Asmaa Hatem

The utility of PSA velocity in prediction of prostate cancer and high grade cancer after an initially negative prostate biopsy

Prostate specific antigen kinetics (PSAK) including prostate specific antigen velocity (PSAV) and PSA doubling time (PSADT) are used as predictors of prostate cancer (PCa) therapeutic outcome, disease prognosis, and cancer‐specific mortality. However controversy persists regarding use of these parameters in cancer detection. Our aim is to evaluate PSAV as a predictor of PCa and intermediate/high grade PCa (HGPCa).

PCA3-based nomogram for predicting prostate cancer and high grade cancer on initial transrectal guided biopsy

To develop a validated prostate cancer antigen 3 (PCA3) based nomogram that predicts likelihood of overall prostate cancer (PCa) and intermediate/high grade prostate cancer (HGPCa) in men pursuing initial transrectal prostate biopsy (TRUS‐PBx).

Low risk patients benefit from extreme anterior apical sampling on initial biopsy for prostate cancer diagnosis.

To assess the effect of additional extreme apical sampling on prostate cancer (PCa) detection and aggressiveness in patients with standard risk versus high risk of a positive biopsy.

MP70-17 DOES PRIOR INTERVENTIONAL THERAPY FOR BPH INCREASE THE RISK OF COMPLICATIONS AFTER PRIMARY WHOLE GLAND PROSTATE CRYOABLATION?

determine toxicity, side-effects and early efficacy as well as to determine optimum treatment delivery of MRI-ultrasound fusion-guided intraprostatic injection of PRX302. METHODS: 18 men with histologically proven, clinically significant, localized low-intermediate risk prostate cancer associated with an MRI lesion were recruited (PSA </1⁄415, T2aN0Mo, Gleason </1⁄44+3 with a maximum cancer core length [MCCL] </1⁄410mm, or Gleason 3+3 with MCCL >/1⁄44mm (May/2015-Nov/2015). Patients had a single lesion injected transperineally using MRI-ultrasound image-fusion software (SmartTarget ), under general anaesthetic with up to 5mL of a standard dosing solution (20ug/mL) of PRX302. Follow-up occurred at 2 days and at 2, 6, 12, 24 and 26 weeks. A mpMRI-targeted transperineal biopsy of the treated area was performed at 24 weeks. All men who enrolled completed the study. RESULTS: Median age and PSA were 66.50 years (IQR 13.00) and 6.25ng/ml (IQR 2.45). 4 patients (22%) had high volume Gleason 6 and 14 (78%) had Gleason 7 cancer with median lesion size 0.3mL (IQR 0.2-0.5). The administration of PRX302 was well tolerated with no serious adverse events and no new safety signals. At 24 weeks following treatment, 2 had complete tumour ablation (no histological evidence of cancer). These 2 showed reductions in PSA of 3.0 to 2.2ng/ mL (26.7%) and 5.7 to 4.8ng/mL (15.8%), respectively. Seven had partial response defined as reductions in MCCL or Gleason grade. 9 had no histological response, with some experiencing increases in MCCL or grade. CONCLUSIONS: Our proof-of-concept study shows that a single intraprostatic administration of PRX302 has a biological effect on prostate tumor cells when focally injected with low side-effect profile. Optimizing the dosing and delivery of PRX302 based on tumour size may increase response rates and will be tested in a multicenter phase 2 study.

PD56-04 SALVAGE PROSTATE CRYOABLATION IN OLDER MEN

INTRODUCTION AND OBJECTIVES: While recto-urethral fistula is a rare complication following salvage cryoablation for radiorecurrent prostate cancer, less is known about the development of recto-urethral fistula after primary whole gland cryoablation. We define the incidence and risk factors for recto-urethral fistula in a multicenter, centralized registry. METHODS: The Cryo-On-Line Data (COLD) Registry was queried for men undergoing primary whole gland cryotherapy between 1990 and 2014 who developed a recto-urethral fistula. Patient factors and disease parameters were correlated with the recto-urethral fistula using chi-squared tests for categorical variables and t-test for continuous variables. Variables with p<0.25 were entered into a binary logistic regression with stepwise backward elimination to determine the factors associated with formation of urethral fistula. RESULTS: We identified 4,102 men who underwent primary whole gland cryotherapy between 1990 and 2014. Median age was 71 years (IQR:66-76). Median PSA was 6.5 (IQR: 4.8-9.8). Available Gleason Score included 8-10:500 pts, 7:1,194 pts and 6:1,601 while pretreatment clinical stage included T1:1539, T2:1,503 T3:328 and T4:20. 1,508 pts received neoadjuvant androgen deprivation. 805 cases were performed at academic centers and 3297 were performed in the private setting. Post-operative recto-urethral fistula was identified in 50 (1.2%) men. On univariate analysis, pre-operative Gleason score, pre-operative incontinence and post-operative urinary retention were statistically significant predictors for development of recto-urethral fistula. On multivariate analysis, postoperative urinary retention (OR 7.26, 95%CI 4.06-13.03, p<0.001) pre-operative Gleason score of 7 (OR 1.92, 95%CI 1.08-3.43, p1⁄40.027) and pre-operative incontinence (OR 2.95, 95% CI 1.127.76, p1⁄40.028) predicted urethral fistula. CONCLUSIONS: In a large, mixed cohort of patients undergoing primary whole gland cryoablation for prostate cancer, the incidence of urethral fistula was very low at 1.2%. The strongest association was present in men with post-procedural urinary retention. Further study regarding instrumentation of the lower tract for retention following cryotherapy in the early post-operative setting is warranted.

Associations Between Prostate Volume and Oncologic Outcomes in Men Undergoing Focal Cryoablation of the Prostate

Introduction The purpose of this study was to assess the relationship of total prostate volume (TPV) and oncologic outcomes following focal prostate cryoablation. Materials and Methods A query of the Cryo On‐Line Database (COLD) registry for men who underwent primary focal prostate cryoablation revealed 829 patients with complete data. The impact of TPV on oncologic outcomes including progression‐free survival (PFS) and post‐cryoablation biopsy outcome was assessed using Kaplan‐Meier curves and Cox and logistic regression models. Results The median follow‐up time was 25.2 months (interquartile range [IQR], 12.7‐48.2 months). The median age at time of treatment was 68 years (IQR, 63‐74 years) with median prostate‐specific antigen (PSA) 5.6 ng/mL (IQR, 4.4‐7.5 ng/mL), and median TPV 35 mL (IQR, 26.5‐46 mL). PFS was achieved in 83.2%, with positive post‐cryoablation biopsy detected in 81 (35.7%) of 228 patients. Higher TPV was associated with higher biochemical progression (BP) using the Phoenix definition (39 vs. 34.5 mL; P = .003) and was an independent predictor of BP (hazard ratio, 1.01; P = .02). Conversely, men who had a positive post‐cryoablation biopsy had significantly smaller median TPV on univariate and multivariate analyses (31 vs. 39 mL; P < .001), (odds ratio, 0.97; P = .001), respectively. Higher median pretreatment PSA density was associated with higher BP (0.18 vs. 0.16; P = .005) and positive post‐cryoablation biopsy rates (0.2 vs. 0.16; P = .003). Conclusion Prostate volume has contradictory effects on BP and post‐cryoablation biopsy outcome in men who underwent primary focal prostate cryoablation. Remnant viable tissue in larger prostates continues to produce more PSA over time, which may impact BP. This may raise the need to develop a new definition for oncologic success following focal gland therapy rather than the American Society for Radiation Oncology (ASTRO) and Phoenix definitions. Micro‐Abstract The purpose of this study was to assess the effect of total prostate volume on biochemical progression and local disease control following primary focal prostate cryoablation. After analyzing 829 men, larger prostate volume is associated with higher rates of biochemical progression, but lower rates of positive biopsy. Remnant viable tissue in larger prostates continues to produce more prostate‐specific antigen over time which may impact biochemical outcomes.

Transrectal Saturation Biopsy Improves Risk Stratification (Reclassification) of Patients with Prostate Cancer on Active Surveillance

Introduction: We assessed the accuracy of transrectal saturation prostate biopsy compared to extended prostate biopsy in patients on active surveillance. Determining prostate cancer aggressiveness is mandatory to determine appropriate candidates for active surveillance and appropriateness to remain on active surveillance protocols. Methods: From our institutional review board approved database we reviewed the biopsies of 277 patients diagnosed with prostate cancer on an active surveillance protocol. Eligibility criteria included clinical stage T1 to T2a, Gleason score 6 or less, prostate specific antigen 10 ng/ml or less and percent of positive cores 33% or less of the total cores taken on diagnostic biopsy. We defined recategorization or pathological progression on first confirmatory and surveillance biopsies as no longer meeting the standard definition of low risk by cancer volume or Gleason score criteria. Results: Of 444 biopsies 279 were extended prostate biopsy (10 to 14 cores) and 165 were saturation prostate biopsy (20 cores or greater). The rate of cancer recategorization (reclassification) was highest on the first confirmatory biopsy at 25%. There was no significant difference between extended and saturation prostate biopsy for detecting recategorization on the first confirmatory biopsy (21.5% vs 29.4%, p = 0.13). Saturation prostate biopsy was significantly more likely to detect cancer progression on all subsequent surveillance biopsies. Conclusions: Disease progression or recategorization was more frequently identified on the first confirmatory biopsy than on subsequent surveillance biopsies. The incidence of disease recategorization was higher in the saturation biopsy group than in the extended biopsy group on the first confirmatory biopsy but the difference was not statistically significant. Disease progression was more likely to be identified by saturation prostate biopsy on subsequent surveillance biopsies.

245 SHOULD STAGING TRANSRECTAL SATURATION BIOPSY BE A STANDARD FOR ASSESSMENT OF DISEASE PROGRESSION & FOLLOW UP FOR PROSTATE CANCER PATIENTS ON ACTIVE SURVEILLANCE?

INTRODUCTION AND OBJECTIVES: Prostate cancer (PCa) aggressiveness assessment is mandatory to determine the appropriateness for Active surveillance (AS). Our objective is to assess the accuracy of staging saturation prostate biopsy (SB) compared to extended prostate biopsy (EB) in patients on AS protocol. METHODS: From IRB approved database we reviewed 485 biopsies from 383 patients diagnosed with PCa on AS protocol from 2000-2011. Gleason sum ,total gland volume ,number of positive cores, maximum cancer % per core, prostate specific antigen (PSA) at time of the biopsy, % free PSA ,high grade prostatic intraepithelial neoplasia(HGPIN) and atypical small acinar cell proliferation (ASAP) were assessed as predictors of cancer progression. We compared the ability of each template to identify Gleason 7 diseases, 2 core involvement and 50% cancer involvement in each core. RESULTS: Among 485 biopsies ,288 were EB (8-14 cores) and 197 were SB( 20 cores) .Our univariate analysis showed that the “recategorization” identified with SB is greater as evidence by gleason 7 disease (p 0.0004) and 2 core involvement (p 0.002) . We also found that the presence of HGPIN (p 0.03) and PSA at time of the biopsy (p 0.02) were statistically significant compared to EB (table 1). Moreover multivariate analysis showed that SB identified higher Gleason ( 7) disease (p 0.04) and number of positive cores ( 2 cores) (p 0.02). (Table 2). CONCLUSIONS: Staging SB identifies more accurately PCa progression in patients electing AS for their low grade, low volume PCa compared to EB. We recommend using SB ( 20 cores) as a standard protocol for patients on AS.