Ovarian Cancer

Background

• Ovarian cancer is a leading cause of death from gynecologic malignancy, with a lifetime risk estimated at 1 in 50-70 women. The highest incidence of ovarian cancer is reported in individuals aged 60-64 years, with most ovarian cancer diagnoses occurring in individuals over age 50 years.
• 90% of primary ovarian tumors are epithelial carcinomas, further grouped histologically into 8 subtypes. Nonepithelial ovarian cancers include germ cell tumors and sex cord-stromal tumors.
• Diagnosis of early-stage ovarian cancer is difficult, as there are no reliable screening tests and symptoms of ovarian cancer often do not present until advanced stages of disease. Symptoms, when present, often include gastrointestinal complaints such as bloating, early satiety, and abdominal and/or pelvic pain.
• Overall survival is estimated at < 50% at 5 years, but survival rates vary by disease stage.

Evaluation

• Initial evaluation should include a bimanual exam (Strong recommendation).
  • Palpable ovaries 3-5 years after menopause should be further evaluated.
  • Physical exam should also include an evaluation for ascites, pleural effusion, or lymph node enlargement, which when present could each raise suspicion for metastatic disease.
• An evaluation for suspected ovarian cancer often includes a transvaginal ultrasound (for premenopausal or postmenopausal patients) or transabdominal ultrasound (for young, non-sexually active, prepubescent adolescents) and a serum cancer antigen 125 (CA-125) test. The work-up may vary depending on patient's age and may include other tumor markers, especially in young adults and adolescents with adnexal masses.
• Clinical prediction rules such as Risk of Malignancy Indices (RMI) I and II, Risk of Ovarian Malignancy Algorithm (ROMA), or QCancer (Ovary) may predict the likelihood of ovarian cancer when an adnexal mass is identified.
• If the ultrasound, serum CA-125, and clinical predictors suggest ovarian cancer, perform a computed tomography (CT) scan of the pelvis, abdomen, (and thorax if clinically indicated) to establish the extent of disease (Strong recommendation).
• Diagnosis is confirmed with a biopsy that may be obtained laparoscopically, with image-guided technology, or at the time of primary surgery. Cytological assessment of aspirated fluid may be used to confirm diagnosis if a tissue diagnosis is not feasible.
• Optimal staging generally occurs during primary surgery, but initial staging can take place at the time of image-guided or laparoscopic biopsy. Most often, the American Joint Committee on Cancer (AJCC) or International Federation of Gynecology and Obstetrics (FIGO) staging conventions are used.

Management

• Management of stage I ovarian cancer (neoplasm confined to the ovaries) should include optimal surgical staging with tumor resection and retroperitoneal lymph node assessment. Total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH-BSO) is recommended (Strong recommendation).
  • Adjuvant platinum-based chemotherapy may be considered for patients with high-risk tumors (grade 3 or stage IC), or for suboptimal surgical staging (Strong recommendation).
  • For patients with clinical stage I ovarian cancer who wish to preserve fertility, unilateral salpingo-oophorectomy or ovarian cystectomy may not compromise prognosis in low-risk patients with complete surgical staging.
• Standard initial treatment of advanced ovarian cancer (stage II-IV disease) consists of cytoreductive surgery followed by combination platinum-based chemotherapy (carboplatin plus paclitaxel for 6 cycles) (Strong recommendation). Chemotherapy before debulking surgery is associated with similar survival.
  • Cytoreductive surgery for ovarian cancer performed by a gynecological oncologist is associated with better survival than when performed by a general surgeon or gynecologist. Interval debulking surgery might increase survival in patients with advanced ovarian cancer who had primary surgery not performed by a gynecologic oncologist.
  • Addition of bevacizumab to chemotherapy may improve progression-free survival but not overall survival in patients with advanced ovarian carcinoma with poor prognostic features (such as stage IV) or with suboptimal debulking (such as > 1 cm residual disease).
  • Secondary cytoreductive surgery may be indicated if initial maximal cytoreduction (residual disease ≤ 1 cm in greatest dimension) is not achieved (Strong recommendation).
• PARP inhibitor maintenance therapy should be offered to PARP-naive patients with newly diagnosed stage III-IV epithelial ovarian cancer (high-grade serous or endometrioid ovarian cancer) who are in complete or partial response to first-line platinum-based chemotherapy (Strong recommendation).
• If tumor recurs > 6 months after completion of first-line platinum chemotherapy (platinum-sensitive disease), carboplatin-doublet chemotherapy is the suggested regimen (Strong recommendation). The addition of paclitaxel to platinum-based chemotherapy may improve survival in patients with relapsed platinum-sensitive ovarian cancer.
• For tumor recurrence in platinum-resistant disease, single-agent therapy with paclitaxel, pegylated liposomal doxorubicin (PLD), topotecan, or gemcitabine is recommended (Strong recommendation).
• Surgical cytoreduction to microscopic disease might increase survival in patients with recurrent epithelial ovarian cancer as well.
• Cancer antigen 125 (CA-125) monitoring is often recommended and may detect progression or recurrence, but early treatment of relapse based on CA-125 levels does not improve survival in patients with ovarian cancer.
• Screening can be considered in high-risk patients electing not to have risk-reducing surgery, such as those with BRCA mutation or hereditary nonpolyposis colon cancer (Lynch syndrome), although there is no clear evidence to support routine use.