MP53-05 PERFORMANCE OF 3T MULTIPARAMETERIC MRI IN DIAGNOSIS OF PROSTATE CANCER IN COMPARISON WITH WHOLE MOUNT HISTOPATHOLOGY: A 5 YEAR EXPERIENCE

INTRODUCTION AND OBJECTIVES: Prostate cancer (PCa) screening and diagnosis would benefit significantly from more accurate, non-invasive techniques. Multimodal approaches incorporating different information sources in a synergistic manner will improve and objectify patient management. In this study a 2-gene (HOXC6 and DLX1) mRNA biomarker assay for the detection of high-grade (GS 7) PCa was validated. These expression levels were combined with traditional PCa risk factors into a risk score expressing an individual patient0s risk for harboring high-grade PCa. METHODS: Urine samples from 905 men from two independent cohorts were collected after digital rectal examination (DRE) and prior to biopsy. The combined cohorts were used to validate the 2-gene mRNA qPCR assay. The first cohort of 519 samples was used as training set for the development of the multimodal highgrade PCa risk score, which was subsequently validated in the second cohort of 386 samples. Logistic regression models were built to model patient risk, of which the performance was evaluated with the area under the curve (AUC) of the receiver operating characteristic (ROC). RESULTS: The mRNA assay could be readily assessed in whole urine samples and proved to be a good predictor for the detection of high-grade PCa with an AUC of 0.74 (95% confidence interval (CI): 0.70-0.78). The multimodal approach reached an AUC of 0.88 (95% CI: 0.85-0.91) for men with high-grade PCa, with the mRNA assay, PSA density and DRE (only in training cohort) as strongest, most significant components, in addition to PSA, age and family history of PCa. The model, trained in the first cohort, proved to be robust, with a successful validation in the second cohort (p1⁄40.222). This mRNA-based approach was significantly better in identifying highgrade PCa patients compared to PCA3 (AUC: 0.68; pu003c0.001) and the prostate cancer prevention trial risk calculator (PCPTRC; AUC: 0.77; pu003c0.001). In a sensitivity analysis the risk score led to improved risk stratification for men in a PSA grey zone, with serum levels u003c10ng/ml. The AUC of 0.82 (95% CI: 0.77-0.87) of the risk score again significantly outperformed PCA3 (AUC: 0.72; p1⁄40.007) and PCPTRC (AUC: 0.66; pu003c0.001). CONCLUSIONS: The risk score based on the 2-gene mRNA urine assay combined with traditional clinical risk factors resulted in a significantly better patient risk stratification compared to current methods in clinical practice.