Ovarian cancer is cancer in women that affects the ovaries. The ovaries are the two female reproductive organs that produce eggs (ova) and hormones (estrogen and progesterone). It goes undetected most times until it has spread within the pelvis and abdomen. There are three different types of ovarian cancers; Epithelial tumors (makeup 90% of all ovarian malignancies) –most originate from the fallopian tubes and affect the thin lining covering the ovaries. Stromal tumors (make up about 7%)-begin in the ovarian tissue, in the hormone-producing cells and are usually detected earlier than other types of ovarian cancers and Germ cell tumors (typically occur in younger women) –originate from the egg-producing cells.
Ovarian cancers are mostly metastases of other cancers especially cancers of the endometrium, breast, colon, cervix, and stomach. The overall five-year survival rate in the United States is 45%. According to WHO, in 2015, 1.2 million women worldwide were diagnosed with ovarian cancer and 161,100 deaths overall (Malvezzi et al.).
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Signs and symptoms
Early stage ovarian cancer is usually asymptomatic or has minimal, on specific symptoms. But commonly patients complain of feeling an abdominal mass. Advanced stage disease has more signs but is sometimes mistaken for benign conditions. Signs and symptoms include; Bloating, abdominal swelling or discomfort, Constipation, Frequent need to urinate, Vaginal bleeding, Irregular menstruation, Discomfort in the pelvis area, Weight loss, Tiredness, Early satiety.
Later-stage disease symptoms are mostly pressured symptoms on the abdominopelvic organs or due to metastases and include; gastrointestinal symptoms such as nausea and vomiting, constipation, diarrhea, difficulty in breathing. There may also be abnormal vaginal bleeding after menopause, hirsutism (Kolata). Leg swelling due to venous thrombosis is not uncommon. In adolescents with ovarian tumors, secondary sex characteristics can be affected and present with amenorrhea, early puberty and in others ascites.
Causes
The specific cause is unknown, but like many other cancers, genetic mutation of cancer has a role to play. Several risk factors increase the chances of acquiring the disease. They include; Older age-it is more common in women aged 50 and above, Inherited gene mutations (in about 10% of the cases)-breast cancer gene 1(BRCA1) and breast cancer gene 2(BRCA2) increase the risk of breast and ovarian cancer (King et al., 646), Family history of ovarian cancer, Estrogen hormone replacement therapy, Fertility medication, Early menarche, Late menopause onset, Nulliparity, Obesity and Women with endometriosis (about 30% develop ovarian cancer).
Diagnosis
The typical age of diagnosis is 63In early disease; physical findings are uncommon. Patients with more advanced disease may present with an ovarian or abdominal mass, pleural effusion (by auscultation), ascites or bowel obstruction (Kolata). Blood tests are also done to identify certain tumor markers that are specific for ovarian cancer by the use of immunohistochemistry. The tumor markers are; CA125, beta-human chorionic gonatropin, alpha-fetoprotein, lactate dehydrogenase. Tumor markers are useful in screening, determining diagnosis and prognosis, assessing response to therapy and monitoring for cancer recurrence. The latter two markers are tested in young girls suspected to have malignant germ cell tumors. Urinalysis can also be done to exclude other causes of abdominal/pelvic pain, such as urinary tract infections or kidney stones.
A pelvic examination may reveal an adnexal mass that can indicate ovarian cancer, mainly if it is fixed, nodular and irregular malignancies cause about 20% of the adnexal masses. Breast examination and digital rectal exam can also be helpful especially in cases of metastases. Palpation of supraclavicular (lung cancer), axillary (breast cancer) and inguinal lymph nodes can show lymphadenopathy that could indicate metastasis.
Imaging is also done especially CT scanning and MRI to assess further the extent of the tumor in the abdomen. Vaginal ultrasonography (most useful initial investigation) is performed after an adnexal mass is found; it may define the morphology of the pelvic tumor. Chest x rays and CT help in excluding pleural effusions or pulmonary spread of malignant disease of the ovary.
A definitive diagnosis of the ovarian cancer is done after surgery and can either be laparotomy (open procedure) or laparoscopy (keyhole surgery- non-invasive). After the surgery, a biopsy of the cancerous tissue is taken for histopathology analysis that helps classify cancer and also staging. Fine needle aspiration or diagnostic paracentesis can also be performed in patients with abdominal fluid to identify cancerous cells and help in staging, in case of absence of obvious ovarian masses.
In the case of gastrointestinal symptoms, a full gastrointestinal workup could be done, particularly an endoscopy or a barium enema. In the case of ascites, abdominal fluid aspiration could be done to check for metastases to other abdominal organs.
Management
Ovarian cancer usually has a poor prognosis because it lacks any clear early detection or screening test and most diagnoses are made when cancer it at advanced stages. It metastasizes in the early stages before even its diagnosis. One year survival rate is 72%.
Standard treatment for patients with ovarian cancer involves surgery and chemotherapy. Surgery usually is for resection of the visible tumors and to know the extent of the tumor growth. Cytoreductive surgery is usually carried out, and the surgeries could involve unilateral or bilateral oophorectomy (Kolata). In advanced disease debulking surgery is performed and it is only done once. Major side effects of oophorectomy especially in younger women are early menopause that can result in osteoporosis. Thus after surgery hormone replacement can be done to reduce this risk.
The patient is then given postoperative chemotherapy; standard chemotherapy is combined therapy with a platinum compound and a taxane, (Armstrong et al., 42). Some additional agents for recurrent disease are also given as well as adjunctive medications like cytoprotective agents and antiemetics. Chemotherapy is curative in about 20% of advanced ovarian cancers, especially with germ cell tumors. It is given intravenously or in the peritoneal cavity. It involves 3 to 6 cycles, which are given 3 to 4 weeks apart to allow the body time to recover from the side effects. The most common side effects reported include; nausea, vomiting, hair loss, loss of appetite, mouth sores, anemia and increased risk of acquiring infections because of the immunosuppression caused by the drugs that also affect normal healthy cells.
Radiotherapy is not commonly done, it is done after surgery, and there is a likelihood of residual disease in the pelvis, but the abdomen is cancer-free. It is also done as palliative care in advanced disease. The radiation cycles are done five days a week for four weeks. The common side effects associated with the procedure include diarrhea, frequent urination, and constipation. Hormonal therapy is rarely used since estrogen does not affect cancer (Armstrong et al., 37).
Immunotherapy is an area that is still under study; the drug Bevacizumab ( a vascular endothelial growth factor inhibitor) is used to treat advanced cancer in combination with chemotherapy. The drugs work by inhibiting tumor vascular permeability and enhance tumor blood flow and thus, drug delivery. There are clinical trials linked to the success of using immunotherapy, reducing the tumor and the patients going into remission. It seems to help in the treatment of a particular rare hypercalcemic small cell ovarian cancer. The drugs allow the immune system to recognize and destroy the tumor cells. Nivolumab is a drug also used in immunotherapy in combination with bevacizumab, especially in recurrent ovarian cancer. Nivolumab has shown promising results in significantly shrinking of ovarian tumors in four women with the advanced disease according to the New York Times. The exact mechanism of how it worked is still not well understood.
Palliative care is given to relieve symptoms and maintain quality of life. It focuses on treating the symptoms and complications that come with cancer. For example, in the case of bowel obstruction, palliative surgery (colostomy, internal bypass) or medication.
Psychosocial care is also necessary for all cancer patients, and some women struggle with self-esteem and body image changes after oophorectomy and hair loss due to chemotherapeutic drugs. The removal of ovaries can cause surgically induced menopause that can then lead to loss of sexual libido, vaginal dryness, pain during sex and feel fatigued, and There are also mental disturbances where they deal with depression, frustration, anxiety. The mental problems can also be observed in their family members. Some also express a fear of death, sadness, and pessimism. By involving the patients in different activities like traveling, having cancer support groups (being involved in spiritual-based events), it has shown to improve their quality of life significantly
Prevention
Individuals with strong genetic risk for ovarian cancer like the people with the BRCA gene and those with familial history of ovarian cancer could consider the surgical removal of their ovaries to reduce the risk of acquiring the disease. It is usually done after the childbearing years, and it reduces the chances of developing both ovarian (by 95%) and breast (by 50%) cancers. The risk of developing ovarian cancer is reduced by; bearing children, using the combined oral contraceptive pills (by 50%), undergoing tubal ligation, undergoing prophylactic bilateral oophorectomy (reduces by 80%).
Ovarian cancer and bacterial vaginosis
Vaginal douching is a common practice by women that involves washing or flushing the vagina with water or other fluids. It is associated with interfering with the necessary balance of vaginal flora (bacteria) and natural acidity in a healthy vagina. It is thus not recommended by doctors as it interrupts the maintenance of the healthy acidic vaginal environment. It increases the risk of developing bacterial infection (bacterial vaginosis) which in turn doubles the risk of ovarian cancer development. Pelvic inflammatory diseases in general increase the risk of acquiring ovarian cancers.
References
Armstrong, Deborah K., et al. "Intraperitoneal cisplatin and paclitaxel in ovarian cancer." New England Journal of Medicine 354.1 (2006): 34-43.
King, Mary-Claire, Joan H. Marks, and Jessica B. Mandell. "Breast and ovarian cancer risks due to inherited mutations in BRCA1 and BRCA2." Science 302.5645 (2003): 643-646.
Kolata, Gina.” Doctors Said Immunotherapy Would Not Cure Her Cancer. They Were Wrong.” The New York Times, 19 February 2018, https://www.nytimes.com/2018/02/19/health/ovarian-cancer-immunotherapy.html?smid=tw-nytimes&smtyp=cur
Malvezzi, M., et al. "Global trends and predictions in ovarian cancer mortality." Annals of Oncology 27.11 (2016): 2017-2025.
