Introduction
Cancer, or “the big C,” is a dreaded diagnosis for patients to receive and sometimes difficult for oncologists to treat. It is a genetic disease often caused by carcinogens -sporadic, or inherited, genetic mutations that act on DNA synthesis, turning normal cells into abnormal cancer cells that grow and divide with the continuous cell division eventually forming a malignant cell mass or tumor which can metastasize, invading and obstructing nearby tissues and organs. Cancer is a general term given to a collection of diseases named after the part of the body where the primary tumor starts, this case being cancerous cells of the tissues in an ovary or both ovaries.
Of gynecological cancers, ovarian cancer is the fifth most common cancer among women and is not only devastating because it is a life-threatening disease, having the highest mortality rate than any other type of female reproductive organ cancer, but also because it negatively affects a woman’s reproductive system consequentially resulting in the inability to reproduce. Unfortunately, there is no current way of detecting early onset of ovarian cancer. Symptoms of early stages of this disease are nonexistent or equivalent to common symptoms of premenstrual syndrome (PMS), indigestion, and other less serious conditions such as ovarian cysts. It isn’t until the cancer has progressed to stage III or stage IV that more painful and dangerous, signs and symptoms begin to show up. These non-specific symptoms and lack of early diagnosis tests causes ovarian cancer to remain undetected until advance stages. This is why it is known as a silent killer.
Late diagnosis has a major effect on the survival rate. Survival rate of this cancer depends on what stage diagnosis occurs. The difference between stage I diagnosis and a stage IV are 5 percent to about 50 percent survival of at least 5 years. Therefore, awareness and early detection is essential in surviving ovarian cancer.
Epidemiology
According to the World Cancer Research Fund International, globally, there are about a quarter of a million new cases of ovarian cancer diagnosed every year resulting in about a 140,000 deaths toll. Ovarian cancer ranks as the seventh most common cancer among women in the world; and is the eighteenth most common cancer worldwide. In 2012, an estimated 239,000 women were diagnosed with this disease; the countries with the largest occurrences were Fiji, with the highest rate of ovarian cancer of about 14.9 per 100,000. Next was Latvia and Bulgaria, at 14.2 and 14.0 per 100,000 respectively. It was estimated that 58% of ovarian cancer cases occurred in less developed countries with the highest occurrences being in Europe and Northern America; and the lowest in Africa and Asia. The same year, the US reported 20,785 women were diagnosed with ovarian cancer and 14,404 women died from it.
In 2015, the American Cancer Society estimates that about 21,290 women will be diagnosed with ovarian cancer in US. They also estimate about 14,180 women will die from it this year. Statistically, the 5-year survival rate for women with ovarian cancer varies from approximately 30% to 50% depending on their prognosis, what stage cancer they’re in, their health, and age. 1 out of every 75 women in America will develop ovarian cancer in her lifetime. If diagnosis is still in its early stages and or, only in one ovary, the 5-year survival rate is around 92%; however only about 19% of all cases are found at this stage. Most cases are diagnosed at advanced stages when the cancer has spread from the localized area to regional or distant regions of the body, making ovarian cancer harder to treat. If it metastasizes to the surrounding organs or tissue (regional spread), the five-year survival rate is approximately 72%. If the cancer has spread to parts of the body far away from the ovary(s) (distant spread), the five-year survival rate is around 27%. The risk and mortality rate of ovarian cancer increases with age and most women are in their fifties and sixties when they are diagnosed having the cancer been latent and progressing into more advanced, lethal, stages. Because of this fact, ovarian cancer is responsible for more deaths in women than any other gynecologic cancer. Advances in treatments today have increased the rate of women surviving more than five years after diagnosis to around 50%, with the overall 10-year survival rate for ovarian cancer being roughly 35%. Fortunately the rate at which women are being diagnosed with this type of cancer has been slowly decreasing over the past 20 years.
Anatomy and Pathophysiology
The ovaries, located in a woman’s abdominopelvic cavity, are the gamete (sex cell) producing organs in females that produce eggs (ova). Generally females have two ovaries connected by uterine or fallopian tubes to each side of the uterus, however the body can survive with one or no ovaries. The function of these are to produce eggs for reproduction by a process of meiosis called oogenesis; the ovaries are also responsible for ovulation, when the ovary releases an ova to travel through the fallopian tubes with the potential to be fertilized by sperm, and if so, continues to the uterus to develop into a fetus. The ovaries also produce female hormones, estrogen and progesterone.
Ovarian cancer causes abnormal, cancerous cells, to rapidly grow to form malignant tumor(s) in a woman’s ovary or both ovaries; affecting the tissues and organs of and around the female reproductive system. There are many types of ovarian cancer that are subcategorized by the three types of cell tissues of an ovary. Each of these cells can develop into different types of cancerous tumors. These include the following:
Epithelial tumors occur on the surface of the ovaries called the epithelium. These tumors are the most common form of ovarian tumors, making up about 90% of all ovarian cancers. Sometimes these tumors are benign and noncancerous such as serous adenomas, mucinous adenomas, and Brenner tumors. However some ovarian epithelial tumors don’t seem cancerous ad are called tumors of low malignant potential (LMP) or otherwise known as borderline epithelial ovarian cancer. These kinds of tumors are slow growing and less life-threatening than other ovarian cancers with fatality being less common. This is because they usually don’t grow into the stroma or metastasize.
Another kind of epithelial ovarian tumor is called carcinomas. This is the most common kind of malignant epithelial ovarian tumor. There are four subtypes; serous which is the most common, mucinous, endometrioid, and clear cell. There is also another tumor called undifferentiated epithelial ovarian carcinomas which don’t look like any of the other four subtypes. These however are the fastest spreading and growing than the other types and they also are given a grade and stage. Grade classifications of these tumors range from 1 to 3. 1 being the grade that looks most normal and has a good chance of patient survival. Grade 3 has tissue that looks abnormal and has the worse prognosis. Grade 2 lies somewhere in between these two extremes. Tumors also develop and progress through stages I – IV which will be covered later.
The second type of ovarian tumor is the ovarian germ cell tumor. These tumors involve germ cells which usually form the ova (egg). Most of these tumors tend to be benign and even those that are cancerous tend to not be life-threatening. Approximately 90% of patients who are diagnosed with this type of ovarian cancer survive at least 5 years. This type of tumor only occurs in less than 2% of ovarian cancer cases. There are four subtypes of germ cell tumors called teratomas, dysgerminomas, endodermal sinus tumors, and choriocarcinomas.
The third type of ovarian cancer tumors are ovarian stromal tumors. These tumors affect the hormone producing cells which produce estrogen. The most prevalent symptom of these tumors is abnormal vaginal bleeding. Some of the symptoms that could indicate this type of tumor in older female patients is vaginal bleeding after menopause. It also can cause young girls who are pre-puberty to have menstrual periods and develop breasts. The occurrence in young girls is very rare, about 5% of stromal tumors; and the occurrence of stromal tumors is about 1% of ovarian cancers. Because of these symptoms, cancerous stromal tumors are found in an early stage and have a positive prognosis with about 75% survival rate.
Ovarian cancer progresses through four different stages similar to other cancers. Stage I being the earliest and stage IV the last.
Stage I ovarian cancer is limited to one or both ovaries. Diagnosis at stage I has the highest rate of survival over 5 years. Within Stage I there are three separate subcategories:
IA: Cancer cells are confined to inside of one ovary. There are no cancer cells are present on the surface of the ovary or anywhere in the pelvis or abdomen.
IB: Cancer is present inside both ovaries, and there are no cancer cells present on the surface of the ovaries, in the pelvis or the abdomen.
IC: Cancer is present inside either or both of the ovaries. Additionally, cancer cells are present on the surfaces of one or both ovaries. There is at least one tumor ruptured on the surface of an ovary or cancer cells are present in fluid samples from the abdomen.
Stage II ovarian cancer spread from the ovary to the pelvic organs, the fallopian tubes, bladder, colon, or uterus. Stage II has three subcategories:
IIA: Cancer is found one or both of the ovaries and has spread into the uterus or fallopian tubes. There are no cancer cells are present in the abdomen or abdomen fluid.
IIB: Cancer is present in either or both of the ovaries and has spread to other pelvic organs beyond the gynecological organs, such as the bladder, colon or rectum.
IIC: Cancer is present in one or both ovaries, and the cancer has spread to the pelvic organs and is found in fluid samples from the abdomen.
Stage III:
In stage III, the cancer has spread from the ovary and beyond the pelvis to the abdomen lining or nearby lymph nodes. This stage has three subcategories:
IIIA: Cancer is present in either or both of the ovaries. They are also found in extremely small amounts in the abdominal fluid.
IIIV: Cancer cells is growing in one or both of the ovaries, and cancer cells are also growing in the abdominal lining. These tumors are smaller than 2 cm.
IIIC: Cancer growths are present in one or both of the ovaries. These cancer tumors are also present and larger than 2 cm in the abdominal lining or in the nearby lymph nodes.
Stage IV:
Stage IV ovarian cancer means that the disease has metastasized or spread from the ovary to distant sites in the body, such as the liver or lungs. The survival rate at this stage is considerably lower than other stages about half as much as stage III.
Testing and Diagnosis
There are several types of tests that can be used to diagnose ovarian cancer. However many of these tests are run after the cancer has progressed to advanced stages due to the lack of defining symptoms during the early stages.
At this time there are no reliable test to screen healthy women for ovarian cancer. Potential ways of identifying this disease is through a vaginal and rectal pelvic exam by a gynecological oncologist. It may be possible for the oncologist to feel something abnormal on the ovaries. This is important especially for women who have family history of any previous cancer such as breast, uterine, or colon cancer. There are genetic tests which are blood tests, available for the BRCA1 or BRCA2 genes, which is believed to be linked to ovarian cancer because of its linkage to breast and colon. It is believed that carrying one of these mutations can be an indicator of high risk of ovarian cancer.
Another test is a transvaginal ultrasound. This uses an instrument called an ultrasound scanner. This instrument creates an electronic picture of the ovaries. These images are interpreted by a radiologist who can determine if the images show signs of abnormal growth on the ovaries or near them. Although these findings are not conclusive of the presence of ovarian cancer, they are strong indicators for the need of further tests. These additional tests usually involve some type of surgical biopsy. Surgical biopsy is the only way to confirm a diagnosis of ovarian cancer. If the biopsy comes back positive for ovarian cancer, a pelvic exam is used to determine the spread of cancer to other parts of the body. This includes examination of the pelvic area to see if the cancer has spread to nearby organs, such as the uterus, vagina, bladder, and rectum.
Another test that measures the progression of ovarian cancer through a protein produced by ovarian cancer cells is called the CA-125 blood test. This measures the level of this protein. The protein, CA-125 measures is known as a tumor marker. This is because the protein is usually at higher levels in women with ovarian cancer. It is the most reliable, and most commonly used test to detect the progression or recurrence of ovarian cancer during treatment and in those women who have been previously treated. Although CA-125 testing is effective in monitoring treatment, it cannot by itself be used to diagnose ovarian cancer; nor does it effectively screen healthy women for ovarian cancer.
Other imaging tests are also used to diagnose the extent of disease. These include: chest X-rays to determine whether cancer has spread to the lungs; Computerized Tomography (CT) Scan which is uses an X-ray machine and computer to create a 3D image of the body. This detailed image is used to provide detailed information about the size, shape, and position of a tumor. It can also identify enlarged lymph nodes that could indicate the cancer has spread beyond the ovary. A Magnetic Resonance Imaging (MRI) is a procedure which uses magnetic fields to create high resolution images in soft tissue. These images can also be used to show growth of cancer outside of the ovaries. Another imaging test is called a PET Scan. This detects the radioactive chemical energy in bloodstream. With the aid of a computer, this energy is converted into a 3D picture that can be used to look at cross-sectional images of the body organs. These images can be examined from any angle in order to detect any functional problems.
Treatment
There are basically three types of treatments for ovarian cancer. These include surgery and chemotherapy, with radiation being used in some cases. The type of treatment for ovarian cancer depends on several factors. These factors include: what stage of the cancer; the size of the tumor, if fertility is desired after treatment; the age and health of the patient.
Surgical biopsy and investigation is used to diagnose ovarian cancer and determine the progression or stage of the disease. It also can determine whether the cancer can be surgically removed and or debulked. Debulking is a surgical procedure to remove as much of the tumor as possible. This is important to optimize the effectiveness of chemotherapy or possible radiation therapy. This usually includes a total hysterectomy. In addition to the hysterectomy, it may also include a unilateral or a bilateral salpingo-oophorectomy, where one or both ovaries and fallopian tubes are removed. Most women with ovarian cancer are treated with bilateral salpingo-oophorectomy.
Chemotherapy uses medications to inhibit the growth of cancer cells either by killing or arresting cellular division. Chemotherapy can be given orally or intravenously. These medications can also be placed directly into an organ or a body cavity to affect cancer cells in those areas. When it is delivered directly into the peritoneal space, it is called intraperitoneal therapy or IP therapy. One of the main chemotherapy treatments for ovarian cancer is a combination of paclitaxel plus a platinum based drug such as carboplatin or cisplatin. Platinum is an important component of the anticancer drugs. Most treatments are delivered systemically in a 3 to 4 week cycle. The length of treatment and dose varies depending on the stage of the disease. Some side effects of chemotherapy would be bloating and abdominal pressure. Chemotherapy affects normal cells as well as cancer cells which can have many side effects such as nausea and vomiting, loss of appetite, diarrhea, fatigue, low blood count, bleeding or bruising after minor cuts or injuries, numbness and tingling in the hands or feet, headaches, hair loss, and darkening of the skin and fingernails. Some medicines used in treatment can cause some hearing loss or kidney damage.
Radiation therapy uses high energy radiation to kill cancer cells or shrink the tumor. This is rarely used in the treatment of ovarian cancer but sometimes can be effective in killing specific remaining cancer cells after other treatments. The main goal of radiation therapy is to control symptoms rather than cure the cancer.
Treatment of recurrent or persistent cancer which doesn’t respond to chemotherapy or is detected after the completion of initial therapy is called “persistent” or “recurrent,” respectively. These are usually detected through a CA-125 blood test and CT imaging. In some cases, a biopsy maybe needed to confirm the diagnosis. Treatment depends on how long it’s been since the last treatment and the patient’s age and overall health. Another surgical debulking may be performed to remove as much of the tumor as possible along with the same chemotherapy. If the recurrence is less than six months after stopping chemotherapy, they are considered “platinum-resistant” and may be given paclitaxel or different treatment drugs. Eventually if reoccurrence continues many of the chemotherapy become ineffective, resulting in the inability to suppress the ovarian cancer.
Prognosis
The prognosis of ovarian cancer depends the stage of the cancer, the type of ovarian cancer, and the size of the tumor after surgical removal of as much of the tumor as possible. The prognosis for diagnosis at different stages is identified in the following table.
Tables of Ovarian Cancer Survival Rates by Type of Cancer
Risk factors and Prevention
• Researchers have discovered several specific factors that change a woman’s likelihood of developing epithelial ovarian cancer. These factors include:
• Age. Older women are more likely to get ovarian cancer. It is rare in women younger than 40. Half of all ovarian cancers are found in women 63 years of age or older.
• Obesity. Research has correlated obesity with a higher risk of developing ovarian cancer. Pregnancy. Women who have been pregnant have a lower risk of ovarian cancer than women who have not. Breastfeeding may lower the risk even further.
• Use of oral contraceptives or hormonal injections. These have a lower risk of ovarian cancer.
• Tubal ligation can reduce the probability of developing ovarian cancer up to two-thirds. Having a hysterectomy can reduce the risk of getting ovarian cancer around one-third.
• Fertility drugs used for longer than one year has shown to increase the risk for ovarian tumors.
• Family history of ovarian cancer, breast cancer or colorectal cancer show an increased risk
• There are several other risk factors and potential preventions but these mentioned above are the main ones.
Conclusion
Even though ovarian cancer is the fifth most common gynecological cancer it is the most deadly. This is mainly due to the nature of ovarian cancer which includes the lack of unique signs and symptoms in the early stages of the disease, and also the lack of definitive noninvasive screening tests allow ovarian cancer to remain undiagnosed or even misdiagnosed until it is in advance deadly stages. For this reason, this type of cancer is known as a “silent killer”. Although there have been some advances in biomedicine and technology research to treat ovarian cancer, survival and mortality rates still remain high. Early detection with gynecologic oncology screening is crucial in reducing these overall rates.
Source: Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray, F. GLOBOCAN 2012 v1.1, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer; 2014. Available from: http://globocan.iarc.fr, accessed on 16/01/2015.
2 Source: The American Cancer Institute, http://www.cancer.org/cancer/ovariancancer/detailedguide/ovarian-cancer-survival-rates
3 http://www.ocrf.org/about-ovarian-cancer/treatment-of-ovarian-cancer/staging-and-grading