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After tracking smokers for 20 years, a large study indicates that
screening for lung cancer with chest X-rays does not save lives. The
new report reinforces original conclusions from the Mayo Lung
Project, published in the mid-1980s, that X-rays at frequent
intervals do not decrease the death rate from lung cancer. The
analysis also points to a potential problem for any type of lung
imaging: the detection of tumors that are not life threatening.
The study by Pamela Marcus, Ph.D., and colleagues from the
National Cancer Institute (NCI), Bethesda, Md., and the Mayo Clinic,
Rochester, Minn., appears in the Aug. 16, 2000, issue of the Journal
of the National Cancer Institute.
In their analysis, Marcus and colleagues present compelling
evidence that a substantial number of tumors uncovered between 1971
and 1983 in the 9,211 participating men turned out never to cause
serious illness or death. In the absence of screening, these tumors
would not have been found. Such over-diagnosis can lead to
unnecessary worry or, more seriously, to expensive and risky
biopsies or surgery.
Marcus' findings arrive in the middle of a debate over a newer
screening technology, spiral computed tomography (CT) scans, and
could slow enthusiasm for the scans until they are properly studied,
she said.
"A significant reduction in death rates is the gold standard for
any cancer screening test. Our follow-up of the Mayo Lung Project
shows that an intense regimen of chest X-rays in the 1970s and 1980s
did not meet this standard. Likewise, until spiral CT scans are
proven to save lives, they should not be recommended as a cancer
screening test. The benefits of any screening test must outweigh the
harm."
The Mayo Lung Project
In the Mayo Lung Project, men were split into two groups: half
received free chest X-rays and sputum tests three times yearly for
six years; half received the Mayo's standard 1970 recommendation to
receive the same tests annually. At the end of 1996, with an average
follow-up of more than 20 years, the number of deaths from lung
cancer was statistically identical for each group: 337 men in the
screening arm had died from the disease, compared with 303 in the
so-called "usual care" arm.
If effective, the screening would have significantly reduced the
number of deaths in the screening arm. Instead, the mortality rates
were indistinguishable (4.4 per 1,000 person-years in the screening
arm vs. 3.9 in the usual care arm -- not statistically significant).
After publication in 1986, the Mayo Lung Project generated
controversy among the medical community. Some researchers argued
that the study did not include enough volunteers to detect a small
benefit for X-ray screening. As designed with the knowledge and
resources available, the study had the statistical power to detect a
50 percent or larger reduction in mortality.
Though such a large decrease was not seen, the possibility of
X-ray screening achieving a smaller benefit -- perhaps a 10 percent
to 20 percent reduction in death rates -- still lingers. A much
larger NCI-funded study, the Prostate, Lung, Colon, and Ovarian (PLCO)
Cancer Screening Trial, is expected to answer this question by 2015.
(Unlike the Mayo Lung Project, PLCO includes women.)
Participant Follow-Up
But another criticism of the Mayo Lung Project remained after
publication in 1986: it did not track participants long enough to
show a true benefit. Some lung tumors grow slowly, and the short
follow-up time after screening (three years, on average) may have
been inadequate to see a true mortality reduction, asserted the
critics.
To test whether they were right, Marcus and her team matched
medical files from the project with death records from the Mayo
Clinic and the National Death Index, housed at the National Center
for Health Statistics. If no death certificate was found for a
participant, the researchers assumed he was still alive. If the
participant was reported dead, the researchers recorded the cause
and date. This process led to the primary finding and to the
conclusion that chest X-rays may lead to over-diagnosis of lung
cancer.
While the men in the screening arm did not experience a mortality
benefit, they did have longer survival times, measured from
diagnosis to death. Intuitively, this sounds like screening worked.
However, according to the authors' analysis, something else
happened: chest X-rays detected tumors that did not lead to death.
"We now have good evidence that lung cancer lesions with limited
clinical relevance exist," said Marcus. "These lesions would never
be diagnosed in the absence of screening, and would not cause death.
The Mayo Lung Project picked them up with chest X-rays. Spiral CT is
much more sensitive and will probably pick up even more of them."
She added that high mortality rates, as seen with lung cancer, do
not imply that all lung cancers are lethal. They simply imply that
clinically diagnosed cancers are lethal.
Other cancers -- prostate and breast, for instance -- also appear
in forms (prostate intraepithelial neoplasia and ductal carcinoma in
situ of the breast) that only sometimes progress to full-blown
cancer. These conditions, virtually unknown before the advent of
widespread screening, account for a substantial portion of all
diagnosed prostate and breast tumors. How -- or if -- to treat them
remains an open question.
Consequences of Over-Diagnosis
Consequences of over-diagnosis of lung cancer include
psychological stress and unnecessary biopsies or surgery. Biopsies
are potentially risky procedures that remove a small amount of
tissue, either through a scope fed down the windpipe (bronchoscopy)
or with a needle through the rib cage (CT-directed needle biopsy).
Possible complications from biopsies include bleeding, infection,
and pain and discomfort. Depending on the size and location of the
lesion, chest surgery (thoracotomy) to obtain a larger biopsy may be
recommended. Thoracotomies are major surgical procedures that remove
substantial amounts of tissue; the procedure can damage nerves in
the chest and may lead to chronic pain.
Lung cancer will be diagnosed in an estimated 164,100 people and
claim 156,900 lives in the United States this year.
This research was supported by funds from NCI's Division of
Cancer Prevention. Co-authors include Richard M. Fagerstrom, Ph.D.,
and Philip C. Prorok, Ph.D., from NCI; and Erik J. Bergstralh, M.S.,
William F. Taylor, Ph.D., David E. Williams, M.D., and Robert
Fontana, M.D., from the Mayo Clinic.
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