Experimental Study of Proclarix as a tumor marker for the Early Detection of Clinically Significant Prostate Cancer

Abstract

Introduction Early detection of clinically significant prostate cancer (csPCa) reduces the mortality of the disease. The initial suspicion of PCa is based on elevated serum prostate-specific antigen (PSA) and/or an abnormal digital rectal examination (DRE), and requires further confirmation with prostate biopsy. However, this approach leads to unnecessary biopsies and an overdetection of insignificant PCa. Proclarix, a recently introduced blood-based marker, that provides a risk score for the detection of csPCa based on the serum determination of Thrombospondin-1, Cathepsin D, total PSA, free PSA, and age. Hypothesis The primary hypothesis of the study was that Proclarix could enhance the early detection of csPCa, reducing the need for mpMRI and improving the selection of candidates for prostate biopsies. Additionally, Proclarix is expected to be correlated with the aggressiveness of PCa. Objective Thus, our main objective was to investigate the clinical utility and effectiveness of Proclarix in men suspected csPCa before and after mpMRI. Materials and Methods The current doctoral thesis is being presented as a compendium of seven publications. The first being a systematic review of the literature to assess Proclarix's clinical utility. The subsequent publications focus on a cohort of 751 men with suspected PCa from two European centers, using prospectively constructed databases and frozen serum samples. Inclusion criteria involved men with elevated serum PSA levels and/or abnormal DRE scheduled for mpMRI before prostate biopsy. Biopsies were conducted within specified timeframes. The aggressiveness of PCa was assessed using surrogate endpoints such as grade group, clinical stage, biochemical recurrence risk, and surgical pathology. Results The systematic review of the literature reported the potential benefits of Proclarix, particularly in patients with specific characteristics (PSA levels between 2 and 10ng/mL, normal DRE and prostate volume >= 35mL). . Subsequent publications demonstrated that Proclarix's utility extended to all men with suspected PCa, regardless of PSA levels or prostate volume. It significantly reduced unnecessary biopsies and improved biopsy candidate selection, particularly in cases of negative mpMRI results and PI-RADS 3 lesions. Proclarix outperformed other prediction tools like PSA density and the Rotterdam-MRI risk-calculator in detecting csPCa. Furthermore, a correlation between Proclarix and PCa aggressiveness was observed. Conclusions Proclarix is a valuable CE-approved test for assessing the risk of csPCa, suitable for all men with suspected PCa, without restrictions based on PSA levels or prostate volume. Combining Proclarix with mpMRI enhances their efficacy. In cases of negative mpMRI, Proclarix showed high sensitivity in detecting csPCa, reducing unnecessary biopsies. In positive mpMRI cases, Proclarix significantly decreased the number of unnecessary biopsies. When compared to other prediction tools, Proclarix proved more effective in csPCa detection. Additionally, it exhibited a correlation with PCa aggressiveness, highlighting its potential in risk assessment and patient management.

Date of Award	13 Dec 2023
Original language	English
Supervisor	Enrique Trilla Herrera (Director) & Juan Morote Robles (Director)