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INTRODUCTION AND OBJECTIVE:Prostate cancer (PCa) incidence in Asia is among the lowest in the world, although it has grown rapidly in recent years. We investigated the impact of race [Asian (ASI) o...

Purpose: The aim of this study was to compare biopsy detection of intraductal and cribriform pattern invasive prostate carcinoma in multiparametric magnetic resonance imaging positive and negative regions of the prostate.Materials and Methods: We queried a prospectively maintained, single institution database to identify patients who underwent multiparametric magnetic resonance imaging/ultrasound fusion targeted biopsy and concurrent systematic sextant biopsy of magnetic resonance imaging negative regions between January 2013 and May 2016. All multiparametric magnetic resonance imaging targets were reviewed retrospectively by 2 readers for the PI-RADS™ (Prostate Imaging-Reporting and Data System), version 2 score, the maximum dimension, the apparent diffusion coefficient parameter and whether positive or negative on dynamic contrast enhancement sequence. Biopsy slides were reviewed by 2 urological pathologists for Gleason score/Grade Group and the presence or absence of an intraductal/cribriform pattern.R...

Purpose: In prostate cancer biopsy Gleason score predicts stage and helps determine active surveillance suitability. Evidence suggests that small incremental differences in the quantitative percent of Gleason pattern 4 on biopsy stratify disease extent, biochemical failure following surgery and eligibility for active surveillance. We explored the overall quantitative percent of Gleason pattern 4 levels and adverse outcomes in patients with low and intermediate risk prostate cancer to whom active surveillance may be offered under expanded criteria.Materials and Methods: We analyzed the records of patients with biopsy Gleason score 6 (3 + 3) or 7 (3 + 4) who underwent radical prostatectomy from January 2008 to August 2015. Age, prostate specific antigen, Gleason score, quantitative percent of Gleason pattern 4, overall percent positive cores (percent of prostate cancer) and clinical stage were explored as predictors of nonorgan confined disease and time to failure after radical prostatectomy.Results: In 1,2...

We evaluated the relative risk of later grade reclassification and outcomes of patients in whom high volume Gleason 6 prostate cancer develops while on active surveillance.A prospectively maintained database was used to identify patients on active surveillance between 1998 and 2013. Tumor volume was assessed based on the number of positive cores and proportion of core involvement. The chi-square and Fisher exact tests were used for analysis as appropriate. The primary end point was the development of grade reclassification, defined as grade only and/or grade and volume at the event biopsy.A total of 555 men met the study inclusion criteria. Mean followup was 46 months. Overall 70 patients demonstrated an increase in tumor volume at or after biopsy 2. Compared to those men never experiencing volume or grade reclassification, prostate specific antigen at diagnosis was not significantly different (p=0.95), but median prostate volume was smaller in patients who demonstrated volume reclassification (p0.001). The incidence of pure volume reclassification was 6.8%, 6.1% and 7.8% at biopsy 2, 3 and 4, respectively. Men with volume reclassification were more likely to experience later grade reclassification than those without at 33.3% vs 9.3%, respectively (p0.0001).While Gleason 6 prostate cancer has a favorable natural history, it appears that patients on active surveillance who experience volume reclassification are at substantially higher risk for grade reclassification. Thus, urologists should pay close attention to tumor core involvement, and monitoring should be adjusted accordingly for early volume reclassification in younger men and those in good health.

Purpose We determined if the USPSTF recommendation against prostate specific antigen screening was associated with a change in biopsy and cancer detection rates. Materials and Methods We conducted a time series analysis (October 2008 to June 2013) of prostate biopsies performed at University Health Network (Toronto). Biopsies for active surveillance or solely targeting magnetic resonance imaging detected lesions were excluded from study. Interventional ARIMA models with step functions were used to examine changes in the number of biopsies performed and cancers detected per month. Low risk prostate cancer was defined as no Gleason pattern 4 or greater, 3 or fewer cores involved, or 1/3 or less of the total number of cores involved, and no core with greater than 50% cancer involvement. Intermediate to high grade prostate cancer was defined as Gleason 7-10. Results A total of 3,408 biopsies were performed and 1,601 (47.0%) prostate cancers were detected (low risk prostate cancer 563 [16.5%], intermediate to high grade prostate cancer 914 [26.8%]). The median number of biopsies per month decreased from 58.0 (IQR 54.5–63.0) before the recommendations to 35.5 (IQR 27.0–41.0) afterward (p=0.003), while the median number of patients undergoing first-time biopsy decreased from 42.5 (IQR 37.5–45.5) to 24.0 (IQR 19.0–32.5, p=0.025). The median number of low risk prostate cancers detected per month decreased from 8.5 (IQR 6.5–10.5) to 5.5 (IQR 4.0–7.0, p=0.012), while the median number of intermediate to high grade prostate cancers per month decreased from 17.5 (IQR 14.5–21.5) to 10.0 (IQR 9.0–12.0, p Conclusions After the USPSTF recommendation the number of biopsies performed (total and first-time), based on referrals from our catchment area, has decreased. This is likely due to decreased use of prostate specific antigen screening. Although it is encouraging that fewer low risk prostate cancers are being diagnosed, the sudden decrease in the detection rate of Gleason 7-10 prostate cancers is concerning.

Purpose: New biomarkers for prostate cancer are needed. We determined whether a novel serum marker, total PSP94 can be used to accomplish these goals.Materials and Methods: We conducted a case-control study of 1,212 men with no previous history of prostate cancer and who underwent a prostate biopsy from 1998 to 2000 because of an increased PSA or an abnormal DRE. Serum PSP94 levels were assessed using a sandwich enzyme-linked immunosorbent assay technique. Cases were patients with prostate cancer, and controls were patients who had no evidence of cancer. Multivariate logistic regression analysis was used to determine whether or not PSP94 levels improved the predictive value for prostate cancer.Results: Of the 1,212 men 596 (49.2%) had cancer detected. The median PSP94 level was significantly lower among cases (2.60 ng/ml) than among controls (3.40 ng/ml, p

The PCPT has demonstrated a higher incidence of high grade (Gleason pattern 4 or greater) prostate cancers among men randomized to finasteride. One plausible explanation for this finding is that tumor grade as assigned by TRUS guided biopsy is artifactually associated with prostate volume.We evaluated our institutional data set of TRUS guided biopsies in the last 3 years and identified 369 cases of prostate cancer that fit the criteria of PSA less than 10 ng/ml, biopsy at our center and RP at our center. We identified risk factors for Gleason pattern 4 or greater on biopsy and then on RP specimens from the same patients using univariate and multiple logistic regression analyses. Assessed covariates included patient age, PSA and TRUS volume.Risk factors for Gleason pattern 4 or greater in the biopsy specimens included age (p = 0.01), hypoechoic lesions on TRUS (p0.001) and TRUS volume (p = 0.008). However, among RP specimens TRUS volume (p = 0.60) became nonsignificant of Gleason pattern 4 or greater on multivariable analysis. Although prostate volume was a predictor for biopsy derived high grade disease it was not predictive of true histological grade.These data suggest that simply having a larger prostate results in fewer high grade cancers diagnosed at biopsy. Prostatectomy results in the same men suggest sampling artifact, as the distribution of cancer grade is not associated with prostate volume. These findings provide evidence that the increase in higher grade tumors among men in the finasteride arm of PCPT may simply result from prostate volume reduction.

Introduction: Clinical confusion continues to exist regarding the underestimation of cancers among patients on active surveillance and among men with repeated negative prostate biopsies despite worrisome prostate-specific antigen (PSA) levels. We have previ ously described our initial experience with magnetic resonance imaging (MRI)-based detection of tumours in the anterior prostate gland. In this report, we update and expand our experience with these tumours in terms of multiparametric-MRI findings, staging, and grading. Furthermore, we report early treatment outcomes with these unique cancers. Methods: We reviewed our prostate MRI dataset of 1117 cases from January 2006 until December 2012 and identified 189 patients who fulfilled criteria for prostate evasive anterior tumors (PEATS). Descriptive analyses were performed on multiple covariates. Kaplan-Meier actuarial technique was used to plot the treatmentrelated outcomes from PEATS tumours. Results: Among the 189 patients who had MRI-detectable anterior tumours, 148 had biopsy proven disease in the anterior zone. Among these tumours, the average PSA was 18.3 ng/mL and most cancers were Gleason 7. In total, 68 patients chose surgical therapy. Among these men, most of their cancers had extra prostatic extension and 46% had positive surgical margins. Interestingly, upgrading of tumours that were biopsy Gleason 6 in the anterior zone was common, with 59% exhibiting upgrading to Gleason 7 or higher. Biochemical-free survival among men who elected surgery was not ideal, with 20% failing by 20 months. Conclusion: PEATS tumours are found late and are disproportionally high grade tumours. Careful consideration to MRI testing should be given to men at risk for PEATS.

INTRODUCTION AND OBJECTIVES: Active surveillance (AS) is an increasingly accepted strategy for patients with low risk, low grade prostate cancer (PCa). Although differences in inclusion criteria exist, high volume Gleason 6 and higher grade of disease are commonly excluded. Yet, no consensus has been established concerning indicators of progression and uncertainties as to when patients should seek more aggressive treatment persist. Some postulate that Gleason 6 PCa has an indolent course and that only Gleason 7 should be considered a histologic trigger to treat. We aimed to elucidate the outcomes of patients who developed increased volume of Gleason 6 PCa ( 4 cores or 50% of core involved) while on AS and compared their risk of later grade progression to those who did not experience volume progression. METHODS: A prospectively maintained database was utilized to identify a total of 555 patients, median age 62.4, who were on AS with Gleason 6 disease between 2008 and 2013. Patients who demonstrated volume progression only at biopsy 2 (B2), biopsy 3 (B3), or biopsy 4+ (B4+) were studied. Univariate statistics were used for comparison. For the purposes of the current work, the endpoint of study was the development of grade progression whether it be grade only or grade + volume at the event biopsy. RESULTS: A total of 70 patients demonstrated volume progression at or after their second or confirmatory biopsy (B2). Mean follow-up was 3.67 years. In comparison to those never experiencing volume or grade progression, the mean age was 62.9 years vs. 62.1(p-value1⁄40.33), respectively. Mean PSA at diagnosis was not significantly different (p-value1⁄40.84), but median prostate volume was significantly smaller in patients who demonstrated volume progression (p-value

Interstitial microwave thermal therapy is experimental treatment for prostate cancer with the goal of curing disease, while causing fewer complications than standard treatment options. We present a method for delivering interstitial microwave thermal therapy using microwave radiating helical antennae inserted percutaneously under transrectal ultrasound guidance. We report the results of a trial of this method in 25 patients in whom primary external beam radiation therapy had previously failed. This patient group currently has limited curative options that are associated with a high complication rate. However, these recurrent tumors often remain localized to the prostate, and so they may be amenable to localized therapy.Patients with proved prostatic adenocarcinoma were candidates for treatment when prostate specific antigen (PSA) was 15 ng./ml. or less and prostate volume was 50 cc. or less. Followup included PSA measurement, digital rectal examination, urinalysis, and documentation of adverse events at 4, 8, 12 and 24 weeks. Sextant biopsy was performed at week 24. The procedure involved the insertion of 5 antennae percutaneously through a modified brachytherapy template. The antenna arrangement was determined based on computer simulated predictions of temperature throughout the prostate. The prostate was dissected away from the rectum by an injection of sterile saline to provide a thermal barrier that protected the rectum from thermal damage. Temperatures were monitored using interstitial mapping thermistor probes that were also inserted through the template. A minimum peripheral target temperature of 55C but less than 70C was maintained for 15 to 20 minutes, while the urethra, rectum and hydrodissection space remained below 42C. The urethra and rectum were actively cooled in addition to hydrodissection.Peripheral target temperatures of 55C were achieved. The urethra and rectum remained at a safe temperature. The procedure, including setup and treatment, required approximately 2.5 hours of operating room time. At 24 weeks the PSA nadir was 0.5 ng./ml. or less in 52% of patients and 0.51 to 4 ng./ml. was achieved in an additional 40%. The negative biopsy rate at 24 weeks was 64%, assuming that 3 patients lost to followup would have had positive results. No major complications were observed and in most cases minor complications resolved within 3 months.Interstitial microwave thermal therapy for prostate cancer was developed to heat the prostate safely to a cytotoxic temperature. Experience with 25 patients in whom external beam radiation therapy for prostate cancer had failed indicates that the treatment is safe. Although our series indicates that this therapy may be effective, further studies and longer followup are required in larger patient groups to confirm the potential role of this therapy as an option for recurrent and primary prostate cancer.

The higher number of high grade cancers noted in the Prostate Cancer Prevention Trial may have arisen due to a previously unknown association between prostate volume and sextant biopsy derived grade, rendering it more difficult to detect high grade cancer in men with a larger prostate (volume-grade bias). A basic tenet of measurement theory is that repeat measurement improves validity. We determined whether an extended pattern prostate biopsy technique could overcome this bias.We reviewed the record of 679 patients who underwent systematic extended (10 cores or greater) biopsy with isoechoic prostate transrectal ultrasound and prostate specific antigen less than 10 ng/ml. Since specimens were separately labeled, we were able to compare the grade of the first 6 cores vs that of the extended pattern. We determined the highest grade achieved using traditional sextant biopsy and the change induced by marginal samples across volume tertiles, hypothesizing that if upgrading did not occur by volume, additional biopsies would be ineffective for minimizing this bias.Prostate cancer detected using a 6-core technique revealed 179 of 679 cancers (26.4%) vs 240 of 679 (35.4%) using the extended core technique (p0.001). The marginal cancer detection rate increased significantly as prostate volume increased. Cancer detection rates for the 1st, 2nd and 3rd tertiles of prostate volume were increased by 16 of 227, 17 of 226 and 28 of 226 cases, respectively (p = 0.05). With respect to Gleason score, upgrading from Gleason 6 to 7 was observed in 14 patients (7.9%) due to the additional procured cores (p0.001). However there was no association among the various prostate volumes (p = 0.87).Although more high grade cancers are detected with extended pattern biopsy, there is no differential upgrading with respect to prostate volume. Based on these observations extended prostate sampling in trials of agents that decrease prostate volume would have minimal impact on volume-grade associations.

INTRODUCTION AND OBJECTIVES: Prostate re-biopsy schema for most published active surveillance (AS) cohorts is based on a standard extended template sampling the peripheral zone (PZ). In an AS population, we investigate the effect of routine transition zone (TZ) biopsy by examining the amount of TZ cancer found and its subsequent impact on pathological re-classification. METHODS: Patients were identified from our tertiary referral centre AS database (1997-2012). Eligibility criteria included PSA 10, clinical stage 2, Gleason score (GS) 6, number of positive cores (PCore) 3, no single core 50% involved, age 75 years and at least 1 prostatic re-biopsy after diagnosis. Biopsies of the TZ were taken routinely after the diagnostic biopsy (B1). By mapping location of all PCores found, patients with cancer and pathological re-classification in the TZ could be identified at each AS biopsy. As the number of TZ cores taken is usually limited to 1-2, pathological re-classification for TZ cancers was defined as GS 7 and/or 50% single core involved. Number of PCores was not used. Logistical regression was performed to identify features at diagnostic biopsy that could predict TZ-only reclassification on the 2nd, otherwise known as the confirmatory biopsy (B2). RESULTS: The frequency of cancer, and reclassification, found in the TZ during subsequent biopsies during AS is shown in Table 1. At each re-biopsy, there was a consistent proportion of men that had TZ cancer detected (13.5-16.6%), and TZ re-classification (7.1-9.8%). After excluding men who re-classified in both TZ and PZ, the frequency of TZ-only re-classification at each biopsy was 4.8-8.4%. There was a total 64 TZ-only re-classification events in our cohort. Breakdown of re-classification type was: 50% single core involved (n 47), GS 7 (n 12), both criteria (n 5). Of the 17 men with TZ grade-related re-classification, most were GS 3 4 (n 15), with few GS4 3 (n 1) and GS 4 4 (n 1). On univariate analysis, only % of core involved at B1 was predictive of TZ-only re-classification at B2 (OR1.04, 1.01-1.09, p 0.008). CONCLUSIONS: Routine TZ biopsy during AS detects cancer in 15% of men at each biopsy. However, only 5% of men at each biopsy re-classify in only in the TZ, and most of these are with GS 3 4 disease. Our results suggest TZ biopsy could be performed less frequently or even not performed at all during routine AS re-biopsy. Frequency of TZ cancer and TZ re-classification found at each subsequent biopsy during AS

INTRODUCTION AND OBJECTIVES: Active surveillance (AS) is a popular method to minimize the morbidity associated with overtreatment of prostate cancer. The rate of patients who progress by grade/volume is reported as 9-35%. We examine factors from the 2nd biopsy, whilst on AS, that may predict pathological progression and need for subsequent therapy. METHODS: We identified patients from our prospectively maintained, single academic institution, database with PSA 20, Gleason sum (GS) 6, stage T1c, 3 cores positive for cancer, 50% of single core involved, age 75y years and had a repeat biopsy within 48 months after the initial biopsy (n 312). Logistical regression was performed on available data (n 278) to identify predictors of pathological progression, which was defined as GS 7, 3 positive cores and 50% tumor involvement of any single core. RESULTS: Of the 278 patients included, 48 patients had pathological progression on 2nd biopsy and 264 did not. For both groups, median number of biopsy cores taken at 2nd biopsy was the same (n 15). Predictors of pathological progression found were PSA velocity (for every 1 unit increase, OR 1.12 (1.03-1.21), p 0.01), total number of cores taken at first biopsy 10 (OR 2.78 (1.2-6.67), p 0.02), and time between 1st and 2nd biopsies (for every 1 month increase, OR 1.05 (1.02-1.08), p 0.002). CONCLUSIONS: We have identified predictors of progression for patients on AS. Patients who had 10 cores on initial biopsy should have confirmatory biopsy to avoid under-sampling. Delay in 2nd biopsy should be avoided and rapid PSAV should trigger early re-biopsy.

INTRODUCTION AND OBJECTIVES: Hemiablation is a minimally invasive treatment option for men with prostate cancer on active surveillance (AS). The main concern with this approach is the possibility of missing an undiagnosed cancer or the growth of a new cancer in another part of the gland. Our aim was to investigate initial positive and repeat TRUS-BX findings in men on AS to determine how often and to what extent an altered disease profile occurred on second biopsy. We also sought to determine histologic predictors of subsequent cancer occurrence in non-cancerous areas. METHODS: A prospective database is maintained at our institution of all patients undergoing prostate biopsy. Three radiologists perform all biopsies ( 2000 systematic biopsies/year) at our institution using a systematic 11 core initial and 15 core repeat biopsy approach. From this database we retrospectively identified 423 AS patients who had at least 2 biopsies. AS inclusion criteria were; 3 cores positive, less than 50% of any core positive, Gleason score 7. We compared the site of occurrence of cancer between the first biopsy and second biopsy. Histologic predictors of contralateral cancer occurrence and worsening disease grade were also assessed. RESULTS: Our AS cohort included 423 men who had 2 biopsies. The mean age was 65 and the median time between biopsies was 14 months with a decrease in mean PSA from 7.3 to 7.0 (p 0.01). On second biopsy, 17% of man had an increase in Gleason score, 49% had no change and 35% had no cancer detected. The mean number of positive cores decreased on second biopsy from 1.9 to 1.4 (p 0.01). Cancer position on second biopsy remained the same in 36%, occurred on the contralateral side in 29%, and was undetectable in 35%. The only predictor of cancer occurrence on the contralateral side on second biopsy was having contralateral ASAP or HGPIN on the first biopsy (OR 1.82, p 0.02). Having 1 core positive on first biopsy was a predictor of higher grade disease on the second biopsy (OR 2.54; p 0.01). CONCLUSIONS: Follow-up prostate biopsy in men on AS can uncover cancers in the contralateral part of the gland in approximately one third of cases with the only pathologic predictors being ASAP or HGPIN in the contralateral area. Prostate hemiablation should not rely on one set of prostate biopsies.