Cancers Arising in the Ovary
Summary of Key Points
Types
• Ninety percent of ovarian cancers represent a collection of “epithelial tumors” that increase in incidence with age, with patients diagnosed at a median age of 63 years. Stromal tumors represent less than 10% of malignant tumors arising in the ovary and typically present with symptoms related to sex hormone production. The remaining tumors are germ cell tumors that occur in adolescents and young adults.
Staging Evaluation
• Patients should usually undergo surgical resection of ovarian tumors with comprehensive surgical staging. Most women with epithelial ovarian cancer present with advanced disease and aggressive surgical cytoreduction is recommended. Approximately 10% of these patients will also present with malignant pleural effusions. Comprehensive surgical staging is recommended for stromal and germ cell tumors although the role of lymphadenectomy is unclear when there is no gross lymphadenopathy.
Primary Therapy (and Results)
• Epithelial tumors are typically treated with carboplatin and paclitaxel as well as maximal surgical cytoreduction. A high percentage of women will experience a complete clinical remission; however, the majority who present with advanced disease will relapse within a few years. Median survivals for women with advanced disease are approaching 5 years. Germ cell tumors typically are treated with bleomycin, etoposide, and cisplatin in regimens initially described in the management of testicular carcinoma with the majority of women cured of disease.
Management of Recurrent Disease
• Most women with epithelial cancer will develop recurrent intraperitoneal tumor. Tumors recurring greater than 6 to 12 months after the prior exposure to platinum are often retreated with platinum-based therapy. Patients with rapid recurrence after platinum therapy may be palliated with a variety of drugs, including liposomal doxorubicin, topotecan, and gemcitabine. In addition, bevacizumab has significant activity in the management of recurrent disease.
1. Which of the following statements is true regarding the primary management of ovarian cancer?
A Patients who undergo primary surgery and with residual disease <1 cm should have KRAS testing to select optimal therapy.
B The addition of bevacizumab to Taxol and carboplatin therapy improves survival in women with suboptimally resected disease.
C Randomized studies have demonstrated a survival advantage for the delivery of intraperitoneal therapy in selected groups of women with ovarian cancer.
D Patients presenting with stage III/IV clear cell carcinoma should be treated with FOLFOX instead of carboplatin and paclitaxel.
2. A women presents with concerns about her risk for ovarian cancer and reveals she has a sister with endometrial cancer at 43 years and a brother with colon cancer at 47 years. Your recommendation is:
A Recommend prophylactic bilateral salpingo-oopherectomy (BSO)
B Recommend she undergo testing for germline BRCA1 and BRCA2 mutations
C Recommend she undergo testing for Li-Fraumeni syndrome
D Recommend her brother be tested for a mutation in MLH1, MSH2, MSH6, or PMS2.
E Recommend the sister be tested for evidence of mutation in Check1 or Rad51 genes
3. An 19-year-old woman presents with a palpable pelvic mass, retroperitoneal adenopathy, and lung metastases. Her α-fetoprotein (AFP) is 14.000 with a human chorionic gonadotropin (hCG) of 12. The most likely diagnosis is:
4. A 50-year-old woman develops a rising CA-125 18 months after primary therapy for a serous carcinoma. Computed tomography reveals ascites, partial small bowel obstruction, and moderate pleural effusion. The best option for her would be:
1. Answer: C. Three randomized trials have demonstrated a survival advantage for the delivery of intraperitoneal therapy. Currently, there is no known utility for KRAS testing in ovarian cancer. Bevacizumab added to platinum-based therapy has been shown to increase progression-free survival but not overall survival. Finally, although advanced clear cell carcinoma tends to respond poorly to carboplatin and paclitaxel chemotherapy, there is currently no known superior regimen.
2. Answer: D. A family history of early-onset colon and endometrial cancer is most suggestive of hereditary nonpolyposis colon cancer (HNPCC) or Lynch syndrome, a mutation of DNA mismatch repair genes. Typically testing is most informative when an affected member of the family is tested for a germline mutation. Families with BRCA 1 or 2 mutations typically have a high incidence of breast and ovarian cancer. Those with Li-Fraumeni syndrome (p53 mutation) typically have leukemia, brain tumor, and very-early-onset cancers (childhood and very young adulthood). Check1 and Rad51 mutations have been reported in a few families with early-onset breast or ovarian cancer. Individuals harboring HNPCC mutations should be counseled to have a total abdominal hysterectomy with bilateral salpingo-oopherectomy not a BSO.
3. Answer: C. Young women with palpable masses in the pelvis with retroperitoneal and lung metastases typically have germ cell tumors of the ovary. A high AFP is consistent with a yolk sac tumor. Granulosa cell tumors typically make steroid hormones (such as estrogens) and inhibins/müllerian inhibiting substance. Choriocarcinoma typically make very high levels of hCG without AFP. Most immature teratoma make a variety of markers including CA-125, CA 19-9, β-hCG and occasionally AFP although remarkable AFP levels (14,000) would not be expected. Epithelial ovarian tumors, including Brenner tumors, are typically are associated with elevated CA-125.
4. Answer: A. Women with symptomatic recurrent ovarian cancer with a first recurrence greater than 12 months from primary platinum-based therapy should return to platinum-based therapy. Several randomized trials demonstrate superior outcomes (either progression-free survival or overall survival) with doublet therapy. Carboplatin with paclitaxel or gemcitabine or liposomal doxorubicin would be reasonable options. Some trials suggest the selection of liposomal doxorubicin with carboplatin might reduce the incidence of hypersensitivity reaction to platinum.
