Prostate Cancer (PCa) is the most commonly diagnosed cancer and the second leading cause of cancer related deaths in men. Major issues associated with PSA testing for the initial diagnosis of PCa are: 1- the absence of a cut-off value associated with high specificity and sensitivity, and 2- PSA is organ but not cancer-specificit SelectMDx is a non-invasive post-digital rectal (DRE) urine methylation assay available in clinical practice to improve patient selection for initial prostate biopsy. A validated urinary 3 genes panel (HOXC6, TDRD1 and DLX1) showed high accuracy (AUC =0.77) for the detection of clinically significant (csPCa) compared with PSA and PCA3 test
Aim of the present study is to prospectively evaluate and compare performance of SelectMDx, total PSA and multiparametric magnetic resonance (mpMRI) of the prostate in men candidate for prostate biopsy.
Primary Objective:- To determine the dignostic performance as area under the curve (AUC), sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV) of SelectMDx in comparison with total PSA and mpMRI in predicting PCa and clincial significant (csPCa) at biopsy.Expected results : - In patients with clinical suspicious of PCa we can expect a positive SelectMDx score for patients with PCa at biopsy, while a negative SelectMDx score in negative biopsies. - SelectMDx may be a more specific biomarker for csPCa tham total PSA,
This is a prospective study. 100 men scheduled for prostate biopsy, based on elevated total PSA level (>3 ng/ml confirmed) or abnormal DRE, will be consecutively enrolled
mpMRI- All subjects included into the analysis will be submitted to a mpMRI using a 3 Tesla MR scanner (GE Discovery MR750).
SelectMDx. - First-voided urine samples (approximately 30 ml) will be collected after a standardized DRE, consisting of three stroke per lobe.
To improve the identification of patients with csPCa new imaging techniques and molecular markers have been developed. However there is too limited data to implement these markers into routine screening programmes. The high sensitivity and NPV of mpMRI for identifying aggressive disease caused an increasing use of this imaging modality in PCa-diagnosis. The novel urinary biomarker-based risk score, SelectMDx, has shown preliminary high sensitivity and NPV for csPCa.
The present study aims to investigate the diagnostic performance of the SelectMDx score and the association between the SelectMDx and mpMRI outcomes in patients undergoing prostate biopsies. The results of our research could have important clinical implications, guiding clinicians in identifying patients at risk for csPCa, selecting patients for further diagnostics and avoiding overtreatment.
Expected results and clinical practice implications:
- In patients with clinical suspicious of PCa (due to increased PSA level and/or abnormal DRE) we can expect a positive SelectMDx score for patients with both PCa and csPCa at biopsy, while a negative SelectMDx score in negative biopsies. If these data would be confirmed, prostate biopsy could be avoided/deferred in selected patients presenting with a negative SelectMDx.
- SelectMDx may be a more specific biomarker for csPCa tham total PSA, increasing the discrimination between neoplasm and benign conditions.
- In patients with csPCa at biopsy we can expect a higher SelectMDx score than those with an indolent PCa. If these data would be confirmed, SelectMDx can be of great help in selecting low-risk patients for Active Surveillance (AS) treatment.
- In patients with a positive mpMRI (PI-RADS 4-5 lesions) we can expect to have a higher SelectMDx score.
- In patients with a negative mpMRI and PCa at biopsy, we can expect to have a positive SelectMDx score. If these data will be confirmed, we can overcome the concern of false-negative mpMRI outcome.
- On the other hand, in patients with a positive mpMRI and no PCa at biopsy, we can expect to have a negative SelectMDx score. If these data could be confirmed, we can select patients to undergo further invasive diagnostic procedures over follow-up.
- In patients with PI-RADS 3 equivocal lesions on mpMRI, for which performing a biopsy is still under debate, we could expect to have a positive and higher SelectMDx score for those with PCa at biopsy when compared to those with a negative biopsy. If these data are confirmed, we can set up our decision whether to biopsy or not these equivocal lesions supported by the SelectMDx score.