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Ovarian
cancer is often fatal because it is usually advanced when diagnosed.
Symptoms are usually absent in early stage and nonspecific in advanced
stage. Evaluation usually includes ultrasonography, CT or MRI, and
measurement of tumor markers (eg, cancer antigen 125). Diagnosis
is by histologic analysis. Staging is surgical. Treatment
requires hysterectomy, bilateral salpingo-oophorectomy,
excision of as much involved tissue as possible, and,
unless cancer is localized, chemotherapy.
In the US, ovarian cancer is the 2nd most common gynecologic cancer (affecting about 1/70) and the deadliest (1% of all women die of it); it is the 5th leading cause of cancer-related deaths in women. Incidence is higher in developed countries.
Etiology
and Pathology
Ovarian cancer affects mainly perimenopausal and postmenopausal women. Nulliparity, delayed childbearing, and delayed menopause increase risk. Oral contraceptive use decreases risk.
A personal or family history of endometrial, breast, or colon cancer increases risk. Probably 5 to 10% of ovarian cancer cases are related to mutations in the autosomal dominant BRCA gene. XY gonadal dysgenesis predisposes to ovarian germ cell cancer.
Ovarian cancers are histologically diverse. At least 80% originate in the epithelium; 75% of these cancers are serous cystadenocarcinoma, and the rest include mucinous, endometrioid, transitional cell, clear cell, unclassified carcinomas, and Brenner tumor. The remaining 20% of ovarian cancers originate in primary ovarian germ cells or in sex cord and stromal cells or are metastases to the ovary (most commonly, from the breast or GI tract). Germ cell cancers usually occur in women < 30 and include dysgerminomas, immature teratomas, endodermal sinus tumors, embryonal carcinomas, choriocarcinomas, and polyembryomas. Stromal (sex cord–stromal) cancers include granulosa-theca cell tumors and Sertoli-Leydig cell tumors.
Ovarian cancer spreads by direct extension, exfoliation of cells into the peritoneal cavity (peritoneal seeding), lymphatic dissemination to the pelvis and around the aorta, or, less often, hematogenously to the liver or lungs.
Symptoms and Signs
Early cancer is usually asymptomatic; an adnexal mass, often solid, irregular, and fixed, may be discovered incidentally. Pelvic and rectovaginal examinations typically detect diffuse nodularity. A few women present with severe abdominal pain secondary to torsion of the ovarian mass (see Benign Gynecologic Lesions: Adnexal Torsion). Most women with advanced cancer present with nonspecific symptoms (eg, dyspepsia, bloating, early satiety, gas pains, backache). Later, pelvic pain, anemia, cachexia, and abdominal swelling due to ovarian enlargement or ascites usually occur. Germ cell or stromal tumors may have functional effects (eg, hyperthyroidism, feminization, virilization).
Diagnosis
Ovarian cancer is suspected in women with unexplained adnexal masses, unexplained abdominal bloating, changes in bowel habits, unintended weight loss, or abdominal pain. An ovarian mass is more likely to be cancer in older women. Benign functional cysts (see Benign Gynecologic Lesions: Benign Ovarian Masses) can simulate functional germ cell or stromal tumors in young women.
If cancer is suspected, ultrasonography is done first; findings that suggest cancer include a solid component, surface excrescences, size > 6 cm, irregular shape, and low vascular resistance on transvaginal Doppler flow studies. A pelvic mass plus ascites usually indicates ovarian cancer but sometimes indicates Meigs' syndrome (a benign fibroma with ascites and right hydrothorax). CT or MRI is usually done before surgery to determine extent of the cancer. Tumor markers, including the β subunit of human chorionic gonadotropin (β-hCG), LDH, α-fetoprotein, inhibin, and cancer antigen (CA) 125, are also measured. CA 125 is elevated in 80% of advanced epithelial ovarian cancers but may be mildly elevated in endometriosis, pelvic inflammatory disease, pregnancy, fibroids, peritoneal inflammation, or nonovarian peritoneal cancer. A mixed solid and cystic pelvic mass in postmenopausal women, especially if CA 125 is elevated, suggests ovarian cancer. Histologic analysis is mandatory for adnexal masses unless they appear benign. Benign-appearing masses include benign cystic teratomas (dermoid cysts), follicular cysts, or endometriomas. For masses that appear benign, ultrasonography is repeated after 6 wk. If women are not surgical candidates, samples are obtained by needle biopsy for masses or by needle aspiration for ascitic fluid.
Staging:
Suspected or confirmed ovarian cancer is staged surgically (see Table 1: Gynecologic Tumors: Surgical Staging of Ovarian Carcinoma* ). An abdominal midline incision that allows adequate access to the upper abdomen is required. All peritoneal surfaces, hemidiaphragms, and abdominal and pelvic viscera are inspected and palpated. Washings from the pelvis, abdominal gutters, and diaphragmatic recesses are obtained, and multiple biopsies of the peritoneum in the central and lateral pelvis and in the abdomen are done. For early-stage cancer, the infracolic omentum is removed, and pelvic and para-aortic lymph nodes are sampled.
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Table 1
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Surgical Staging of Ovarian
Carcinoma*
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Stage
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Description
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I
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Tumor limited to the ovaries
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IA
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Tumor limited to one ovary; no tumor on the external surface, and capsule intact
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IB
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Tumor limited to both ovaries; no tumor on the external surface, and capsules intact
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IC
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Stage IA or IB but with tumor on the surface of one or both ovaries, with capsule ruptured, or with ascites or peritoneal washings containing malignant cells†
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II
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Tumor involving one or both ovaries with pelvic extension or metastases
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IIA
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Extension and/or metastases to the uterus, fallopian tubes, or both
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IIB
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Extension to other pelvic tissues
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IIC
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Stage IIA or IIB but with tumor on the surface of one or both ovaries, with capsule ruptured, or with ascites or peritoneal washings containing malignant cells†
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III
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Histologically confirmed peritoneal metastases outside the pelvis, superficial liver metastases, positive retroperitoneal or inguinal lymph nodes, or tumor limited to the true pelvis but with histologically verified malignant extension to the small intestine or omentum
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IIIA
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Gross tumor limited to the true pelvis with negative lymph nodes but with histologically confirmed microscopic tumor outside pelvis
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IIIB
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Histologically confirmed abdominal peritoneal metastases that extend beyond the pelvis and are < 2 cm in diameter and negative lymph nodes
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IIIC
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Abdominal peritoneal metastases that extend beyond the pelvis and are > 2 cm in diameter, positive retroperitoneal or inguinal lymph nodes, or both
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IV
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Distant metastases, including parenchymal liver metastases; if pleural effusion is present, cytologic test results must be positive to signify stage IV
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*Based on staging established by the International Federation of Gynecology and Obstetrics (FIGO) and American Joint Committee on Cancer (AJCC), 1999, 2002.
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†For stages IC and IIC, knowing whether capsule rupture was spontaneous or caused by the surgeon and whether the source of malignant cells was ascites or peritoneal washings helps determine prognosis.
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Cancers are also graded histologically from 1 (least aggressive) to 3 (most aggressive).
Screening asymptomatic women using ultrasonography and serum CA 125 measurements can detect some cases of ovarian cancer but has not been shown to improve outcome, even for high-risk subgroups.
Prognosis
and Treatment
The 5-yr survival rates with treatment are 70 to 100% with stage I, 50 to 70% with stage II, 15 to 35% with stage III, and 10 to 20% with stage IV. Prognosis is worse when tumor grade is higher or when surgery cannot remove all visibly involved tissue; then, prognosis is best when the involved tissue can be reduced to < 1 cm in diameter. With stages III and IV, recurrence rate is about 70%.
Hysterectomy and bilateral salpingo-oophorectomy are usually indicated. An exception is nonepithelial or low-grade unilateral epithelial cancer in young patients; fertility can be preserved by not removing the unaffected ovary and uterus. All visibly involved tissue is surgically removed if possible. If it cannot be removed completely, removing as much as possible (cytoreductive surgery) improves the efficacy of other therapies. Cytoreductive surgery usually includes infracolic omentectomy, sometimes with rectosigmoid resection (usually with primary reanastomosis), radical peritoneal stripping, resection of diaphragmatic peritoneum, or splenectomy.
Stage IA or B/grade 1 epithelial adenocarcinoma requires no postoperative therapy. Stage IA or B/grade 2 or 3 cancers and stage II cancers require 6 courses of chemotherapy (typically, paclitaxel and carboplatin ).
Stage III or IV cancer requires 6 courses of similar chemotherapy. Intraperitoneal chemotherapy or high-dose chemotherapy with bone marrow transplantation is under study. Radiation therapy is used infrequently.
Even if chemotherapy results in a complete clinical response (ie, normal physical examination, normal serum CA 125, and negative CT scan of the abdomen and pelvis), about 50% of patients with stage III or IV cancer have residual tumor. Of patients with persistent elevation of CA 125, 90 to 95% have residual tumor.
If cancer recurs or progresses after effective chemotherapy, chemotherapy is restarted. Other useful drugs may include topotecan , liposomal doxorubicin , docetaxel , vinorelbine , gemcitabine , hexamethylmelamine, and oral etoposide .
Most patients with germ cell cancer or stage II or III stromal cancer are treated with combination chemotherapy, usually bleomycin , cisplatin , and etoposide .
Last full review/revision November 2005
Content last modified November 2005
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