Precision intervention for prostate cancer: Re-evaluating who is at risk

Abstract

The vast majority of new prostate cancer diagnoses are low-grade tumors that are monitored by active surveillance rather than undergoing immediate treatment. However, a subset of men will progress to advanced prostate cancer which may result in lethality, and these men are likely to benefit from early intervention to prevent or delay such progression. For this high-risk group, which includes aged men, men of African descent, and those with a hereditary predisposition to prostate cancer, informed risk stratification can be the cornerstone of clinical decision making and treatment intervention. In this review, we discuss the importance of a precision intervention approach that considers the cumulative risk for a given patient or population to develop prostate cancer or to progress to lethal disease, with particular focus on the interplay of major determinants of high-risk disease.

Keywords: Active surveillance; Genetic variants; Mitochondrial DNA; Precision prevention and treatment; Risk factors.

Figure 1.. Prostate cancer progression and risk factors.

Progression pathway for prostate cancer. The stages of prostate cancer development and progression are shown, together with the risk factors likely to be significant at each stage and their suggested contribution to increasing prostate cancer risk (from low to high risk). Specific major genetic alterations are depicted for the risk of genetic predisposition.

Figure 2.. Cumulative prostate cancer risk assessment model for improved precision intervention.

A comprehensive risk assessment is employed for the population at risk for prostate cancer, which incorporates genetic risk profiling, to determine the cumulative risk for prostate cancer (low to high) for each individual or population. Of note is that genetic risk profiling includes the assessment of both nuclear (e.g., PRS, HOXB13 G84E, BRCA2, NKX3.1 154C<T) as well as mitochondrial (e.g., mtDNA mutations, mtSNPs) alterations. Patient stratification to the most effective mode of intervention based on their cumulative prostate cancer risk is depicted that highlights a precision intervention paradigm for prostate cancer.