Ovarian Cancer

General Information / Anatomy / Function / Statistics

• The ovaries are paired glands, located on either side of the pelvic cavity, almond-shaped, measuring about 4 cm in length. They produce the female sex hormones, as well as egg cells (ova).
• The outer layer consists of a thin epithelium, beneath this the ova (germ cells) are produced during menstrual life in fluid-filled sacs (ovarian follicles). The cells of the walls of the follicles produce the female hormones, the follicles are embedded in a connective tissue stroma. The rupture of the follicles allows the escape of the ovum (ovulation). This monthly cycle of rupture and healing of the epithelium may set the stage for changes that can lead to a cancer.
  Ovulation is prevented by birth control medication, pregnancy and lactation (breast-feeding).
• Ovarian cancers can be of several types:
  the most common is epithelial cancer which arises from the surface cells, affecting middle-aged and older women,
• Germ cell tumours are rare, affecting the young,
• Stromal tumours, also rare, occur at any age.
• Epithelial ovarian cancer is not common (about 1 in 70 Canadian women will develop this disease compared to 1 in 9 for breast cancer), however it is an important disease, the fourth greatest cause of years of life lost to cancer in women (after lung, breast, and bowel cancers).
• For statistics, please click here.

Symptoms / Signs

• Growing ovarian tumours are most often associated with vague, non-specific symptoms.
• An enlarging mass can compress the urinary bladder, producing a sense of diminished bladder capacity and a need to urinate more often.
• A mass can compress the lower bowel (rectosigmoid) producing a sense of incomplete evacuation of feces, or narrowing of fecal calibre.
• Further enlargement of the tumour can produce pelvic discomfort or lower abdominal swelling or a sensation of a mass. Some patients report gaseousness. If tumours become more widespread within the abdomen, the effects on the digestive system increase.
• Abdominal distention as a result of fluid build-up (ascites).
• Tumours that involve the surface of the ovary can shed cells into the main body cavity (peritoneal cavity), these cell clusters can adhere to other surfaces, creating "daughter" tumours. Epithelial tumours are composed of gland cells, and can produce fluid which can collect in the abdomen (ascites).
• Occasionally, fluid containing suspended tumour cells can traverse the diaphragm, producing fluid collections (effusions) in the chest cavity, leading to cough and discomfort.
• Tumours that spread to the lymphatic system can block lymph flow, producing swelling of the lower body.
• Ovarian tumours tend not to spread via the blood stream, so that involvement of distant organs such as bone is rare.
• Abnormal vaginal bleeding is rather uncommon.
• Occasionally, growing tumours will have hormonal effects.
• The behaviour of ovarian tumours can vary widely, some can grow very slowly, others (particularly germ cell tumours) can grow very rapidly. This growth rate is associated with the degree of malignancy, and risk and speed of spread (metastasis) of the disease.

Etiology / Carcinogens / Risks

• The exact cause of epithelial ovarian cancer is unknown, most cases are sporadic, occurring in women without any apparent predisposition
• Familial/hereditary ovarian cancer: Approximately 5% of epithelial ovarian cancers appear to be the result of inherited genes. The progress of research into these genetic mechanisms is very rapid, recently new genes associated with ovarian cancer (BRCAI, BRCA2) have been identified, these genes can be associated with greatly increased risks of breast and other forms of cancer as well.
• The incidence of ovarian cancer appears to be weakly influenced by ovulatory history: those with the greatest number of ovulatory menstrual cycles appear to be at modestly greater risk, a reduction in the number of ovulations (by birth control medication, pregnancy, and lactation) reduces risk.

Prevention

• The inhibition of ovulation modestly reduces the risk of epithelial ovarian cancer (see above).
  Women who have inherited a hereditary ovarian cancer gene may be protected by the surgical removal of the ovaries (prophylactic oophorectomy).

Diagnosis / Staging / Grading / Types

Screening

• No "high risk groups" can be identified for whom screening might be appropriate (with the rare exception of families with hereditary ovarian cancer)
• No screening methods have proven to be effective at this time - trials examining screening based upon physical examination, ultrasound imaging, and biomarker (CA 125) examination had been unreliable, and productive of a high rate of "false positives".
• The routine Pap smear is not effective for ovarian cancer screening.

Diagnosis

• Physical examination, including examination of the vagina and rectum can detect most important ovarian masses.
• Pelvic ultrasound can be very valuable in determining the characteristics of ovarian and other pelvic masses.
• A tissue sample is necessary to make an unequivocal diagnosis, this may be obtained by exploratory laparotomy (laparotomy: surgical incision of the abdominal wall to examine the contents of the peritoneal cavity) or laparoscopy.
• Surgeons should take care to avoid rupturing ovarian masses when a diagnosis of cancer is suspected, so as not to spread the disease.
• CA 125 is a material often produced by epithelial ovarian tumours that can help characterize ovarian masses and monitor the extent of disease. Other tumour markers (beta HCG, alpha fetoprotein) can be useful in cases of germ cell tumours.

Staging

Stage I - Growth limited to ovaries
Stage II - Growth in one or both ovaries with pelvic extension
Stage III - Tumor involving one or both ovaries with peritoneal implants outside the pelvis and/or positive retroperitoneal or inguinal nodes or superficial liver metastases.
Stage IV - Growth involving one or both ovaries with distant metastases, if a pleural effusion is present there must be positive cytology; parenchymal (internal) liver metastases - Stage IV.

Grading

• Tumours are assigned a grade by the pathologist.
• The grade reflects the biological aggressiveness or virulence of the tumour.
  • Grade 3 - such lesions, also called high grade or undifferentiated, tend to develop and spread more quickly.
  • Grade 2 - describes a moderately differentiated tumour of intermediate behaviour
  • Grade 1 - describes well-differentiated or low-grade lesions of more indolent behaviour.
• Borderline tumours (or low malignant potential tumours) are relatively uncommon and do not possess all of the features of a fully malignant tumour

Types

Epithelial cell tumors

• Adenocarcinoma make up 90% of ovarian malignancies
• These adenocarcinoma cell types include serous, mucinous, endometrioid, clear cell and undifferentiated.

Germ Cell Tumours:

• Include dysgerminomas, immature teratomas, endodermal sinus tumours.
• These tumours are particularly sensitive to treatment, cures are anticipated, and treatment can be designed to preserve fertility in younger women.

Stromal Tumors

• These relatively uncommon tumours arise from supportive tissue within the ovary.

Krukenberg Tumors

• This is a historical or older term for cancers that have spread from other sites, eg. stomach to the ovaries (ie. not a primary ovarian cancer)

Treatment

• Women who are referred to BCCA for assessment receive a case review by the multidisciplinary Gynecology Disposition Conference, including gynecologic oncologists (surgical subspecialists), medical oncologists, radiation oncologists, subspecialist pathologists, and ancillary staff.
• We attempt to "tailor" postoperative treatment to the patient, pursuing a curative intent where appropriate (the patient with no visible residual tumour), and providing high-grade palliation in those where cure is rarely possible (the patient intolerant of intensive therapy or with macroscopic residual disease).

Surgery

• Successful treatment requires particular attention to the details of initial surgery which also provides crucial information about the disease.
• The extent of surgery depends on the type of ovarian cancer and the stage of disease.
• The objective of surgery for epithelial cell tumours should be the removal of all visible tumour, which usually means hysterectomy (removal of the uterus) and removal of both ovaries and fallopian tubes (bilateral salpingo-oophorectomy) and omentectomy (removal of the fatty tissue which attaches to the stomach and transverse colon.
• Where possible, tumour masses should be removed without rupture or spillage to avoid the potential for spread of malignant cells.
• In cases of early epithelial ovarian cancer and germ cell tumours, once a diagnosis of malignancy has been made, it may be possible to perform more limited surgery to preserve fertility.

Chemotherapy and Radiotherapy

• Chemotherapy is the cornerstone of postoperative treatment. The most effective drugs are the so-called "platinum drugs", including cisplatin and carboplatin. Useful additional drugs include paclitaxel (TAXOL®), etoposide (VP16), TOPTECAN®, CAELYX® and others.
• Radiotherapy can be part of a curative-intent treatment program for those with early epithelial tumours.
• Efforts are made to "get the most from" each type of treatment, sometimes combining or sequencing surgery, chemotherapy and radiotherapy.

Revised April 2000