Ovarian Cancer (Ab Ovo)
Ovarian cancer is the 5th most common cancer in women after lung, breast, colorectal and pancreatic cancers. It accounts for only three percent of cancer in women, and fortunately there has been a decline in incidence of this type of cancer by about 1% over the last twenty years. Unfortunately, diagnosis is usually late as there are very subtle and often protean symptoms and signs. Ovarian cancer is not just a cancer of old age, it can occur at any age, even infancy, however, the incidence of this cancer does rise significantly after the age of 50.
There are certain risk factors for ovarian cancer, chief amongst them is family history and some associated genetic syndromes. A blood relative with ovarian cancer raises the risk for their female relative by 5% for this cancer. There is a syndrome of hereditary breast and ovarian cancer which occurs in one out of every 500 women and being an autosomal dominant genetic disorder results in BRCA1 and/or BRCA2 gene mutation. The other is Lynch II syndrome a hereditary non-polyposis colorectal cancer syndrome, again autosomal dominant, which increases risk for ovarian cancer by 12%. However, the majority of women diagnosed with ovarian cancer have no family history and the etiology remains unknown. When ovarian cancer occurs and is not detected early when localized to one ovary, the cancer will usually spread to the unaffected ovary and uterus first, but can spread to the liver, lungs, adrenal glands, spleen and other intraperitoneal organs.
Some things that reduce risk are the protective effects of oral contraceptives, late menarche, early menopause, multipariety (having more than one child) and breastfeeding. Progesterone appears to be protective, but there is controversy as a 2009 Danish study suggests that all HRT results in increased risk (the study was performed with estrogen alone (unopposed) or estrogen & progestin (progestin is a synthetic progesterone compound). Further study in the use of natural bio-identical hormones for prevention will need to be performed to clear up this controversy as earlier studies showed HRT to be protective. There are modifiable factors such as reducing weight (avoiding obesity), smoke cessation, reducing a high starch and fat diet that can reduce risk of this cancer. It has been shown that a well balanced diet high in carotene, vitamin C and E and unsaturated fats with moderate physical activity all help reduce ovarian cancer risk.
There is much difficulty in making an early diagnosis due to the fact that signs and symptoms are very often subtle and non specific, and unless you go looking for this disease with specific diagnostic lab and radiology tests you are not likely to find it early on. Some symptoms include abdominal pain and fullness, back pain, nausea, constipation, diarrhea, fatigue, pelvic pain and urinary symptoms. Laboratory testing should be considered in women over 40-years of age if these symptoms persist as they are a higher risk population for ovarian cancer. Testing usually involves a CBC, metabolic panel and serum CA 125 levels. CA 125 is a cancer marker that is rather sensitive and specific for ovarian cancer, however there are some other conditions that can elevate this marker such as pelvic inflammatory disease (PID), endometriosis, ovarian cysts and pregnancy. CA 125 is a good test but not perfect since it is elevated in 90% of patients with advanced disease, but only upwards of 50% with stage I tumors. Additionally, there are other markers that make themselves useful, and they include the beta subunit of human chorionic gonadotropin (Beta-HCG), serum alpha-fetoprotein (AFP), neuron-specific enolase (NSE), and lactate dehydrogenase (LDH). Diagnosis is also made by diagnostic imaging, such as the Doppler transvaginal ultrasound (ultrasonography or US), often used as an initial evaluation for a pelvic mass. US is helpful in determining benign ovarian lesions such as simple cysts from those that appear more malignant such as complex solid tumors. Other modes of radiological imaging useful to the diagnostician are CT scan and gadolinium-enhanced MRI.
Treatment usually includes (after thorough diagnostic testing and staging) excision of the mass/tumor by surgery. Depending on the stage of the disease other organs may also be removed, for example the appendix is generally removed due to its potential target for metastasis. Following removal of the tumor, chemotherapy is typically initiated with a combination of platinum and taxane-based agents. Carboplatin and Taxol are two chemotherapeutic agents that are often used. For those women beyond their reproductive years, a total hysterectomy is often considered, while radiation therapy is reserved for palliative and persistent disease that reappears after a regiment of chemotherapy.
Prognosis is a bit complicated as it is based on the staging of the disease as well as the histological grade (type of tumor etiology) that typically plays a role in recurrence rates. For example, an epithelial ovarian cancer (histologically) has a low malignant potential if diagnosed at stage I and has a 95 – 99% survival rate at 10-years.
Screening for ovarian cancer should include annual physical examination and directed exams by markers and imaging only when warranted. Routine screening with CA 125 yield too many false positives and misses too many tumors early on to be a good general screening test. BRCA analysis should be reserved for descendents of those with mutated BRCA1 & BRCA2 genes, it is not recommended as a general screening tool. The current recommendations for women meeting criteria for high risk or very high risk for ovarian cancer is to be screened with a transvaginal ultrasound and have a CA 125 measured every six months during days 1 through 10 of their menstrual cycle beginning at age 35.
The take home message here is that women need to be diligent with regard to their annual physical examinations and to not ignore persistent symptoms that may point a finger to an underlying more serious condition.
Roett, M. Evans, P., "Ovarian Cancer: An Overview", American Family Physician, Vol. 80, Num 6, September 15, 2009, p.609-616.
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