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

Abstract

395 Background: The prevalence of prostate cancer (PCa) increases with age, with the average age of diagnosis being 66. Current guidelines emphasize risk stratification and life expectancy in choosing next steps in management. In the growing elderly population, chronological age may be insufficient in choosing treatment and predicting outcomes. Therefore, additional biomarkers may be needed to help tailor treatment strategies. We evaluated age-related differences with clinic-genomic prognostic indices of aggressiveness, using the Prolaris test, in patients harboring localized prostate cancer. Methods: Clinical and genomic data for 107,471 patients from the Myriad Prolaris (PCa) Database were obtained. Conventional and genomic prognostic indices were analyzed, including Prolaris treatment grouping recommendations (active surveillance (AS) vs single treatment vs multimodal treatment), cell cycle risk scores, NCCN risk groups, tumor stage, and Gleason groups (GG). MVLR was performed to evaluate the association of age, 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 recommendations). Results: With increasing age, we observed a higher proportion of high-risk GG and more aggressive Prolaris scores. Even within the same prostate cancer GG, the Prolaris scores worsened with age. On MVA, age was associated with a statistically significant increase in Prolaris scores (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, and as expected, 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) & number of positive biopsy cores (HR 4.02; 95% CI 3.79-4.27) were all associated with a more aggressive Prolaris score (Table). Conclusions: Our data suggests that age may be associated with higher Prolaris scores, signaling possible worse disease outcomes with age, even with lower GGs. Whether this increase in Prolaris score is suggestive of aggressive disease or results from age alone is yet to be determined and needs to be further studied. On MVA, there was a statistically significant increase in Prolaris treatment scores with increasing age groups. Multivariable logistic regression model for predicting outcome. Variable OR 95% CI p-value Age group (ref: <60)  60-64 1.15 1.04–1.28 0.007  65-69 1.3 1.18–1.43 <0.001  70-74 1.39 1.26–1.54 <0.001  75-79 1.56 1.40–1.74 <0.001  ≥80 1.83 1.60–2.08 <0.001  PSA level (ng/ml; log) 1.21 1.20–1.21 <0.001 Tumor stage (ref: T1a-T1c)  T2a-T2c 1.27 1.17–1.39 <0.001  T3a 9.94 6.25–15.82 <0.001 Gleason grade group (ref: 1-2)  3-5 105.7 96.75–115.47 <0.001