The interval to biochemical failure versus biochemical failure as predictors for cause specific and overall survival following dose-escalated external beam radiation therapy for prostate cancer.

Abstract

4585 Background: Prostate cancer (PCa) recurrence can be identified by biochemcial failure (BF) many years prior to clinical recurrence. A short IBF (<18 months) has been proposed as a surrogate for cause specific survival (CSS). Since dose-escalated RT influences both the rate and timing of BF we sought to validate the association between short IBF and both CSS and overall survival (OS). Methods: From 1998-2008, 718 patients (median age 69.3 (IQR: 63-74) were treated with definitive external beam radiation therapy (RT) with or without androgen deprivation therapy (ADT) at the University of Michigan (minimum dose 75 Gy, median follow-up 64 months). BF was defined by the Phoenix definition (nadir +2 ng/ml). Log-rank and Cox-proportional hazard regressions were used to assess the association of BF, the IBF, and other clinical factors with CSS and OS. Results: There were 149 BFs (21%), and no low-risk patients had a short IBF while for intermediate- and high-risk disease it accounted for 14% and 40% of all BFs, respectively. BF had no significant impact on OS (p=0.36) even in patients with NCCN high-risk disease (p=0.8). However, in those with recurrence a short IBF predicted decreased CSS (p<0.0001 HR: 5.6 [2.4-13.0]) and OS (p<0.0001, HR: 4.8 [2.3-10.3]). Further, the 10-year rate of OS was 74% in those without BF, compared to 77% in those with a long IBF (p=0.1, HR: 0.7 [0.4-1.1]) and only 33% in those with a short IBF (p<0.0001, HR: 3.7 [2.3-5.9]). On multivariate analysis, after accounting for age, co-morbid illness, PSA, T-stage, Gleason score, and the use of ADT, a short IBF increased the risk of prostate cancer death (p<0.0001, HR: 18.1 [8.4-39]) and all cause mortality (p=0.0027, HR: 1.5 [1.2-2.1]) while late BF did not. Conclusions: We validated the relationship between the IBF and CSS in patients treated with dose-escalated RT. The IBF is associated with OS while BF by itself is not. Prompt salvage therapy should be considered for all patients with a short IBF while those with a long IBF might be appropriately managed with a more conservative approach. Further evaluation of the IBF as a surrogate end-point for clinical trials is warranted.