Systemic Effects Reflected in Specific Biomarker Patterns Are Instrumental for the Paradigm Change in Prostate Cancer Management: A Strategic Paper

SIMPLE SUMMARY: Prostate cancer (PCa) incidence is increasing globally. The costs of treating PCa are currently increasing more rapidly than those of any other cancer, due to an overtreatment of slowly developing disease on one hand and underestimation/therapy resistance of particularly aggressive PCa subtypes on the other hand. How to reverse this trend? PCa is a multi-factorial disease resulting from an imbalanced interplay between health risks and protective factors. Suboptimal behavioural patterns and abnormal stress reactions, amongst others, cause negative systemic effects synergistically involved in PCa development and progression. Further, systemic effects are relevant for the entire human body and, therefore, are reflected in body fluids such as blood. Blood profiles specific for PCa are, therefore, instrumental for the risk assessment in PCa predisposed individuals, targeted disease prevention and personalised treatment algorithms—altogether 3P (predictive, preventive and personalised/PPPM) medicine as a new paradigm in PCa management. This strategic article initiated by the European Association for Predictive, Preventive and Personalised Medicine (EPMA, Brussels) and European Medical Association (EMA, Brussels) and created by an international multi-professional group of experts, highlights systemic effects in PCa initiation, development and progression, demonstrates evident challenges and provides expert recommendations in the framework of 3P medicine. ABSTRACT: Prostate cancer (PCa) is reported as the most common malignancy and second leading cause of death in America. In Europe, PCa is considered the leading type of tumour in 28 European countries. The costs of treating PCa are currently increasing more rapidly than those of any other cancer. Corresponding economic burden is enormous, due to an overtreatment of slowly developing disease on one hand and underestimation/therapy resistance of particularly aggressive PCa subtypes on the other hand. The incidence of metastatic PCa is rapidly increasing that is particularly characteristic for young adults. PCa is a systemic multi-factorial disease resulting from an imbalanced interplay between risks and protective factors. Sub-optimal behavioural patterns, abnormal stress reactions, imbalanced antioxidant defence, systemic ischemia and inflammation, mitochondriopathies, aberrant metabolic pathways, gene methylation and damage to DNA, amongst others, are synergistically involved in pathomechanisms of PCa development and progression. To this end, PCa-relevant systemic effects are reflected in liquid biopsies such as blood patterns which are instrumental for predictive diagnostics, targeted prevention and personalisation of medical services (PPPM/3P medicine) as a new paradigm in the overall PCa management. This strategic review article highlights systemic effects in prostate cancer development and progression, demonstrates evident challenges in PCa management and provides expert recommendations in the framework of 3P medicine.