ClinLabNavigator Blog: PSA Threshold for Prostate Biopsy

PSA Threshold for Prostate Biopsy
Sunday, September 02, 2007

One of the most difficult dilemmas that has arisen after widespread PSA testing is deciding the optimal PSA threshold at which prostate biopsy should be performed in asymptomatic patients. Using a PSA value that is too low results in unnecessary biopsies and detects indolent cancers, while using a threshold that is too high misses aggressive tumors. Traditionally, a PSA of 4.0 ng/mL has been recognized as the lower limit for biopsy consideration. Approximately 35% of men with a PSA level between 4 and 10 ng/mL have cancer. However, more recent studies have suggested that a cutoff of 4.0 is too high of a threshold for biopsy because 25% of men with PSA levels in the range of 2.5 to 4.0 have clinically significant cancer. Lowering the threshold to 2.6 would nearly double the rate of detecting cancer in men younger than 60 years old with little loss of specificity.

A recent study published in BJU International (2007;99:1427-31) examined the performance of the five most commonly used methods to measure PSA concentration. The study was comprised of 596 untreated Caucasian males referred to a urology clinic. Of this total, 314 men had histologically confirmed prostate cancer while 282 did not have detectable cancer in 8 to 12 biopsy cores. The median age of men with cancer was 66 years and the median age of the men without cancer was 63 years. The median PSA concentration in men with cancer was 6.2 ng/mL (range 5.8-6.6) compared to a median value of 3.8 ng/mL (range 3.1-4.5) in men without cancer.
The performance of the Beckman Coulter PSA assay in detecting prostate cancer at a threshold of 4.0 and 2.5 is shown below.

True Positive rate at 4.0 ng/mL was 78%
True Positive rate at 2.5 ng/mL was 92%
True Negative rate at 4.0 ng/mL was 51%
True Negative ratge 2.5 ng/mL was 34%

Another way to look at this data is to realize that 68 out of 314 men with prostate cancer (22%) had PSA values less than 4.0 ng/mL and would not have been referred for biopsy using this threshold. In contrast, only 26 men with prostate cancer (8%) were missed, when the PSA threshold was lowered to 2.5 ng/mL. Clearly, lowering the PSA threshold detects significantly more cancer cases.

However, the trade off for increased sensitivity is decreased specificity. When a PSA threshold of 4.0 ng/mL was used, 139 of 282 men without cancer (49%) had elevated PSA values, but the number of false positives increased to 187 (66%) when the threshold was lowered to 2.5 ng/mL. Thus, lowering the PSA threshold to 2.5 ng/mL, meant that almost two thirds of men referred for biopsy did not have detectable cancer.

The National Comprehensive Cancer Network guidelines recommend biopsy for men with a PSA higher than 2.5 ng/mL.

posted by Fred Plapp @ 7:08 PM,