PSA screening may benefit younger, at-risk men

Issue: June 25, 2012

Screening younger men and those at risk for prostate cancer can help reduce mortality from the disease and should not be abandoned, according to an analysis published in the Canadian Medical Association Journal.

The US Preventive Services Task Force (USPSTF) last fall issued a draft recommendation against PSA screening for prostate cancer.

Much of the response to that recommendation focused on how PSA screening has not been shown to reduce overall mortality, Monique J. Roobol, PhD, of the department of urology at Erasmus University Medical Centre in Rotterdam, the Netherlands, and colleagues wrote in their analysis.

Cancer-specific mortality, however, is the primary outcome of screening trials.

“Because deaths from prostate cancer are a small proportion of all deaths, comparisons of overall mortality are underpowered,” Roobol and colleagues wrote. “Thus, a screening program that reduces cancer-specific mortality should not be stopped because of a lack of reduction in overall mortality.”

The USPSTF last issued prostate cancer screening guidelines in 2008. The results of several randomized trials have become available since then, Roobol and colleagues said.

The European Randomized Study of Screening for Prostate Cancer, which involved 162,243 men aged 55 to 69 years, provided “high-quality evidence that screening reduces prostate cancer-specific mortality,” Roobol and colleagues wrote.

Men assigned to screening underwent PSA every 4 years. After a median follow-up of 9 years, the study demonstrated screening led to a 20% reduction in prostate cancer mortality (RR=0.8; 95% CI, 0.65-0.98). The reduction increased to 31% after adjustments for noncompliance and contamination (RR=0.69, 95% CI, 0.51-0.92). A subsequent update with a median follow-up of 11 years confirmed the finding.

Researchers also determined screening was associated with a 41% reduction in metastatic disease at diagnosis (P<.001).

Other trials, such as the US Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, showed screening did not contribute to a reduction in prostate cancer-specific mortality in the overall population. Roobol and colleagues suggested several factors — including high PSA screening rates among participants before their entry into the study, poor compliance of biopsy recommendations and frequent screening in the control arm of the study — may help explain the different results.

Also, a follow-up analysis of the US trial found that that screening significantly reduced disease-specific mortality in men with minimal comorbidity (HR=0.56; 95% CI, 0.33-0.95). The data showed only five healthy men needed to be screened to prevent one death from prostate cancer.

In addition, among men assigned to screening, the rate of death from prostate cancer was 2.35 per 10,000 person-years among those aged 55 to 64 years at the time of randomization vs. 6.17 per 10,000 person-years among those aged 65 to 74 years. Young healthy men also were at lower risk for complications from biopsy and adverse effects during treatment.

“These combined results show that individual factors such as age and comorbidity have a substantial impact on the balance of the benefits and harms of screening,” Roobol and colleagues wrote.

They concluded that screening should be encouraged for healthy younger men and for those with risk factors — including family history and black ancestry — and discontinued for elderly men with limited life expectancy and multiple comorbidities.

“Rather than abandoning a screening test that reduces death and suffering, efforts should be focused on selecting patients more carefully,” they wrote. “Greater benefits of screening will likely emerge with additional follow-up from the ongoing randomized trials. Meanwhile, investigation into more specific biomarkers, the use of multivariable predictive tools in decision-making, increased use of conservative management for low-risk patients and ongoing technological advances in treatment can help further improve the ratio of benefits to harms.”

References:

Roobol MJ. CMAJ. 2012;doi:10.1503/cmaj.111962.

Disclosure:

Dr. Roobol reports no relevant financial disclosures.