Physicians fine-tune PSA velocity measurements to improve cancer detection

Factors like age, PSA history and the presence of prostatitis are adding more relevance to PSA velocity measurements.

Issue: April 1, 2006

SAN FRANCISCO — Physicians are continually developing new ways to interpret the rate of prostate-specific antigen (PSA) change over time (PSA velocity) and how it relates to the aggressiveness of prostate cancer. Three studies presented at the 2006 Prostate Cancer Symposium showed that factors like age, PSA history and the presence of prostatitis can all affect PSA velocity measures.

“There are a lot of recent data supporting the biological significance of PSA kinetics in every stage of prostate cancer,” said presenter Laurence Klotz, MD, chief of the division of urology at the University of Toronto. “Untreated patients with low-grade cancer whose PSA takes many years to double are likely to have slow-growing disease and may not require any treatment. But those whose PSA doubles in less than three years, even with favorable-risk disease, appear to have a more aggressive course, and are the patients in whom definitive therapy is warranted.”

Age and PSA

A study led by Judd W. Moul, MD, chief of urologic surgery at Duke University Medical Center (DUMC), Durham, N.C., found that adjusting PSA velocity for age enabled physicians to find more prostate cancers among younger men than traditional PSA velocity testing.

Moul and colleagues compared the traditional PSA velocity threshold value, where more than 0.75 ng/ml/year is considered high for all age groups with age-adjusted values where the threshold values were set at 0.25 ng/ml/yr for patients aged 40 to 59 and 0.50 ng/ml/yr for those aged 60 to 69. Men older than 70 were evaluated with traditional PSA velocity criteria.

They examined a cohort of 11,347 men undergoing PSA testing at DUMC from January 1988 to February 2005. The age-normalized PSA velocity values detected prostate cancer in an additional 37 men aged 40 to 59 and an additional 18 men aged 60 to 69. The new PSA velocity values in men ages 40 to 59 and 60 to 69 had sensitivity values of 0.519 and 0.398 compared to a sensitivity of 0.265 and 0.306 for the traditional threshold. Specificity values in these two groups were only slightly diminished, 0.841 and 0.773, from those associated with traditional value (0.935 and 0.907).

They concluded that age-normalized PSA velocity threshold was more sensitive than traditional PSA velocity threshold for detecting prostate cancer.

PSA history

Another study conducted by the Scandinavian Prostate Cancer Group Trial-4 found that initial PSA levels and PSA velocity taken two years after a prostate cancer diagnosis may predict which men are most likely to develop aggressive disease.

Researchers led by Katja Fall, MD, PhD, of the department of medical epidemiology and biostatistics at Sweden’s Karolinska Institute in Stockholm, assessed serial PSA measurements among 297 men with localized prostate cancer who were being observed as part of a watchful waiting approach. The researchers followed patients for a mean of 7.8 years, during which time 21% developed metastases and 12% died of prostate cancer.

Fall and colleagues found that both initial PSA level at the diagnosis of prostate cancer and PSA velocity over the following two years provided information about a man’s prognosis.

Aggressive-disease risk increased by about 5% for each 2 ng/ml/yr increase in initial PSA. Twenty-one percent 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, researchers could not determine a definitive threshold to support a decision for therapy or watchful waiting. Fall concluded that reliable decision-making tools are still needed to distinguish the patients who would most benefit from treatment.

Prostatitis and PSA velocity

A third study found that physicians should be cautious with PSA readings, because high PSA values can result from either prostate cancer or prostatitis. Led by Scott Eggener, MD, urologic oncology fellow at Memorial Sloan-Kettering Cancer Center, New York, and William Catalona, MD, professor of urology at Northwestern University, the study calculated PSA velocity among 1,851 men who had a first biopsy between 1991 and 2001. They evaluated the potential association between PSA velocity in the year prior to biopsy and the rate of prostate cancer and prostatitis found on the first biopsy.

Men with a modest increase in PSA velocity (< 1.0 ng/ml/yr) had an increased risk of prostate cancer on biopsy. However, more dramatic rises in PSA, especially over a very short time interval, raised the probability of prostatitis while lowering the probability of cancer. Men with very high PSA velocity (> 4.0 ng/ml/yr) were just as likely to have prostatitis.

The researchers concluded that dramatic rises in PSA are as likely to be caused by prostatitis as by cancer, which is associated with modest PSA increases. – by Mark Palacio

For more information:

Eggener SE, Roehl KA, Catalona WJ. Prostatitis confounds the use of PSA velocity for prostate cancer detection. Abstract 4. Presented at: 2006 Prostate Cancer Symposium; Feb. 24-26, 2006; San Francisco.

Fall K, Garmo H, Andrén O, et al. Early PSA-curve characteristics and development of aggressive prostate cancer. Abstract 2. Presented at: 2006 Prostate Cancer Symposium; Feb. 24-26, 2006; San Francisco.

Moul JW, Sun L, Hotaling J, et al. Age-adjusted PSAV and prostate cancer screening. Abstract 1. Presented at: 2006 Prostate Cancer Symposium; Feb. 24-26, 2006; San Francisco.