Adding PCA3 to PSA improves prostate cancer detection
Despite revolutionizing the evaluation and treatment of prostate cancer, PSA testing is hampered by a lack of agreement over the optimal PSA thresholds for cancer detection. PCA3 encodes a prostate-specific messenger (m)RNA that is the target of a novel urinary molecular assay for prostate cancer detection.
To examine the utility of adding PCA3 to PSA testing to predict prostate cancer detection, John Wei and colleagues from the University of Michigan in Ann Arbor gathered urinary samples after attentive digital rectal examination (DRE) from 187 men before they underwent ultrasound-guided, 12-core prostate biopsy.
The team notes in the journal Cancer that the urine PCA3/RNA mRNA ratio scores were calculated within 1 month, and serum PSA was measured within 6 months of the biopsy, and the findings related to biopsy results.
An abnormal DRE was recorded for 16% of patients. The average PSA level was 8.7 ng/ml, while the average PCA3 score was 41.1. In all, 46.5% of patients were diagnosed with prostate cancer at biopsy, of who 74.7% had Gleason 6 or 7 disease, and 25.3% had Gleason score ≥8.
A PCA3 score >35 had a sensitivity, specificity, positive predictive value, and negative predictive value for predicting a positive biopsy of 52.9%, 80%, 69.7%, and 66.1%, respectively. Serum PSA alone had an area under the receiver operating characteristics curve for predicting prostate cancer of 0.63, which rose to 0.71 with the combination of PSA and PCA3.
Logistic regression analysis demonstrated that PCA3 was an independent predictorfor positive biopsy, even after adjusting for factors such as age, family history, number of previous biopsies, DRE results, and PSA.
It was found that increasing PCA3 scores led to a rise in the proportion of positive biopsies, such that a PCA3 score <5 indicated a low risk, a score of 5–34 indicated moderate risk, a score of 35–100 indicated a high risk, and a score >100 indicated a very high risk, with 10.5%, 38.2%, 64.7%, and 86.7%, respectively, of biopsies being positive.
The team concludes: “PCA3 may serve as a useful adjunct to determine the risk for a positive prostate biopsy and may be useful in counseling men who are contemplating a repeat biopsy; although the question remains whether we merely are contributing to the over-diagnosis of prostate cancer that is not clinically significant.”
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By Liam Davenport