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Ovarian cancer is the fifth leading cause of cancer deaths among U.S. women and has the highest mortality of any of the gynecologic cancers. The lifetime risk of dying from ovarian cancer is 1.1%. According to the U.S. Cancer Statistics: 2004 Incidence and Mortality report, 20,095 women in the U.S. learned they had ovarian cancer in 2004. About 6,600 women are diagnosed with ovarian cancer in the UK each year, around 1,500 and 2,300 in Canada. The death rate for this disease has not changed much in the last 50 years.
Unfortunately, almost 70 percent of women with the common epithelial ovarian cancer are not diagnosed until the disease is advanced in stage - i.e., has spread to the upper abdomen (stage III) or beyond (stage IV). The overall 5-year survival rate is at least 75% if the cancer is confined to the ovaries and decreases to 17% in women diagnosed with distant metastases. Symptoms usually do not become apparent until the tumor compresses or invades adjacent structures, ascites develops, or metastases become clinically evident. As a result, two thirds of women with ovarian cancer have advanced (Stage III or IV) disease at the time of diagnosis. Carcinoma of the ovary is most common in women over age 60. Other important risk factors include low parity and a family history of ovarian cancer. Less than 0.1% of women are affected by hereditary ovarian cancer syndrome, but these women may face a 40% lifetime risk of developing ovarian cancer.
There are many types of tumors that can start in the ovaries. Some are benign, or noncancerous, and the patient can be cured by surgically removing one ovary or the part of the ovary containing the tumor. Some are malignant or cancerous.The treatment options and the outcome for the patient depend on the type of ovarian cancer and how far it has spread before it is diagnosed.
Ovarian tumors are named according to the type of cells the tumor started from and whether the tumor is benign or cancerous.
The three main types of ovarian tumors are:
Epithelial ovarian tumors develop from the cells that cover the outer surface of the ovary. Most epithelial ovarian tumors are benign. There are several types of benign epithelial tumors, including serous adenomas, mucinous adenomas, and Brenner tumors. Cancerous epithelial tumors are carcinomas. These are the most common and most deadly of all types of ovarian cancers. There are some ovarian epithelial tumors whose appearance under the microscope does not clearly identify them as cancerous; these are called borderline tumors or tumors of low malignant potential (LMP tumors). Epithelial ovarian carcinomas (EOC's) account for 85 to 90 percent of all cancers of the ovaries. This group of cancers are commonly referred to as "ovarian cancer".
The cells that make up EOC have several forms that can be recognized under the microscope. They are known as serous, mucinous, endometrioid, and clear cell types. Undifferentiated EOC's lack distinguishing features of any of these four subtypes and tend to grow and spread more quickly.
In addition to their classification by cell type, EOC's are given a grade and stage. The grade is on a scale of 1, 2, or 3. Grade 1 EOC more closely resembles normal tissue and tends to have a better prognosis than Grade 3 EOC, which looks less like normal tissue and usually implies a worse outlook than Grade 1 EOC.
The stage of the tumor can be ascertained during surgery, when it can be determined how far the tumor has spread from where it started in the ovary.
The following are the various stages of ovarian cancer:
Stage I - Growth of the cancer is limited to the ovary or ovaries.
Stage IA - Growth is limited to one ovary and the tumor is confined to the inside of the ovary. There is no cancer on the outer surface of the ovary. There are no ascites present containing malignant cells. The capsule is intact.
Stage IB - Growth is limited to both ovaries without any tumor on their outer surfaces. There are no ascites present containing malignant cells. The capsule is intact.
Stage IC - The tumor is classified as either Stage IA or IB and one or more of the following are present: (1) tumor is present on the outer surface of one or both ovaries; (2) the capsule has ruptured; and (3) there are ascites containing malignant cells or with positive peritoneal washings.
Stage II - Growth of the cancer involves one or both ovaries with pelvic extension.
Stage IIA - The cancer has extended to and/or involves the uterus or the fallopian tubes, or both.
Stage IIB - The cancer has extended to other pelvic organs.
Stage IIC - The tumor is classified as either Stage IIA or IIB and one or more of the following are present: (1) tumor is present on the outer surface of one or both ovaries; (2) the capsule has ruptured; and (3) there are ascites containing malignant cells or with positive peritoneal washings.
Stage III - Growth of the cancer involves one or both ovaries, and one or both of the following are present: (1) the cancer has spread beyond the pelvis to the lining of the abdomen; and (2) the cancer has spread to lymph nodes. The tumor is limited to the true pelvis but with histologically proven malignant extension to the small bowel or omentum.
Stage IIIA - During the staging operation, the practitioner can see cancer involving one or both of the ovaries, but no cancer is grossly visible in the abdomen and it has not spread to lymph nodes. However, when biopsies are checked under a microscope, very small deposits of cancer are found in the abdominal peritoneal surfaces.
Stage IIIB - The tumor is in one or both ovaries, and deposits of cancer are present in the abdomen that are large enough for the surgeon to see but not exceeding 2 cm in diameter. The cancer has not spread to the lymph nodes.
Stage IIIC - The tumor is in one or both ovaries, and one or both of the following is present: (1) the cancer has spread to lymph nodes; and/or (2) the deposits of cancer exceed 2 cm in diameter and are found in the abdomen.
Stage IV - This is the most advanced stage of ovarian cancer. Growth of the cancer involves one or both ovaries and distant metastases (spread of the cancer to organs located outside of the peritoneal cavity) have occurred. Finding ovarian cancer cells in pleural fluid (from the cavity which surrounds the lungs) is also evidence of stage IV disease.
Ovarian germ cell tumors develop from the cells that produce the ova or eggs. Most germ cell tumors are benign, although some are cancerous and may be life threatening. The most common germ cell malignancies are maturing teratomas, dysgerminomas, and endodermal sinus tumors. Germ cell malignancies occur most often in teenagers and women in their twenties. Prior to the modern era of combination chemotherapy, the most aggressive of these tumors, the GNP abnormal sinus tumor, was associated with a 1-year disease-free survival of only 10 to 19 percent. This occurred despite the fact that 70 percent of these tumors were diagnosed as stage I disease. Today, 90 percent of patients with ovarian germ cell malignancies can be cured and fertility preserved.
Ovarian stromal tumors develop from connective tissue cells that hold the ovary together and those that produce the female hormones, estrogen and progesterone. The most common types among this rare class of ovarian tumors are granulosa-theca tumors and Sertoli-Leydig cell tumors. These tumors are quite rare and are usually considered low-grade cancers, with approximately 70 percent presenting as stage I disease.
These statistics, and the information regarding tumor stage and grade, demonstrate that there is a critical need to establish an agenda for more research into the areas of basic and translational research, genetic susceptibility and prevention, diagnostic imaging, screening and diagnosis, and therapy. These could hold the most promise for future discoveries that will lead to improved prevention, detection, and treatment of ovarian cancer, particularly the common epithelial cancers.