Using Gleason pattern 5 to refine risk stratification for prostate cancer patients treated with dose-escalated radiotherapy and androgen-deprivation therapy.

Abstract

15 Background: The division of Gleason score (GS) into three categories (2-6, 7, 8-10), may not fully utilize its prognostic power as shown by recent reports demonstrating that the presence of Gleason Pattern 5 (GP5) is a strong adverse prognostic factor. Therefore, we analyzed clinical outcomes for patients treated with dose-escalated radiation therapy (RT) based upon the presence or absence of GP5 within the biopsy specimens. Methods: Clinical outcomes were analyzed for 718 men treated for localized prostate cancer with definitive external beam RT to at least 75 Gy. We assessed the impact of GP5 as well as pre-treatment and treatment related factors on freedom from biochemical failure (FFBF), freedom from metastasis (FFM), cause-specific survival (CSS), and overall survival (OS). Results: Median follow-up was 64 months. At biopsy, 89% of patients had no GP5 while 11% had GP5. There was no difference in age, co-morbid illness, clinical T-stage, PSA, or the use or duration of androgen deprivation therapy (ADT) between GS8 without GP5 and GS8-10 with GP5. The presence of GP5 predicted lower FFM (p<0.002 [HR: 3.4{1.7-7.1}]), CSS (p<0.0001 [HR: 12.9 {5.4-31}]), and OS (p<0.0001 [HR: 3.6 {2.0-6.5}]) when compared to GS8 (without GP5). Ten-year FFM, CSS, and OS were 89%, 98%, and 57% for those with Gleason 8 prostate cancer without GP5 as compared to 61%, 55%, and 31% for those with GP5. In addition, both FFM and CSS were strongly influenced by ADT use concurrent with RT. On multivariate analysis GP5 was the strongest prognostic factor for all clinical end-points. Conclusions: The presence of GP5 predicts for worse clinical behavior, which therefore needs to be accounted for by risk stratification schemes. Further intensification of local and/or systemic therapy may be appropriate for such patients. No significant financial relationships to disclose.