open access: Cancer screening in the United States, 2012 - Smith - 2012 - CA: A Cancer Journal for Clinicians - Wiley Online Library

Cancer screening in the United States, 2012 CA: A Cancer Journal for Clinicians


section related to ovarian cancer:

Testing For Early Ovarian Cancer Detection

Although the annual incidence of ovarian cancer is low compared with breast cancer and precursor lesions of the cervix, it is the most lethal of the gynecologic cancers.21 Fewer than one-half of women diagnosed with ovarian cancer survive longer than 5 years, and although the 5-year survival rate for patients with localized ovarian cancer is greater than 90%, only 15% of all patients are diagnosed with localized disease.5

Screening and diagnostic methods for ovarian cancer include pelvic examination, CA 125 antigen as a tumor marker, transvaginal ultrasound (TVU), and, potentially, multimarker panels and bioinformatic analysis of proteomic patterns. The sensitivity and specificity of pelvic examination for the detection of symptomatic ovarian cancer are not well established, but are poor and do not support physical examination as a screening method. CA 125 has limited sensitivity and specificity (ie, while CA 125 levels are increased in many women with ovarian cancer, only approximately one-half of early ovarian cancers produce enough CA 125 to cause a positive test, and noncancerous diseases of the ovaries and other cancers, as well as other noncancerous influences, also can increase the blood levels of CA 125).45-47  TVU is capable of detecting small ovarian masses and may distinguish some benign masses from some malignant adnexal masses, although it still only poorly predicts which masses are cancers and which are due to benign diseases of the ovary. As an independent test, ultrasound has shown poor performance in the detection of ovarian cancer in women at average or high risk.48 There have been research and attempts to develop a blood test for ovarian cancer based on measuring genes, proteins, or multiple marker assays that may be present in higher or lower amounts in women with ovarian cancer compared with women who do not have ovarian cancer. This is a relatively new area of investigation that is accumulating promising results, but still requires prospective studies for validation.49 Thus, at this time, the lack of supporting evidence indicating that any one or a combination of these strategies is efficacious has prevented recommendations for ovarian cancer screening, although several prospective randomized trials have been underway.

Two large, prospective, randomized trials, one in the United States and the other in the United Kingdom, have been studying screening average-risk women with a combination of CA 125 and TVU. The US trial, the Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening trial,50 reported results in 2011.51 In the PLCO trial, 78,216 women ages 55 to 74 years were randomized to a group that was offered 6 annual rounds of screening with CA 125, and TVU for 4 years (n = 39,105) or a group that received usual care (n = 39,111). Participants were followed for a maximum of 13 years, with mortality from ovarian cancer as the main study outcome. At the conclusion of the study, the number of deaths from ovarian cancer was similar in each group (ie, there were 3.1 ovarian cancer deaths per 10,000 women-years in the group invited to screening vs 2.6 deaths per 10,000 women-years in the control group [relative risk, 1.18; 95% confidence interval, 0.82-1.71]). The authors concluded that simultaneous screening with CA 125 and TVU was not associated with a reduction in ovarian cancer mortality compared with usual care.51 However, the authors also noted that the absence of a stage shift in the group invited to screening compared with the control group suggests that the screening protocol in the PLCO study may not have been sensitive enough to diagnose ovarian cancer sufficiently early to alter its natural history. Nonetheless, for each of the 2 tests under evaluation, lower cutoff values would result in higher false-positive rates. An alternative approach, which is currently under evaluation in the UK Collaborative Trial of Ovarian Cancer Screening, is assessing the efficacy of multimodal screening including annual CA 125 screening with a risk of ovarian cancer algorithm and TVU as a second-line test versus annual screening with TVU only.52 The risk of ovarian cancer algorithm measures changes in CA 125 over time rather than with a single cutoff point, and is believed to improve sensitivity for smaller tumors without measurably increasing the false-positive rate.

While no organization recommends screening average-risk women for ovarian cancer, in 1994, a National Institutes of Health Consensus Panel concluded that women with 2 or more first-degree relatives diagnosed with ovarian cancer should be offered counseling about their ovarian cancer risk by a gynecologic oncologist (or another specialist qualified to evaluate family history and discuss hereditary cancer risks) since these women have a 3% chance of being positive for an ovarian cancer hereditary syndrome.53 The panel further advised that women with a known hereditary ovarian cancer syndrome, such as mutations on BRCA1 and BRCA2 (including breast-ovarian cancer syndrome, site-specific ovarian cancer syndrome, and (Lynch Syndrome) HNPCC), should receive annual rectovaginal pelvic examinations, CA 125 determinations, and TVU until childbearing is completed or at least until age 35 years, at which time prophylactic bilateral oophorectomy is recommended. Although women with these hereditary syndromes are estimated to represent only 0.05% of the female population, they have a 40% estimated lifetime risk of ovarian cancer." (Blogger's Note: the 40% would depend on which mutation)