Thoracic Imaging 2003 - Society of Thoracic Radiology

Principles and ethics of lung cancer screening
Caroline Chiles, M.D.
Objectives
The participant will understand the biases of cancer screening
(length-time bias, lead time bias, and overdiagnosis), and
the necessary elements of informed consent for cancer screening
programs.
Introduction
Screening is the application of a test to detect a disease or
condition in an individual who has no known signs or symptoms
of that disease or condition. The goal of imaging studies for
cancer screening is the early detection of disease at a point
when treatment is more effective. The assumption is that early
detection (the preclinical phase of disease, prior to the onset of
clinical manifestations of the disease) will lead to a more favorable
outcome. In lung cancer, the improved survival in Stage I
disease as a result of surgical resection fuels the effort towards
finding an effective screening test.
Lung cancer meets many of the criteria required for screening
programs to be effective. It is a disease that affects a large
number of people, and which has serious consequences
(150,000 lung cancer deaths in the US in 2002). It is possible to
choose a population at increased risk (smokers, former smokers)
in whom a preclinical phase of the disease is detectable (the
asymptomatic patient with a solitary pulmonary nodule).
Screening tests can detect lung cancer not only prior to its clinical
presentation, but prior to a critical point – metastatic disease.
Both CXRs and CTs are widely available, “affordable” examinations
with little morbidity. Most importantly, an individual
with an early stage lung cancer may have surgically respectable
disease, and the potential for cure.
Principles of cancer screening
The preclinical
phase of lung cancer can be divided into two parts: (1) the interval
from the onset of disease, before the disease is detectable to
the time at which the disease becomes detectable by the screening
test, and the interval from the time at which the disease is
detectable by the screening test to the onset of signs and symptoms.
This is most clearly shown by use of time lines, which are
adapted from Black and Welch, AJR 1997; 168: 3-11. The lead
time is defined as the interval between the diagnosis of a disease
at screening and the time it would have otherwise been detected
due to the appearance of clinical signs and symptoms. The
amount of lead time that can be gained by a screening test is a
function of the time from disease detectability to the onset of
symptoms and the frequency of testing.
Figure1
The lead time bias describes the comparison between the
survival time in patients who are not screened and those who
are. Even if intervention in the course of disease has no effect,
the individual who has screening-detected cancer can appear to
have a longer survival than the individual who has a diagnosis
made on the basis of clinical presentation, as survival is measured
from the date of diagnosis, rather than from the true onset
of disease. The rate of progression of screening-detected lung
cancers cannot be known at this time and therefore it is impossible
to accurately adjust survival times to account for lead time.
Figure2
Length bias describes the tendency of screening to detect
slowly growing cancers, rather than rapidly progressing ones.
As can be seen by looking at the timeline in Figure 1, if the
detectable phase of disease is long, there is a greater likelihood
that a screening test will be performed and the disease will be
detected. More rapidly growing tumors have a shorter detectable
preclinical phase and are less likely to be detected by a screening
examination prior to the onset of symptoms. Therefore, lung
cancer screening programs are more likely to detect slowly
growing lung cancers.
Overdiagnosis bias has been become a widely appreciated
phenomenon as a result of prostate cancer screening using PSA.
Overdiagnosis relates to the number of cases that would not
have caused the death of the patient even without screening. The
survival in these patients may be erroneously attributed to early
detection and treatment.
The biases inherent in screening can be reduced with a randomized
controlled trial in which effectiveness is measured by
disease-specific mortality --- comparing the number of deaths
from lung cancer in a screened population to the number of
deaths from lung cancer in an unscreened population.
Ethics of lung cancer screening
The ethics of lung cancer screening can be considered from
two perspectives: screening as part of a research study evaluating
lung cancer screening and screening within a clinical environment.
Research involving human subjects is governed by the
Declaration of Helsinki, first adopted by the World Medical
Association in 1964, and most recently revised in 2002.
(http://www.wma.net/e/policy/17-c_e.html) The Declaration
contains 32 ethical principles for medical research. A basic
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