Prognosis after androgen deprivation therapy in men with a rising PSA after prostatectomy

Abstract

4552 Introduction: PSA levels decline after androgen deprivation therapy (ADT) by cessation of gene expression, decreased cell proliferation and apoptosis. The median duration of response to ADT in men with a rising PSA after radical prostatectomy (RP) is ∼11yrs. We analyzed a large cohort to identify prognostic factors which would predict the duration of response to ADT, including the nadir level of PSA within a defined time after initiation of ADT. Methods: Of 4,035 men treated with RP, 346 received ADT, 81% and 19% for a rising PSA (rPSA) or metastases (M+). They were followed prospectively for a median of 8.4 (interquartile, 5.6 - 11.5) years after RP and 63 died from disease. We incorporated the pathologic stage,Gleason grade, time to rising PSA, PSA doubling time (PSA DT), pre-ADT PSA, and PSA nadir (<0.2ng/ml) within 8 months of ADT (8mPSA0) in our prognostic models aiming at duration of response and cancer specific survival (CSS) from 8 months after ADT Results:Within 8 months of ADT, PSA nadir was <0.2 in 224 (80%) and 44 (66%) patients with rPSA and M+, respectively (p=0.01). There was no difference in CSS rates at 10 years between men treated continuously (61%) or intermittently (68%). The median CSS rate for those who failed to reach an undetectable PSA was 4.8 (95%CI, 2.6–7.1) years. For those with 8mPSA0, the CSS rate at 10 years was 71%, and not significantly affected by the presence or absence of M+. The only independent predictor of 8mPSA0 was the pre-ADT serum PSA level. Independent predictors of duration of response and CSS were 8mPSA0, pre-ADT PSA and PSA DT. Conclusions: For men with a rising PSA after RP, the duration of response to ADT is prolonged. Independent prognostic factors for duration of response to ADT include PSA level at ADT, PSA DT, and PSA nadir at undetectable levels within 8 months of ADT. Predictive models can be developed from this data to identify patients at high risk for early relapse after ADT who may benefit from alternative approaches No significant financial relationships to disclose.