Clinical-genomic Characterization Unveils More Aggressive Disease Features in Elderly Prostate Cancer Patients with Low-grade Disease

Abstract Background Over 20% of men diagnosed with prostate cancer (PC) are ≥75 yr old. More objective disease-specific indices for predicting outcomes beyond chronological age are necessary. Objective To analyze age-related differences in clinical-genomic prognostic features of aggressiveness in localized PC. Design, setting, and participants A retrospective multicenter cross-sectional study reported the use of the Reporting Recommendations for Tumor Marker Prognostic Studies (REMARK) guidelines. Clinical-genomic data of patients who underwent a prostate biopsy or radical prostatectomy (RP) were obtained from the Decipher Genomic Resource Information Database (NCT02609269). Intervention Our analyses focused on the 22-gene Decipher genomic classifier (GC) and 50-gene (PAM50) models in the biopsy and RP cohorts stratified by age. Outcome measurements and statistical analysis The primary endpoint was the impact of age on GC scores and PAM50 molecular subtypes. Prognostic indices including Decipher GC scores, PAM50 molecular subtypes, National Comprehensive Cancer Network risk categories, and ISUP grade groups (IGGs) were stratified by age using multivariable logistic regression analyses. Results and limitations Within histological low-risk IGGs, there were a higher proportion of patients with high-risk Decipher biopsy scores with age (age Conclusions These data demonstrated that elderly men with favorable pathology (IGG 1–2), might harbor more aggressive disease than younger patients based on validated GC scores. Patient summary The presented clinical-genomic data demonstrate that elderly patients with low-risk prostate cancer might harbor more aggressive disease than their younger counterparts. This suggests that standard well-accepted paradigm of elderly prostate cancer patients not being aggressively treated, based solely on their chronological age, might need to be reconsidered.