Translating Genetic Risk for Prostate Cancer to the Clinic
Translating Genetic Risk for Prostate Cancer to the Clinic
Various PrCa biomarkers have been developed with PCA3 being one of the best validated candidates. PCA3 is a noncoding, prostate-specific mRNA that is highly overexpressed in PrCa cells, and upregulated more than 60-times compared with normal PrCa cells. It is feasible to perform quantitative PCA3 testing from urine sediments. The assay utilizes whole urine following a DRE. PCA3 and PSA mRNAs are quantified and the PCA3 score is determined based on the PCA3/PSA mRNA ratio.
PCA3 has been approved by the US FDA as a guide for repeating a prostate biopsy in men with an initial negative biopsy and PSA of 2 ng/ml or above and as a guide for initial biopsies in patients with PSA of between 4 and 10 ng/ml and a negative DRE. Unlike serum PSA, the PCA3 score does not increase with prostate volume. PCA3 is independent of PSA levels and previous biopsies. The PCA3 score is significantly correlated with total tumor volume in prostatectomy specimens and is also associated with a prostatectomy Gleason score of 7 or greater. In a prospective European study of 463 men, the positive repeat prostate biopsy rate following an initial negative biopsy was 28%. It was found that the higher the PCA3 score, the greater the probability of a positive repeat biopsy. The PCA3 score (cutoff of 35) had a greater diagnostic accuracy than free:total PSA ratio.
The application of PCA3 as a biomarker in patients on active surveillance was evaluated as part of the PASS. Urine samples for PCA3 analysis were collected prospectively from 387 men participating in the PASS study and correlated with clinical and pathology findings. PCA3 scores were associated with higher volume of disease, biopsy positivity and the presence of high-grade disease. The association of a high PCA3 score with a positive prostate biopsy was statistically significant with an OR of 1.41.
PCA3 mRNA Assay
Various PrCa biomarkers have been developed with PCA3 being one of the best validated candidates. PCA3 is a noncoding, prostate-specific mRNA that is highly overexpressed in PrCa cells, and upregulated more than 60-times compared with normal PrCa cells. It is feasible to perform quantitative PCA3 testing from urine sediments. The assay utilizes whole urine following a DRE. PCA3 and PSA mRNAs are quantified and the PCA3 score is determined based on the PCA3/PSA mRNA ratio.
PCA3 has been approved by the US FDA as a guide for repeating a prostate biopsy in men with an initial negative biopsy and PSA of 2 ng/ml or above and as a guide for initial biopsies in patients with PSA of between 4 and 10 ng/ml and a negative DRE. Unlike serum PSA, the PCA3 score does not increase with prostate volume. PCA3 is independent of PSA levels and previous biopsies. The PCA3 score is significantly correlated with total tumor volume in prostatectomy specimens and is also associated with a prostatectomy Gleason score of 7 or greater. In a prospective European study of 463 men, the positive repeat prostate biopsy rate following an initial negative biopsy was 28%. It was found that the higher the PCA3 score, the greater the probability of a positive repeat biopsy. The PCA3 score (cutoff of 35) had a greater diagnostic accuracy than free:total PSA ratio.
The application of PCA3 as a biomarker in patients on active surveillance was evaluated as part of the PASS. Urine samples for PCA3 analysis were collected prospectively from 387 men participating in the PASS study and correlated with clinical and pathology findings. PCA3 scores were associated with higher volume of disease, biopsy positivity and the presence of high-grade disease. The association of a high PCA3 score with a positive prostate biopsy was statistically significant with an OR of 1.41.