Incorporation of Urinary Prostate Cancer Antigen 3 and TMPRSS2:ERG into Prostate Cancer Prevention Trial Risk...

Area of Science:

• Urology
• Oncology
• Biomarker Research

Background:

• The Prostate Cancer Prevention Trial Risk Calculator (PCPTRC) is a widely used tool for predicting prostate cancer biopsy outcomes.
• Established risk factors are utilized in the PCPTRC, but its predictive accuracy can be further enhanced.

Purpose of the Study:

• To evaluate the impact of integrating novel urinary markers, prostate cancer antigen 3 (PCA3) and TMPRSS2:ERG (T2:ERG), into the PCPTRC.
• To determine if these markers improve the risk calculator's discrimination, accuracy, and clinical net benefit for predicting prostate cancer.

Main Methods:

• A Bayesian modeling approach was employed to update the PCPTRC by combining data from a Michigan cohort with existing PCPTRC data.
• The updated PCPTRC was validated on an independent Early Detection Research Network (EDRN) cohort.
• Discrimination, calibration, and decision curve analysis were used to compare the updated and existing PCPTRC models.

Main Results:

• The updated PCPTRC incorporating PCA3 demonstrated improved predictive accuracy on the independent validation cohort.
• The area under the curve for predicting high-grade prostate cancer increased from 70.0% for the original PCPTRC to 76.4% with PCA3 added.
• Adding T2:ERG provided negligible additional predictive utility beyond PCA3, with the combined model achieving 77.1% AUC.

Conclusions:

• Incorporating PCA3 into the PCPTRC significantly enhances its predictive performance on an independent cohort.
• T2:ERG offers limited additional value when PCA3 is already included in the risk prediction model.
• The updated PCPTRC with PCA3 has been made available online for clinical use, pending further validation.