Low-risk prostate lesions: An evidence review to inform discussion on losing the “cancer” label

Abstract

Background: Active surveillance (AS) mitigates harms from overtreatment of low-risk prostate lesions. Recalibration of diagnostic thresholds to redefine which prostate lesions are considered “cancer” and/or adopting alternative diagnostic labels could increase AS uptake and continuation. Methods: We searched PubMed and EMBASE to October 2021 for evidence on: (1) clinical outcomes of AS, (2) subclinical prostate cancer at autopsy, (3) reproducibility of histopathological diagnosis, and (4) diagnostic drift. Evidence is presented via narrative synthesis. Results: AS: one systematic review (13 studies) of men undergoing AS found that prostate cancer-specific mortality was 0%−6% at 15 years. There was eventual termination of AS and conversion to treatment in 45%−66% of men. Four additional cohort studies reported very low rates of metastasis (0%−2.1%) and prostate cancer-specific mortality (0%−0.1%) over follow-up to 15 years. Overall, AS was terminated without medical indication in 1%−9% of men. Subclinical reservoir: 1 systematic review (29 studies) estimated that the subclinical cancer prevalence was 5% at <30 years, and increased nonlinearly to 59% by >79 years. Four additional autopsy studies (mean age: 54−72 years) reported prevalences of 12%−43%. Reproducibility: 1 recent well-conducted study found high reproducibility for low-risk prostate cancer diagnosis, but this was more variable in 7 other studies. Diagnostic drift: 4 studies provided consistent evidence of diagnostic drift, with the most recent (published 2020) reporting that 66% of cases were upgraded and 3% were downgraded when using contemporary diagnostic criteria compared to original diagnoses (1985−1995). Conclusions: Evidence collated may inform discussion of diagnostic changes for low-risk prostate lesions.