|
Minimizing the cost effects of false positives in cancer testing
April 2010
SHARING OPTIONS:
In
recent months, controversy has swirled around the proper
age at which women should have their first mammograms and Pap smears. Yet even
as these
questions dominate the headlines, we ought not lose sight of a larger
issue that affects the lives of every potential cancer patient, male and
female:
the emotional and economical costs associated with false positives in
cancer testing. Given the profusion of tests for different types of cancers,
false positives pose a substantial challenge to healthcare providers who are
dedicated to ensuring the most accurate diagnoses. As we will see,
however,
there are solid grounds for optimism on the horizon. The key to reducing the
incidence of false positives is to increase the specificity of
the detection
method, and there is solid evidence that this is feasible.
The
dictionary defines a "false positive" as a test result
that shows evidence of a disease or abnormal condition, even though the
condition being tested
for is not actually present. To get an idea of the
extent to which false positives pose a problem for cancer testing, consider the
results of a study
reported in Annals of Family Medicine this past
June.1 Over a period of three
years, 68,436 male and female subjects underwent a battery of tests for
prostate, lung, colorectal and ovarian
cancer. After being subjected to 14
tests, the cumulative risk of having at least one false-positive screening was
found to be 60.4 percent for men and
48.8 percent for women. It has also been
reported that in any given 10-year period, half of American women screened
receive a false-positive mammogram;
as many as 90 to 95 percent of women in the
United States who get a positive mammogram do not have breast cancer. Such
stark numbers must be balanced
against the potential benefits of early cancer
screening for those judged to be at high risk—a thriving controversy in its own
right.
The first of several types of cost associated with false
positives in cancer screening is psychological. It is
easy to envision how one
could experience great mental trauma after being informed that one has tested
positive for cancer; this phenomenon is doubly
insidious since a heightened
level of anxiety can negatively impact one's physical health. For example, a
research study published in Urology in
2007 reported that men who receive false-positive
prostate cancer screening
results report more problems with sexual function, despite having negative biopsy
findings.2
A related cost can be triggered by "horror stories" in the
popular media regarding false positives. Tales of
unnecessary surgery can
influence the general public's view of the need for cancer screening. Should
such stories dissuade individuals from coming in
for tests, they risk having a
potentially serious condition go undiagnosed.
A second
major cost connected to false positives is
practical in nature. When hospitals allocate their time and manpower to the
performance of unnecessary
invasive procedures motivated by a spurious test
result, precious resources are taken away from treating those patients with
genuine health issues.
Perhaps even more serious is the risk of complications
that can arise in the wake of such unnecessary biopsy or surgery. For example,
a woman who has
undergone breast cancer surgery must watch for signs of
infection (including redness and swelling of the incision), lymphedema (the
swelling of the arm
or hand on the side of the surgery due to the removal of
the lymph nodes under the arm), seroma (accumulation of fluid in the location
of the surgery)
and other warning signs. All of this worry could be avoided if
it were known in advance that no surgery was needed and none performed.
Perhaps the most well-publicized cost of false positives is
the economic one. Not only will a patient who undergoes an unnecessary
invasive
procedure incur a potentially very large expense for no good reason, but also
the healthcare provider that is performing the procedure must
pay the surgeon
for work done unnecessarily.
False positive mammograms are costly, with more
than $100 million
spent annually in the United States on follow-up testing and
treatment. For a separate example, consider women who make the choice to
undergo surgery
to have their ovaries removed. As is now well-known, pelvic
ultrasound, or sonography, has a hard time distinguishing ovarian cancer from
cysts on the
ovaries, which are almost always benign. These benign cysts are
much more common than ovarian cancer and most of them do not need to be treated
at
all.
According to the authors of a 2005 research study,3,4
we can calculate that if all
American women over the age of 50 (the authors
used 43 million for this number) had a pelvic ultrasound every year, we might expect
2.5 million of them
to have an abnormality detected. Let us envision the most
extreme scenario: 37,000 of these women would be found to have ovarian cancer
that would
otherwise have not been detected so early. But, at least in theory,
the other 2,463,000 women might go on to have unnecessary surgery. Of those
women,
2,500 might be expected to die from the procedure, and 112,500 would
suffer a serious complication. The cost of performing this number of
ultrasounds
would be $11.8 billion per year; the cost of the unnecessary
surgeries would be about $37.5 billion per year. These extraordinary numbers
starkly
illustrate the need for more reliable testing that would justify
surgical intervention.
A related
perspective on the economic costs stems from statistics
linked to the use of the Prostate-Specific Antigen (PSA) test. While the false
positive rate
for this test is 75 percent, the rate of false negatives is
around 30 percent. This means that many men who ought to be receiving treatment
for early
stage prostate cancer are not. When their disease subsequently makes
itself evident at a later stage, the cost of treating them is greater than it
otherwise would have been.
Faced with this challenge, there have been a number of
attempts made to reduce the rate of false positives in cancer screening,
including the creation of unique and highly specific monoclonal antibodies
(Mabs) targeted against several cancers (e.g. ovarian and prostate carcinomas)
that that could potentially identify these diseases in their earliest
stages.
The development of diagnostic tests harnessing this technology could lead to
far earlier and more reliable diagnoses than has ever been
possible, as well as
reduce the incidence of false positives.
A second approach that could help
reduce the incidence of
false positives was reported by a research team at Johns Hopkins University
last year.5 Using tiny crystals called quantum dots, the JHU team
has developed a highly sensitive test to
look for DNA modifications that often
are early warning signs of cancer. The target of their test is a biochemical
change called DNA methylation. When
this change occurs at critical gene
locations, it can halt the release of proteins that suppress tumors. When this
takes place, it is easier for cancer
cells to form and multiply. The team
engineered quantum dots that attract methylated DNA strands. When the dots are
exposed to certain types of light,
they transfer the energy to fluorescent
molecules that emit a glow. This enables researchers to detect and count the
DNA strands linked to cancer.
Nanotechnology is also the key to an approach, pioneered in
2009 at Yale University, for improving the sensitivity of detecting very small
quantities of an antigen in physiological fluids.6
The Yale team
used nanowire sensors to detect and
measure the concentrations of two specific
cancer biomarkers in whole blood—one for prostate cancer and the other for
breast cancer. The researchers
developed a novel device that acts as a filter,
catching the biomarkers (in this case, antigens specific to prostate and breast
cancer) on a chip while
washing away the rest of the blood. Creating a buildup
of the antigens on the chip allows for detection down to extremely small
concentrations, on the
order of picograms per milliliter, with 10 percent
accuracy. This is the equivalent of being able to detect the concentration of a
single grain of salt
dissolved in a large swimming pool.
Another study released last year7
focuses on
detecting the presence of microRNAs in saliva—a method that could aid in the
detection of oral cancer. MicroRNAs are molecules produced in
cells that have
the ability to simultaneously control activity and assess the behavior of
multiple genes. They are a thriving research topic right now,
and researchers believe
they could hold the key to early detection of cancer. The emergence of a
microRNA profile in saliva represents a major step
forward in the early
detection of oral cancer. The team measured microRNA levels in the saliva of 50
patients with oral squamous cell carcinoma and 50
healthy control patients.
They detected approximately 50 microRNAs, two of which were present at
significantly lower levels in patients with oral
cancer than in the healthier
controls.
As we have seen above, there is a variety of promising
leads
on the road toward minimizing the costs—psychological, practical, and
economic—of false positives in cancer testing. And although there are no
guarantees that any specific method (or combination of methods) will eradicate
the problem completely, the widespread awareness of a need to resolve
this
issue, coupled with exciting advances on the frontiers of medical research,
contribute to the expectation of a brighter future.
Dr. Amnon Gonenne is president, CEO and director of
MabCure Inc. Gonenne has more than 20 years experience in the United States
biotechnology field and
has held a number of top executive positions in
regulatory affairs and supervision of international clinical trials. He served
as vice president of
corporate development at BioTechnology General Corp., CEO
of Immunotherapy Inc. and CEO of venture capital fund Elscint Biomedical
Investment in Israel. Gonenne holds
a doctoral degree in biochemistry and
biophysics from Syracuse
University and completed his postdoctoral training at
the University
of California San Diego, School of Medicine.
References:
1. Croswell, JM, et al.
"Cumulative incidence of false-positive results in repeated, multimodal cancer
screening." Ann Fam Med., 2009.
2.
Katz DA, et al.
"Health perceptions in patients who undergo screening and workup for prostate
cancer." Urology, 2007.
3. Parker, WH, et al.
"Ovarian conservation at the time of hysterectomy for benign disease." Obstet
Gynecol, 2005.
4. Parker, WH, et al.
"Are there any good tests for ovarian cancer?" Available at: http://www.ovaryresearch.com/screening.htm.
5. Bailey,
VJ, et al.
"MS-qFRET: a quantum dot-based method for analysis of DNA methylation." Genome
Res. 2009.
6. Stern, E, et al.
"Label-free
biomarker detection from whole blood." Nature
Nanotech. Available at: http://www.nature.com/nnano/journal/vaop/ncurrent/abs/nnano.2009.353.html.
7. Park, NJ, et al.
"Salivary microRNA: discovery, characterization and clinical utility for oral
cancer detection." Clin Cancer Res.
2009. Back |
Home |
FAQs |
Search |
Submit News Release |
Site Map |
About Us |
Advertising |
Resources |
Contact Us |
Terms & Conditions |
Privacy Policy
|