Ovarian Cancer

Nurses should know the recommended screening guidelines, symptoms and risk factors.

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Learning Scope #432
1 contact hour
Expires May 3, 2015

You can earn 1 contact hour of continuing education credit in three ways: 1) Grade and certificate are available immediately after taking the online test. 2) Send the answer sheet (or a photocopy) to ADVANCE for Nurses, Learning Scope, 2900 Horizon Dr., King of Prussia, PA 19406. 3) Fax the answer sheet to 610-278-1426. If faxing or mailing, allow 30 days to receive certificate or notice of failure. A certificate of credit will be awarded to participants who achieve a passing grade of 70% or better.

Merion Matters is an approved provider of continuing nursing education by the Pennsylvania State Nurses Association (No. 221-3-O-09), an accredited approver by the American Nurses Credentialing Center's Commission on Accreditation.

Merion Matters is also approved as a provider by the California Board of Registered Nursing (No. 13230) and by the Florida Board of Nursing (No. 3298).

The goal of this continuing education offering is to provide the latest information to nurses about ovarian cancer. After reading this article, you will be able to:

1. Identify the risk factors for developing ovarian cancer.
2. Describe the cluster of symptoms associated with ovarian cancer.
3. Explain the current diagnostic and treatment recommendations for ovarian cancer.

The author has completed a disclosure form and reports no relationships relevant to the content of this article.

Ovarian cancer is the second most common female genital malignancy diagnosed every year, and the eighth most common overall cause of cancer in women in the U.S.1 More than half of all those diagnosed will die, making it the fifth most deadly cancer among women.2 Survival of ovarian cancer is directly related to the stage of disease at diagnosis; however, more than 75% of patients are diagnosed at advanced stages, leading to poor prognosis.3

The current methods available for screening have not demonstrated an improvement in morbidity and mortality because of the high incidence of false-positive results leading to unnecessary procedures.4 This article will focus on risk factors, recommended screening, prevention, symptoms, diagnostic work up and treatment associated with ovarian cancer.

Risk Factors
There are three theories associated with ovarian cancer development. One is that repeated ovulations disrupt the ovarian surface and lead to mutations, which result in cancer. Another theory holds that persistent hormone stimulation or an increased concentration of estrogen causes a direct carcinogenic effect on the ovaries. The third theory is that the ovaries process chemical carcinogens (i.e., talc, benzenes), which lead to a malignancy.5 None of these theories have been proven, but they seem to coincide with known risk factors.

Identified risk factors for ovarian cancer are family history, age greater than 50 years, infertility, endometriosis and hormone replacement therapy. Ovarian cancer risk is decreased in women who have reduced the number of occurring ovulations by pregnancy, use of hormonal contraception, breastfeeding, tubal ligation and/or hysterectomy with bilateral oophorectomy. However, age and genetic predisposition appear to be the strongest predictors for risk.4 Women with strong family histories or known hereditary syndromes are considered high risk and have specific screening and prevention recommendations.6 Currently, no data support routine ovarian screening or prevention in women without known risk factors.

The two most common hereditary syndromes identified are Lynch II syndrome and breast-ovarian cancer syndrome (HBOC) and account for approximately 5-10% cases of ovarian cancer.4 HBOC is due to mutations in the breast cancer (BRCA) 1 and 2 gene. Women who have a known family history of the mutation or personal diagnosis of ovarian cancer should be screened for HBOC.7 Women identified as a BRCA half-carrier should have a discussion with their healthcare provider about having a prophylactic hysterectomy with bilateral salpingo-oophorectomy at ages 35-40, after child-bearing is complete, for risk reduction. For women who do not wish to have a total hysterectomy, National Comprehensive Cancer Network guidelines recommend transvaginal ultrasound and CA-125 tumor marker every six months starting at age 30.8

Lynch II syndrome, also known as hereditary nonpolyposis colorectal cancer syndrome, is linked to approximately 2-4% of all cases. Lynch syndrome is clinically diagnosed using the Amsterdam I or II criteria.8 The Amsterdam I criteria include first-degree relatives with a colorectal cancer diagnosed at age 50 or younger. The Amsterdam II criteria includes any of the Lynch syndrome-associated cancers: colon, endometrial, small bowel, ureter or renal pelvis.9 Management guidelines for women diagnosed with Lynch syndrome include prophylactic hysterectomy and bilateral salpingo-oophorectomy after completion of childbearing.8 There are currently no recommendations for transvaginal ultrasound or CA-125 blood tests.

Peutz-Jeghers syndrome (PJS) is a rare autosomal dominant genetic syndrome that has shown increased risk for development of ovarian cancer as well as other epithelial malignancies. Ovarian cancer screening recommendations for people with PJS should begin by age 18-20 and include pelvic examination and Papanicolaou smear annually.7 Experts also recommend transvaginal ultrasound yearly starting at age 18.8

Patients who have a risk of hereditary ovarian cancer may opt for prophylactic oophorectomy, as recommended. However, even those patients who undergo a prophylactic oophorectomy for family history of ovarian cancer still have a 1-2% chance of developing a histopathologically and clinically similar tumor to primary ovarian cancer.10

Screening in the General Population
There are currently no routine screening recommendations in the general population due to lack of sensitivity or ability to detect early stage disease.3 However, there is ongoing investigation into biomarkers for early detection and include the CA-125 protein antigen, human epididymis protein 4 (HE4) and multiple cytokine marker panels.4 The serum CA-125 glycoprotein antigen has limited specificity and can be elevated in many co-morbidities and fluctuate with the menstrual cycle, ethnicity and smoking status, making it less predictable in the general population. CA-125 also can be falsely elevated in endometriosis, so it is not useful when used alone for diagnosis.5

The HE4 marker has shown improved sensitivity and specificity and is being studied further for its use in detecting cancers. However, there is some evidence HE4 can be falsely elevated in chronic kidney disease.11 Therefore, it is thought linking this test with others in a panel may be more beneficial. The risks associated with routine screening are not benign, and, in fact, they may lead to further unnecessary testing and surgical procedures.4

Symptoms of Ovarian Cancer
Most women diagnosed with ovarian cancer typically present with vague complaints that may easily be ignored by the patient, as well as healthcare providers. This potentially delays diagnosis and allows the cancer to progress to an advanced stage. The early identification of ovarian cancer greatly impacts the treatment outcome and prognosis, so it is important to recognize the symptoms and act upon them. Early-stage ovarian cancer patients have a 90-95% chance for cure compared to 20-30% of late-stage patients living for five years.3

Knowing the anatomy of the pelvic cavity and the organs in close proximity to the ovaries helps determine the most common symptoms of cancer. The organs typically affected by an ovarian tumor are the fallopian tubes, uterus, bladder, large bowel and the peritoneum. Ovarian cancer usually spreads to the peritoneal cavity followed by implantation on the peritoneum and also by way of local invasion to the bowel and/or bladder.12 Women diagnosed with ovarian cancer typically had experienced - and may or may not have reported to their healthcare provider - persistent, frequent and severe abdominal, gastrointestinal and genitourinary symptoms.3

The most common early symptom description from women include vague abdominal bloating and discomfort; others complain of difficulty eating and feeling full quickly.5,13 Late symptoms include abdominal swelling, bloating and pain with or without ascites. If the cancer has metastasized, pleural effusion or bowel obstruction may be present. The National Comprehensive Cancer Network also recommends further work up if patients report symptoms of difficulty eating or feeling full quickly.7

Diagnostic Tests
Medical work up for suspected ovarian cancer includes a transvaginal ultrasound or abdominal/pelvic ultrasound, chest X-ray, CT scan of the abdomen and pelvis or MRI along with complete blood count, chemistry profile and liver function test.7 Because the patient has symptoms prompting further work up, a CA-125 and/or other tumor markers should be obtained. The primary treatment for a suspicious or palpable pelvic mass is a hysterectomy including bilateral salpingo-oophorectomy, omentectomy, appendectomy, pelvic and para-aortic lymph node dissection, followed by pathological staging. Further treatment is based on the pathological stage of ovarian cancer. The diagnosis also can be made by pathological evaluation of a fine needle aspiration, cytoreduction or paracentesis if the patient has bulky disease or is a poor surgical candidate, but it is not preferred.7

Staging for ovarian cancer may follow the Federation of International Gynecologists and Obstetricians (FIGO) or American Joint Committee on Cancer's TNM system. However, the FIGO system is most commonly used.12 Both classifications are based on the extent of the primary tumor, whether there is cancer present in the lymph nodes, and whether it has metastasized to distant sites. The TNM system includes a stage 0, carcinoma in-situ, and the FIGO system does not; otherwise, they are very similar.

The sites most frequently involved in direct tumor extension, and not included as a distant metastatic site, are the uterus, fallopian tubes and peritoneal surface. Distant metastatic sites are extraperitoneal, parenchymal liver, lung, skeletal, supraclavicular and axillary lymph nodes.10 Impairment of lymphatic drainage is thought to lead to the development of ascites in advanced stages.12

The histology and grade of the tumor provide important information regarding prognosis and help guide the treatment recommendations. Women with well-differentiated lesions typically have a much better prognosis than women with poorly differentiated tumors. Epithelial tumors also have less favorable outcomes and account for approximately 80% of patients diagnosed with ovarian cancer.10 The other types of ovarian cancer include germ cell and stromal tumors. These types of tumors are usually benign or low grade. If the patient has advanced disease, the amount of remaining cancer following surgical resection determines prognosis. Therefore, if the patient has been diagnosed with advanced disease but does not have any residual disease following the initial surgical procedure, the prognosis becomes more favorable.10

Treatment Following Primary Surgical Resection
Surgical resection is the primary treatment for ovarian cancer. Further analysis of the mass, surrounding tissues and lymph nodes to determine the pathology, stage and grade of the tumor provides the best prognostic factors. The patient may be able to have a laparoscopic procedure, if the disease is limited, to help improve recovery time.5 If patients are pre-menopausal or wish to bear more children, they should have immediate access to information about fertility options and counselors.

Most patients will go on to receive chemotherapy after surgical resection of primary ovarian cancer. The chemotherapy may be delivered intravenously or intraperitoneal and generally consists of a taxane and carboplatin for three to eight cycles depending on the stage at diagnosis.7 Radiation therapy is seldom used in ovarian cancer because the whole pelvis would need to be treated, leading to significant radiation toxicity. CA-125 does not indicate prognosis when measured before or at the time of diagnosis; however, there is a correlation when measured during treatment and should be checked periodically.12 CT scans of the abdomen, pelvis and chest also are done at the midpoint and end of treatment to assess response.5

Taxanes are common mitotic inhibitors. The class description suggests that the drugs mostly work to prevent cell division in the mitotic (M) phase of the cell cycle, but they also can affect other phases. The most common side effects of taxanes are peripheral neuropathies, bone marrow suppression, hypersensitivity reactions and hepatic impairment.14

Carboplatin is classified as an alkylating agent. The action of an alkylating agent is the substitution of an alkyl group for a hydrogen ion in the cell that results in a single or double strand break in DNA as well as inhibiting the DNA strand from separating during any phase of the cell cycle.15 The general class side effects for carboplatin include bone marrow suppression, nausea and vomiting, neuropathies, ototoxicity, and nephrotoxicity.14 Other symptoms related to the disease and the treatment also should be evaluated periodically and may include fatigue, weakness, constipation, edema and pain.

Monitoring & Follow-Up
Monitoring patients after complete response to ovarian cancer treatment includes follow-up with physical exam, review of any potential or recurrent symptoms and/or side effects from treatment every three to six months for the first five years. CA-125 should be obtained at every follow-up visit. Other lab tests (i.e., CBC and CMP) and imaging (chest X-ray, CT scans, PET, MRI) should be done as clinically indicated. If there is any evidence of recurrence, further work up should be done.7 Patients should be evaluated for rehabilitation needs following treatment as well.

Women diagnosed with ovarian cancer may experience psychological distress related to anxiety, body image disturbances or changes in sexuality. Surgical removal of the ovaries can result in sudden menopausal symptoms leading to depressive symptoms, hot flashes, vaginal dryness and atrophy due to the lack of estrogen. The psychological needs of women should be given priority with opportunities for them to discuss the concerns.5

Unfortunately, over half of all those diagnosed with ovarian cancer will die despite treatment, making open discussion of advanced care planning an important element throughout treatment.2 While it is always difficult to predict a patients overall survival, patients should be encouraged to verbalize their wishes related to quality and quantity of life throughout the treatment and palliation of symptoms. Support for common symptoms relating to advancing disease such as bowel obstruction, ascites and pleural effusions may need to be addressed.5

Healthcare Provider-Patient Relationship
Patients diagnosed with ovarian cancer are generally in the late stage of disease. The symptoms are hard to identify and there are no clear screening guidelines at this time. The American College of Obstetricians and Gynecologists recommends healthcare providers discuss symptoms of ovarian cancer with their female patients so they can be alert to the most common presenting symptoms.1 ACOG also recommends healthcare providers perform annual pelvic exams to screen for adnexal masses.1 No other public agency supports routine screening without reported symptoms or high risk factors. There are several clinical trials under way to improve current standards of detection and treatment.12

Nurses should know the recommended screening guidelines, symptoms and high risk factors associated with ovarian cancer. The quality of the healthcare provider-patient relationship remains a key ingredient in the early diagnosis of ovarian cancer which directly affects survival outcomes, and nurses are in a favorable position to improve patient knowledge and communication. Nurses also can help educate communities and bring awareness of risk factors and symptoms of ovarian cancer and encourage patients not to ignore or attribute persistent symptoms to aging.

References
1. Bernstein R, DeJoseph D, Buchanan EM. When to stop screening: a review of breast, gynecologic, and colorectal cancer screening in women over age 65. Care Manag J. 2010;11(1): 48-57.

2. Siegel R, Naishadham D, Jemel A. Cancer statistics. CA Cancer J Clin. 2012;62(1):10-29.

3. Jayde V, White K, Blomfield P. Symptoms and diagnostic delay in ovarian cancer: a summary of the literature. Contemp Nurse. 2009;34(1):55-65.

4. Carlson KJ. Screening for ovarian cancer. UpToDate. http://www.uptodate.com/contents/screening-for-ovarian-cancer

5. Lanceley A, Fitzgerald D, Jones V, et al. Ovarian cancer: symptoms, treatment and long-term patient management. Primary Health. 2011;21(7):31-38.

6. Greene H. Advanced Oncology Nursing Certification Review and Resource Manual. Philadelphia: Oncology Nursing Society; 2009.

7. National Comprehensive Cancer Network. Ovarian cancer. http://www.nccn.org/professionals/physician_gls/pdf/ovarian.pdf

8. Weissman S, Weiss S, Newlin A. Genetic testing by cancer site: ovary. Cancer J. 2012;18(4): 320-327.

9. Mahon S. Advanced Oncology Nursing Certification Review and Resource Manual. Philadelphia: Oncology Nursing Society; 2009.

10. Edge SB. Cancer Staging Handbook. Chicago: American Joint Committee on Cancer; 2010.

11. Nagy B Jr, Krasznai Z, Balla H, et al. Elevated human epididymis protein 4 concentrations in chronic kidney disease. Ann Clin Biochem. 2012;49(4):377-380.

12. National Cancer Institute. Ovarian epithelial cancer treatment. http://www.cancer.gov/cancertopics/pdq/treatment/ovarianepithelial

13. Karlan BY, Markman MA, Eifel PJ. Cancer: Principles and Practice of Oncology. 7th ed. Philadelphia: Lippincott Williams & Wilkins; 2005.

14. Levine A. Cancer Basics. Pittsburgh: Oncology Nursing Society; 2010.

15. Wilkes GM, Barton-Burke M. Oncology Nursing Drug Handbook. Boston: Jones and Bartlett; 2009.

Ingrid Bowser is an oncology nurse practitioner at Indiana University Health Goshen Center for Cancer Care, in Goshen.




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