New Data on How Age-Adjusted PSA Velocity Can Improve Prostate Cancer Detection in Different Settings

SAN FRANCISCO—The use of age-adjusted PSA velocity values can improve the sensitivity of prostate cancer detection among younger men, a new study shows. And a second study suggests that PSA velocity values in the two years following diagnosis can help predict which men with prostate cancer are most likely to develop aggressive disease. However, these indicators are still not sensitive or specific enough to help oncologists identify which patients require treatment, the researchers reported here at the Prostate Cancer Symposium. The meeting is cosponsored by ASCO, ASTRO, the Prostate Cancer Foundation, and the Society of Urologic Oncology Currently, men with a rise in PSA velocity of 0.75 ng/mL/year or more are typically referred for biopsy. But a team led by Judd W. Moul, MD, hypothesized that lower prostate-specific-antigen velocity values could boost the sensitivity of prostate cancer detection among younger men. “In the past few years, 60 or younger has become the peak age for prostate cancer diagnosis,” said Dr. Moul, Chief of Urologic Surgery at Duke University Medical Center. “Using age-adjusted PSA velocity makes it much more likely that we will detect cancers in men of this age.”Figure: Judd Moul, MD: “Using age-adjusted PSA velocity makes it much more likely that we will detect cancers in men under 60.”11,347 Men The researchers correlated age-normalized PSA velocity values with biopsy status in 11,347 men who underwent PSA testing between January 1988 and February 2005. A total of 145,593 PSA values were assessed. The study showed that for men aged 40 to 59 years, a PSA velocity above 0.25 ng/mL/year can improve sensitivity with reasonable specificity. For men aged 60 to 70, a PSA velocity of 0.50 ng/mL/year is a reasonable cutoff, Dr. Moul reported. The conventional threshold of 0.75 ng/mL/year is an accurate predictor for men at or above age 70, he said. The age-adjusted thresholds identified prostate cancer in an additional 37 men aged 40 to 59 and an additional 18 men aged 60 to 69, compared with using the traditional 0.75 ng/mL/year threshold. The new PSA velocity cutoffs for men 40 to 59 and 60 to 69 had sensitivity values of 52% and 40%, respectively, compared with 26.5% and 31% for the traditional cutoffs. Specificities were only slightly diminished, from 94% to 84% in the younger men and from 91% to 77% in those aged 60 to 70. The researchers used receiver operating curves, a graphical representation of the tradeoff between the false-negative and false-positive rates for every possible cutoff, to arrive at the age-adjusted values. There were limitations to the study, Dr. Moul noted. All the PSA values came from urology patients rather than the general public. In addition, the study did not adjust for abnormal digital rectal exams, because it identified only 4.7% of prostate cancers in the study. The moderator of an ASCO news conference that highlighted the study, Laurence Klotz, MD, Professor of Surgery at the University of Toronto, called the findings encouraging. “We need a better way to determine who should be biopsied and this is one way to refine it,” he said. “But before the new thresholds are put into practice, the concept needs validation.” Prediction of Aggressiveness The second study, conducted by the Scandinavian Prostate Cancer Group Trial-4, found that PSA change during the first two years of follow-up can help to predict the development of advanced prostate cancer. But the use of this variable as a decision tool for clinical intervention appears limited because of its low sensitivity and specificity in predicting outcomes, the researchers concluded.Figure: Laurence Klotz, MD: “The research supports the idea that PSA kinetics may be a way to identify individuals who have aggressive disease.”Led by Katja Fall, MD, PhD, of the Department of Medical Epidemiology and Biostatistics at the Karolinska Institute in Stockholm, the researchers assessed serial PSA measurements in a cohort of 297 men who were diagnosed with localized, Stage T1b, T1c, or T2 prostate cancer and who were randomized to watchful waiting. The patients were followed for a mean of 7.8 years, during which time 21% developed metastases and 12% died of their disease. During the first two years of follow-up, the risk of aggressive disease increased by 5% for each 2 ng/ml/year increase in initial PSA. Overall, 21% of men with fast-rising PSA developed metastatic disease or died within six years of diagnosis, compared with 8% of men with slow-rising PSA. However, there was no specific cutoff point for PSA velocity above which high sensitivity in predicting outcomes was combined with high specificity. Dr. Klotz said that like Dr. Moul's study, “the Scandinavian research supports the idea that PSA kinetics may be a way to identify individuals who have aggressive disease.” That said, other studies do not support the use of PSA kinetics in prostate cancer detection, he added. “We still need more sophisticated ways of looking at it.”

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