Table 1.

Precision prevention and early-detection principles

PrincipleKey concepts
Risk quantificationIdentification of individuals who will maximally benefit from prevention or early-detection strategies based on genetic, molecular, and other biomarker information. Risk may be conferred by inheritance, existence of preneoplastic conditions, or exposure.
Mechanistic foundationAn understanding of the basic biology of early carcinogenesis events, including genomic susceptibility, metabolic reprogramming, drivers of preneoplasia, the tumor microenvironment, immune modulation, and biomarkers that may define etiologic and risk heterogeneity.
Heterogeneity in phenotype and responsePreventive interventions or early-detection strategies may have different efficacy and toxicities in certain individuals based on their biological characteristics (Fig. 2).
TimingA prevention “sweet spot” may exist in terms of the timing of the preventive intervention or detection method. Optimal timing of preventive interventions or early-detection strategies requires a clear understanding of the etiologic window in which carcinogenic events are working.
Effective prevention modalitiesEffective interventions including risk-reducing surgery to remove tissue at risk, exposure modification, vaccination including immunoprevention, chemoprevention, treatment or removal of premalignant lesions, screening and early-detection methods based on molecular events. The optimal application of these interventions may depend on an individual's underlying risk profile.
Consideration of unintended effectsFavorable risk–benefit ratios for patients and/or cost–benefit ratios to governments or insurers may exist. Some very high-risk individuals may accept more intensive/invasive extreme preventive strategies (that may confer higher levels of toxicity) that would not be acceptable to the general population.