Ovarian cancer remains the leading cause of gynecologic malignancy mortality in the United States and is fourth overall in women behind lung, breast and colorectal cancer. Although significant advances have been made in the evaluation and treatment of ovarian cancer, the overall long-term survival has not changed significantly during the past 20 years. More than 70% of women have their disease diagnosed in advanced stages (III or IV) and have a 5-year survival less than 30%. Because of such grim statistics, effective secondary methods of treatment or preferably preventive approaches must be developed.

Screening

The 1994 National Institutes of Health (NIH) Consensus Conference on ovarian cancer concluded that there is no effective method for screening and detecting early ovarian cancer.

Diagnosis

The usual symptomatology associated with ovarian malignancies is that of advanced disease: abdominal pain, bloating, increasing abdominal girth, general digestive disturbances, abdominal and pelvic discomfort, and, at times, uterine bleeding. It is noted that all are essentially nonspecific and, once present, are most often associated with spread of malignancy throughout the abdominal cavity with involvement of the visceral and parietal peritoneal surfaces. When ascites or upper abdominal metastatic disease is present, bloating, heartburn, diminished appetite, nausea, and generalized discomfort are often the case. Stage I and lower pelvic disease may be detected by palpation of an asymptomatic mass or be associated with pelvic pressure and urinary frequency.

Diagnostic Techniques

Physical Examination

It has been estimated that routine pelvic examination will detect only 1 case of ovarian carcinoma in 10,000 asymptomatic women examined. Although the character of a mass found at the time of examination is not diagnostic, a unilateral, cystic mass that is mobile and less than 10 cm in diameter is more consistent with a benign process when compared to the solid, bilateral, fixed and larger lesion with cul-de-sac nodularity. Other physical findings are those that would be expected with the presence of abdominal disease, chiefly, ascites or a ballottable omental mass.

Radiographic and Other Studies

The evaluation of presenting symptoms of the pelvic mass would include other gynecologic disorders, such as leiomyomata, tubo-ovarian abscesses, endometriomas, gastrointestinal disorders, such as diverticular disease and neoplasia, and, rarely, urologic disorders, such as a pelvic kidney. In general, further diagnostic evaluation is directed toward the patient’s symptoms, physical examination, and general medical considerations, and may include some of the following: chest x-ray, intravenous pyelogram, barium enema and/or colonoscopy, upper gastrointestinal tract roentgenograms, ultrasonography, computed tomography (CT), and magnetic resonance imaging (MRI). While CT may not detect the presence of a gastrointestinal tract primary as well as barium enema or colonoscopy, the preoperative identification of parenchymal liver metastases, suprarenal lymphadenopathy, or extensive mesenteric disease by CT may influence the degree of intraoperative cytoreductive efforts.

The following tumor markers may be evaluated to be used for diagnostic and therapeutic response evaluations:

• Alpha-fetoprotein (AFP) is elevated in most endodermal sinus tumors, embryonal cell carcinomas, or mixed germ cell tumors containing these elements and is useful not only in their diagnosis but in evaluating therapeutic response.Human chorionic gonadotropin (hCG) is elevated in patients with nongestational ovarian choriocarcinoma and may also be elevated in patients with dysgerminoma and embryonal cell carcinoma.
  
  
• Lactate dehydrogenase (LDH) may be of potential value in patients with ovarian dysgerminoma.
  
  
• CA 19-9 is potentially useful in following patients with mucinous ovarian carcinomas.
  
  
• Carcinoembryonic antigen (CEA) levels, although not specific for ovarian tumors, are sometimes found to be elevated in patients with mucinous ovarian tumors, and, hence, serial levels may prognosticate the clinical course, with rising values preceding clinical disease. If elevated initially, primary bowel cancer should be considered.
  
  
• CA-125 is known to be elevated in more than 80% of patients with epithelial ovarian malignancies, especially serous. CA-125 measurements may be useful in following the response to therapy and the presence of persistent or recurrent disease in women who had an elevation at the time of known disease. In postmenopausal women with a pelvic mass, an elevation of CA-125 greater than 65 U/mL is predictive of malignancy in up to 75% of cases. Benign conditions, such as uterine fibroids, endometriosis, or inflammatory or infectious processes, produce CA-125 elevations that limit the specificity of this tumor marker.

Radionuclide imaging utilizes radioisotopes chelated to antibodies directed against tumor-specific antigens. Although a promising research technique, its role in the diagnosis of preclinical disease and its usefulness in the follow-up of patients with disease is still under evaluation.

Diagnostic paracentesis is generally not considered of definitive value since patients with ovarian malignant ascites will not always demonstrate malignant cells in diagnostic specimens. Paracentesis can, however, be performed in the selected patient to evaluate cirrhosis as an etiology for ascites or to relieve symptoms.

Laparoscopy is helpful in evaluating patients with ovarian enlargement that is not well defined on pelvic examination and ill defined radiographically. Its role in the evaluation of patients with persistent symptomatology and negative diagnostic evaluation has been shown as well. Uncomplicated ovarian cysts satisfying benign criteria may be managed laparoscopically in selected cases. Its role in the actual management of malignancy without laparotomy, however, remains controversial and under evaluation. The use of diagnostic laparoscopy in the face of ascites or suspicious disease results in unnecessary anesthesia, morbidity, expense, and delay in initiating definitive therapy.

Staging

Appropriate determination of stage, or the extent of disease at the time of diagnosis, is of critical importance in the management of epithelial ovarian cancer, since both treatment and prognosis are strongly dependent on stage. Historically, inadequate assessment of stage has been a major problem in the management of patients with ovarian cancer.

Unlike many other human malignancies, the staging system for ovarian cancer is based on the results of a properly performed surgical procedure, together with the results of clinical and histopathologic evaluations. The current staging system of the International Federation of Gynecology and Obstetrics (FIGO) is shown in Table 1.

Appropriate determination of the stage of disease in patients with ovarian cancer requires a properly performed surgical procedure. Surgery generally involves exploratory laparotomy through a vertical abdominal incision to allow access to the upper abdomen. Peritoneal washings or ascites are obtained for cytologic analysis upon entering the abdomen.

A complete and systematic exploration of the abdominal cavity from the diaphragms to the pelvic floor must be performed, and any suspicious areas biopsied. In patients who appear grossly to have stage I or stage II disease, an infracolic omentectomy and sampling of aortic and pelvic lymph nodes are mandatory for complete staging. In these early stages, random peritoneal biopsies should also be performed from multiples areas, including the pelvis, pericolic gutters, and diaphragms. Clinically positive nodes should be excised to the maximum extent possible.

Surgery should include hysterectomy, bilateral salpingo-oophorectomy, and omentectomy, except in selected patients with a well-differentiated tumor limited to one ovary, in whom it may be possible to preserve reproductive potential. A supracervical hysterectomy may be indicated in the presence of extensive carcinomatosis in the cul-de-sac.

A thorough preoperative discussion with the patient about the risks of staging laparotomy and her wishes regarding future childbearing are critical in surgical planning for ovarian cancer. The surgical goal should be optimal cytoreduction to less than 1 to 2 cm to optimize response to chemotherapy.

A gynecologic oncologist, if available, should be consulted regarding the appropriate procedures and participate in the surgical staging. Studies in the United States and abroad have shown that ovarian cancer patients staged by a gynecologic oncologist have significantly smaller residual disease and improved survival compared to those operated on by nongynecologic oncologists.