2012 EDUCATIONAL BOOK - American Society of Clinical Oncology

Screening for Prostate Cancer with Prostate-
Specific Antigen: What’s the Evidence?
By Pamela M. Marcus, PhD, and Barnett S. Kramer, MD, MPH
Overview: In October 2011, the U.S. Preventive Services Task
Force (USPSTF, or “Task Force”) released draft recommendations
on prostate cancer screening with prostate-specific
antigen (PSA), concluding that “PSA-based screening results
in small or no reduction in prostate cancer–specific mortality
and is associated with harms related to subsequent evaluation
and treatments, some of which may be unnecessary.” This
statement was accompanied by a grade “D” recommendation,
which indicates 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.” The Task Force, an
independent panel of nonfederal (U.S.) experts in prevention
and evidence-based medicine, conducts systematic evidence
reviews of preventive health care services and makes recommendations
about preventive services in primary care. Task
Force recommendations do not set U.S. federal policy but can
THE USPSTF IS an independent panel of nonfederal
(U.S.) primary care providers and scientists with expertise
in prevention and evidence-based medicine. The Task
Force conducts systematic evidence reviews of preventive
health care services and makes recommendations about
preventive services in primary care. Task Force recommendations
do not set U.S. federal policy but can and do
influence clinical practice as well as health care coverage
and reimbursement. Therefore, they are important and
often controversial, particularly when the recommendation
questions a common medical intervention. Under the Task
Force’s purview is cancer screening, a prevention strategy
that has, over the years, proven to be contentious and
emotionally charged.
In October 2011, the Task Force released a draft of
recommendations on prostate cancer screening with PSA. 1
They concluded that “PSA-based screening results in small
or no reduction in prostate cancer–specific mortality and is
associated with harms related to subsequent evaluation and
treatments, some of which may be unnecessary.” This statement
was accompanied by a grade “D” recommendation,
which indicates 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.” As of this
writing, the recommendations are still in draft form, and the
Task Force is assessing a large number of comments sent to
them during the public comment period. Whatever the
ultimate conclusions of the Task Force, prostate cancer
screening with PSA will remain a Medicare benefit for men
of all ages and risk factor profiles.
Screening for prostate cancer with PSA is an example of
mass screening. A mass cancer screening program strives to
screen asymptomatic persons with certain characteristics
(usually based on age) and reduce the rate of disease-specific
mortality in the population being screened. For a mass
cancer screening program to be of value, mortality from the
target cancer must be reduced, but harms associated with
the screening process and downstream events triggered by
screening cannot outweigh the benefit. Persons who are
screened have no symptoms of the disease in question and
therefore are healthy with regard to that illness. It is
96
and do influence reimbursement and clinical practice. In this
article, we will present evidence the Task Force considered
when making its decision, including two highly influential
randomized controlled trials (RCTs) of prostate cancer
screening, the European Randomized Study of Prostate Cancer
(ERSPC) and the Prostate, Lung, Colorectal and Ovarian
Cancer Screening Trial (PLCO). The two trials arrived at
different conclusions about the efficacy of routine prostate
cancer screening, but similar conclusions about the accompaniment
of clinically relevant harms with prostate cancer
screening, including overdiagnosis (screen detection of cancers
that never would be diagnosed in the absence of screening).
We also will present other available evidence on benefits
and harms of PSA-based screening and consider that evidence
and the findings of ERSPC and PLCO in conjunction with one
another.
difficult to make healthy individuals any healthier, especially
with an intervention like cancer screening, which puts
large numbers of people in harm’s way. Therefore, there
should be strong evidence of benefit from cancer screening
before mass screening programs are implemented.
In this article, we discuss the evidence that led to the Task
Force’s decision to recommend against routine prostate
cancer screening with PSA. We first present prostate cancer
statistics for the United States. Before presenting the evidence
that influenced the Task Force’s recommendation, we
provide an overview of cancer screening, as such knowledge
is necessary for proper evaluation of evidence. For a thorough
treatment of the topic, please see Prorok and colleagues.
2
Prostate Cancer in the United States
Prostate cancer is the most frequently diagnosed nonskin
cancer and the second-leading cause of cancer death in U.S.
men. More than 240,000 cases are expected to be diagnosed
in 2012 and more than 28,000 men are expected to die of the
disease. 3 Early prostate cancer is treatable but usually has
no symptoms; advanced prostate cancer, on the other hand,
is symptomatic but not curable. More than 90% of prostate
cancers in the United States are detected at a treatable
stage, however, and the 5-year relative survival for those
cancers approaches 100%. Because treatments often lead to
urinary and erectile dysfunction, some clinicians have adopted
a “watchful waiting” or “active surveillance” strategy
rather than an initial surgical one for older patients and
those who appear to have less aggressive tumors.
Historically, prostate cancer incidence rates began to rise
rapidly in the mid- to late 1980s, continued to do so until the
From the Division of Cancer Control and Population Sciences, National Cancer Institute,
Bethesda, MD.
Authors’ disclosures of potential conflicts of interest are found at the end of this article.
Address reprint requests to Pamela M. Marcus, PhD, Division of Cancer Control and
Population Sciences, National Cancer Institute, 6130 Executive Blvd., Room 4106,
Bethesda, MD 20892-7344; email: marcusp@mail.nih.gov.
© 2012 by American Society of Clinical Oncology.
1092-9118/10/1-10