PROLIPSY

Prostate cancer (PCa) is one of the leading causes of cancer-related death in men (1). The aim of screening for PCa is to detect malignancy at an early and potentially treatable stage, thereby increasing the chance of cure. Current European standard for early PCa detection is the use of PSA screening (2). Although serum PSA has been used as a screening test for prostate cancer for over 20 years, the practice is controversial. As a screening test for prostate cancer, PSA lacks sensitivity and specificity for early disease. Furthermore, screening may lead to unnecessary biopsies, over-diagnosis, and overtreatment (3). Recently, new CE-IVD assays for early detection of prostate cancer such as Prostate Health Index (PHI) and prostate cancer associated 3 (PCA3) expression have been cleared by the FDA (4).
Blood-based biomarkers such as circulating tumour cells (CTCs), circulating free tumour DNA (cfDNA) and microRNAs (miRNAs) are potential indicators for the tumour burden of patients living with cancer. These minimal-invasive "Liquid biopsies" have received enormous attention because of its obvious clinical implications for personalized medicine such as identification and stratification of cancer patients. Prediction of prognosis in patients with curable disease can already be achieved in several tumour entities, particularly in breast cancer (5, 6). The application of Liquid biopsies for the early detection of PCa is of high public interest, but it faces serious challenges regarding specificity and sensitivity of the current assays. The systematic approach chosen in this project aims to assess different recently developed Liquid biopsy approaches for analytical, and clinical validity as novel non-invasive methods for early detection of PCa (in particular aggressive PCa) and minimal residual disease (MRD), which could improve risk assessment and stratification of PCa patients to future adjuvant therapies.
Reliable biomarkers enabling the detection of primary or minimal systemic disease that help to guide selective application of secondary therapies are urgently needed. Quantification and molecular characterization of circulating tumour cells (CTCs) as Liquid biopsy approaches are promising to gain profound understanding of the biology of PCa. A number of new innovative technologies to improve methods for CTC detection with extraordinarily high sensitivity have recently been developed (5, 7, 8). CTC enrichment and detection includes a large panel of technologies based on the different properties of CTCs that distinguish them from the surrounding normal hematopoietic cells, including: (i) physical properties (size, density, electric charges, deformability) and (ii) biological properties (surface protein expression, viability and invasion capacity) (5). Among the various CTC technologies, the CellSearch® system (CS) has gained considerable attention over the past years and is at present the only CTC assay cleared by the FDA for its use in patients with metastatic breast, prostate and colon cancer. Although this automated assay provides a high degree of reproducibility, a major consideration in detecting CTCs is the recent realization that CTCs that have undergone epithelial-mesenchymal transition (EMT) will not be detected by systems that rely upon EpCAM expression (5). The sensitivity and clinical utility of Liquid biopsy assays for early detection of PCa in eligible patients has still to be demonstrated in multicentre studies to reach the highest level of evidence required for introduction into clinical practice.
In this project, we will combine different Liquid biopsy approaches (CTCs, cfDNA, exosomes,
miRNA and proteins) for early detection of PCa with a special focus on the identification of
patients with aggressive PCa. The detection of high-risk PCa before metastasis signals
incurability is of utmost importance to lower mortality of PCa patients.