2012 EDUCATIONAL BOOK - American Society of Clinical Oncology

PSA SCREENING: HARMS WITHOUT CLEAR BENEFIT
mid-1990s, and then started to fall. This trend is thought by
many to be primarily attributable to changes in use of PSA
screening rather than radical changes in risk factors or
classification schemes for invasiveness of disease. In the
early 1990s, at the height of PSA screening, the age-adjusted
prostate cancer incidence rate was in excess of 200 per
100,000 man-years, but in 2008 (the most recent data
available), it was about 150 per 100,000 man-years. 4 Prostate
cancer mortality peaked in 1993 at about 39 per 100,000
man-years but in 2008 had fallen to about 23 per 100,000
man-years. 4
Cancer Screening
Cancer screening refers to the routine testing of persons
who are asymptomatic for cancer of a particular organ. The
goal of screening is to decrease the risk of death from a given
cancer by detecting the cancer at a time when treatment can
lead to cure. A reduction in disease-specific mortality with
screening, relative to established care without that exam,
KEY POINTS
● A 2010 meta-analysis of prostate-specific antigen’s
(PSA’s) effect on prostate cancer mortality that included
five randomized controlled trials (including
the two largest, the European Randomized Study of
Prostate Cancer and the Prostate, Lung, Colorectal
and Ovarian Cancer Screening Trial) generated a
summary risk ratio of 0.88 (95% CI: 0.71–1.09),
indicating no statistically significant benefit of PSA
screening.
● If PSA screening does reduce prostate cancer mortality,
the reduction is likely to be small.
● The harms associated with prostate cancer screening
(false-positive exams), diagnostic evaluation of positive
exams (e.g., hematospermia, hematuria, sepsis),
treatment of prostate cancer (e.g., urinary incontinence
and impotence), and overdiagnosis (screen detection
of cancers that never would be diagnosed in
the absence of screening) are well-established and clinically
relevant, and should be considered in concert with
any benefit of PSA screening that might exist.
● In October 2011, the U.S. Preventive Services Task
Force (USPSTF) released a draft statement advising
against prostate cancer screening with PSA and assigned
a grade “D” recommendation, which states
that in the Task Force’s judgment there “is moderate
or high certainty that the service has no net benefit or
that the harms outweigh the benefits.” Nevertheless,
prostate cancer screening with PSA will remain a
Medicare benefit for men of all ages and risk profiles.
● The USPSTF recommendation reflects two core concepts
in the field of cancer prevention and screening:
1) it is difficult to make healthy persons even healthier;
and 2) strong evidence of benefit should exist
before routinely administering a clinical intervention
to healthy persons if that measure is likely to incur
harm.
Table 1. The Potential Positive and Negative Consequences
of Cancer Screening
Positive
Reduced risk of death from the target cancer
Provides some reassurance to those who are concerned that they may have
cancer
Negative
False reassurance if cancer is present, which may lead to disregard of symptoms
Harms of the screening test (e.g., perforation from endoscopy)
False-positive exams, including the need to undergo diagnostic evaluation and
experience any harms that accompany it
Earlier detection of cancer that does not lead to a change in outcome
Identification of overdiagnosed* cancers, with accompanying unnecessary,
potentially harmful diagnostic evaluation and treatment
* Cancers that never would have been diagnosed in the absence of screening.
indicates that screening works. RCTs are used to determine
whether screening reduces cancer mortality, as that study
design provides the most definitive evidence. Other study
designs, such as case-control studies or comparisons of
temporal trends in screening and mortality, are subject to
powerful confounding because of the inability to control for
factors that are related to both screening and death due to
the disease of interest. Metrics such as an increase in 5-year
survival, number of cases detected, and number of earlystage
cases are insufficient on their own to demonstrate a
benefit of screening as a result of the presence of certain
methodologic biases.
There are both positive and negative consequences of
cancer screening (Table 1). Screening may benefit patients
by reducing the risk of death from the target cancer, relative
to what it would be in the absence of that screening exam. A
negative screening exam can provide some reassurance to
those who are concerned that they may have cancer, although
occasionally the reassurance is false and may lead to
disregard of cancer symptoms. Screening, however, can lead
to substantial harm. Medical misadventures may occur as
part of the screening exam itself. Many positive screening
exams will be false positives, which lead to unnecessary
anxiety as well as diagnostic evaluation that may be accompanied
by harm. Screening can result in earlier detection of
a cancer that does not lead to a change in date of death; in
this instance, the patient spends more of his or her life as a
patient with cancer, but life expectancy and cause of death
are unchanged. Screening also can result in the detection of
overdiagnosed cancers, cancers that never would have been
diagnosed in the absence of screening. Patients with overdiagnosed
cancers receive unnecessary treatment, experience
unnecessary treatment-related morbidity, and can even die
prematurely as a result of unnecessary treatment (e.g.,
lethal cancers induced by radiotherapy, postoperative death,
and heart disease or leukemia caused by chemotherapy).
The U.K. National Screening Committee has compiled a
list of criteria for “appraising the viability, effectiveness, and
appropriateness” of a screening program 5 (www.screening.
nhs.uk/criteria/fileid9287). We have identified and adapted
the most relevant criteria to prostate cancer screening with
PSA, and the 13 we consider most relevant are listed in
Table 2. Among those criteria are at least five that either are
known not to be true for PSA screening or whose veracity is
uncertain: the natural history of the detected lesions is not
fully understood, PSA screening appears not to preferentially
detect lesions that are most likely to progress, there is
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