Ovarian cancer: the silent killer since no symptoms or signs

Ovarian cancer is caused by the abnormal growth of cells in the ovaries, the reproductive glands found only in women that produce eggs for reproduction. This cancer accounts for more deaths than any other gynecological cancer among women. It is the eighth most common cancer and the fifth leading cause of death overall among both men and women. Ovarian cancer is more common in Caucasians than in African Americans.

There are three different types of ovarian cancer, classified based on the type of cell where the cancer originates:

• Epithelial tumors: these tumors develop in the epithelium (the tissue covering the outer surface of the ovary). Approximately 90% of ovarian cancers are of this type. The risk of epithelial ovarian cancer increases with age, primarily affecting women over 60, though it can occur at any age. Subtypes of epithelial ovarian cancers include:
  • Serous
  • Endometrioid
  • Clear cell
  • Mucinous
  • Undifferentiated or unclassifiable

• Germ cell tumors: these tumors originate in the egg-producing cells of the ovary. This type of ovarian cancer can occur at any age but primarily affects adolescents and young women under 30. Germ cell tumors account for about 5% of all ovarian cancers. Subtypes include:
  • Teratoma
  • Dysgerminoma
  • Endodermal sinus tumor

• Sex cord-stromal tumors: these tumors develop in the connective tissue that holds the ovary together and produces female hormones (like estrogen and progesterone). These tumors are relatively rare, representing about 1% of all ovarian cancers. Subtypes include:
  • Pure stromal tumors
  • Pure sex cord tumors
  • Mixed sex cord-stromal tumors

Several factors can increase the risk of developing ovarian cancer. Some risk factors are modifiable, such as quitting smoking, while others, like family history, are not.

Risk factors for ovarian cancer include:

• Age
• Obesity
• Reproductive history
• Use of birth control or fertility drugs
• Gynecological surgery
• Androgens
• Estrogen and hormone therapy
• Family history of ovarian, breast, or colorectal cancer
• Hamartoma tumor syndrome
• Lynch syndrome (hereditary nonpolyposis colorectal cancer)

Ovarian cancer can present with various signs and symptoms. Women are more likely to experience symptoms if the disease has spread beyond the ovaries, though some early-stage ovarian cancers may also present symptoms. Ovarian cancer is often referred to as the "silent killer" because many women do not show any symptoms. Common symptoms include:

• Bloating
• Pelvic or abdominal pain
• Difficulty eating or feeling full quickly
• Urinary symptoms such as urgency or frequency
• Fatigue
• Stomach pain
• Back pain
• Pain during intercourse
• Constipation
• Menstrual changes
• Abdominal swelling with weight loss

Survival rates for ovarian cancer are strongly linked to the tumor stage. When the cancer is detected early (stages I or II), the 5-year survival rate is 95% and 65%, respectively. However, due to the lack of specific symptoms, 75% of cases are diagnosed at advanced stages (III or IV) without prior symptoms, where survival rates are significantly lower.

Additionally, as with lung cancer, all suspected ovarian masses must be biopsied to confirm malignancy. Most cases are benign (200,000 to 300,000 suspicious masses are removed annually in the U.S. alone).

IMPORTANT: EARLY CANCER DIAGNOSIS IS CRUCIAL BECAUSE CANCERS DIAGNOSED AT AN EARLY STAGE — BEFORE THEY HAVE GROWN SIGNIFICANTLY OR SPREAD TO OTHER PARTS OF THE BODY — ARE MORE LIKELY TO BE SUCCESSFULLY TREATED. IN CONTRAST, IF THE CANCER HAS SPREAD TO OTHER ORGANS, TREATMENT BECOMES MORE DIFFICULT, AND SURVIVAL PROBABILITY IS MUCH LOWER.

Currently, there is no effective method for early detection of ovarian cancer. It is generally diagnosed at advanced stages, and only half of women survive more than five years after diagnosis.

Multiple studies have shown that prognosis and survival largely depend on the amount of tumor remaining after initial surgery. Patients with no residual tumor or nodules smaller than one centimeter in diameter have the greatest chance of cure and long-term survival.

Most women with ovarian cancer experience symptoms. However, these symptoms are often vague and may be attributed to less serious conditions like indigestion, weight gain, or aging, making diagnosis challenging. When malignancy is suspected, a physical exam is usually followed by various diagnostic procedures—ultrasound, computed tomography (CT), positron emission tomography (PET), or magnetic resonance imaging (MRI)—if ovarian enlargement or abdominal fluid (ascites) is detected during palpation.

To improve early diagnosis, different methods have been tested, including the use of the tumor marker CA 125. However, this marker has low sensitivity in early stages and a high rate of false positives in premenopausal women.

In recent years, serum HE4 levels have offered greater sensitivity for early stages and higher specificity. Combining CA 125, HE4, and menopausal status led to the development of the ROMA (Risk of Ovarian Malignancy Algorithm), a low-complexity algorithm with three variables to aid doctors in diagnosing ovarian cancer. However, it still has high false-positive and false-negative rates.

Another approach combined CA 125 with ovarian mass characteristics from ultrasound, resulting in the RMI (Risk of Malignancy Index). However, lacking HE4, it shares many issues with false positives and negatives in premenopausal women.

Both algorithms are helpful for diagnosing abdominal masses and monitoring treatment. Nevertheless, they can be improved. ROMA does not consider ultrasound or patient age, while RMI does not use the best tumor marker for ovarian cancer diagnosis—HE4—or other variables associated with the disease.