Early Detection Of Ovarian Cancer

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CME/CE: Women’s Health

Ovarian cancer is the fifth leading cause of cancer death among U.S. women, accounting for 3% of all cancers in women.1 While it is not ubiquitous in the United States, ovarian cancer nonetheless earns its title as the deadliest cancer of the female reproductive system.1 In 2011, about 22,000 U.S. women were diagnosed with cancer of the ovary, and more than 15,000 women died as a result of it.2 It has been aptly described as a low-prevalence, high-consequence disease.3

Ovarian cancer screening in average-risk women is not recommended by any medical organization.4 In addition to a lack of an effective screening method, ovarian cancer’s vague clinical presentation makes it a challenging disease that eludes early detection.5 Women with ovarian cancer generally develop symptoms that are not specific to the gynecologic system – most often gastrointestinal, abdominal and urinary symptoms resembling common conditions such as gastritis, irritable bowel syndrome (IBS) and urinary tract infections.6

Due to this delay in diagnosis, 75% of ovarian cancers are diagnosed at a late stage (stage III or IV), at which time prognosis and survival rates are worse.7 If diagnosed early, when the cancer is localized to the ovary (stage I), the 5-year survival rate is close to 90%. If the cancer is diagnosed at later stages, survival decreases to 41% at stage IIIA and only 11% at stage IV.8 Early detection of ovarian cancer depends on a multifaceted coordinated approach that recognizes symptoms early and responds appropriately.

‘It Whispers . So Listen’

Ovarian cancer mistakenly has been called a “silent killer” because of the misconception that it is asymptomatic until late in the disease. Research6,9-11 has consistently shown that ovarian cancer does have symptoms, with only 11% of women with early-stage ovarian cancer and 3% of women with late-stage ovarian cancer reporting no symptoms.6 Ovarian cancer should no longer be labeled as a silent killer but instead as the “whispering disease” whose symptoms providers and patients must listen to carefully.

Clinical Presentation

Women with ovarian cancer frequently experience abdominal, gastrointestinal and urinary symptoms, but gynecologic symptoms are less common.6 Abdominal pain and abdominal distension are among the most commonly reported symptoms.10 Attention should be paid to differentiating between intermittent bloating and persistent bloating, since only persistent bloating has been associated with ovarian malignancy.11

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Studies show that the symptoms of women with ovarian cancer differ from those of women without it. Ovarian cancer symptoms are more likely to be progressive (abdominal pain and bloating),12,13 persistent,14 frequent (20 to 30 times a month),9,15 and severe,9,15 and they are more likely to occur in conjunction with other symptoms.9 Close attention should be paid to such characteristics, because they can help distinguish ovarian cancer from conditions with symptoms that are similar but less frequent (2 to 4 times a month) and severe.9

Although considerable overlap exists in symptoms of early- and late-stage ovarian cancer, certain symptoms are more likely to occur with a given stage. While early-stage ovarian cancer is more likely to have urinary and gynecologic symptoms,9 late-stage ovarian cancer is more often characterized by gastrointestinal and abdominal symptoms.9,16

Because no screening tool is recommended to detect asymptomatic ovarian cancer, some experts propose using symptoms as a way to detect the disease early. Goff and colleagues have developed an ovarian cancer symptom index (OCSI) that looks for patterns in symptom presentation (i.e., occurrence of at least 1 of 6 symptoms for more than 12 months and more than 12 times per month).15 The OCSI has a sensitivity of 56.7% for early-stage disease and 79.5% for advanced stage-disease, with specificity ranging from 86% to 90%.15

Contributors to Late Diagnosis

Research has shown that ovarian cancer symptoms often begin months before ovarian cancer is diagnosed.6,9,14 Given that most women are diagnosed months after their symptoms began, a window of opportunity exists to diagnose ovarian cancer early. Research has focused on patient- and provider-related delays and ovarian cancer awareness among women as contributors to diagnostic delays.

Patient-related delays. Although most women with ovarian cancer experience symptoms, the majority of them do not take their symptoms seriously, attributing them to other factors such as menstrual irregularities, menopause, aging, pregnancy or stress rather than cancer.6,17 In one study, the time until they sought care for their symptoms varied from a few weeks to more than 12 months, but on average they waited 2 to 3 months after symptom onset to seek medical attention.6 These observations demonstrate the need for more patient education about ovarian cancer symptoms.

A study at the Mayo Clinic identified failure to follow up or to complete a screening test as the main factor contributing to patient-related delays.5 Despite having scheduled appointments, some women did not complete screening tests, and healthcare providers failed to follow up with these patients. This demonstrates a need for better patient education about the reasons for ordering tests.

Provider-related delays. Once women seek care for symptoms, the time until ovarian cancer diagnosis can vary from less than 2 months to more than a year.6,18 Many women with ovarian cancer are misdiagnosed initially and treated for another condition.6,18 Among the most common misdiagnoses are IBS, stress, gastritis, depression, constipation and urinary tract infection; a number of women with ovarian cancer are told that nothing is wrong.6 The delay in diagnosis could be attributed to the vague presentation of ovarian cancer symptoms. Providers need to view gastrointestinal symptoms that do not resolve or worsen as potential warning signs of ovarian malignancy.

The Mayo Clinic study identified extended or delayed workup as the main provider-related reason for a delay in diagnosis.5 Some providers failed to follow up promptly with patients after finding a mass during the physical exam or on ultrasound.5 The researchers found that delays of more than 1 month were common between an initial ultrasound or physical exam finding and appropriate follow-up. Some of these delays were related to scheduling; others were a result of providers’ inadequate documentation of the need for follow-up in their notes.5

Ovarian cancer awareness. Lockwood-Rayermann and colleagues surveyed 1,211 women without a history of ovarian cancer. The results showed that 85% of the women were unfamiliar with ovarian cancer symptoms, two-thirds incorrectly identified the Pap test as effective in detecting this cancer, and most (80.6%) have never spoken with their healthcare provider about ovarian cancer symptoms.3 When asked why they had not talked with their provider about the symptoms, the majority of women responded with either “Since my physician didn’t bring it up, I didn’t think it was an issue” or “I did not think I was at risk.”

Earlier Diagnosis Through Education

Ovarian cancer prognoses might be improved by addressing and minimizing the identified gaps in knowledge among women and healthcare providers, but the approach must be multifaceted, targeting many areas within the healthcare system in addition to patient and provider education. Simply educating patients and providers about ovarian cancer is not enough, since this approach does not consider the larger system within which this must be implemented. Other members of the healthcare team, such as nursing and scheduling staff, also could be crucial to promoting changes in the care of patients with ovarian cancer.

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Provider education. Given that a large percentage of women initially see a primary care provider about their symptoms,9 it is important to target educational initiatives at primary care providers. The goal should be to educate practicing and future providers that ovarian cancer is not a silent killer and that it should be included in the differential diagnosis when symptoms warrant.

Healthcare providers must be reminded that the majority of ovarian cancer cases present with gastrointestinal and abdominal symptoms rather than gynecologic ones.6 Educational initiatives also should focus on the differences in the presentations of IBS and ovarian cancer, because many women with ovarian cancer initially are misdiagnosed with IBS.6 IBS is a diagnosis of exclusion that should not be diagnosed routinely in women older than 50 with no history of the condition. Ovarian cancer and other conditions must be ruled out before an IBS diagnosis can be established.

A survey of 1,725 women from 46 states and four Canadian provinces showed that 33% of women with ovarian cancer did not have a pelvic exam during their initial clinic visit.6 Although gastrointestinal tests may be performed initially to rule out more common conditions, a pelvic exam still should be performed in all women who complain of abdominal or pelvic pain to better assess the pain’s origin. Given that the majority of ovarian cancers, regardless of stage, cannot be palpated vaginally or rectally,12 providers should not rely on rectovaginal examination alone to rule out ovarian cancer.

Because of documented inadequate follow-up for ovarian cancer by providers and patients,5 providers must be thorough in their clinical notes and orders, clearly indicating when ovarian cancer is suspected. By documenting this information, they can later follow up with patients who do not complete tests or follow up themselves. Adding a level of urgency to the orders also could limit or avoid scheduling delays. Educating patients about the reasons for ordering certain tests might improve follow-up.

Patient education. Healthcare providers are ideally positioned to educate women about ovarian cancer symptoms and risk factors. A woman’s annual pelvic exam is a good time to address the topic, since it is an appropriate time at which to clarify any misconceptions about the Pap test. Focusing patient education on ovarian cancer symptoms and risk factors might increase awareness among women and prompt them to seek medical attention sooner if they experience symptoms.

Given that some ovarian cancer symptoms are common among women without the disease or with other conditions, patient education should focus on seeking care for symptoms that have not resolved, have worsened or have become more frequent. Identifying these red flags early might allow healthcare providers to see women who are more likely to have ovarian cancer. Because gastrointestinal and abdominal symptoms are the most common ones associated with ovarian cancer, women should pay attention to them. To enhance detection of early-stage ovarian cancer, women also should bring to a provider’s attention any persistent urinary symptoms such as frequency, urgency or incontinence.5

Facilitating Change

Writing about the implementation of clinical guidelines in general to improve the way clinicians practice, Ockene and Zapka stated that “while clinician education is necessary, it is not sufficient; systems must be added to education in order to change clinician behaviors.”19 The goal is to turn acquired knowledge into behavior changes. Ideally, interventions at the policy, organizational and clinical setting levels should be cost-effective and easily implemented.

New diagnostic guidelines are needed. Clinical practice guidelines for the diagnosis of epithelial ovarian cancer from the National Comprehensive Cancer Network20 list the symptoms commonly seen in practice without including important details (e.g., duration, frequency, severity) that could help identify patients who would benefit from an extensive diagnostic workup for ovarian cancer. Given that ovarian cancer is not commonly seen in primary care, guidelines should be modified to help primary care providers navigate through what often is an unfamiliar diagnostic process. (The figure on the previous page is an example of a detailed diagnostic algorithm.21)

Symptom diaries are helpful. An early diagnosis depends not only on women’s ability to recognize symptoms and seek care, but also on their ability to accurately describe their symptoms. A symptom diary can help women track their symptoms and identify any characteristics and patterns,21 and it can enable providers to detect patterns in symptom presentation, too.

Reminder system. Pop-up reminders in electronic health records (EHR) can remind providers to follow up with patients who do not complete tests or do not return to the clinic. In one study, patients’ compliance with osteoporosis medications and follow-up tests improved when primary care providers were reminded about them through an EHR message, compared with when reminders and educational materials were sent directly to patients’ homes.22

The Future of Ovarian Cancer

Although the approach to early diagnosis of ovarian cancer seems straightforward – that is, increase recognition of symptoms – getting to that point involves implementing changes across many areas of healthcare in a coordinated way. Not everyone will see an urgent need for these changes, and other competing and, in many cases, no less urgent demands make this goal even more challenging.

Until an effective screening tool is developed, early detection of ovarian cancer will continue to depend on prompt symptom recognition leading to earlier diagnosis and improved prognosis.

References

1. American Cancer Society. Ovarian Cancer Detailed Guide. http://www.cancer.org/acs/groups/cid/documents/webcontent/003130-pdf.pdf. Updated July 18, 2011. Accessed Nov. 17, 2011.

2. National Cancer Institute, Surveillance Epidemiology and End Results. Cancer of the Ovary: SEER Stat Fact Sheets. http://seer.cancer.gov/statfacts/html/ovary.html. Accessed Nov. 17, 2011.

3. Lockwood-Rayermann S, et al. Women’s awareness of ovarian cancer risks and symptoms. Am J Nurs. 2009;109(9):36-46.

4. U.S. Preventive Services Task Force. Screening for Ovarian Cancer: Recommendation Statement. http://www.uspreventiveservicestaskforce.org/3rduspstf/ovariancan/ovcanrs.htm. Published May 2004. Accessed Nov. 17, 2011.

5. Yawn BP, et al. Ovarian cancer: the neglected diagnosis. Mayo Clin Proc. 2004;79(10):1277-1282.

6. Goff BA, et al. Ovarian carcinoma diagnosis: results of a national ovarian cancer survey. Cancer. 2000;89(10):2068-2075.

7. Chan JK, et al. Do clear cell ovarian carcinomas have poorer prognosis compared to other epithelial cell types? A study of 1411 clear cell ovarian cancers. Gynecol Oncol. 2008;109(3):370-376.

8. Ovary and primary peritoneal carcinoma. In: Edge SB, et al, eds. AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer; 2010:419-428.

9. Goff BA, et al. Frequency of symptoms of ovarian cancer in women presenting to primary care clinics. JAMA. 2004;291(22):2705-2712.

10. Bankhead CR, et al. Symptoms associated with diagnosis of ovarian cancer: a systematic review. BJOG. 2005;112(7):857-865.

11. Bankhead CR, et al. Identifying symptoms of ovarian cancer: a qualitative and quantitative study. BJOG. 2008;115(8):1008-1014.

12. Hamilton W, et al. Risk of ovarian cancer in women with symptoms in primary care: population based case-control study. BMJ. 2009 Aug 25;339:b2998.

13. Devlin SM, et al. Identification of ovarian cancer symptoms in health insurance claims data. J Womens Health (Larchmt). 2010;19(3):381-389.

14. Rossing MA, et al. Predictive value of symptoms for early detection of ovarian cancer. J Natl Cancer Inst. 2010;102(4):222-229.

15. Goff BA, et al. Development of an ovarian cancer symptom index: possibilities for earlier detection. Cancer. 2007; 109(2):221-227.

16. Lurie G, et al. Prediagnostic symptoms of ovarian carcinoma: a case-control study. Gynecol Oncol. 2009;114(2):231-236.

17. Fitch M, et al. Women’s experiences with ovarian cancer: reflections on being diagnosed. Can Oncol Nurs J. 2002;12(3):152-168.

18. Wikborn C, et al. Delay in diagnosis of epithelial ovarian cancer. Int J Gynaecol Obstet. 1996;52(3):263-267.

19. Ockene JK, Zapka JG. Provider education to promote implementation of clinical practice guidelines. Chest. 2000;118(2 suppl):33S-39S.

20. Morgan RJ Jr, et al. NCCN Clinical Practice Guidelines in Oncology: epithelial ovarian cancer. J Natl Compr Canc Netw. 2011;9(1):82-113.

21. Ovarian Cancer National Alliance. Interim guidance for the management of average-risk women with symptoms suggestive of ovarian cancer. http://www.ovariancancer.org/diary/. Accessed Nov. 18, 2011.

22. Feldstein A, et al. Electronic medical record reminder improves osteoporosis management after a fracture: a randomized, controlled trial. J Am Geriatr Soc. 2006;54(3):450-457.

Olga Trouskova is a senior student at the Augsburg College physician assistant program in Minneapolis. Beth Alexander is an associate professor at the program. They have completed disclosure statements and report no relationships related to this article. The ADVANCE for NPs & PAs CME coordinator, John McGinnity, MS, PA-C, discloses receiving honoraria from Boehringer Ingelheim.

Learning Objectives:

1. Review the clinical presentation of ovarian cancer.

2. Summarize the factors that contribute to provider-related delays in ovarian cancer diagnosis.

3. Summarize the factors that contribute to patient-related delays in ovarian cancer diagnosis.

4. Identify patient-focused strategies for early diagnosis of ovarian cancer.

5. Identify provider-focused strategies for early diagnosis of ovarian cancer.

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