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 . Chapter 093. Gynecologic Malignancies (Part 9) Clinical Presentation Molar pregnancies are generally associated with. 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. 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