Ovarian cancer is somewhat of a mystery to many women. We know that it is serious, and difficult to detect at an early stage. We also know that it is deadly. It is important to understand the symptoms, and seek medical attention if symptoms are present. Let's try to demystify this disease.
The ovaries are two organs that reside in the pelvis, next to the uterus, which produce eggs or ova, to allow conception. Most of our estrogen comes from our ovaries. The fallopian tubes are located next to the ovaries and carry the fertilized egg to the uterus for implantation. Fertilization actually occurs in the fallopian tube.
There are several types of ovarian cancer, but most of the time we refer to epithelial ovarian cancer, which originates from the surface of the ovary. We now know that some "ovarian" cancers actually start inside the fallopian tube, and these malignant cells may attach to the ovary, and they may also attach to the peritoneum, the lining of the abdominal cavity. For this discussion, we will include fallopian tube and peritoneal cancer when we talk about ovarian cancer.
The lifetime incidence of ovarian cancer in the general population is 1.48% There are about 22,000 new cases of ovarian cancer diagnosed each year in the U.S, and 15,000 deaths. If you compare this to breast cancer, the risk of developing breast cancer in your lifetime is 12%, with 229,000 new cases per year and 39,000 deaths attributable to it. Therefore, breast cancer is about
10 times more common, but the mortality is much less.
Of all cancer that occur in women, ovarian is the 9th most common, but the 5th in mortality. The majority of cases are diagnosed after cancer has spread to adjacent organs, making it stage 3 or 4. We know that early detection improves survival outcomes. The survival after 5 years if the disease is diagnosed as stage 1 in 90%. With Stage 3 & 4, the survival after 5 years is only 25%
Risk factors for ovarian cancer are the following.
1. Family history: if you have a first degree relative with ovarian cancer (mother or sister), your risk increases to 5%. If you have
two first degree relatives, your risk is 7%
2. If you carry the BRCA gene you have a 25-40% risk of having ovarian cancer in your lifetime
3. Age is a risk factor
3. Nulliparity: never having children increases the risk. Pregnancy is protective
4. Other cancers: breast, colon, uterine and rectal cancers are sometimes associated
5. Hormone: prolonged hormone replacement and fertility drugs are controversial, as studies have shown mixed results
Factors that decrease risk
1. Younger age
2. Oral contraceptives: having used birth control pills for 4 years reduces the risk of ovarian cancer 50%
3. Tubal ligation and hysterectomy
4. Bilateral salpingo-oophorectomy: removing both ovaries and tubes markedly decreases risk, but not 100%,
as some cancers may originate in the lining of the peritoneal cavity
5. Removing ovaries can reduced the risk of breast cancer also
The BRCA gene
The BRCA gene is gene that produces a protein that protects us from breast and ovarian cancer. If you carry a gene mutation, your risk of having breast cancer increases to 75-85%, and your risk of having ovarian cancer is 25-40%. This gene can be inherited from the maternal or paternal side of the family by autosomal dominant inheritance, which means that you only need to inherit one copy of the mutated gene to see its consequences. The incidence of the gene in the general population is about 0.2%, but if you are of Jewish Ashkenazi inheritance, your risk is 2.5% We now know that 1/10 ovarian cancers are caused by this gene.
You may be a candidate for genetic testing. If you have multiple family members with breast and/or ovarian cancer, testing should be considered. If a family member had two breast cancers, or breast and ovarian cancer, the risk of carrying the gene increases.
Premenopausal breast cancer, or a male with breast cancer in the family, Ashkenazi Jewish background, and having a triple-negative breast cancer are additional risk factors.
Patients that test positive for the BRCA gene are managed with increased surveillance or prophylactic oophorectomy. If you carry the BRCA gene, it is recommended that you have a pelvic exam twice yearly with a biologic marker test, CA125. A sonogram also is recommended once or twice yearly. After childbearing is completed, it is recommended that the tubes and ovaries be removed. This can be done laparoscopically. This risk-reducing surgery decreases the risk of ovarian cancer 96%. It is not 100% because, as previously mentioned, some "ovarian" cancer can originate in the lining of the abdominal cavity, the peritoneum.
Ovarian cancer has the highest mortality of all gynecologic cancers. The reason for this is that it is often diagnosed in later stages. Symptoms can be vague, and often mimic gastrointestinal problems. Symptoms are often present for months prior to diagnosis, and many women receive the diagnosis from a gastroenterologist during an evaluation for bloating or abdominal pain.
When ovarian cancer is confined to the ovaries, it is often painless, but if there is pain, it is often vague. A larger tumor on the ovary may cause pressure on the bladder, causing bladder discomfort, frequency and urgency. If the tumor presses on the rectum, there may be discomfort during bowel movements. Intercourse may become painful.
If the disease spreads to the abdominal cavity, a women may feel bloated. She may note vague discomfort, gas, nausea, bloating, early satiety (feeling full with a small amount of food), and a change in bowel habits. The abdomen may become enlarged, and clothing feels tight. If there is pain, it can occur in the abdomen, pelvis, back or legs. If ovarian cancer spreads to the lining of the lungs, there can be shortness of breath and fatigue.
Many, many women feel bloated at times. This is not unusual and is almost always of GI origin. Although it is hard to differentiate, GI symptoms often fluctuate, and bloating from ovarian cancer is usually persistent and gets worse with time. The advice here is to think about ovarian cancer, have a pelvic exam, and entertain the diagnosis so that the proper tests can be ordered.
The diagnosis of ovarian cancer can often be made on pelvic exam, although small tumors can be difficult to detect. The ovary in the postmenopausal women in not palpable, so if the ovary can be felt, it may be enlarged. An abdominal exam can detect a large mass and fluid in the abdomen. A rectal exam is important because if an ovary is abnormal, it may be heavy or large and sink into the space next to the rectum, and it is best felt that way. A pelvic ultrasound is an easy and inexpensive test that is widely available and can detect ovarian masses. Blood tests called tumor markers can be done to determine if there are chemicals in the bloodstream that are indicative of cancers.
A CT scan or MRI may be ordered to determine if there are other causes of symptoms, or if there is extension of tumor to other organs.
A pelvic sonogram is a test using sound waves to make a black-and white image of the pelvic organs. The transducer is used abdominally and vaginally to obtain the best images of the ovary. Both ovaries can usually be visualized and they are measured for size. Ovarian cancers usually appear as complex ovarian cysts. Ovarian cysts are very common in the ovary: an ovarian cyst is formed each month during ovulation and the ova is extruded from a small cyst or follicle. Cysts are very common and often multiple in perimenopausal women, as the ovaries are working hard to continue ovulation. A sonogram done in a perimenopausal woman will often demonstrate multiple small cysts that are simple and clear. Simple means that the lining of the cyst is thin, and clear means that the cyst is filled with clear fluid. These cysts are very common and do not need to be removed surgically.
Complex cysts usually demonstrate irregularities in the wall of the cyst, and often have solid and fluid components. Ovarian cancers usually present as cysts that are often bilateral, complex with solid components, septations or thickened walls, nodularity, and often fluid in the pelvis
Markers for ovarian cancer
A CA125 is a chemical marker for ovarian cancer, but it is not specific. This test is most often used to monitor the effects of treatment and recurrence, after surgery or chemotherapy. It has been used to diagnose ovarian cancer, but its use is limited. CA125 if often negative in early stage ovarian cancer, and it can be elevated in other diseases.
There are several additional markers that use multiple proteins to provide an algorithm that predicts the risk of ovarian cancer once an ovarian cyst is detected. These tests can be obtained to determine of a women should be referred to a gynecologic oncologist for management of her ovarian tumor.
Once at tumor is detected, a CT scan of the abdomen and pelvis may be obtained to determine if there is extension of disease beyond the pelvis, or to adjacent organs such as the bladder, rectum, and lymph nodes. A chest x-ray is obtained to rule out disease in the chest. A colonoscopy may be suggested to determine extension to the colon.
A CT scan is used to monitor recurrence of disease after treatment.
Is a yearly pelvic exam enough?
It has been suggested that women do not need yearly pelvic exams because it is difficult to detect ovarian cancers in the earliest stage. Although not all early stage cancers are detected, some can be. A visit with a gynecologist allows the physician to ask questions about family history and other symptoms, which might indicate that additional testing should be performed, such as an ultrasound. Since the most important risk factor is family history, always mention to your gynecologist this element of family history. A CA125 test should not be done routinely on low risk patients, but should be done on women at increased risk of ovarian cancer.
Multiple studies have been done to determine if low risk women with ovaries should be screened with yearly sonograms and CA- 125 blood tests. Several of the studies have shown no difference in stage of disease at the time of detection, and no increased survival. One of the side effects of doing routine screening is that more women will be subjected to a surgical procedure for a cyst that is not clearly benign, and some of them will have complications from surgery, for what will turn out to be a benign tumor. One additional study is under way, the UK Collaborative Trial of Ovarian Cancer Screening. Its initial results do show a significant reduction in mortality for women followed for 14 years. They have found that 641 screenings needed to be done to prevent one ovarian cancer death. Cost-benefit analysis are pending for these findings. (Ob.Gyn.News, February 2017, Vol. 52, No. 2)
Managing high risk patients
If you are at high risk of ovarian cancer, high-risk surveillance includes twice yearly exams, pelvic sonograms once or twice yearly, and a CA125 at each pelvic exam. The problem with screening is that there is no guarantee that with screening, ovarian cancer will be found in Stage 1 or 2. Once ovarian cancer is diagnosed, the treatment includes a hysterectomy, removal of both tubes and ovaries, removal of pelvic lymph nodes, and omentum (which is the fatty pad around the bowel). Chemotherapy is almost always suggested.
The risks and benefits of preventive removal of the tubes and ovaries should be considered for women at increased risk of ovarian cancer, especially those who carry the BRCA gene. This surgery can be done laparosocopically as an in-and-out procedure with about a week of recovery. The risks of this surgery are low.
We know that the ovaries have benefits in preventing cardiovascular disease and osteoporosis, and that abrupt removal of ovaries in women before menopause can cause severe vasomotor symptoms and mood changes. This is not a decision to be taken lightly, and in most cases, ovaries should not be removed at the time of hysterectomy for benign disease in women who are premenopausal if the ovaries are normal.
Treatment for ovarian cancer is a combination of surgery and chemotherapy. Most often, surgery is performed first. A debulking procedure involves a hysterectomy, removal of ovaries and tubes, lymph nodes in the pelvis, and removal of the omentum around the bowels. It also involves removing any visible tumor that may be present on other organs. Surgery might include removing portions of the bowel or other organs that might be involved. Surgery is usually followed by chemotherapy, although sometimes if tumor burden is extensive, chemotherapy is done prior to surgery. If ovarian cancer is suspected, a gynecologic oncologist is most expert in dealing with this type of extensive surgery.