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| Journal of the New Zealand Medical Association,
11-February-2005, Vol 118 No 1209
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Prostate cancer screening: is it possible to explain
diametrically opposed views?
Ann Richardson
Prostate cancer screening is
controversial.1–3 Clearly, the views of
those who support and actively offer prostate cancer screening are very
different from the views of those who see no justification for screening at
present. How can we understand and explain such opposing views?
It is likely that differences of opinion about prostate
cancer screening reflect differences in the way people assess the benefits and
risks of screening. By examining each of these in turn, it is possible to
understand the controversy, but also determine whether prostate screening is
ethical.
BenefitsUnderlying the discrepant views on
screening is the extent to which people assume that screening is beneficial. If
men and their doctors assume that screening
must be beneficial, then irrespective
of the outcome of prostate-specific antigen (PSA) testing, both the man and his
doctor will be positively reinforced:
A
physician is positively reinforced for recommending screening, regardless of the
test result, because a negative result makes the patient grateful for
reassurance and a positive result makes a patient grateful for early detection.
A patient who is impotent and incontinent after a decision for curative
treatment may attribute his survival to surgery and be grateful for having his
cancer cured. Individual experience provides almost no negative feedback that
early detection and aggressive treatment may not
work.4
But is prostate cancer screening beneficial? Intuitively it
seems obvious; surely picking up disease earlier must be good? Unfortunately we
know that screening is not always
beneficial. Randomised controlled trials (RCTs) have revealed that some
screening procedures (for instance, screening for lung cancer using chest
radiography and sputum cytology in high-risk individuals, and screening for
breast cancer with breast self-examination), which were previously assumed to be
beneficial, are not.5–7
Using methods such as survival comparisons, observational
studies, or ecological studies to assess screening is dangerous. These studies
are vulnerable to biases, which can cause any benefit of screening to be
overestimated, and at worst, can make screening appear beneficial even when it
is not (Table 1). Only an appropriately designed and analysed RCT can avoid
these biases, and determine whether screening for prostate cancer really is
beneficial.
At present, we do not know if there is any benefit from
prostate cancer screening, because there is not yet evidence from appropriately
designed and analysed randomised controlled
trials.8–11 Two large RCTs are presently
underway.12
Table 1. Why do we need randomised controlled trials of
prostate cancer screening?
_____________________________________________________________________
Bias
is a defect in study design or analysis that causes results to deviate from the
truth. The following biases can affect the assessment of prostate cancer
screening:
Lead time biasScreening
can detect prostate cancer early, thereby extending the interval between
diagnosis and death,
even if the time of
death is unchanged. Because survival time
is measured from time of diagnosis to death, men whose prostate cancer was
detected by screening will have longer survival times than men diagnosed
clinically, even if screening does not actually extend life.
Length
bias
Fast
growing prostate tumours, which tend to have the worst prognosis, are less
likely to be detected by screening, because they grow so rapidly that the period
when the tumour could be detected by screening before signs or symptoms develop,
may be very short. Screening will therefore detect a disproportionate number of
slow growing tumours with a good prognosis. Comparisons of outcome between men
with screen-detected prostate cancer and men with clinically-diagnosed prostate
cancer are likely to be invalid because of this.
Selection
bias
Men
who take up the offer of screening may differ in their underlying risk of dying
from prostate cancer, so that their prognosis would have differed from
non-participants even in the absence of screening. Thus, comparing the outcome
for men who have been screened with men who have not may be inappropriate.
Selection bias can be avoided in a randomised-controlled trial by appropriate
(intention to treat) analysis.
Overdiagnosis
bias
Screening
may detect abnormalities that are of questionable malignancy and cancers that
would not have been diagnosed in the absence of screening. Although some of
these abnormalities and cancers may never have been diagnosed, nor affected a
man’s life in the absence of screening, they will be counted as
‘screen-detected’ cancers. Because of the inclusion of these
cancers, the outcome for a group of screened men with prostate cancer will
appear better than the outcome for unscreened men with prostate
cancer.
_____________________________________________________________________
RisksPeople who are unwell are often
prepared to take risks in order to get better. Many patients will accept
treatments that carry risks; for instance, drugs that have potential side
effects, and radiotherapy or surgery despite their possible complications.
Clinicians are used to interacting with people who are unwell and who tolerate
potential harm in order to get better. Clinicians may transfer this tolerance of
harm to the screening situation, hence urologists may be more likely to support
prostate cancer screening than public health physicians.
But people who are
well may not share the same tolerance
towards potential harm, especially if the benefit is uncertain. If there is
no benefit, the net effect of screening
will be to harm those who take part. Apart from the obvious harms related to
false negative and false positive screening results, overdiagnosis is likely to
be a major problem in prostate cancer screening.
Autopsy studies, where prostate biopsies were taken from men
who had died of causes other than prostate
cancer,13,14 have shown that the histological
evidence of prostate cancer in such men is much higher than the lifetime
incidence and mortality from prostate cancer. In other words, histological
evidence of prostate cancer can be found in far more men than would ever be
expected to suffer from or die from the disease.
Further evidence of overdiagnosis comes from the Finasteride
Trial,15 which was designed to find out whether
the drug Finasteride could prevent prostate cancer. Men aged 55 years and over
were randomly allocated to an intervention group (which took Finasteride) and a
control group (which took a placebo). All the men had normal digital rectal
examinations (DRE) and PSA results at entry to the trial. During the trial, the
men underwent annual DRE and PSA tests.
At the end of the trial, all men who had not been diagnosed
with prostate cancer during the trial were offered an end-of-study prostate
biopsy. Of 4692 men in the control group who had prostate biopsies, nearly a
quarter (24.4%) had histological
evidence of prostate cancer at the end of the 7 years’ follow-up. The
investigators had expected 6.0% of the men to be diagnosed with prostate cancer
during the trial, and the expected lifetime prevalence in these men was 16.7%.
The trial investigators themselves stated
‘The rate of 24.4% suggests the
possibility of overdiagnosis of
disease.’15
The results from autopsy studies and the Finasteride trial
are a warning. If healthy men have PSA tests, some will be diagnosed with
prostate cancer that they would otherwise never have known about, and that would
never have threatened their lives. This would be bad enough, but many men who
are diagnosed with prostate cancer are offered treatment such as radiotherapy or
surgery, and these treatments have significant side effects. The potential side
effects include impotence, incontinence, diarrhoea, and
death.9
Some of the men who suffer these side effects would never
have known they had prostate cancer in the absence of screening, so they will
have been directly harmed as a consequence of being screened.
ConclusionAlthough it is possible to
understand and perhaps explain opposing views on prostate cancer screening,
examining the risks and benefits shows that prostate cancer screening is not
justified at present. Whether there is any benefit from prostate cancer
screening is unknown. It is inappropriate to support screening in the hope that
it will be found to be beneficial, since this would be gambling with men’s
health.
Prostate cancer screening fails to meet criteria for
screening,16,17 and carries potentially serious
risks. In the absence of conclusive evidence of benefit, it is entirely possible
that prostate cancer screening could cause more harm than good. Therefore, at
present, it is unethical to offer prostate cancer
screening.18 In the future, screening should
only be offered if the randomised controlled trials of prostate screening that
are currently underway, demonstrate a benefit.
Author information:
Ann K Richardson, Associate Professor, Department of Public Health and General
Practice, Christchurch School of Medicine and Health Sciences, University of
Otago, PO Box 4345, Christchurch
Correspondence: Dr
Ann Richardson, Department of Public Health and General Practice, Christchurch
School of Medicine and Health Sciences, University of Otago, PO Box 4345,
Christchurch. Fax: (03) 364 3614; email: ann.richardson@chmeds.ac.nz
References:
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