2012 EDUCATIONAL BOOK - American Society of Clinical Oncology

PSA SCREENING: HARMS WITHOUT CLEAR BENEFIT
Fig. 1. Prostate cancer in the United States, 1975 to
2008: new cases and deaths.
noninfectious biopsy-related complications, but not to the
same degree. A similar pattern for biopsy-related hospitalizations
was observed in Ontario, Canada, during the 2000s. 13
The complications associated with prostate cancer treatment
are unpleasant and life-altering. Urinary incontinence
and erectile dysfunction occur as a result of treatment,
although the percentage of men whose morbidities are
attributable solely to treatment likely varies by patient
characteristics, treatment received, the definition of incontinence
and erectile dysfunction employed, whether the
diagnosis is self-assigned, and the prevalence of these morbidities
in the study population before screening, and thus is
difficult to pinpoint. Nevertheless, those receiving prostatectomy
have been shown in research settings to have a 2- to
11-fold increase in risk of urinary incontinence and a 1.2- to
2.1-fold increase in risk of erectile dysfunction, relative to
men who are treated with “watchful waiting.” 1 In the Task
Force’s 2011 review, 1 the smallest and largest absolute
percentile differences for urinary incontinence following
prostatectomy compared with watchful waiting were nine
(19% vs. 10%) and 40 (44% vs. 4%). For erectile dysfunction,
the figures were 21 (89% vs. 68%) and 36 (81% vs. 45%). In
a community-based (U.S.) study of experiences of men diagnosed
with prostate cancer in 1994 and 1995 who had
radical prostatectomy, 87% of men reported that they had
total urinary control prior to their surgery as compared with
less than 40% at 6, 12, 24, and 60 months postsurgery. 14
Eighty-one percent reported that they had erections firm
enough for intercourse before their surgery, as compared
with less than 30% at the same postsurgery time points. 14
Radiation therapy may confer a lower relative risk of incontinence
and erectile dysfunction, but androgen deprivation
therapy may increase the risk of the latter. 15 Postoperative
deaths or cardiovascular events occur about 0.5% of the
time, although rates are age-dependent.
Men with overdiagnosed prostate cancers are harmed the
most by PSA screening. In the case of overdiagnosis, any
expense, inconvenience, discomfort, sexual dysfunction,
morbidity, hospitalization, or death that results from diagnostic
evaluation for a positive screen and treatment of a
diagnosed cancer is entirely unnecessary. Figure 1 provides
convincing evidence of overdiagnosis: the number of prostate
cancer cases in the United States was substantially higher
in 2008 than it was in the early 1970s, but the prostate
cancer mortality rates between the early 1970s and 2008
were not very different. This increase in risk correlates with
two changes in medical practice: an increase in transurethral
resection of the prostate (which could serendipitously
detect prostate cancers when performed for other reasons)
beginning in the 1970s and the adoption of PSA in the late
1980s. A true “epidemic” of prostate cancer cannot explain
this rise in incidence because the rise was unaccompanied by
extreme shifts in risk factor prevalence or the identification
of a new, widespread exposure that strongly increased risk;
even if it had, not all cancers would have been curable.
Additional data supporting the existence of overdiagnosis
come from a comparison of prostate cancer incidence and
mortality in Connecticut and the Seattle-Puget Sound
area, 16 two areas that differed with regard to the uptake of
PSA screening in the 1980s and 1990s. Connecticut, where
PSA screening was less common, had consistently lower
prostate cancer incidence rates from 1987 through 2001, but
prostate cancer mortality rates were very similar, with
Seattle data showing a possible, although not statistically
significant, increase in prostate cancer mortality for men
ages 75 to 79. A nearly identical reduction in the prostate
cancer mortality rate in both regions over time has been
observed; if PSA screening was reducing mortality in addition
to reductions due to treatment, the reduction for Seattle
would have been even more pronounced.
Microsimulation methods have been used to estimate the
percentage of prostate cancers that are considered to be
overdiagnosed disease. Using ERSPC data, Draisma and
colleagues estimated that among men screened annually
from age 55 to 67, 50% of screen-detected cases would be
overdiagnosed cases. 17 Using SEER data, overdiagnosis
ranged from 23% to 42% of all screen-detected cases. 18
Modeling using PLCO data is not yet available, but an
excess of cases existed in the intervention arm in every
study, including after 13 years of follow-up. 8 Two years after
the last screen (i.e., the end of study year 7), the excess of
479 cases indicates that overdiagnosis could have accounted
for about 17% of cases in the screened arm. That figure is an
underestimate, as contamination occurred in the control
arm. Although it is unclear whether the extent of overdiagnosis
is moderate or extreme, it is clear that it exists with
PSA screening.
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