Ovarian Cancer

Definition of Ovarian Cancer

Ovarian cancer is a cancerous growth arising from the ovary. Symptoms are frequently very subtle early on and may include: bloating, pelvic pain, difficulty eating and frequent urination, and are easily confused with other illnesses.

Most (more than 90%) ovarian cancers are classified as “epithelial” and are believed to arise from the surface (epithelium) of the ovary. However, some evidence suggests that the fallopian tube could also be the source of some ovarian cancers. Since the ovaries and tubes are closely related to each other, it is thought that these fallopian cancer cells can mimic ovarian cancer. Other types may arise from the egg cells (germ cell tumor) or supporting cells. Ovarian cancers are included in the category gynecologic cancer.

Cause of Ovarian Cancer

In most cases, the exact cause of ovarian cancer remains unknown. The risk of developing ovarian cancer appears to be affected by several factors:

Older women, and in those who have a first or second degree relative with the disease, have an increased risk.
Hereditary forms of ovarian cancer can be caused by mutations in specific genes (most notably BRCA1 and BRCA2, but also in genes for hereditary nonpolyposis colorectal cancer).
Infertile women and those with a condition called endometriosis, and those who use postmenopausal estrogen replacement therapy are at increased risk. Analysis of 316 high-grade serous ovarian adenocarcinomas found that the TP53 gene was mutated in 96% of cases. Other genes commonly mutated were NF1, BRCA1, BRCA2, RB1 and cyclin-dependent kinase 12 (CDK12).

Signs and Syptoms of Ovarian Cancer

Signs and symptoms of ovarian cancer are frequently absent early on and when they exist they may be subtle. In most cases, the symptoms persist for several months before being recognized and diagnosed. Most typical symptoms include: bloating, abdominal or pelvic pain, difficulty eating, and possibly urinary symptoms. If these symptoms recently started and occur more than 12 times per month the diagnosis should be considered.

Other findings include an abdominal mass, back pain, constipation, tiredness and a range of other non-specific symptoms, as well as more specific symptoms such as abnormal vaginal bleeding or involuntary weight loss. There can be a build-up of fluid (ascites) in the abdominal cavity.

Ovarian cancer is associated with age, family history of ovarian cancer (9.8-fold higher risk), anaemia (2.3-fold higher), abdominal pain (sevenfold higher), abdominal distension (23-fold higher), rectal bleeding (twofold higher), postmenopausal bleeding (6.6-fold higher), appetite loss (5.2-fold higher), and weight loss (twofold higher).

Risk Factors for Ovarian Cancer

Women who have had children are less likely to develop ovarian cancer than women who have not, and breastfeeding may also reduce the risk of certain types of ovarian cancer. Tubal ligation and hysterectomy reduce the risk and removal of both tubes and ovaries (bilateral salpingo-oophorectomy) dramatically reduces the risk of not only ovarian cancer but breast cancer also. A hysterectomy that does not include the removal of the ovaries has a one-third reduced risk of developing ovarian cancer, it also has no higher risk of developing other types of cancer, heart disease or hip fractures, researchers from the University of California at San Francisco revealed in the journal Archives of Internal Medicine

Diagnosis of Ovarian Cancer

Diagnosis of ovarian cancer starts with a physical examination (including a pelvic examination), a blood test (for CA-125 and sometimes other markers), and transvaginal ultrasound. The diagnosis must be confirmed with surgery to inspect the abdominal cavity, take biopsies (tissue samples for microscopic analysis) and look for cancer cells in the abdominal fluid.

Ovarian cancer at its early stages(I/II) is difficult to diagnose until it spreads and advances to later stages (III/IV). This is because most symptoms are non-specific and thus of little use in diagnosis. The serum BHCGlevel should be measured in any female in whom pregnancy is a possibility. In addition, serum alpha-fetoprotein (AFP) and lactate dehydrogenase (LDH) should be measured in young girls and adolescents with suspected ovarian tumors because the younger the patient, the greater the likelihood of a malignant germ cell tumor.

When an ovarian malignancy is included in the list of diagnostic possibilities, a limited number of laboratory tests are indicated. A complete blood count (CBC) and serum electrolyte test should be obtained in all patients. A blood test called CA-125 is useful in differential diagnosis and in follow up of the disease, but it by itself has not been shown to be an effective method to screen for early-stage ovarian cancer due to its unacceptable low sensitivity and specificity. Another tests used is OVA1.

Current research is looking at ways to combine tumor markers proteomics along with other indicators of disease (i.e. radiology and/or symptoms) to improve accuracy. The challenge in such an approach is that the disparate prevalence of ovarian cancer means that even testing with very high sensitivity and specificity will still lead to a number of false positive results (i.e. performing surgical procedures in which cancer is not found intra-operatively). However, the contributions of proteomics are still in the early stages and require further refining. Current studies on proteomics mark the beginning of a paradigm shift towards individually tailored therapy.

A pelvic examination and imaging including CT scan and trans-vaginal ultrasound are essential. Physical examination may reveal increased abdominal girth and/or ascites (fluid within the abdominal cavity). Pelvic examination may reveal an ovarian or abdominal mass. The pelvic examination can include a Rectovaginal component for better palpation of the ovaries. For very young patients, magnetic resonance imaging may be preferred to rectal and vaginal examination.

To definitively diagnose ovarian cancer, a surgical procedure to take a look into the abdomen is required. This can be an open procedure (laparotomy, incision through the abdominal wall) or keyhole surgery(laparoscopy). During this procedure, suspicious areas will be removed and sent for microscopic analysis. Fluid from the abdominal cavity can also be analysed for cancerous cells. If there is cancer, this procedure can also determine its spread (which is a form of tumor staging).

Prevention from Ovarian Cance

Tubal ligation appears to reduce the risk of ovarian cancer in women who carry the BRCA1 (but not BRCA2) gene. The use of oral contraceptives (birth control pills) for five years decreases the risk of ovarian cancer in later life by half.

Screening

Routine screening of women for ovarian cancer is not recommended by any professional society. This is because no trial has shown improved survival for women undergoing screening. Screening for any type of cancer must be accurate and reliable — it needs to accurately detect the disease and it must not give false positive results in people who do not have cancer. As yet there is no technique for ovarian screening that has been shown to fulfil these criteria. However, in some countries such as the UK, women who are likely to have an increased risk of ovarian cancer (for example if they have a family history of the disease) can be offered individual screening through their doctors, although this will not necessarily detect the disease at an early stage.

The purpose of screening is to diagnose ovarian cancer at an early stage, when it is more likely to be treated successfully. However, the development of the disease is not fully understood, and it has been argued that early-stage cancers may not always develop into late-stage disease. With any screening technique there are risks and benefits that need to be carefully considered, and health authorities need to assess these before introducing any ovarian cancer screening programmes.

Treatment of Ovarian Cancer

Treatment usually involves chemotherapy and surgery, and sometimes radiotherapy.

Surgery

Surgical treatment may be sufficient for malignant tumors that are well-differentiated and confined to the ovary. Addition of chemotherapy may be required for more aggressive tumors that are confined to the ovary. For patients with advanced disease a combination of surgical reduction with a combination chemotherapy regimen is standard. Borderline tumors, even following spread outside of the ovary, are managed well with surgery, and chemotherapy is not seen as useful.

Surgery is the preferred treatment and is frequently necessary to obtain a tissue specimen for differential diagnosis via its histology. Surgery performed by a specialist in gynecologic oncology usually results in an improved result. Improved survival is attributed to more accurate staging of the disease and a higher rate of aggressive surgical excision of tumor in the abdomen by gynecologic oncologists as opposed to general gynecologists and general surgeons.

The type of surgery depends upon how widespread the cancer is when diagnosed (the cancer stage), as well as the presumed type and grade of cancer. The surgeon may remove one (unilateral oophorectomy) or both ovaries (bilateral oophorectomy), the fallopian tubes (salpingectomy), and the uterus (hysterectomy). For some very early tumors (stage 1, low grade or low-risk disease), only the involved ovary and fallopian tube will be removed (called a “unilateral salpingo-oophorectomy,” USO), especially in young females who wish to preserve their fertility.

In advanced malignancy, where complete resection is not feasible, as much tumor as possible is removed (debulking surgery). In cases where this type of surgery is successful (i.e. < 1 cm in diameter of tumor is left behind ["optimal debulking"]), the prognosis is improved compared to patients where large tumor masses (> 1 cm in diameter) are left behind. Minimally invasive surgical techniques may facilitate the safe removal of very large (greater than 10 cm) tumors with fewer complications of surgery.

Chemotherapy

Chemotherapy has been a general standard of care for ovarian cancer for decades, although with highly variable protocols. Chemotherapy is used after surgery to treat any residual disease, if appropriate. This depends on the histology of the tumor; some kinds of tumor (particularly teratoma) are not sensitive to chemotherapy. In some cases, there may be reason to perform chemotherapy first, followed by surgery.

Intraperitoneal chemotherapy

For patients with stage IIIC epithelial ovarian adenocarcinomas who have undergone successful optimal debulking, a recent clinical trial demonstrated that median survival time is significantly longer for patient receiving intraperitoneal (IP) chemotherapy. Patients in this clinical trial reported less compliance with IP chemotherapy and fewer than half of the patients received all six cycles of IP chemotherapy. Despite this high “drop-out” rate, the group as a whole (including the patients that didn’t complete IP chemotherapy treatment) survived longer on average than patients who received intravenous chemotherapy alone.

Some specialists believe the toxicities and other complications of IP chemotherapy will be unnecessary with improved IV chemotherapy drugs currently being developed.

Although IP chemotherapy has been recommended as a standard of care for the first-line treatment of ovarian cancer, the basis for this recommendation has been challenged, and it has not yet become standard treatment for stage III or IV ovarian cancer.

Radiation therapy

Radiation therapy is not effective for advanced stages because when vital organs are in the radiation field, a high dose cannot be safely delivered. Radiation therapy is then commonly avoided in such stages as the vital organs may not be able to withstand the problems associated with these ovarian cancer treatments.