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)
