Can clinico-genomic characterization reveal more aggressive prostate cancer among older patients with lower Gleason grade groups?

e17150 Background: The prevalence of prostate cancer increases with age, with the majority of patients over 65 estimated to harbor the disease. Current guidelines emphasize risk stratification and life expectancy in choosing next steps in management. In the growing elderly population, further biomarkers are needed to predict outcomes beyond chronologic age to tailor treatment strategies. We evaluated age-related differences in clinic-genomic prognostic indices of aggressiveness in localized prostate cancer. Methods: Clinical and genomic data for 107471 patients from the Myriad Prolaris Prostate Cancer Database was obtained. Conventional and genomic prognostic indices were analyzed including Prolaris treatment grouping (active surveillance (AS) vs single treatment vs multimodal treatment), cell cycle risk (CCR) scores, NCCN risk groups, tumor stage, and Gleason groups (GG). Multivariable logistic regression analyses were performed to evaluate the association of age (less than vs greater than 75), prostate specific antigen level (PSA), tumor stage (T1a-T1c vs T2a-T2c vs T3a), positive biopsy cores (less than vs greater than 50%), and GG (1-2 vs 3-5) with Prolaris treatment scores (AS and single treatment vs multimodal treatment). Results: With increasing age, we observed a higher proportion of high GG and more aggressive Prolaris treatment grouping. Even within the same prostate cancer GG, the suggested treatment increased in aggressiveness by age (Figure). On multivariable analysis, there was a statistically significant increase in Prolaris treatment scores with increasing age groups (60-65 – HR 1.15; 95% CI 1.04-1.28, 65-70 – HR 1.30; 95% CI 1.18-1.43, 70-75 – 1.39; 95% CI 1.26-1.54, 75-80 – 1.56; 95% CI 1.40-1.74, > 80 – HR 1.83; 95% CI 1.60-2.08). Additionally, higher PSA levels (HR 1.21; 95% CI 1.20-1.21), GG (HR 105.70; 95% CI 96.75-115.47), tumor stages (T2a-T2c – HR 1.27; 95% CI 1.17-1.39), T3a (HR 9.94; 95% CI 6.25-15.82) and number of positive biopsy cores (HR 4.02; 95% CI 3.79-4.27) was associated with more aggressive Prolaris treatment scores. Conclusions: Older men tend to harbor worse disease based on genomic risk models compared to their younger counterparts. Using chronologic age can cause significant undertreatment in this population. Using clinical-genomic characterization can provide better treatment individualization decisions.