Most Men Don’t Need Yearly PSA Screening: PLCO Study

ORLANDO—Men with PSA levels below 2 ng/mL can safely defer repeat testing to once every 2 years, and those with PSA levels less than 1 ng/mL can reduce re-tests to once every 5 years, according to data from the National Cancer Institute’s nationwide PLCO (Prostate, Lung, Colorectal, Ovarian) cancer screening trial.

E. David Crawford, MD, reported the PLCO data at the plenary session of the 38th Annual Meeting of the American Society of Clinical Oncology (abstract 4). Dr. Crawford is senior associate director of the University of Colorado’s Health Sciences Center, Denver.

The PLCO trial was started in 1993 to address the controversy of screening for a number of cancers; 154,000 men and women have been entered into this large trial, with ages of 55 to 74 years. "Prostate cancer screening is controversial, and one purpose of this trial is to evaluate the value (if any) of prostate cancer screening," Dr. Crawford said.

The goal of the PSA analysis was to estimate the risk that a subject’s normal baseline PSA level would rise above the normal limit (defined as 4 ng/mL) during years 1 through 5.

All men in the trial had PSA testing yearly for 6 years and digital rectal exam yearly for the first 4 years. Baseline PSA levels were less than 4 ng/mL in 92% of the men and less than 2 ng/mL in 55%. Dr. Crawford reported data on nearly 30,000 men who had baseline PSA levels of less than 4 ng/mL and at least one subsequent PSA exam. Exclusion criteria included use of finasteride (Proscar) or history of prostate cancer.

Dr. Crawford reported that 98.4% of men with baseline PSA levels less than 1 ng/mL continued to have PSA levels less than 4 ng/mL for each of the next 5 years (see Table). Of men with baseline PSA levels of 1 to 2 ng/mL, 98.8% continued to have PSA less than 4 ng/mL the following year.

"We found that the vast majority of men whose initial PSA levels are very low do not need to worry that they would skyrocket within 1 year," Dr. Crawford said.

The implication of the findings is that men whose initial screening tests show PSA levels less than 1 ng/mL can safely wait 5 years for their next PSA test (if they choose to be tested), and those men with PSA levels between 1 ng/mL and 2 ng/mL can be tested every 2 years rather than every year.

"This strategy would produce a 55% reduction in the number of PSA tests, but result in only a small percentage of men missing an earlier potentially positive test. The estimated cost savings of this strategy is on the order of $500 million to $1 billion annually," Dr. Crawford said.

Men with baseline PSA levels above 2 ng/mL should continue to have yearly PSA tests, Dr. Crawford said. Of those with baseline PSA of 2 to 3 ng/mL, 12.8% will have PSA above 4 ng/mL within 2 years, as will 44% of those with baseline PSA of 3 to 4 ng/mL. The conversion rates at 5 years for these two groups are 34.6% and 83%, respectively. "These men are candidates for prostate cancer prevention trials and other research," Dr. Crawford said.

Potential Harmful Effects

Dr. Crawford stressed that the PLCO has yet to answer the question of whether PSA screening provides any survival benefits. Discussant Steven H. Woolf, MD, MPH, of the Departments of Family Practice and Preventive Medicine and Community Health, Virginia Commonwealth University, said that the "more pivotal" question concerning PSA screening "is not how often to screen but whether to screen," and the answer to that question awaits the long-term results of PLCO and the European Randomized Study of Screening for Prostate Cancer (ERSPC), which has prostate cancer mortality as an endpoint.

Although less frequent screening can reduce costs, Dr. Woolf said that from a clinical perspective, a more important benefit of less frequent screening is the decrease in the potentially harmful effects of unnecessary screening to the patient, including false-positive results, anxiety, repeat testing, unnecessary biopsies and the risk of unnecessary treatment.

"Even if a prostate cancer is diagnosed as a result of screening and subsequent biopsy, we know that many of these histologically apparent cancers are latent and likely to remain so," Dr. Woolf said at the press conference. "There is a risk that screening is increasing the use of radical prostatectomy and radiation therapy for a condition that never would have threatened the patient’s health in the first place."

Dr. Woolf also pointed out that the results were not stratified by age, and a significant proportion of the participants were older men. "Because of the natural PSA progression with age, these men would be expected to have a higher risk of converting to abnormal PSA levels," he said at the plenary session.

Although, overall, the study showed that men with higher baseline PSA levels do have a higher probability of converting to abnormal, he said, "whether that translates into the same risk of conversion for younger men is not known."