'Ovarian cancer' is a
malignant tumor (a kind of
neoplasm) located on an
ovary. Although many ovarian tumors are
benign, most have the potential to become malignant unless treated.
Causes
Ovarian cancer is the fifth leading cause of
cancer death in
women, the leading cause of death from
gynecological malignancy, and the second most commonly diagnosed gynecologic malignancy
[1].
The exact cause is usually unknown. The disease is more common in industrialized nations, with the exception of
Japan. In the
United States, females have a 1.4% to 2.5% (1 out of 40-60 women) lifetime chance of developing ovarian cancer.
Older women are at highest risk. More than half of the deaths from ovarian cancer occur in women between 55 and 74 years of age and approximately one quarter of ovarian cancer deaths occur in women between 35 and 54 years of age.
The risk of developing ovarian cancer appears to be affected by several factors. The more children a woman has, the lower her risk of ovarian cancer. Early age at first pregnancy, older ages of final pregnancy and the use of low dose
hormonal contraception have also been shown to have a protective effect. Ovarian cancer is reduced in women after
tubal ligation.
The link to the use of
fertility medication, such as
Clomiphene citrate, has been controversial. An analysis in 1991 raised the possibility that use of drugs may increase the risk of ovarian cancer. Several
cohort studies and
case-control studies have been conducted since then without providing conclusive evidence for such a link.
[2] It will remain a complex topic to study as the infertile population differs in
parity from the "normal" population.
There is good evidence that in some women genetic factors are important. Carriers of certain mutations of the
BRCA1 or the
BRCA2 gene and certain populations (e.g.
Ashkenazi Jewish women) are at a higher risk of both
breast cancer and ovarian cancer, often at an earlier age than the general population. Patients with a personal history of breast cancer or a family history of breast and/or ovarian cancer, especially if at a young age, may have an elevated risk. A strong family history of
uterine cancer,
colon cancer, or other
gastrointestinal cancers may indicate the presence of a syndrome known as
hereditary nonpolyposis colorectal cancer (HNPCC, also known as
Lynch II syndrome), which confers a higher risk for developing ovarian cancer. Patients with strong genetic risk for ovarian cancer may consider the use of
prophylactic i.e. preventative
oophorectomy after completion of child-bearing.
A Swedish study, which followed more than 61,000 women for 13 years, has found a significant link between milk consumption and ovarian cancer. According to the BBC, "[Researchers] found that milk had the strongest link with ovarian cancer - those women who drank two or more glasses a day were at double the risk of those who did not consume it at all, or only in small amounts."
[3] Recent studies have shown that women in sunnier countries have a lower rate of ovarian cancer, which may have some kind of connection with exposure to Vitamin D.
Other factors that have been investigated, such as
talc use,
asbestos exposure, high dietary fat content, and childhood
mumps infection, are controversial and have not been definitively proven.
"Associations were also found between alcohol consumption and cancers of the ovary and prostate, but only for 50 g and 100 g a day."
[4]
Classification
Ovarian cancer is classified according to the
histology of the tumor, obtained in a
pathology report. Histology dictates many aspects of clinical treatment, management, and
prognosis.
★
Surface epithelial-stromal tumour, including serous and mucinous
cystadenocarcinoma, is the most common type of ovarian cancer.
★
Sex cord-stromal tumor, including
estrogen-producing
granulosa cell tumor and 'virilizing'
Sertoli-Leydig cell tumor or
arrhenoblastoma, accounts for 8% of ovarian cancers.
★
Germ cell tumor accounts for approximately 5% of ovarian cancers. It tends to occur in young women and girls, and has a better prognosis than other ovarian tumors.
★ 'mixed' tumors, containing elements of more than one tumor histology
Ovarian cancer often is 'primary', but can also be 'secondary', the result of
metastasis from a primary cancer elsewhere in the body. For example, from
breast cancer, or from
gastrointestinal cancer (in which case the ovarian cancer is a
Krukenberg cancer). Surface epithelial-stromal tumor can originate in the lining of the abdominal cavity, in which case the ovarian cancer is secondary to
primary peritoneal cancer, but treatment is basically the same as for primary ovarian cancer of this type.
Symptoms
Studies on the accuracy of symptoms
Two
case-control studies, both subject to results being inflated by
spectrum bias,have been reported. The first found that women with ovarian cancer had symptoms of increased abdominal size, bloating, urge to pass urine and pelvic pain.
[5] The smaller, second study found that women with ovarian cancer had pelvic/abdominal pain, increased abdominal size/bloating, and difficulty eating/feeling full.
[6] The latter study created a symptom index that was considered positive if any of the 6 symptoms "occurred >12 times per month but were present for <1 year".They reported a
sensitivity of 57% for early-stage disease and
specificity 87% to 90%.
''Ovarian Cancer Symptoms Consensus Statement''
In 2007, the Gynecologic Cancer Foundation, Society of Gynecologic Oncologists and American Cancer Society originated the following consensus statement regarding the symptoms of ovarian cancer.
[7]
Historically ovarian cancer was called the “silent killer” because symptoms were not thought to develop until the chance of cure was poor. However, recent studies have shown this term is untrue and that the following symptoms are much more likely to occur in women with ovarian cancer than women in the general population. These symptoms include:
★ Bloating
★ Pelvic or abdominal pain
★ Difficulty eating or feeling full quickly
★ Urinary symptoms (urgency or frequency)
Women with ovarian cancer report that symptoms are persistent and represent a change from normal for their bodies. The frequency and/or number of such symptoms are key factors in the diagnosis of ovarian cancer. Several studies show that even early stage ovarian cancer can produce these symptoms.
Women who have these symptoms almost daily for more than a few weeks should see their doctor, preferably a gynecologist. Prompt medical evaluation may lead to detection at the earliest possible stage of the disease. Early stage diagnosis is associated with an improved prognosis.
Several other symptoms have been commonly reported by women with ovarian cancer.
These symptoms include fatigue, indigestion, back pain, pain with intercourse, constipation and menstrual irregularities. However, these other symptoms are not as useful in identifying ovarian cancer because they are also found in equal frequency in women in the general population who do not have ovarian cancer.
Diagnosis
Ovarian cancer at its early stages(I/II) is difficult to diagnose until it spreads and advances to later stages(III/IV). This is due to the fact that most of the common symptoms are non-specific.
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.
The serum
BHCG level should be measured in any female in whom pregnancy is a possibility. In addition, a serum
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.
The blood test called
CA-125 is useful in differential diagnosis and in follow up of the disease, but it has not been shown to be an effective method to screen for early-stage ovarian cancer and is currently not recommended for this use.
Current research is looking at ways to combine tumor markers along with other indicators of disease (i.e. radiology and/or symptoms) to improve accuracy. The challenge in such an approach is that the very low population prevalence of ovarian cancer means that even testing with very high sensitivity and specificity will still lead to unacceptable numbers of false positive results (i.e. performing surgical procedures in which cancer is not found intra-operatively). This is exemplified by the recent discovery of
proteomic predictors that showed 100% sensitivity and 95% specificity.
[8]
A pelvic examination, including CT scan, trans-vaginal ultrasound, is also of utility. 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 exam 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.
Staging
Ovarian cancer staging is by the
FIGO staging system and uses information obtained after surgery, which can include a total abdominal
hysterectomy, removal of (usually) both ovaries and fallopian tubes, (usually) the
omentum, and pelvic (peritoneal) washings for
cytology. The
AJCC stage is the same as the FIGO stage.
★ Stage I - limited to one or both ovaries
★
★ IA - involves one ovary;
capsule intact; no tumor on ovarian surface; no malignant cells in
ascites or peritoneal washings
★
★ IB - involves both ovaries; capsule intact; no tumor on ovarian surface; negative washings
★
★ IC - tumor limited to ovaries with any of the following: capsule ruptured, tumor on ovarian surface, positive washings
★ Stage II - pelvic extension or implants
★
★ IIA - extension or implants onto uterus or fallopian tube; negative washings
★
★ IIB - extension or implants onto other pelvic structures; negative washings
★
★ IIC - pelvic extension or implants with positive peritoneal washings
★ Stage III - microscopic peritoneal implants outside of the pelvis; or limited to the pelvis with extension to the small bowel or omentum
★
★ IIIA - microscopic peritoneal metastases beyond pelvis
★
★ IIIB - macroscopic peritoneal metastases beyond pelvis less than 2 cm in size
★
★ IIIC - peritoneal metastases beyond pelvis > 2 cm or lymph node metastases
★ Stage IV - distant metastases--in the liver, or outside the peritoneal cavity
Para-aortic lymph node metastases are considered regional lymph nodes (Stage IIIC).
Treatment
Surgery is the preferred treatment and is frequently necessary for diagnosis via
histology. Studies have shown that surgery performed by a specialist in
gynecologic oncology usually result in an improved outlook. 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 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 disease as much tumor as possible is removed (debulking surgery). In cases where this type of surgery is successful, the prognosis is improved compared to patients where large tumor masses (more than 1 cm in diameter) are left behind.
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. At present many oncologists are still recommending intravenous chemotherapy including a platinum drug with a
taxane as a preferred method of treating advanced ovarian cancer.
Three recent randomized studies
clinical trials have suggested that chemotherapy regimens delivered partly via direct infusion into the abdominal cavity (intraperitoneal or "IP") improve median survival time over regimens that are only given intravenously (in the vein or "IV"). Reported toxicities are generally higher and the advantages of IP chemotherapy are still debated among specialists.
Radiation therapy is not effective for advanced stages because when vital organs are in the radiation field, a high dose cannot be safely delivered.
Prognosis
Ovarian cancer has a poor
prognosis. It is disproportionately deadly because symptoms are vague and non-specific, hence diagnosis is late. More than 60% of patients presenting with this cancer already have stage III or stage IV cancer, when it has already spread beyond the ovaries.
Ovarian cancers that are
malignant shed cells into the naturally occurring fluid within the abdominal cavity. These cells can implant on other abdominal (peritoneal) structures included the
uterus,
urinary bladder,
bowel, lining of the bowel wall (
omentum) and can even spread to the
lungs. These cells can begin forming new tumor growths before cancer is even suspected.
More than 50% of women with ovarian cancer are diagnosed in the advanced stages of the disease because no cost-effective screening test for ovarian cancer exists. The
five year survival rate for all stages is only 35% to 38%. If, however, diagnosis is made early in the disease, five-year survival rates can reach 90% to 98%.
Germ cell tumors of the ovary have a much better prognosis than other ovarian cancers, in part because they tend to grow rapidly to a very large size, hence they are detected sooner.
Complications
★ spread of the cancer to other organs
★ progressive function loss of various organs
★ ascites (fluid in the abdomen)
★ Intestinal obstruction
References
1. The Merck Manual of Diagnosis and Therapy Section 18. Gynecology And Obstetrics Chapter 241. Gynecologic Neoplasms
2. Ovulation induction and cancer risk, Brinton LA, Moghissi KS, Scoccia B, Westhoff CL, Lamb EJ, , , Fertil. Steril., 2005
3. BBC News Milk link to ovarian cancer risk 29 November 2004
4. Alcohol consumption and cancer risk
5. Frequency of symptoms of ovarian cancer in women presenting to primary care clinics, Goff BA, Mandel LS, Melancon CH, Muntz HG, , , JAMA, 2004
6. Development of an ovarian cancer symptom index: possibilities for earlier detection, Goff BA, Mandel LS, Drescher CW, ''et al'', , , Cancer, 2007
7. Ovarian Cancer Symptoms Consensus Statement
8. Use of proteomic patterns in serum to identify ovarian cancer, Petricoin EF, Ardekani AM, Hitt BA, ''et al'', , , Lancet, 2002
See also
★
List of notable women who have battled ovarian cancer
★
Germ cell tumor
★
Desmoplastic small round cell tumor
★
Ovarian cyst
External links
★
"How to tell if an Ovarian Mass is Malignant?"
★ Schrecengost A. "Ovarian mass--benign or malignant?" AORN J. 2002 Nov;76(5):792-802, 805-6; quiz 807-10. PMID 12463079
Article
★
Information about ovarian cancer,treatment and cure
★
Ovarian cancer forum - a fellowship among survivors, caregivers, supporters to promote OVCA awareness and fund for research
★
Historical account of 24-year-old girl's battle with ovarian cancer
★
'Ovarian Cancer Action' site, which funds awareness and research into early detection
★
'Ovarian Cancer Institute', a research-based organization dedicated to finding an early detection test for ovarian cancer
★
Wyllie O Hagan site for artists who use their work to raise international awareness of ovarian cancer missions
★
The Johns Hopkins Ovarian Cancer Web Site
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The Ovarian Cancer National Alliance, a National organization uniting ovarian cancer activists, advocates and health care professionals working towards increasing public and professional understanding of ovarian cancer
★
US National Institutes of Health - High quality, peer-reviewed medical information. The source of the PDQs, a must read for all cancer patients interested in technical literature
★
★
★
Ovarian mailing list - A very active and helpful mailing list for 1200+ ovarian cancer patients
★
'Ovarian Cancer Canada'
★
MOCA - 'Minnesota Ovarian Cancer Alliance'
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Ovarian Cancer blog by a woman with Stage 3c ovarian cancer
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NOCA - 'National Ovarian Cancer Association (Canada)'
★
'Canadian Cancer Society'
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'Ovacome' - ovarian cancer support and information network (UK)
★
'Ovarian Register' - UK register of families affected by ovarian cancer (Cambridge, UK)
★
'The Ovarian Cancer Research Fund'
★
Diary of a woman's fight against ovarian cancer including links to many helpful resources
★
'Teal Talk' - online ovarian cancer community providing a message board and chat room for sharing information, inspiration, and support
★
'Chicago Ovarian Cancer Alliance' - a Chicago-based resource and advocacy group
★
'Memorial Sloan-Kettering Cancer Center'
★
'MedHelp Ovarian Cancer Forum' - an online health forum where questions are fielded by Mass General Hospital and other members
★
'The Official Patient's Sourcebook on Ovarian Germ Cell Tumors'
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