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Ovarian Cancer

 

For patients it's worth reading the Up to Date, patient  sites here and here and read the recent symposium here. Read the recent review article here

For current best treatment, Start with the NCCN patient guidelines. The mainstay of treatment is complete surgical resection (if possible) followed by chemotherapy (usually 3 to 6 cycles of Taxol and Carboplatinum for the early stages and 6 to 8 cycles for the more advanced stages) with newer studies looking at adding drugs to Carbo/Taxol (e.g. GOG 182 adds liposomal doxorubicin or topotecan or Gemzar to Carbo/Taxol) or other drug regimens (e.g. GOG 175 which follows Carbo/Taxol with low dose weekly Taxol at 40mg/m2 as an angiogenesis inhibitor.)

 More studies are using Avastin along with chemoRx as noted below

 

 
In 2003 the GOG (Bell, Brady) compared 6 cycles of Carbo/Taxol with 3 cycles in early stage ovarian cancer and at 5 years there were fewer recurrences (19% versus 27%) and better survival (84% versus 79%) with using 6 cycles. New data suggests that giving some of the chemotherapy directly into the peritoneal cavity may be best (see study) and see summary here.

Radiation
- is used only occasionally in ovarian cancer, it used to be common to treat patients with whole abdominal radiation for advanced ovary cancer (see here) the current standard is with surgery followed by chemotherapy (see NCCN flow chart, though it may be considered for relapses see here.) There is some contradictory evidence that whole abdominal radiation may be effective for very small sized residual cancer after surgery or chemotherapy. There is good evidence that radiation can relieve symptoms for tumor masses that are no loner responding to chemotherapy (palliative treatment.) For a summary of radiation go here.

Response to Modern Chemotherapy for Ovarian Cancer (1999 Review)
Stage Complete Response Relapse Free Time Median Survival Long Term Survival
IA,IB, gr 1,2 100% na na > 95%
IC, II, gr 3, clear cell 100% na 77% at 5 years 85%
optimal (1cm) III 80-90% 22 months 50 - 55 months 35 - 40%
adv III or IV 50% 18 months 28 - 36 months 10%
There is evidence that the cure rates for ovarian cancer are improving:
 
Year Interval 5 Year Survival
1988 - 1991 33%
1992 - 1996 45%
1997 - 2001 53%


 

Cancers of the ovary include celomic epithelial carcinomas, germ cell neoplasms, and stromal tumors. Celomic epithelial carcinomas, however, account for 90% of these lesions and for most of the clinical research into the management of ovarian cancer.
 

Etiology and risk factors
The etiology of ovarian carcinoma is not known, although certain factors associated with a higher risk of developing the disease have been identified. There is an association between uninterrupted ovulation and the disease.There is also an association between family history and increased risk. Data now suggest that women with one first-order relative with ovarian carcinoma have a risk 3.6-fold higher than that of the
general population. For those who have two or more relatives with ovarian carcinoma, at least one of whom is a first-order relative, risk is estimated to be at least 4.6-fold higher. For those with true familial syndromes by genetic testing (BRCA1) or genetic linkage studies, risk is considerably higher, with estimates as great as 50% reported but not necessarily substantiated. These hereditary syndromes include hereditary breast-ovarian cancer syndrome, hereditary ovarian cancer syndrome, and the Lynch II syndrome (associated with colon cancer). These syndromes typically appear at a younger age than sporadic ovarian carcinoma and appear to be vertically transmitted by an autosomal dominant mode with incomplete penetrance.

The practical implications of these observations are not clear. Insufficient data exist to justify prophylactic oophorectomy because not all of the tissue at risk (the celomic epithelial lining of the peritoneal cavity) would be removed by this procedure. Similarly, no screening techniques of proven efficacy are available, although serum CA 125 levels and transvaginal sonography are under investigation.

Initial presentation and approach
Patients with celomic epithelial carcinomas initially have feelings of fullness or heaviness in the pelvis or increasing abdominal girth. These symptoms unfortunately reflect advanced disease. Efforts to detect the disease earlier have been unsuccessful. Initial evaluation of patients with suspected ovarian carcinoma, after obtaining the patient history, a physical examination, laboratory testing, and CA 125 levels, should include a detailed assessment of the abdominal cavity. Various imaging techniques for the abdomen are now available, but none provides the detail necessary to accurately stage ovarian carcinoma. Nevertheless, CT scanning of the abdominal cavity, chest roentgenography, and bone scanning should be done.

Unless these measures reveal disease outside the abdominal cavity, exploratory laparotomy is essential. The laparotomy should be done through an incision adequate to evaluate the entire peritoneal surface, including the undersurface of the diaphragm and the right paracolic gutter as well as the para-aortic lymph nodes. If there is no evidence of gross disease outside the pelvis, multiple biopsies of the peritoneal surface should be performed. Accurate staging of the disease will direct urther management.

Prognostic factors
The most significant prognostic factors for ovarian carcinoma are age, histologic type and grade, extent of disease (stage), and volume of residual disease. The most important among these is the extent of disease (stage) at diagnosis. Almost 75% of patients will present with advanced (stage III or IV) disease, most with disease confined to the peritoneal cavity (stage III), reflecting intraperitoneal dissemination as the most common route of spread.

Management
Advanced disease

Exploratory laparotomy, in addition to establishing the extent of disease, also affords the first step in therapy. In addition to the diagnostic measures described earlier, the procedure should include an aggressive attempt at surgical cytoreduction. Patients who complete surgery with small-volume residual disease (nodules < 2 cm in diameter) have a higher response rate to chemotherapy and improved survival. The mainstay of treating advanced disease is chemotherapy. Several chemotherapeutic agents are active against ovarian carcinoma, the most important of which are the platinum compounds, paclitaxel (Taxol), and the alkylating agents. The standard of care for first-line therapy is a combination of paclitaxel plus a platinum compound. In patients with large-volume advanced disease, this combination yields a response rate of 73%-77%, a clinically complete response rate of 50%-51%, no gross residual disease at second-look laparotomy in 40%, progression-free survival of 16.6 to 18 months (median), and overall survival of more than 35-38 months (median). In patients with small-volume residual disease, results should be even better. Another combination that has been used with somewhat less success is an alkylating agent plus a platinum compound with or without doxorubicin

Limited disease
Exploratory laparotomy is essential to determine whether disease is confined to the ovaries and pelvis and permits the classification of low-risk and high-risk patients. Patients at low risk have a cure rate exceeding 90% with total abdominal hysterectomy, bilateral salpingo-oophorectomy, and omentectomy; they require no further therapy. Patients at high risk have a recurrence rate of 40% and should receive adjuvant platinum-based chemotherapy.

Salvage Therapy
For patients with disease recurrence after initial therapy, appropriate management is determined by response to initial treatment. Patients who first respond to platinum-based chemotherapy and have a recurrence more than 6 months after treatment are clinically platinum sensitive. Repeated platinum-based therapy yields response rates as high as 60%. In contrast, patients with progressive disease despite platinum-based treatment, with persistent disease at the conclusion of platinum-based therapy, or with recurrence less than 6 months after initial treatment are clinically platinum resistant. Treatment should consist of paclitaxel or, in those who received paclitaxel as initial therapy, oral etoposide, topotecan, tamoxifen or, in some instances, gemcitabine, liposomal doxorubicin (Doxil) vinorelbine tartrate (Navelbine) or ifosfamide. These seven agents all have a demonstrated ability to induce responses in patients with platinum- or paclitaxel-resistant disease.