Results released today from the Prostate,
Lung, Colorectal and Ovarian (PLCO) Cancer
Screening Trial show that six years of
aggressive, annual screening for prostate
cancer led to more diagnoses of prostate
tumors but not to fewer deaths from the
disease.
The study, led by researchers at
Washington University School of Medicine in
St. Louis and conducted at 10 sites, will
appear online March 18 in the New England
Journal of Medicine (and in the journal’s
print edition on March 26).
“The important message is that for men with
a life expectancy of seven to 10 years or
less, it is probably not necessary to be
screened for prostate cancer,” says the
study’s lead author and principal
investigator Gerald Andriole, M.D., chief
urologic surgeon at the Siteman Cancer
Center at Washington University School of
Medicine and Barnes-Jewish Hospital.
But it’s too soon, he added, to make broad
screening recommendations for all men based
on the study’s initial findings.
“So far, only a minority of men enrolled in
the PLCO study have died, so it may be
premature to make generalizations about the
ultimate results of the trial,” he says.
“We don’t have enough data yet about the
youngest men in the study – those in their
50s – and it may be that over time, we will,
in fact, see a benefit from screening.”
The PLCO trial began in 1992 with funding
from the National Cancer Institute and was
designed to determine whether prostate
cancer screening reduces deaths from the
disease.
It involves men ages 55 to 74 who received
either annual PSA blood tests and digital
rectal exams or “routine care,” meaning they
had the screening tests only if their
physicians recommended them.
After seven to 10 years of follow up, deaths
from prostate cancer were very low in both
groups and did not differ significantly
between the groups.
Health guidelines issued last year by the
U.S. Preventive Services Task Force
recommend against prostate cancer screening
for men age 75 or older and concluded there
is insufficient evidence to assess the
balance of benefits and harms of prostate
cancer screening in men younger than 75.
However, the American Urological Association
and the American Cancer Society recommend
annual prostate cancer screening tests
beginning at age 50 for most men.
More than 186,000 U.S. men will be diagnosed
with prostate cancer this year, and nearly
29,000 will die from the disease, according
to the National Cancer Institute.
PSA blood tests, introduced in 1988, have
increasingly been used as a screening tool
for prostate cancer, despite a lack of
evidence showing they reduce death rates
from disease.
The controversy over prostate cancer
screening has arisen because most men who
undergo a biopsy for an abnormal PSA test do
not have prostate cancer.
For those who have cancer, the tumors
generally grow so slowly that most men die
of other causes.
Furthermore, prostate cancer treatment can
result in incontinence and impotence.
However, some tumors can be aggressive, and
the difficulty has been distinguishing
aggressive cancers from those that are slow
growing.
“We definitely need to find better ways to
detect and treat aggressive tumors, those
that are truly life-threatening, so that men
with slow-growing tumors can avoid
unnecessary treatments,” says Andriole.
Today’s results are the first to detail
death rates from prostate cancer among men
in the PLCO study and are being released to
coincide with the presentation of the data
at the European Association of Urology
meeting in Stockholm, Sweden.
The PLCO data are being made public now
because the study’s Data and Safety
Monitoring Board, an independent review
committee that meets every six months, saw a
continuing lack of evidence that screening
reduces deaths due to prostate cancer as
well as the suggestion that screening may
cause men to be treated unnecessarily.
The PLCO investigators will continue to
follow patients for several more years to
see whether annual screening eventually
reduces prostate cancer deaths.
The trial involved 76,693 men, who were
randomly assigned to receive either annual
PSA blood tests for six years and digital
rectal exams for four years or routine care,
which included physical checkups but no
mandate for annual prostate cancer
screening.
The new report includes data for all
participants seven years after they joined
the trial and for 67% percent of
participants 10 years after they joined the
trial.
At seven years, there were 22 percent more
prostate cancer diagnoses in the men
screened annually (2,820 men in the
screening group vs. 2,322 in the
routine-care group).
This trend has continued in data collected
up to 10 years (currently there are 17
percent more prostate cancer diagnoses in
the screening group).
Deaths from prostate cancer did not differ
significantly between the groups.
Seven years after the start of screening,
there were 50 deaths from prostate cancer in
the screening group and 44 deaths in the
routine-care group.
Ten years after the start of screening,
there were 92 prostate cancer deaths in the
screening group and 82 in the routine-care
group.
“My recommendation is that, for now, men
with a life expectancy of more than seven to
10 years continue to be screened for
prostate cancer,” says Andriole.
“On the other hand, screening is probably
not necessary for elderly men and men with
significant health issues.
"These men should have a conversation with
their doctors to make an individual decision
about whether they want to be screened,
because clearly there can be harmful side
effects related to treatment, while for
these men, there has been no demonstration
that screening will prolong their lives.”
Of the men who received annual screening, 85
percent had PSA tests and 86 percent had
digital rectal exams.
Men in the routine-care arm sometimes had
prostate cancer screening tests: PSA
screening ranged from 40 percent of men at
the beginning of the study to 52 percent of
men by the last screening year, and
screening with rectal exams ranged from 41
percent initially to 46 percent by the last
screening year.
The exam involves a doctor inserting a
lubricated, gloved finger into the rectum to
feel for anything that is not normal.
Men were referred for follow up testing for
prostate cancer if their PSA level was
higher than 4.0 ng/ml or if the rectal exam
was abnormal.
The researchers noted that the vast majority
of men in both groups who developed prostate
cancer were diagnosed with stage II disease
(out of IV).
The number of later-stage cases was similar
in the two groups. However, men in the
routine-care group had more aggressive
tumors (Gleason score 8-10).
The reduced number of men with prostate
cancer with a Gleason score of 8-10 in the
intervention group may eventually lead to a
mortality difference, but data analyzed so
far have not shown such a benefit.
Additionally, men in both groups received
similar treatments for their disease, which
was not dictated by being a participant in
the PLCO.
Another study reported in this same online
issue of the NEJM is the large European
Randomized Trial of Screening for Prostate
Cancer (ERSPC), which shows a 20 percent
reduction in the rate of death from prostate
cancer but with a high risk of overdiagnosis.
In the ERSPC, unlike the PLCO trial, men
were referred for follow-up testing if their
PSA level was 3.0 ng/mL or higher and were
also screened, on average, every four years
as opposed to annually in the PLCO.
Lowering the threshold for what is
considered an abnormal PSA to 3.0 ng/ml is
likely to diagnose more tumors but not
necessarily identify those that are more
likely to be aggressive, Andriole says.
Andriole GL, Grubb RL, Buys SS, Chia D,
Church TR, Fouad MN, Gelmann EP, Kvale PA,
Reding DJ, Weissfeld JL, Yokochi LA,
Crawford ED, O’Brien B, Clapp JD, Rathmell
JM, Riley TL, Hayes RB, Kramer BS, Izmirlian
G, Miller AB, Pinsky PF, Prorok PC, Gohagan
JK, and Berg CD. Mortality Results from a
Prostate-Cancer Randomized Screening Trial.
Washington University School of Medicine's 2,100
employed and volunteer faculty physicians
also are the medical staff of Barnes-Jewish
and St. Louis Children's hospitals.
The School of Medicine is one of the leading
medical research, teaching and patient care
institutions in the nation, currently ranked
third in the nation by U.S. News & World
Report.
Through its affiliations with Barnes-Jewish
and St. Louis Children's hospitals, the
School of Medicine is linked to BJC
HealthCare.
