Improved Risk Stratification for Biochemical Recurrence after Radical Prostatectomy Using a Novel Risk Group System based on Prostate Specific Antigen Density and Biopsy Gleason Score

Abstract

Previous studies have suggested that prostate specific antigen (PSA) density is a significant independent predictor of biochemical failure after primary therapy. We determined whether pathological PSA density using surgical weight of the radical prostatectomy specimen was an independent predictor of adverse pathological features or biochemical recurrence after radical prostatectomy. We also examined whether combining pathological PSA density with biopsy Gleason score improved risk stratification compared with serum PSA and biopsy Gleason score for predicting PSA recurrence after prostatectomy. Multivariate analysis was used to determine whether pathological PSA density was an independent predictor of adverse pathology or PSA recurrence after radical prostatectomy in 325 patients treated at a Veterans Affairs medical center. Cutoff points of pathological PSA density were generated to identify patients at various risks for biochemical recurrence. These cutoffs were combined with biopsy Gleason cutoff points 2 to 6, 7 and 8 to 10 to generate a risk stratification system that was compared with a previous risk stratification system using PSA and biopsy Gleason score cutoff points. The validity of the risk stratification system using pathological PSA density and biopsy Gleason score was evaluated in another cohort of 490 patients treated with radical prostatectomy at a tertiary care medical center. Pathological PSA density was an independent predictor of positive surgical margins (p <0.001), nonorgan confined disease (p <0.001), seminal vesicle invasion (p = 0.003) and biochemical recurrence after radical prostatectomy (p <0.001). The cutoff points for pathological PSA density of less than 0.3, 0.3 to 0.7 and greater than 0.7 ng./ml./gm. separated patients into 3 distinct groups at increasing risk for biochemical failure after radical prostatectomy (p <0.001). Pathological PSA density cutoffs combined with biopsy Gleason score cutoffs 2 to 6, 7 and 8 to 10 provided better risk stratification for biochemical failure than cutoffs based on a combination of PSA and biopsy Gleason score in patients treated at the Veterans Affairs (hazards ratio 3.04, confidence interval 2.25 to 4.11, p <0.001) and tertiary care (hazards ratio 2.38, confidence interval 1.78 to 3.18, p <0.001) medical centers. Pathological PSA density was a strong predictor of advanced pathology and biochemical failure after radical prostatectomy. Pathological PSA density combined with biopsy Gleason score defined a novel risk group system that improved risk stratification compared with a combination of PSA and biopsy Gleason score. These results were validated in another cohort of patients treated with radical prostatectomy at a tertiary care medical center. Further studies are required using PSA density values calculated from preoperative transrectal ultrasound measurements to determine whether a combination of PSA density and biopsy Gleason score provides significant pretreatment risk stratification.