Prostate cancer screening should monitor subgroup of young, high-risk men, study suggests

January 1, 2012

Almost half of prostate cancer deaths occur among men with PSA levels in the top 10% when assessed at age 44 to 50 years. This small group could benefit from intense surveillance over the ensuing years, whereas in about half of men, three lifetime PSA tests appear sufficient to capture the risk of prostate cancer metastases or death 10 or more years in advance.

Key Points

New York-Almost half of prostate cancer deaths occur among men with PSA levels in the top 10% when assessed at age 44 to 50 years. This small group could benefit from intense surveillance over the ensuing years, whereas in about half of men, three lifetime PSA tests appear sufficient to capture the risk of prostate cancer metastases or death 10 or more years in advance, according to American and Swedish researchers.

Their conclusions were derived from a large, retrospective, case-control study of previously unscreened men who participated in the Swedish Malmö Preventive Project, in which men were followed for up to 30 years.

Shortcomings of PSA-based screening are its modest specificity and its inability to discriminate between indolent and significant disease, said first author Hans G. Lilja, MD, PhD, attending research clinical chemist at Memorial Sloan-Kettering Cancer Center, New York.

In the study, PSA levels in archived blood plasma collected between 1974 and 1986 were analyzed from 12,090 men and from 4,999 repeat samples 6 years later. An independent cohort of 1,167 men provided blood at 60 years of age. A group of 252 men with evidence of prostate cancer metastasis or death were matched in a 3:1 ratio with controls.

In a previous analysis of the 1,167 men who provided blood at age 60 (BMJ 2010; 341:c4521), it was demonstrated that PSA at 60 years of age is a strong predictor of lifetime risk of cancer death, that 90% of prostate cancer deaths occurred in men with PSA levels of 2.0 ng/mL or greater, and that men with PSA levels of 1.0 ng/mL or less at age 60 were unlikely to get life-threatening cancer, meaning that half of all men at age 60-those with PSA levels of 1.0 ng/mL or less-may be exempted from retesting.

Using the blood samples, the median PSA levels were assessed at ages 44 to 50 years, 51 to 55 years, and 60 years.

Forty-four percent of prostate cancer deaths occurred in men with PSA levels in the top 10% (>1.6 ng/mL) when tested between the ages of 44 and 50 years at a median follow-up of 27 years. As a result, nearly half of all prostate cancer deaths could potentially be prevented by intense surveillance of this small group of men with PSA greater than 1.6 ng/mL, said Dr. Lilja, who presented the findings at the 2011 American Society of Clinical Oncology annual meeting in Chicago.

"Our results appear to identify a subgroup of relatively young men at very high risk of aggressive prostate cancer who would likely benefit from close monitoring as they age," he said.

As men aged, if their PSA level remained below the median for the population in their age group, the risk of death from metastatic prostate cancer progressively declined:

Based on progressively declining risks, Dr. Lilja concluded that men with PSAs below the population median in each age group remain at increasingly lower risk for dying of prostate cancer as they age. As a result, testing only three times between ages 44 and 60 years could be recommended for 50% of men. The other half of men with PSAs above the median would be followed more closely.

A single PSA test at ages 45 to 51 years would not be sufficient to rule out the risk of metastasis or death at follow-up to 30 years, he added.

If confirmed in prospective trials, the screening approach developed from this study could have a significant impact on future prostate cancer screening programs, Dr. Lilja said.