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

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.

Keywords: BMI; DNA damage; PPPM/3P medicine; ageing; apoptosis; behavioural patterns; benignancy; biomarker panel; blood; cell-free nucleic acids; chronic inflammation; endothelin-1; homocysteine metabolism; immune system; individualised patient profiling; ischemia; liquid biopsy; malignancy; melatonin; metabolomics; microbiome; mitochondriopathy; modifiable; molecular patterns; nitric oxide; non-modifiable; oxidative stress; patient stratification; personalisation of medical services; predictive diagnostics; preventable; prostate cancer; risk factors; sleep quality; strategic paper; systemic effects; targeted prevention.

Figure 1

Systemic effects involved in PCa development and progression. Explanatory notes: (A) mitochondrial dysfunction, excessive ROS, oxidative stress; (B) circadian rhythm disruption; (C) inflammation; (D) hypoxia; (E) dysbacteriosis.

Figure 2

PCa-relevant risk assessment, individualised prediction and targeted prevention [3].