HOUSTONA multimodal strategy for screening asymptomatic
postmenopausal women for ovarian cancer shows promise of being able
to find the disease early and improve survival. Researchers for the
Ovarian Cancer Screening Project (OCSP) at St. Bartholomews
Hospital, London, are testing a strategy combining the tumor marker
CA 125 with transvaginal ultrasound and a mathematical instrument
called the Risk for Ovarian Cancer Algorithm (ROCA).
Speaking at an ovarian cancer conference sponsored by M.D. Anderson
and Memorial Sloan-Kettering, Ian Jacobs, MD, a gynecologic
oncologist at St. Bartholomews and an OCSP collaborator, said
that the studies have produced compelling evidence in support of this
Our results to date demonstrate that this multimodal strategy
is not only feasible and cost-effective but also highly specific and
sensitive, with a positive predictive value of over 20%, he
Ovarian cancer occurs predominantly in postmenopausal women. It
presents at a late stage, and fewer than 30% of its victims survive
for 5 years. If the disease can be detected early, in stage I, it is
possible that overall survival will be dramatically increased. Dr.
Jacobs feels these factors present a convincing argument for more
aggressive screening research.
The inaccessibility of the ovaries and the absence of a confirmed
premalignant condition have complicated attempts to develop
preclinical screening strategies for ovarian cancer. However, recent
advances in tumor marker interpretation and ultrasound technology
have made such screening viable, he said.
CA 125 elevation can be detected several years before women
present with clinical signs of ovarian cancer, Dr. Jacobs said.
Transvaginal ultrasound is an effective follow-up to CA 125,
and the ROCA enhances the clinicians ability to interpret CA
In phase I of the OCSP study, 22,000 postmenopausal women underwent
initial prevalence screening involving CA 125, ultrasound if the CA
125 level was 30 U/mL or higher, and surgery if the ultrasound scan
showed an abnormality. The results showed sensitivity of 79% at
1-year follow-up, specificity of 99.9%, and positive predictive value
of 27%. CA 125 was not elevated in the preclinical phase of
nonovarian malignancy but was a powerful indicator of relative risk
for ovarian cancer (RR = 36 for CA 125 greater than 30 U/mL).
In the second phase of the study, the same 22,000 women were
randomized to receive no further screening or annual screening for 3
years. The 16 women who continued screening and developed ovarian
cancer had a median survival of 72.9 months, compared with 41.8
months for the 20 women in the control group who developed ovarian
cancer (P = .011).
Among women who developed ovarian cancer, we noted a
significant difference in duration of survival between the women who
continued to be screened for 3 years and those who discontinued
screening, Dr. Jacobs said. There was an 85.5% rate of
compliance with follow-up screening, which we consider satisfactory.
And the positive predictive value was high at 21%.
In the third phase of the study, ROCA was used to interpret serial CA
125 levels. Retrospective analysis with ROCA suggested that
mathematical-based interpretation of the presence of this tumor
marker could increase the sensitivity of screening to greater than
85% at 1-year follow-up, Dr. Jacobs said.
Phase IV of the research program is a randomized controlled trial of
120,000 women using the ROCA to interpret CA 125 levels as a primary
test and ultrasound as a secondary test. Recruitment is continuing,
but preliminary results reveal a specificity of 99.9% and positive
predictive value of 25%, he said.
Although some issues must be addressed before widespread ovarian
cancer screening can be advocated, Dr. Jacobs feels this clinical
series presents encouraging evidence for the positive effect of
screening on survival for women with ovarian cancer. Our data
justify further investigation to provide definitive information about
the impact of multimodal ovarian cancer screening on survival and on
the health economic and psychosocial implications of screening in