14555 Background: Traditionally PSA, Gleason sum and Clinical Stage are considered independent predictors of outcome for prostate cancer. The purpose of this study is to investigate a codependence between prostate specific antigen (PSA) and Gleason sum and whether this relationship has evolved during the PSA era. Methods: The Columbia Urologic Oncology Database was reviewed and 2,522 patients were identified who underwent radical prostatectomy from 1988 to 2005; a retrospective cohort of 1,786 patients with complete data was included. Patients were stratified by Gleason sum into groups with Gleason sum <7, =7 and >7. PSA was correlated to Gleason sum to examine a possible relationship between the two variables. Two-sample t-tests with 95% confidence intervals were utilized to determine differences between groups and were confirmed by ANOVA techniques. A Cox regression model using an interaction term between PSA and Gleason sum was fit to determine if an interaction exists between the two variables. Patients were further stratified into two cohorts by median year of surgery (1998) and the PSA-Gleason sum relationship was evaluated over time. Results: Median patient age was 61.9 years. 1,081 patients were identified with Gleason sum <7. 540 patients had a Gleason sum =7. 165 patients had a Gleason sum >7. The mean PSA values were 6.05, 6.89 and 8.41 for <7, =7 and >7 groups respectively. Differences between the means were statistically significant and validated by the ANOVA technique (p < 0.001). A Cox regression model validated PSA, Gleason sum and clinical stage as independent predictors of outcome. The addition of an interaction term into the Cox regression model between PSA and Gleason sum demonstrated a significant interaction effect between PSA and Gleason sum (p < 0.001). The relationship remained between PSA and Gleason sum within the pre and post 1998 groups (p < 0.001). Conclusions: PSA and Gleason sum are highly interrelated variables, although they each carry additional information that significantly contributes to the prediction of biochemical failure (PSA ≥0.2 ng/ml). For an individual patient, the higher the initial PSA the higher the risk of having a high Gleason sum on biopsy. This relationship has remained constant over the PSA era. No significant financial relationships to disclose.