RESEARCH HIGHLIGHTS Nature Reviews Urology 12, 1 (2015); published online 25 November 2014; doi:10.1038/nrurol.2014.326
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prospective validation trial has shown that measurement of urinary prostate cancer antigen 3 (PCA3) noncoding RNA adds value to screening for early detection of prostate cancer, but the data also suggest that the predictive value of PCA3 could be further improved by integrating it into a multifactorial risk calculator. The measurement of serum levels of PSA has enabled routine screening for prostate cancer, and treatment before the manifestation of advanced disease. However, PSA is a blunt instrument that can fail to differentiate between cancer and nonmalignant prostate pathologies, and between low-grade and high-grade cancer, leading to extensive overtreatment. To discriminate between these possibilities, a finding of an elevated serum PSA level is followed by biopsy of the prostate and histopathological characterization. Biopsy carries risks of sepsis and morbidity, as well as the possibility of false‑negative results, which means that initial negative results are not definitive, and repeat biopsies are frequently required. To improve the diagnosis of prostate cancer, urologists must have access to tools that can accurately predict the risk of clinically relevant, high-grade disease, to enable optimal targeting of biopsy and treatment procedures. PCA3 testing is FDA-approved to facilitate biopsy decision-making, specifically in men with previous negative biopsy results. High sensitivity and specificity have been reported for this test, but validation has been lacking. Wei and colleagues at 11 US institutions have addressed this issue by comparing PCA3 levels with biopsy results in 859 men, 562 undergoing initial biopsy and 297 having a repeat procedure. In all cases, biopsy was indicated by screening characteristics, principally elevated or increasing PSA, or abnormal digital rectal examination (DRE). The relationship between PCA3 scores and biopsy results was examined in several different ways.
In the initial biopsy group, the positive predictive value was 80%, as 140 men had PCA3 >60 (the test uses an arbitrary, unitless scale), and 112 of these had prostate cancer, of any grade. Sensitivity was 0.42, as 112 of 264 men with cancer had PCA3 >60, and specificity was 0.91, as only 28 of 298 men with negative biopsies had PCA3 >60. In the repeat biopsy group, the negative predictive value was 88% (of 135 men with PCA3
PROSTATE CANCER
A
prospective validation trial has shown that measurement of urinary prostate cancer antigen 3 (PCA3) noncoding RNA adds value to screening for early detection of prostate cancer, but the data also suggest that the predictive value of PCA3 could be further improved by integrating it into a multifactorial risk calculator. The measurement of serum levels of PSA has enabled routine screening for prostate cancer, and treatment before the manifestation of advanced disease. However, PSA is a blunt instrument that can fail to differentiate between cancer and nonmalignant prostate pathologies, and between low-grade and high-grade cancer, leading to extensive overtreatment. To discriminate between these possibilities, a finding of an elevated serum PSA level is followed by biopsy of the prostate and histopathological characterization. Biopsy carries risks of sepsis and morbidity, as well as the possibility of false‑negative results, which means that initial negative results are not definitive, and repeat biopsies are frequently required. To improve the diagnosis of prostate cancer, urologists must have access to tools that can accurately predict the risk of clinically relevant, high-grade disease, to enable optimal targeting of biopsy and treatment procedures. PCA3 testing is FDA-approved to facilitate biopsy decision-making, specifically in men with previous negative biopsy results. High sensitivity and specificity have been reported for this test, but validation has been lacking. Wei and colleagues at 11 US institutions have addressed this issue by comparing PCA3 levels with biopsy results in 859 men, 562 undergoing initial biopsy and 297 having a repeat procedure. In all cases, biopsy was indicated by screening characteristics, principally elevated or increasing PSA, or abnormal digital rectal examination (DRE). The relationship between PCA3 scores and biopsy results was examined in several different ways.
In the initial biopsy group, the positive predictive value was 80%, as 140 men had PCA3 >60 (the test uses an arbitrary, unitless scale), and 112 of these had prostate cancer, of any grade. Sensitivity was 0.42, as 112 of 264 men with cancer had PCA3 >60, and specificity was 0.91, as only 28 of 298 men with negative biopsies had PCA3 >60. In the repeat biopsy group, the negative predictive value was 88% (of 135 men with PCA3
