August 5, 2008 — Men who are 75 years or older should not be screened for prostate cancer, says the US Preventive Services Task Force (USPSTF). For these men, and others who have a life expectancy of 10 or fewer years, the incremental benefit from treating prostate cancer detected by screening is "small to none. Therefore, harm outweighs benefit."

This new advice comes in an update to recommendations from the USPSTF, reported in the August 5 issue of the Annals of Internal Medicine. It marks a significant change from the previous statement from the USPSTF, issued in 2002, which concluded there was insufficient evidence to recommend for or against routine screening with prostate specific antigen (PSA), but did not stipulate any age. Now it recommends no screening for men who are 75 years or older and reiterates that the benefits of screening men younger than this remain unproven.

For men who are 75 years or younger, the "evidence is inadequate to determine whether screening improves health outcomes," the USPSTF states. "Therefore the balance of harms and benefits cannot be determined."

The advice to clinicians is to discuss the potential benefits and known harms of PSA screening with male patients who are younger than 75 years. "Men in this age group should be informed of the gaps in the evidence, and their personal preferences should guide the decision of whether or not to order the test," write the authors, headed by Kenneth Lin, MD, from the Agency for Healthcare Research and Quality in Rockville, Maryland.

This advice is in line with that of most major medical organizations in the United States, the authors comment. Most other organizations also recommend that clinicians discuss the potential benefits and known harms of PSA screening with their patients, that they consider patients preferences, and that they individualize screening decisions.

Age Stipulation Is New and Surprising

However, the age stipulation is new and surprising, says David Penson, MD, associate professor of urology and preventive medicine at the Keck School of Medicine, University of Southern California. "Most other groups recommend that the individual provider should determine the patient's life expectancy and, on the basis of this, screen (or discuss screening) if the life expectancy is more than 10 years," he explained to Medscape Oncology.

"The USPSTF is the first group to tie the threshold to stop screening to a numerical age," Dr. Penson pointed out. This did surprise him, he said, adding: "It almost strikes me as ageism. After all, there are a fair number of patients over age 75 who live more than 10 years. And conversely, patients who are under age 75 who don't have a 10-year life expectancy."

"The use of an age threshold strikes me as arbitary, and doesn't take into account for individual variations or patient preferences," Dr. Penson said.

A similar reaction came from the American Cancer Society, from their director of prostate and colorectal cancer, Durado Brooks, MD, MPH. "It is surprising," he said in an interview. Establishing a fixed age at which to stop screening introduces a "new element," although one could argue that this is not strikingly different from recommending screening only for men who have a life expectancy of 10 years or more. However, this new age stipulation does not take into account the significant number of very active men who are 75 years or older, who may have a life expectancy of more than 10 years.

There is evidence in the United States that there is a significant amount of screening in men in their upper 70s and even into their 80s, Dr. Brooks commented. One recent study, which looked at PSA screening in 7 Veterans Health Administration hospitals, found this test was performed in 15% of men older than 75 years of age (Ann Int Med. 2007;167:1367-1372). "This study cannot be viewed as representative of screening practices across the United States, as the analyzed data is from Veterans hospitals and clinics in one region of the US," Dr. Brooks commented. "It does, however, give us an idea of the kinds of screening practices that are occurring in some settings."

Lead author Dr. Lin, medical officer with the USPSTF confirmed to Medscape Oncology that this is the first time that any major guideline group has made a recommendation with an explicit age cutoff value for prostate cancer screening. "Most organizations advise discontinuing prostate cancer screening in men with a life expectancy of fewer than 10 years, but this recommendation has largely gone unheeded in practice as it is extremely difficult for clinicians to predict life expectancy with any degree of precision," Dr. Lin said.

PSA screening is common in the elderly population, Dr. Lin commented. In the United States, up to one third of all men aged 75 years and older are currently receiving PSA testing, as reported in recent national surveys. There was also a study published in the Journal of the American Medical Association in 2006 that showed that even higher percentages of elderly men were receiving PSA testing within the Veterans Administration system.

Dr. Penson agrees that PSA screening is being carried out regularly in older men. "I think that most clinicians are smart enough to have detailed discussions with patients and are able to assess the patients comorbid conditions in a such a way that they can intelligently apply this test to men over 75 years of age, and often do."

Will the new advice curb this practice? "Possibly," says Dr. Brooks, as clinicians say that they consider recommendations from the USPSTF as being important. However, in practice, clinicians are often guided by their own experience with patients as much as they are by clinical guidelines, so this recommendation may influence but will not eliminate PSA screening in the older age group, he predicted.

The USPSTF also suggests that 4-year screening intervals may be as beneficial as annual screening, although the evidence base for this statement is unclear. At present, the American Cancer Society and the American Urological Association recommend annual PSA screening as well as digital rectal examinations for men older than 50 years. "I have seen some suggestions in the literature that 2-year screening intervals may be as good as annual intervals, but have not come across this 4-year interval suggestion before," Dr. Brooks commented.

Little New Evidence Considered

The USPSTF comments that since its last review in 2002, no good-quality randomized controlled trials of screening for prostate cancer have been completed. However, in 1 cross-sectional study and 2 prospective cohort studies which were of fair to good quality, false-positive PSA screening results caused psychological adverse effects for up to 1 year after the test.

Also, several case-control studies, conducted in a variety of settings and populations, have yielded conflicting results about the relationship between PSA screening and prostate cancer-related morbidity and mortality, the authors comment.

There was no new evidence of harm from screening, the USPSTF says. However, the 2002 review noted that treatment of prostate cancer can cause clinically significant harm, which can include erectile dysfunction, urinary incontinence, bowel dysfunction, and death. "A proportion of those treated, and possibly harmed, would never have developed cancer symptoms during their lifetime," the authors point out.

Larger, longer-term studies are urgently needed, they comment. Two large randomized clinical trials of PSA screening are currently underway. The European Randomized Study of Screening for Prostate Cancer (ERSPC) involves 190,000 men, while the prostate component of the US National Cancer Institute's Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial is being conducted in 76,705 men.

"These trials may provide valuable and complementary information about the health outcomes associated with PSA screening in the general primary care population," the authors write. However, even if 1 or both of these trials ultimately demonstrate a population-level mortality benefit, the authors state, individual screening decisions will still need to be made by weighing the benefits and harms of prostate cancer screening and treatment as summarized by the USPSTF in its recommendations.

The authors have disclosed no relevant financial relationships.

Ann Intern Med. 2008;149:185-191, 192-199.

Clinical Context

Study Highlights

• Older men, African American men, and those with a positive family history are at increased risk for prostate cancer and mortality.
• The PSA test is more sensitive than the digital rectal examination for detecting prostate cancer.
• However, most studies on PSA screening suggest that overdiagnosis rates range from 29% to 44%, and there is a burden of harm associated with false-positive results.
• At a cutoff value of 4.0 μg/L PSA level or higher, sensitivity has been reported as 91% for aggressive cases of prostate cancer and 56% for nonaggressive cancer cases.
• Lowering the cutoff value of screening PSA from 4.0 to 2.5 μg/L would more than double the number of men aged 40 to 69 years with abnormal results.
• There is insufficient evidence to show that variations on PSA screening, including PSA density, slope, velocity, and doubling time improves health outcomes.
• There are no good randomized clinical trials on tests other than single-threshold PSA screening.
• For men 75 years and younger with a life expectancy of at least 10 years, the benefits and harms for prostate cancer screening cannot be determined, and the clinician should discuss current evidence with the patient before testing is performed.
• Patients aged 75 years or younger should be informed about the gap in evidence, and their personal preferences should guide clinical decision making.
• The population most likely to benefit from prostate cancer screening is men aged 50 to 74 years. PSA screening conducted every 4 years may be as beneficial as annual screening.
• The USPSTF determined that the evidence was insufficient to recommend screening in men younger than 75 years.
• For men 75 years and older or with a life expectancy of less than 10 years, there is moderate certainty that the harm outweighs the benefits.
• Harms documented for prostate cancer screening include additional PSA test and biopsies, pain, anxiety, sexual dysfunction, bowel and bladder dysfunction, and death.
• The USPSTF thus recommends against prostate cancer screening in men older than 75 years.
• There is no consensus regarding optimal treatment of asymptomatic prostate cancer detected in men younger than age 75 years.
• Treatment strategies include watchful waiting (observation with palliative treatment of symptoms only), active surveillance (periodic biochemical testing with active treatment of disease progression), and invasive treatment (such as radical prostatectomy, external-beam radiation, and brachytherapy).
• Recommendations from the American Academy of Family Physicians, American College of Physicians, and the American Medical Association generally agree that screening is appropriate for men 50 years or older who have a life expectancy of at least 10 years and recommend that clinicians and patients discuss benefits and harms of PSA screening and individualize treatment options.
• The American Cancer Society and the American Urological Association recommend offering PSA measurement and digital rectal examination to men annually from age 50 years.

Pearls for Practice

• One in 6 US men will receive a diagnosis of prostate cancer in their lifetime, and the median age of death from prostate cancer is 80 years with death occurring in 71% of those older than 75 years.
• There is insufficient evidence to recommend prostate cancer screening in men younger than 75 years, and patient discussion should guide decision making, and screening is not recommended for men aged 75 years and older.