Chapter 093. Gynecologic Malignancies (Part 9) pps

Chapter 093. Gynecologic
Malignancies
(Part 9)

Clinical Presentation
Molar pregnancies are generally associated with first-trimester bleeding and
excessive uterine size. About 45% of patients have ovarian theca-lutein cysts
present on ultrasound. The β-hCG levels are generally markedly elevated. Fetal
parts and heart sounds are not present. The diagnosis is generally made by the
passage of grapelike clusters from the uterus, but ultrasound demonstration of the
hydropic mole can be diagnostic. Patients suspected of a molar pregnancy require
a chest film, careful pelvic examinations, and weekly serial monitoring of β-hCG
levels.
Gestational Trophoblastic Neoplasia: Treatment
Patients with hydatidiform moles require suction curettage coupled with
postevacuation monitoring of β-hCG levels. In most women (80%), the β-hCG
titer progressively declines within 8–10 days of evacuation (serum half-life is 24–
36 h). Patients should be monitored on a monthly basis and should not become
pregnant for at least a year. Patients found to have invasive mole at curettage are
generally treated with hysterectomy and chemotherapy. Approximately half of
patients with choriocarcinoma develop the malignancy after a molar pregnancy,
and the other half develop the malignancy after abortion, ectopic pregnancy, or
occasionally after a normal full-term pregnancy.
Chemotherapy is used for gestational trophoblastic neoplasia and often as
chemoprophylaxis after molar evacuation to reduce postmolar tumors. It is also
used in hydatidiform mole if β-hCG levels rise or plateau or if metastases develop.
Patients with invasive mole or choriocarcinoma require chemotherapy. Several
regimens are effective for low-risk patients, including methotrexate at 30 mg/m
2

intramuscularly on a weekly basis until β-hCG titers are normal. However,

methotrexate (1 mg/kg) every other day for four doses, followed by leukovorin
(0.1 mg/kg) intravenously 24 h after methotrexate, is associated with a cure rate of
≥90% and low toxicity. Intermittent courses are continued until the β-hCG titer
becomes undetectable for 3 consecutive weeks; then patients are monitored
monthly for a year.
Patients with high-risk tumors (high β-hCG levels, disease presenting ≥4
months after antecedent pregnancy, brain or liver metastasis, or failure of single-
agent methotrexate) are initially treated with combination chemotherapy. EMA-
CO (a cyclic non-cross-resistant combination of etoposide, methotrexate, and
dactinomycin alternating with cyclophosphamide and vincristine); cisplatin,
bleomycin, and vinblastine; and cisplatin, etoposide, and bleomycin are effective
regimens. EMA-CO is now the regimen of choice for patients with high-risk
disease because of excellent survival rates (>80%) and less toxicity. The use of
etoposide carries a 1.5% lifetime risk of acute myeloid leukemia (sixteenfold
relative risk) and other solid tumors. As a result, etoposide-containing regimens
should be reserved for patients with high-risk features. Patients with brain or liver
metastases are usually treated with local irradiation to metastatic sites in
conjunction with chemotherapy. Long-term studies of patients cured of
trophoblastic disease have not demonstrated an increased risk of maternal
complications or fetal abnormalities with subsequent pregnancies.
Further Readings
Champion V et al: Quality of life in long-
term survivors of ovarian germ
cell tumors: A gynecologic oncology group study. Gynecol Oncol 105:687, 2007
[PMID: 17355890]
Koutsky LA: A controlled trial of a human papilloma virus type 16 vaccine.
N Engl J Med 347:1645, 2002 [PMID: 12444178]
Lindor NM et al: Recommendations for the care of individuals with an
inherited predisposition to Lynch Syndrome. JAMA 296:1507, 2006 [PMID:
17003399]

Modugno F: Ovarian Cancer and High Risk Women Symposium
Presenters. Ovarian cancer and high-
risk women: Implications for prevention,
screening and early detection. Gynecol Oncol 91:15, 2003 [PMID: 14529658]
Ozols RF et al: Phase III study of cisplatin/paclitaxel compared with
carboplatin/paclitaxel in patients with
optimally resected stage III epithelial
ovarian cancer. J Clin Oncol 21:3194, 2003 [PMID: 12860964]
Randall ME et al: Randomized phase III trial of whole abdominal
irradiation vs. doxorubicin and cisplatin chemotherapy in advanced endometrial
carcinoma:
A Gynecologic Oncology Group study. J Clin Oncol 24:36, 2006
[PMID: 16330675]
Rose PG: Secondary surgical cytoreduction for advanced ovarian cancer. N
Engl J Med 351:2489, 2004 [PMID: 15590951]
Solomon D et al: The 2001 Bethesda System. JAMA 287:2114, 2002
[PMID: 11966386]
Stehman FB et al: Innovations in the treatment of invasive cervical cancer.
Cancer 98:2052, 2003 [PMID: 14603542]
Trimbos JB: International Collaborative Neoplasm Trial I a
nd Adjuvant
Chemotherapy in Ovarian Neoplasm Trial: Two parallel randomized phase III
trials of adjuvant chemotherapy in patients with early stage ovarian carcinoma. J
Natl Cancer Inst 95:105, 2003 [PMID: 12529343]
Wright JD, Mutch DG: Treatment of high-
risk gestational trophoblastic
tumors. Clin Obstet Gynecol 46:593, 2003 [PMID: 12972740]
Young RC
et al: Adjuvant therapy in stage I and stage II epithelial ovarian
cancer. Results of two prospective trials. N Engl J Med 327:1021, 1990

Bibliography
Garner EI et al: Gestational trophoblastic disease. Clin Obstet Gynecol
50:112, 2007 [PMID: 17304028]
Jacobs IJ: Screening for ovarian cancer: A pilot randomized trial. Lancet
353:1207, 1999 [PMID: 10217079]
Lurain JR et al: Primary treatment of metastatic high-
risk gestational
trophoblastic neoplasia with EMA-
CO chemotherapy. J Reprod Med 10:767, 2006
Ozols RF et al: Epithelial ovarian cancer, in
Principles and Practice of
Gynecologic Oncology, 4th ed, WJ Hoskins et al (eds). Philadelphia, Lippinc
ott
Williams & Wilkins, 2005, pp 895–987
Randall ME et al: Uterine cervix, in
Principles and Practice of Gynecologic
Oncology
, 4th ed, WJ Hoskins et al (eds). Philadelphia, Lippincott Williams &
Wilkins, 2005, pp 743–822
Trope C: Corpus: Epithelial tumors, in
Principles and Practice of
Gynecologic Oncology
, 4th ed, WJ Hoskins et al (eds). Lippincott, Williams &
Wilkins, Philadelphia, 2005, pp 823–872
VanderBurg ME
et al: Intervention debulking surgery does improve
survival in advanced epithelial ovarian cancer. N Engl J Med 332:629, 1995