Prevention and Early Detection of Ovarian Cancer: Mission Impossible?

Bast, Robert C.; Brewer, Molly; Zou, Changping; Hernandez, M.; Daley, Mary; Ozols, Robert F.; Lu, Karen H.; Lü, Zhen; Badgwell, Donna; Mills, Gordon B.; Skates, Steven J.; Zhang, Zhen; Chan, Dan; Lokshin, Anna; Yu, Yinhua

doi:10.1007/978-3-540-37696-5_9

Cited by 95 publications

(61 citation statements)

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“…A two-line screening procedure has been suggested in which candidates with high CA125 undergo follow-up transvaginal ultrasonography. 6 Unfortunately, this combination still has only a limited sensitivity because of the low sensitivity of the initial CA125 test.7 Even when high-risk women are screened, the test does not provide considerable advantages 8 ; it does not detect tumors early enough to influence outcomes.9 As a result, low sensitivity and a high rate of false-negative results of the CA125 test reduce access to transvaginal ultrasonography; on the other hand, the low sensitivity of transvaginal ultrasonography for early cancer suggests that the effect on prognosis would be negligible. …”

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Differential Methylation Profile of Ovarian Cancer in Tissues and Plasma

Melnikov

Scholtens

Godwin

et al. 2009

The Journal of Molecular Diagnostics

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An accurate biomarker for detection of ovarian cancer may reduce cancer-related mortality. Using a previously developed microarray-based technique, we evaluated differences in DNA methylation profiles in a panel of 56 genes using sections of serous papillary adenocarcinomas and uninvolved ovaries (n ‫؍‬ 30) from women in a high-risk group. Methylation profiles were also generated for circulating DNA from blood of patients (n ‫؍‬ 33) and healthy controls (n ‫؍‬ 33). Using the most differentially methylated genes for naïve Bayesian analysis, we identified ten of these profiles as potentially informative in tissues. Various combinations of these genes produced 69% sensitivity and 70% specificity for cancer detection as estimated under a stratified , fivefold cross-validation protocol. In plasma , five genes were identified as informative; their combination had 85% sensitivity and 61% specificity for cancer detection. These results suggest that differential methylation profiling in heterogeneous samples has the potential to identify components of a composite biomarker that may detect ovarian cancer in blood with significant accuracy. Despite its relatively low prevalence, 1 ovarian cancer is the most frequent cause of death from gynecological malignancies. At early stages, women are mostly asymptomatic or present with vague and non-specific symptoms, so early ovarian cancer is difficult to diagnose. Considering that patients diagnosed with stage I ovarian cancer have a 5-year survival rate over 90%, early detection of ovarian cancer may reduce cancer-related mortality.It has been suggested that a screening test for ovarian cancer should have a positive predictive value of 10% or more; such that 10 women would undergo exploratory surgery to diagnose one cancer.2 The low prevalence of ovarian cancer requires that a screening test has a sensitivity of at least 75% and a specificity of at least 99.6%. 2The screening test should also be simple, inexpensive, and produce only minimal discomfort for the patient. Such a test has yet to emerge.The most widely used procedure for ovarian cancer detection and monitoring is a blood-based test for cancer antigen 125 (CA125).3,4 Its specificity for early-stage disease is high (96% to 100%), but the sensitivity is low, 5 so the test must be combined with other diagnostic techniques. A two-line screening procedure has been suggested in which candidates with high CA125 undergo follow-up transvaginal ultrasonography. 6 Unfortunately, this combination still has only a limited sensitivity because of the low sensitivity of the initial CA125 test.7 Even when high-risk women are screened, the test does not provide considerable advantages 8 ; it does not detect tumors early enough to influence outcomes.9 As a result, low sensitivity and a high rate of false-negative results of the CA125 test reduce access to transvaginal ultrasonography; on the other hand, the low sensitivity of transvaginal ultrasonography for early cancer suggests that the effect on prognosis would be negligible. 9To impro...

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Differential Methylation Profile of Ovarian Cancer in Tissues and Plasma

Melnikov

Scholtens

Godwin

et al. 2009

The Journal of Molecular Diagnostics

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“…Although certain ovarian cancer screening tests have been shown to decrease mortality rates, the possibility of efficient screening that may be used in everyday practice remains elusive. Measurement of serum CA125 antigen remains the gold standard (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18).…”

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HE4 protein and SMRP: Potential novel biomarkers in ovarian cancer detection

et al. 2012

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“…Greater than 30 serum markers have been evaluated alone and in combination with CA 125. 3 Proteomic technology is advancing and promises to improve screening results. 1 Now that serous TIC has been identified as the potential ''precursor'' of the most lethal ovarian cancers, researchers will have the challenge to identify a very specific tumor biomarker that can detect the cancer in its preclinical phase.…”

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Early detection of ovarian cancer

Bell

2011

Cancer

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For years, Dr. Goff and colleagues have carried the banner for getting physicians to recognize that early stage ovarian cancer causes symptoms for months before diagnosis. For this they deserve accolades from gynecologists and primary care physicians, and appreciation from all the women we serve.In this issue of Cancer, Goff et al report the results from a survey that was mailed to 3200 primary care physicians (gynecologists, family physicians, and internists). 1 The respondents declared which tests they would order to evaluate patients who presented with various symptoms. The outcome measure was the proportion of physicians ordering the tests that would detect ovarian cancer: ultrasound, pelvic computed tomography (CT), and cancer antigen 125 (CA 125). The data essentially demonstrate that these physician groups have gotten the message: ''Do not forget that early ovarian cancer causes symptoms.'' This is a remarkable change in dogma. Before this knowledge, how many times had we explained to our patients with advanced ovarian cancer that we could not have made the diagnosis earlier; that the cancer already had metastasized by the time the patient had reported abdominal distension, bloating, and early satiety?Some remarkable data emerge from this study. Nearly 90% of physicians reported that they would recommend at least 1 of the appropriate diagnostic tests; 71% chose an ultrasound, which, in my opinion, is the test most likely to indicate the risk of malignancy. This high rate of appropriate clinical management reflects positively on the efforts of Dr. Goff and others who have published on the symptoms of early stage ovarian cancer. Developing an educational process to improve this outcome would be very difficult.Another encouraging finding was that gynecologists were more likely than other primary care groups to order the appropriate tests. The authors adequately explain that this is because of the core education of gynecology, which includes ovarian malignancies. Nevertheless, the appropriate response rates for family physicians and internists still were outstanding: 88% for both.Less impressive findings of this study are the statistically significant but clinically insignificant outcomes. The large number of respondents enabled small differences to be statistically significant. The ''adjusted'' risk ratios of 1.07 (urologic [GU] vs gastrointestinal [GI] symptoms), 1.06 (group practice vs solo practitioner), and 1.04 (clinical teaching, yes or no) were all statistically significant, but a 4% to 7% relative difference in these variables does not seem to have much practical clinical value. For example, both GI symptoms and GU symptoms triggered excellent responses for ordering appropriate tests, 86% and 92%, respectively, a statistically significant difference. In my opinion, this 6% difference is relatively minor and should not overshadow the positive tribute that the vast majority of physicians would make the diagnosis of ovarian cancer in women presenting with either GI or GU symptoms.Dr. Goff and colleagues...

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Prevention and Early Detection of Ovarian Cancer: Mission Impossible?

Cited by 95 publications

References 50 publications

Differential Methylation Profile of Ovarian Cancer in Tissues and Plasma

Differential Methylation Profile of Ovarian Cancer in Tissues and Plasma

HE4 protein and SMRP: Potential novel biomarkers in ovarian cancer detection

Early detection of ovarian cancer

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