Cancer Research Lab

Current biopsy thresholds for prostate specific antigen (PSA) and PSA velocity underestimate prostate cancer risk in younger men, researchers report in the February issue of the Journal of Urology.

“It has been known for over a decade that PSA rises more quickly in men who have prostate cancer,” lead investigator Dr. Judd W. Moul said. “We show, for the first time, that this rate of change should be age-adjusted. In other words, in younger men, smaller rises in PSA predict cancer while in older men, larger rises indicate cancer.”

Dr. Moul and colleagues at Duke University Medical Center, Durham, North Carolina studied data on 11,861 men who had had two or more PSA tests within 2 years.

Prostate cancer prevalence in the cohort was 8.0% in men 50 to 59 years old, 14.9% in those of 60 to 69 years and 17.9% men aged 70 years or more.

In the men with prostate cancer, median PSA level in those aged 50 to 59 years was 5.6 ng/mL compared with 8.1 ng/mL in men aged 70 years or more. Corresponding values for PSA velocity were 1.37 and 1.89 ng/mL per year.

The sensitivity and specificity of the standard PSA cutoff point of 4.0 ng/ml for detecting prostate cancer were 76.7% and 69.8% in men aged more than 70 years. When a 2.0 ng/mL PSA cutoff value was used in those aged 50 to 59 years, the sensitivity was 84.1% and the specificity was 74.4%.

In the younger men, a PSA velocity cutoff of 0.40 ng/mL per year gave a sensitivity of 84.3% and a specificity of 72.4%. These again were higher than those in men over 70 years old using a standard PSA velocity cutoff of 0.75 ng/mL per year.

Using cutoffs of 2.0 ng/ml PSA and 0.40 ng/ml per year PSA velocity led to a lower negative biopsy rate in the youngest group compared to that in the oldest group.

The team concludes that standard PSA and PSA velocity cutoff points could be decreased to 2.0 ng/ml and 0.40 ng/ml per year in order to improve cancer detection in these younger men.

The author of an editorial comment, Dr. H. Ballentine Carter of Johns Hopkins School of Medicine, Baltimore told Reuters Health that in studies he and his colleagues conducted “men with PSA levels below 4.0 ng/mL who have a PSA velocity exceeding 0.3 to 0.4 ng/mL per year” have about a fivefold greater risk “of being diagnosed with life-threatening prostate cancer over the next 2 decades” when compared to those with a lower PSA velocity. “Thus, these men require more careful monitoring.”

However, in another editorial, Dr. Donna Pauler Ankerst of the University of Munich, Germany and Dr. Ian M. Thomson of the University of Texas Health Science Center at San Antonio, take Dr. Moul and colleagues to task on a number of issues including verification bias. They also find fault with a somewhat comparable study by other investigators that had contrasting results.

“The biostatistics of this discussion seem far removed from the clinical practice of urology,” the editorialists conclude. “However, they are not, because conclusions reached from studies of PSA have an enormous impact on millions of men annually.”