sidewalls or paraaortic regions.

Benign or low-grade tumors generally require unilateral salpingo-oophorectomy, whereas bilateral involvement of malignant or widely metastatic tumors requires bilateral salpingo-oophorectomy with or without total abdominal hysterectomy. If patients are at or near term, delivery of the fetus is performed and hysterectomy may be performed.

Postoperative progesterone and uterotonic agents (eg, nifedipine, magnesium sulfate, terbutaline) have unproven efficacy postoperatively for the prevention of preterm labor, so treatment should be individualized and plans made in conjunction with consultation from obstetrical or maternal-fetal medicine specialists.

The 5-year patient survival rate for dysgerminoma in pregnancy is 90%. The fetal mortality rate approaches 25%, especially if surgery is performed in the first trimester.

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Consultations

Consultation with a gynecologic oncologist is recommended when suspicion for an ovarian malignancy is high, especially if resection requires surgery beyond the straightforward unilateral or bilateral salpingo-oophorectomy and hysterectomy.

Further follow-up with a medical oncologist and/or radiation oncologist is dictated by the stage and extent of disease.

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Diet

No specific dietary restrictions are mandated during therapy for dysgerminoma.

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Activity

During the immediate postoperative recovery period, heavy lifting and vigorous activity should be discouraged to prevent strain on the abdominal wound.

Sexual activity should be limited during the postoperative period if hysterectomy was performed. However, sexual activity can resume postoperatively for other patients as long as there is no discomfort. There are no limitations for sexual activity during chemotherapy, although patients may experience vaginal dryness during chemotherapy if menstrual function is reduced.

Attempts to become pregnant should be postponed until completion of postoperative convalescence and/or chemotherapy.

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Contributor Information and Disclosures
Author

Chad M Michener, MD Assistant Professor, Obstetrics/ Gynecology and Women's Health Institute, Section of Gynecologic Oncology, The Cleveland Clinic

Chad M Michener, MD is a member of the following medical societies: American College of Obstetricians and Gynecologists, Society of Gynecologic Oncology

Disclosure: Nothing to disclose.

Coauthor(s)

Allan Y Wu, MD Director, The Midwest Women's Specialty Group; Adjunct Clinical Professor, Department of Molecular Biology, The Terre Haute Center for Medical Education, Indiana University School of Medicine

Allan Y Wu, MD is a member of the following medical societies: American College of Obstetricians and Gynecologists

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Michel E Rivlin, MD Former Professor, Department of Obstetrics and Gynecology, University of Mississippi School of Medicine

Michel E Rivlin, MD is a member of the following medical societies: American College of Obstetricians and Gynecologists, American Medical Association, Mississippi State Medical Association, Royal College of Surgeons of Edinburgh, Royal College of Obstetricians and Gynaecologists

Disclosure: Nothing to disclose.

Chief Editor

Warner K Huh, MD Professor, Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Senior Scientist, Comprehensive Cancer Center, University of Alabama School of Medicine

Warner K Huh, MD is a member of the following medical societies: American College of Obstetricians and Gynecologists, American College of Surgeons, Massachusetts Medical Society, Society of Gynecologic Oncology, American Society of Clinical Oncology

Disclosure: I have received consulting fees for: Merck; THEVAX.

References
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Ovarian dysgerminomas. Microscopic image at 20 X.
 
 
 
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