Ovarian cancer

Introduction and incidence

According to recent classifications, epithelial ovarian cancer, fallopian tube cancer and primary peritoneal carcinoma are considered a common entity (a single disease that can begin in any of the listed organs). They arise from the same type of tissue and are treated the same. The ovaries are paired organs in women located in the pelvis and produce sex hormones and produce eggs, which then travel through the fallopian tubes to the uterus, where, if fertilized by sperm, a fetus is created (Figure 1). The peritoneum (also known as the peritoneal membrane) is a serous membrane that covers the abdominal cavity and most of the organs located in it. According to data for 2017, there were over 400 new cases of ovarian cancer and over 300 deaths from ovarian cancer in Croatia. Ovarian cancer accounted for 4% of all newly diagnosed malignant tumors in women. Ovarian cancer can be divided into a number of subtypes, but they can be grouped into several larger groups: epithelial ovarian cancer (also the most common type), germ cell tumors, ovarian tumors of low malignant potential, childhood ovarian cancer.

​Risk factors

Some of the risk factors that increase the risk of developing ovarian cancer are a positive family history (ovarian cancer in the family), some hereditary changes/syndromes (for example, mutations in the BRCA1 or 2 gene, which also increases the risk of developing breast cancer, or Lynch syndrome, in which there is an increased risk of developing several types of malignant tumors such as colorectal cancer), endometriosis, hormone replacement therapy during menopause, obesity and older age. In general, it is believed that about 20% of ovarian cancer cases are genetically determined, and women with an increased risk may consider preventive surgery, especially if they do not plan to have children anymore.

Figure 1. Illustration of the female reproductive system. The ovaries are a paired organ, connected by a fallopian tube to the uterus. (source: Wikimedia commons)

Signs and symptoms

In the early stages, the disease often does not cause symptoms. Symptoms and signs associated with ovarian cancer include abdominal pain and enlargement, irregular and/or heavy vaginal bleeding (especially after menopause), clear, white or bloody vaginal discharge, a tumor mass in the pelvis, digestive problems (e.g., flatulence, bloating, constipation). Many of the symptoms listed can often occur with other health problems, so it is definitely a good idea to consult a doctor.

Diagnosis

The basis is a detailed examination of the patient and taking a thorough medical history. A manual gynecological examination is definitely required, which analyzes, among other things, the size, shape and location of the uterus and ovaries (Figure 2), and a digital rectal examination, which uses a finger through the rectum to detect the presence of possible tumor formations. CA125 is used as a tumor marker, which is often elevated in other tumors of the female reproductive system, as well as benign conditions such as endometriosis. Imaging tests include ultrasound (examination of the abdomen and pelvis from the outside, i.e. through the skin, and transvaginally, i.e. by inserting an ultrasound probe into the vagina), CT, MRI, PET/CT, and other techniques as needed, to evaluate the possible spread of the disease to other parts of the body.

Stage of the disease

Stage I: Cancer is located in one or both ovaries and/or fallopian tubes.

Stage II: Cancer has spread in addition to the ovary and fallopian tube to the uterus or the peritoneal cavity (the space that contains the abdominal organs).

Stage III: The disease has spread outside the pelvis into the abdomen or to nearby lymph nodes. Primary peritoneal cancer is automatically stage III, since the disease is located in the abdomen.

Stage IV: Metastatic disease stage, i.e. spread to other organs and tissues.

Figure 2. A manual gynecological examination (pelvic examination), which analyzes, among other things, the size, shape, and location of the uterus and ovaries. The gynecologist inserts the fingers of one hand through the vagina to the cervix, while placing the other hand on the abdomen towards the upper edge of the uterus. (Source: Wikimedia commons)

Treatment

Surgical treatment is an option for most patients with ovarian cancer, even when the tumor cannot be completely removed. It has been shown that the prognosis is better the more tumor mass is removed. There are several types of possible operations, including hysterectomy (removal of the uterus), unilateral or bilateral adnexectomy (removal of the ovaries and fallopian tubes on one or both sides) and omentectomy (removal of the omentum, i.e. the tissue of the peritoneum that contains blood and lymph vessels, nerves and lymph nodes). A combination of several techniques in the same operation is common. Chemotherapy is often administered intravenously (systemic therapy) and/or intraperitoneally, i.e. directly into the peritoneal cavity (regional therapy). Intraperitoneal chemotherapy is often administered through the so-called HIPEC technique (hyperthermic intraperitoneal chemotherapy), where it is used during surgery - after the tumor mass is removed, the peritoneal cavity is additionally washed with chemotherapy heated to high temperatures. Two basic groups of drugs are used in targeted therapy: 1. angiogenesis inhibitors, i.e. the growth of new blood vessels necessary for tumor progression (bevacizumab, cediranib), 2. PARP (Poly ADP-ribose polymerase) inhibitors that block the DNA repair process (more in Interesting facts at the bottom of the page) which prevents tumor cells from surviving (olaparib, rucaparib, niraparib, veliparib). Targeted therapy can be used with chemotherapy or alone (maintenance therapy). Radiotherapy and immunotherapy are currently used less frequently.

Looking at the stages, early ovarian cancer (stage I) is mainly treated surgically. For patients who still want to have children, unilateral removal of the ovary and fallopian tube may be considered instead of the standard bilateral procedure. After surgery, some patients will need to receive additional chemotherapy.

Treatment of advanced ovarian cancer also often begins with surgery, the goal of which is to remove as much tumor tissue as possible (ideally all). After surgery, treatment continues, which may include intravenous chemotherapy, intraperitoneal chemotherapy (during surgery), a combination of chemotherapy and targeted therapy, or participation in one of the clinical trials.

Additional interesting facts

Since 2013, World Ovarian Cancer Day has been celebrated on May 8th every year around the world, with the aim of raising awareness about this disease.

How does the use of so-called PARP inhibitors work in the treatment of ovarian cancer? This is a relatively new group of drugs. PARP proteins are normally involved in repairing damage to DNA molecules, so at first glance it seems unusual that their inhibitors (drugs that inhibit their action) are used in treatment. However, in the treatment of cancer with chemotherapy, this is exactly what we want - some of the tumor cells have damaged DNA after chemotherapy, but manage to repair this damage. This is where PARP inhibitors come in, preventing DNA repair and thus preventing the recovery of the tumor cell. They are particularly useful in patients who have a BRCA mutation, because these patients already have impaired DNA repair ability from the start, and this enhances the effect.

Continue reading: Neuroendocrine tumors

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