Annually in the United States, about 22,530 new cases are found and 13,980 women die of ovarian cancer. Incidence begins to rise in the fifth decade, peaking in the eighth decade. Risk is increased in nulliparous women and reduced by pregnancy (risk decreased about 10% per pregnancy) and oral contraceptives. About 5% of cases are familial.
Mutations in BRCA-1 and BRCA-2 predispose women to both breast and ovarian cancer. Cytogenetic analysis of epithelial ovarian cancers that are not familial often reveals complex karyotypic abnormalities, including structural lesions on chromosomes 1 and 11 and loss of heterozygosity for loci on chromosomes 3q, 6q, 11q, 13q, and 17. C-myc, H-ras, K-ras, and HER2/neu are often mutated or overexpressed. Unlike in colon cancer, a stepwise pathway to ovarian carcinoma is not apparent. Ovarian cancers may also occur in the setting of Lynch syndrome, inherited nonpolyposis colorectal cancer, due to mutations in the genes that repair DNA mismatches. The subset of women with endometrioid histology often have a mutation in ARID1A, a DNA repair complex component.
No benefit has been seen from screening women of average risk. Hereditary ovarian cancer accounts for 10% of all cases. Women with BRCA-1 or -2 mutations should consider prophylactic bilateral salpingo-oophorectomy by age 40.
Most pts present with abdominal pain, bloating, urinary symptoms, and weight gain indicative of disease spread beyond the true pelvis. Localized ovarian cancer is usually asymptomatic and detected on routine pelvic examination as a palpable nontender adnexal mass. Most ovarian masses detected incidentally in ovulating women are ovarian cysts that resolve over one to three menstrual cycles. Adnexal masses in postmenopausal women are more often pathologic and should be surgically removed. CA-125 serum levels are ≥35 U/mL in 80-85% of women with ovarian cancer, but other conditions may also cause elevations.
Half of ovarian tumors are benign, one-third are malignant, and the rest are tumors of low malignant potential. These borderline lesions have cytologic features of malignancy but do not invade. Malignant epithelial tumors may be of five different types: serous (50%), mucinous (25%), endometrioid (15%), clear cell (5%), and Brenner tumors (1%, derived from urothelial or transitional epithelium). The remaining 4% of ovarian tumors are stromal or germ cell tumors, which are managed like testicular cancer in men (Chap. 73 Genitourinary Tract Cancer). Histologic grade is an important prognostic factor for the epithelial varieties.
Extent of disease is ascertained by a surgical procedure that permits visual and manual inspection of all peritoneal surfaces and the diaphragm. Total abdominal hysterectomy, bilateral salpingo-oophorectomy, partial omentectomy, pelvic and paraaortic lymph node sampling, and peritoneal washings should be performed. The staging system and its influence on survival are shown in Table 74-1 Staging and Survival in Gynecologic Malignancies. About 23% of pts are stage I, 13% are stage II, 47% are stage III, and 16% are stage IV.
| TREATMENT | ||
Ovarian CancerPts with stage I disease, no residual tumor after surgery, and well- or moderately differentiated tumors need no further treatment after surgery and have a 5-year survival of >95%. For stage II pts totally resected and stage I pts with poor histologic grade, adjuvant therapy with single-agent cisplatin or cisplatin plus paclitaxel produces 5-year survival of 80%. In the setting of bulky disease, maximal surgical cytoreduction is attempted. Those in whom no gross residual disease is left have a median survival of 39 months; those left with visible tumor, 17 months. Giving chemotherapy before definitive surgery (neoadjuvant) may increase the fraction of pts whose gross disease is resectable. Advanced-stage pts should receive paclitaxel, 175 mg/m2 by 3-h infusion, followed by carboplatin dosed to an area under the curve (AUC) of 6 every 3 or 4 weeks. Carboplatin dose is calculated by the Calvert formula: dose = target AUC × (glomerular filtration rate + 25). Some data support intraperitoneal delivery of the chemotherapy and some data support the use of heated chemotherapy. The complete response rate is about 55%, and median survival is 38 months. |