August 2014, Vol 3, No 5

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PSA Trend Analysis May Help Avoid Unnecessary Biopsies

Delaying a prostate-specific antigen (PSA)-triggered prostate biopsy to allow for additional PSA assessments might have avoided more than 70% of subsequent biopsies, according to a study of negative biopsies for 28,000 men.

An analysis based on deceleration of PSA growth rate suggested that 80% of negative biopsies might have been avoided. A decline to a level below the prebiopsy PSA growth rate might have eliminated 72% of the biopsies, as reported at the 2014 American Urological Association Annual Meeting.

“This analysis of the diverse Veterans Affairs population suggests that a delay in a biopsy to allow for additional PSA testing may help avoid the biopsy,” Thomas Neville, PhD, founder and CEO, Soar BioDynamics, and colleagues concluded in a poster presentation.

“In many cases, subsequent PSA trends showed a decrease that could have reduced unnecessary biopsies by 72%. The fastest growth in PSA per year was also the most likely to decrease, with a 93% potential reduction in biopsies.”

Aggressive, potentially lethal prostate cancers exhibit a faster PSA growth rate compared with low-risk, indolent cancers. Most lethal prostate cancers produce smooth exponential growth in PSA above a no-cancer baseline, according to Neville. As the PSA growth rate increases, so does the lethality of the prostate cancer.

Benign conditions can also spark an increase in PSA growth rate, but unlike in aggressive cancers, the increase is often followed by a decline, which provides strong justification to delay a biopsy, Neville continued.

To estimate the potential of PSA growth rate trends to reduce unnecessary prostate biopsies, the researchers analyzed the Veterans Affairs health system database, which comprises 33 million PSA test results for 14 million men. The investigators searched for men who had negative prostate biopsies from 2001 to 2012 and at least 3 PSA measurements in the 2 years before biopsy plus at least 1 PSA measurement after the biopsy. The search yielded 28,314 men aged 50 to 75 years.

Using the resulting data from PSA tests, the investigators calculated estimates for 4 PSA-based parameters: the baseline cutoff value associated with no cancer, the PSA values associated with cancer, trends in cancer-
associated PSA values over time, and annual cancer-
associated PSA growth rate.

Neville and colleagues identified men who had decreases in PSA after a prostate biopsy that had been associated with an increasing PSA trend. The investigators grouped the men according to PSA growth rate and calculated the proportion of men who had postbiopsy declines in PSA for each PSA growth rate category.

The results suggest that the proportion of biopsies that could have been avoided increased with the baseline PSA growth rate. For example, 52% of biopsies could have been avoided for men with the slowest PSA growth rates of 0% to 5%. The estimated biopsy avoidance rate reached 93% for men whose PSA growth rates exceeded 100%.

The investigators then calculated the PSA levels associated with an 80% probability of finding cancer on biopsy across the categories of PSA growth rate. The calculations suggested that a PSA level of 5.2 ng/dL would be the 80% threshold value for men who had PSA growth rates of 15% to 30%. By contrast, a PSA level of 2.5 ng/dL would be the threshold for 80% cancer probability among men with PSA growth rates of >100%.

Long-term PSA monitoring can help distinguish the nature of a PSA elevation, such as an initial increase followed by a decrease, frequently observed in association with benign prostate conditions, Neville and colleagues noted in their presentation.

The results suggest several screening strategies to take advantage of the information provided by PSA trend analysis. PSA testing beginning when men are in their 40s could be used to establish a baseline for long-term trend analysis. Dynamic trend analysis could help inform PSA testing intervals and lead to earlier identification of lethal prostate cancers. Multivariable algorithms could be developed to individualize decision making regarding prostate biopsies.

“These new screening methods have the potential to identify early the men at greatest risk of life-threatening disease, while reducing unnecessary biopsies and over­diagnosis, treatment, and side effects,” the investigators concluded.

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