Ovarian Epithelial Cancer

Introduction

Ovarian cancer is the most common cause of cancer death from gynecologic tumors in the United States. Early disease causes minimal, nonspecific, or no symptoms. Therefore, most patients are diagnosed in an advanced stage. Overall, prognosis for these patients remains poor. Standard treatment involves aggressive debulking surgery followed by chemotherapy. Many histological types of ovarian tumors are described. However, more than 90% of malignant tumors are epithelial tumors. Therefore, the remainder of this article focuses on these tumors. For specific information on malignant lesions of the ovaries, see Malignant Lesions of the Ovaries.

Pathophysiology

Ovarian carcinoma can spread by local extension, lymphatic invasion, intraperitoneal implantation, hematogenous dissemination, and transdiaphragmatic passage. Intraperitoneal dissemination is the most common and recognized characteristic of ovarian cancer. Malignant cells can implant anywhere in the peritoneal cavity but are more likely to implant in sites of stasis along the peritoneal fluid circulation. As discussed later, these mechanisms of dissemination represent the rationale to conduct surgical staging, debulking surgery, and intraperitoneal administration of chemotherapy. On the other hand, early hematogenous spread is clinically unusual, although it is not infrequent in patients with advanced disease.

Frequency United States

Approximately 22,430 new cases of ovarian cancer are diagnosed annually. Estimates indicate that 1 in 70 women will develop ovarian cancer in her lifetime. Ovarian cancer accounts for 3.3% of all new cases of cancer.

Mortality/Morbidity

• Overall, the prognosis of ovarian cancer remains poor, with a 45% 5-year survival rate. Approximately 15,280 women die every year in the United States from ovarian cancer.
• The prognosis of ovarian cancer is closely related to the stage at diagnosis.
• Ovarian cancer is staged using the International Federation of Gynecology and Obstetrics (FIGO) staging system. Approximately 20%, 5%, 58%, and 17% of women present with stage I, II, III, and IV, respectively. Despite this, the 5-year survival rate for ovarian cancer has improved significantly in the last 30 years. The overall survival rate in 1975-1977 was 36%, compared to 45% in 1995-2002.

Ovarian cancer affects females.

• The disease is uncommon in patients younger than 40 years, after which incidence increases.
• Most cases are diagnosed in the seventh decade of life.

• The signs and symptoms of ovarian cancer are nonspecific. Most patients present with symptoms of several months' duration.
• Symptoms include the following:
  • Abdominal/pelvic pain
  • Vaginal bleeding
  • Bloating
  • Abdominal distension
  • Irregular menses
  • Change in bowel habit

Physical

• Physical findings are uncommon in patients with early disease.
• Patients with more advanced disease present with the following:
  • Ovarian or pelvic mass
  • Ascites
  • Pleural effusion
  • Abdominal mass or bowel obstruction

Causes

Traditionally, ovarian cancer has been suggested to originate from cells in the serosa of the ovary. However, some authors suggest a different cell of origin. The precise cause of ovarian cancer is unknown, but several risk and contributing factors have been identified.

• Reproductive factors
  • Parity is an important risk factor. Women who have been pregnant have a 50% decreased risk for developing ovarian cancer compared to nulliparous women. Multiple pregnancies offer an increasingly protective effect.
  • Oral contraceptive use decreases the risk of ovarian cancer.
  • These factors support the theory that risk for ovarian cancer is related to ovulation and that conditions that suppress this ovulatory cycle play a protective role.
  • Ovarian cancer may develop from an abnormal repair process of the surface of the ovary, which is ruptured and repaired during each ovulatory cycle. Therefore, the probability of ovarian cancer may be related to the number of ovulatory cycles.
• Genetic factors
  • Family history plays an important role in the risk of developing ovarian cancer.
  • The lifetime risk for developing ovarian cancer is 1.6% in the general population. This compares to a 4-5% risk when 1 first-degree family member is affected, rising to 7% when 2 relatives are affected.
  • A history of breast cancer increases a woman's risk of developing ovarian cancer.
• Hereditary ovarian cancer
  • Families in which multiple members have ovarian cancer (alone or associated with other tumors) are defined as having hereditary ovarian cancer.
  • Fewer than 5% of all ovarian cancers have a hereditary predisposition. At least 2 syndromes are clearly identified, as follows:
    • Breast/ovarian cancer syndrome: This is associated with early onset of breast or ovarian cancer. Inheritance follows an autosomal dominant transmission. It can be inherited from either parent. Most cases are related to the BRCA1 gene mutation. BRCA1 is a tumor suppressor gene that inhibits cell growth when functioning properly; the inheritance of mutant alleles of BRCA1 leads to a considerable increase in risk for developing ovarian cancer.
    • Lynch II syndrome or hereditary nonpolyposis colorectal cancer: These families are characterized by a high risk for developing colorectal, endometrial, stomach, small bowel, breast, pancreas, and ovarian cancers. This syndrome is caused by mutations in the mismatch repair genes.

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