Initial Prostate Research Articles

Racial variation in the reliability of prostate cancer indicators in men undergoing subsequent prostate biopsy.

115 Background: Many men with an initial negative prostate biopsy have a persistently elevated prostate specific antigen (PSA) prompting physicians to perform repeat biopsies. African American men (AA) are at particular risk as they have a greater prostate cancer (PCa) incidence and mortality, yet traditional PSA testing may be less reliable in this cohort. We sought to determine the predictors of PCa and PCa severity in a racially diverse population on subsequent biopsy following an initial benign biopsy. Methods: Upon receiving Institutional Review Board approval, a retrospective analysis was performed on men with repeat prostate biopsies at Tulane Medical Center and Southeast Louisiana Veterans Health Care Services in New Orleans, Louisiana from 2003-2015. Inclusion criteria included patients with a benign initial prostate biopsy and underwent subsequent repeat prostate biopsy within 5 years. Race, age, serum PSA, PSA density (PSAD), and prostate volume by transrectal ultrasound (TRUS) were evaluated to determine if they correlate with the presence and severity of PCa. Aggressive PCa was defined as Gleason score >6. Results: A total of 209 men were included; 127 (61%) were AA, and 82 (39%) were Caucasian American men (CA). The two groups were similar with respect to PSA, PSAD, and TRUS. More AA (25.2% vs. 17.1%) had a repeat biopsy showing any PCa. Of those with PCa, 28.1% of AA and 28.6% of CA had aggressive PCa. PSAD positively correlated with any PCa (p=.015). TRUS negatively correlated with any PCa (p=.008). PSA levels (p<.001) and PSAD (p<.001) positively correlated with aggressive PCa in CA but not in AA. Conclusions: The goal of prostate biopsy particularly for those with a prior negative biopsy is to detect aggressive PCa. PSA and PSAD positively correlated with finding any PCa in both AA and CA but not with aggressive PCa in AA. PSA and PSAD are less accurate predictors of aggressive PCa in AA, and novel biomarkers are needed. [Table: see text]

Impact of comorbidity and PSA doubling time on the risk of death in men experiencing PSA failure following radiation therapy with or without androgen deprivation therapy for unfavorable-risk prostate cancer.

68 Background: The optimal management of men with PSA failure following initial prostate cancer therapy based on comorbidity is unknown. We investigated the impact that PSA doubling time (DT) and comorbidity had on the risk of all cause (AC), prostate cancer-specific (PCS) and other cause mortality (OCM) following PSA failure. Methods: Between 1995 and 2001, 206 men with unfavorable-risk PC were randomized to receive radiation therapy alone or in combination with 6 months of androgen deprivation therapy (ADT). After a median follow up of 16.2 years, 108 men experienced PSA failure (85, no or minimal; 23, moderate to severe comorbidity) and formed the study cohort. Cox and Fine-Gray regression analysis was used to determine whether PSA DT was associated with the risk of ACM and PCSM/OCM respectively, stratified by ACE-27 comorbidity score. Results: After a median follow up of 13.71 years following PSA failure, 81 of the 108 men (75%) died. Longer PSA DT was associated with a decreased risk of PCSM in men with no/minimal (AHR 0.33, 95% CI 0.17-0.65, p= 0.001) and moderate/severe comorbidity (AHR 0.014, 95% CI 0.002-0.129, p= 0.0002) with a trend toward an increased risk of OCM in men with no/minimal (AHR 1.42, 95% CI 0.94-2.16, p= 0.10) and moderate/severe comorbidity (AHR 1.68, 95% CI 0.85-3.35, p= 0.14). However, increasing PSA DT was only associated with a decreased risk of ACM in men with no/minimal (AHR 0.69, 95% CI 0.50-0.96, p = 0.03) but not moderate/severe comorbidity (AHR 0.95, 95% CI 0.51-1.78, p= 0.87). Conclusions: The extent and natural history of comorbidity as well as PSA DT should be taken into consideration when deciding on appropriate management and/or clinical trial eligibility at the time of PSA failure. Specifically, randomized studies are needed to determine whether survival is prolonged in men with life-shortening comorbidity with salvage ADT at the time of PSA failure versus surveillance and reserving ADT use for symptomatic progression. For all other men, trials comparing ADT with or without novel agents shown to prolong survival in men with metastatic castrate resistant PC is warranted.

Italian Prostate Biopsies Group: 2016 Updated Guidelines Insights.

To present a summary of the updated guidelines of the Italian Prostate Biopsies Group following the best recent evidence of the literature. A systematic review of the new data emerging from 2012-2015 was performed by a panel of 14 selected Italian experts in urology, pathology and radiology. The experts collected articles published in the English-language literature by performing a search using Medline, EMBASE and the Cochrane Library database. The articles were evaluated using a systematic weighting and grading of the level of the evidence according to the Grading of Recommendations Assessment, Development and Evaluation framework system. An initial prostate biopsy is strongly recommended when i) prostate specific antigen (PSA) >10 ng/ml, ii) digital rectal examination is abnormal, iii) multiparametric magnetic resonance imaging (mpMRI) has a Prostate Imaging Reporting and Data System (PIRADS) ≥4, even if it is not recommended. The use of mpMRI is strongly recommended only in patients with previous negative biopsy. At least 12 cores should be taken in each patient plus targeted (fusion or cognitive) biopsies of suspicious area (at mpMRI or transrectal ultrasound). Saturation biopsies are optional in all settings. The optimal strategy for reducing infection complications is still a controversial topic and the instruments to reduce them are actually weak. The adoption of Gleason grade groups in adjunction to the Gleason score when reporting prostate biopsy results is advisable. These updated guidelines and recommendations are intended to assist physicians and patients in the decision-making regarding when and how to perform a prostatic biopsy.

Improving the Rotterdam European Randomized Study of Screening for Prostate Cancer Risk Calculator for Initial Prostate Biopsy by Incorporating the 2014 International Society of Urological Pathology Gleason Grading and Cribriform growth

BackgroundThe survival rate for men with International Society of Urological Pathology (ISUP) grade 2 prostate cancer (PCa) without invasive cribriform (CR) and intraductal carcinoma (IDC) is similar to that for ISUP grade 1. If updated into the European Randomized Study of Screening for Prostate Cancer (ERSPC Rotterdam) risk calculator number 3 (RC3), this may further improve upfront selection of men who need a biopsy. ObjectiveTo improve the number of possible biopsies avoided, while limiting undiagnosed clinically important PCa by applying the updated RC3 for risk-based patient selection. Design, setting, and participantsThe RC3 is based on the first screening round of the ERSPC Rotterdam, which involved 3616 men. In 2015, histopathologic slides for PCa cases (n=885) were re-evaluated. Low-risk (LR) PCa was defined as ISUP grade 1 or 2 without CR/IDC. High-risk (HR) PCa was defined as ISUP grade 2 with CR/IDC and PCa with ISUP grade≥3. Outcome measurements and statistical analysisWe updated the RC3 using multinomial logistic regression analysis, including data on age, PSA, digital rectal examination, and prostate volume, for predicting LR and HR PCa. Predictive accuracy was quantified using receiver operating characteristic analysis and decision curve analysis. Results and limitationsMen without PCa could effectively be distinguished from men with LR PCa and HR PCa (area under the curve 0.70, 95% confidence interval [CI] 0.68–0.72 and 0.92, 95% CI 0.90–0.94). At a 1% risk threshold, the updated calculator would lead to a 34% reduction in unnecessary biopsies, while only 2% of HR PCa cases would be undiagnosed. ConclusionsA relatively simple risk stratification tool augmented with a highly sensitive contemporary pathologic biopsy classification would result in a considerable decrease in unnecessary prostate biopsies and overdiagnosis of potentially indolent disease. Patient summaryWe improved a well-known prostate risk calculator with a new pathology classification system that better reflects disease burden. This new risk calculator allows individualized prediction of the chance of having (potentially aggressive) biopsy-detectable prostate cancer and can guide shared decision-making when considering prostate biopsy.

The impact of comorbidity and PSA doubling time on the risk of death in men experiencing PSA failure following radiation therapy with or with androgen deprivation therapy for unfavorable-risk prostate cancer.

The optimal management of men with PSA failure following initial prostate cancer (PC) therapy stratified by comorbidity is unknown. We investigated the impact that PSA doubling time (DT) and comorbidity had on the risk of all-cause mortality (ACM), prostate cancer-specific mortality (PCSM) and other-cause mortality (OCM) following PSA failure. Between 1995 and 2001, 206 men with unfavorable-risk PC were randomized to receive radiation therapy alone or in combination with 6 months of androgen deprivation therapy (ADT); 108 men experienced PSA failure and formed the study cohort. Cox and Fine-Gray regression analysis was used to determine whether PSA DT was associated with the risk of ACM and PCSM/OCM, respectively, stratified by comorbidity status using a validated metric. After a median follow-up of 13.71 years following PSA failure, 81 of the 108 men (75%) died. Longer PSA DT was associated with a decreased riskof PCSM inmen with no/minimal (adjusted hazard ratio (AHR) 0.33, 95% confidence interval (CI) 0.17-0.65, P=0.001) and moderate/severe comorbidity (AHR 0.014, 95% CI 0.002-0.129, P=0.0002). However, because of the different contributions of the risk of OCM to risk of ACM within comorbidity subgroups, increasing PSA DT was onlyassociated with a decreased risk of ACM in men with no/minimal (AHR 0.69, 95% CI 0.50-0.96, P=0.03) butnot moderate/severe comorbidity (AHR 0.95, 95% CI 0.51-1.78, P=0.87). Both the extent of comorbidity and the PSA DT should be taken into consideration when deciding on appropriate management and/or clinical trial eligibility at the time of PSA failure.

Clinical validation of the iXip index in avoiding unnecessary prostate biopsy: Results from a prospective multicenter study involving 426 patients

PurposeTo assess the diagnostic accuracy of iXip, a novel biomarker for prostate cancer detection at initial biopsy based on an algorithm including patient age, prostate volume, PSA and PSA-IgM levels,. Materials and methodsThis was a prospective multicenter study involving 426 consecutive men undergoing initial prostate biopsy with at least 12 cores in a real-life clinical setting. Diagnostic accuracy of iXip for prostate cancer detection was calculated with AUC and compared to that of prostate volume, PSA and PSA-IgM levels. The correlation of iXip with tumor aggressiveness, defined as any cancer with Gleason score ≥7, was evaluated by Spearman ρ coefficient analysis. ResultsProstate cancer was diagnosed in 193/426 patients (45%), of which 65 (35%) had Gleason score ≥7. iXip values were significantly higher in patients with cancer than in those without cancer (median value 55% vs. 39%, p<0.001). iXip was the most accurate predictor of cancer (AUC=0.711), followed by prostate volume (AUC=0.660) and PSA level (AUC=0.543). By setting iXip cut-off at 20%, no patients with iXip values below the cut-off were diagnosed with cancer, resulting in a 5.6% (24/426) reduction of unnecessary prostate biopsies. A significant correlation between iXip values and Gleason score was observed (ρ=0.347; p<0.001). ConclusionsOur prospective multicenter study suggests that the novel biomarker iXip may be used with a 20% cut-off value in order to reduce the proportion of prostate biopsies by approximately 5%, without missing a single case of cancer. Moreover, higher iXip values are significantly correlated with tumor aggressiveness.

Indications for a second prostate biopsy in patients suspected with prostate cancer after an initial negative prostate biopsy.

BackgroundThe present study aimed to evaluate the indications for a second prostate biopsy in patients suspected with prostate cancer after an initial negative prostate biopsy.MethodsThe present study included 421 patients who underwent repeat prostate biopsy between January 2007 and December 2015 at three hospitals. Clinicopathological data, including patient age, body mass index, history of prostate biopsy, prostate volume, prostate-specific antigen (PSA) level, PSA density, PSA velocity, and PSA fluctuation patterns, were analyzed. The patients were stratified into two groups based on the first PSA pattern (increase/decrease) within 1 year after the initial negative prostate biopsy.ResultsProstate cancer was detected in 100 (23.8%) of the 421 patients at the second prostate biopsy. In patients with a PSA decrease at the first follow-up, prostate volume and number of increases in the PSA level from the initial prostate biopsy were predictors for prostate cancer diagnosis at the second prostate biopsy. In patients with a steady PSA increase after the initial prostate biopsy, prostate volume and number of biopsy cores were predictors for prostate cancer diagnosis at the second prostate biopsy.ConclusionThe indications for a second prostate biopsy are a low prostate volume and a high number of increases in the PSA level among patients with a PSA decrease at the first follow-up and a low prostate volume and a high number of biopsy cores among patients with a PSA increase at the first follow-up.

Blood-based and urinary prostate cancer biomarkers: a review and comparison of novel biomarkers for detection and treatment decisions.

The diagnosis of prostate cancer (PCa) is currently based on serum PSA testing and/or abnormal digital rectal examination and histopathologic evaluation of prostate biopsies. The main drawback of PSA testing is the lack of specificity for PCa. To improve early detection of PCa more specific biomarkers are needed. In the past few years, many new promising biomarkers have been identified; however, to date, only a few have reached clinical practice. In this review, we discuss new blood-based and urinary biomarker models that are promising for usage in PCa detection, follow-up and treatment decision-making. These include Prostate Health Index (PHI), prostate cancer antigen 3 (PCA3), four-kallikrein panel (4K), transmembrane protease serine 2-ERG (TMPRSS2-ERG), ExoDx Prostate Intelliscore, SelectMDx and the Mi-Prostate score. Only few head-to-head studies are available for these new fluid-based biomarkers and/or models. The blood-based PHI and urinary PCA3 are two US Food and Drug Administration-approved biomarkers for diagnosis of PCa. In the second part of this review, we give an overview of published studies comparing these two available biomarkers for prediction of (1) PCa upon prostate biopsy, (2) pathological features in radical prostatectomy specimen and (3) significant PCa in patients eligible for active surveillance. Studies show opposing results in comparison of PHI with PCA3 for prediction of PCa upon initial and repeat prostate biopsy. PHI and PCA3 are able to predict pathological findings on radical prostatectomy specimen, such as tumor volume and Gleason score. Only PHI could predict seminal vesicle invasion and only PCA3 could predict multifocality. There is some evidence that PHI outperforms PCA3 in predicting significant PCa in an active surveillance population. Future research should focus on independent validation of promising fluid-based biomarkers/models, and prospective comparison of biomarkers with each other.

P052 - Updating of the ERSPC Rotterdam Prostate Cancer Risk Calculator for initial prostate biopsy to contemporary practice including the 2014 ISUP Gleason grading and cribriform growth patterns

P052 - Updating of the ERSPC Rotterdam Prostate Cancer Risk Calculator for initial prostate biopsy to contemporary practice including the 2014 ISUP Gleason grading and cribriform growth patterns

Indications, Utilization and Complications Following Prostate Biopsy: New York State Analysis

Uptake of active surveillance and changes in prostate cancer care may affect the utilization of and complications following prostate needle biopsy. Wecharacterized recent trends and risk factors for prostate needle biopsy complications using a statewide, all-payer cohort. We used SPARCS (New York Statewide Planning and Research Cooperative System) to identify prostate needle biopsies performed between 2011 and 2014 via the transrectal and the transperineal approach (9,472 and 421 patients, respectively). We characterized trends in utilization and complications using Poisson regression and the Cochrane-Armitage test. We applied logistic regression to examine predictors of complications within 30 days of prostate needle biopsy. Ambulatory use of prostate needle biopsy decreased with time (p <0.01). The most common indication for prostate needle biopsy was elevated prostate specific antigen in 53.2% of patients, followed by active surveillance for cancer in26.7%, abnormal digital rectal examination in 2.6% and atypia in 1.6%. Theprostate needle biopsy associated infection rate increased from 2.6% to 3.5% during the study period (p = 0.02). Among the 777 repeat prostate needle biopsies, the complication rate was comparable to that of initial prostate needle biopsy. Preprocedural rectal swab was done in less than 1% of prostate needle biopsies. On multivariable analysis, patient race, procedure year, diabetes (OR1.92, 95% CI 1.29-2.86, p <0.01), transrectal approach (OR 3.48, 95% CI1.27-9.54, p = 0.02) and recent hospitalization (OR 2.03, 95% CI 1.43-2.89, p<0.01) were significantly associated with infection. The median total charge for infectious complications was $4,129 (IQR 711-19,185). Across New York State, infectious complications after prostate needle biopsy have increased over time. With higher complications using thetransrectal approach and minimal utilization of targeted antibiotic prophylaxis, further efforts should focus on the evaluation and implementation of these strategies to reduce post-prostate needle biopsy complications nationally.

Ultrasound analysis of seminal vesicles in prostate cancer invasion: monocentric experience of an extended prostate biopsy scheme.

At present, uniformity does not exist with regard to the indication criteria of seminal vesicle (SV) biopsies. The aim of this study was to define the ultrasonographic (US) patterns observed in SV invaded by prostate cancer (PCa), and propose an extended prostate biopsy protocol when SV invasion (SVI) is suspected. We reviewed 1.252 patients who underwent an initial transrectal ultrasound-guided prostate biopsy for suspicious PCa. We performed a 14-core biopsy scheme, as first intention, including 1 SV sample on each side when SVI is suspected: a nodule at the base of prostate (determined by digital rectal examination or US) and/or an US pattern that suggests a SVI. US patterns of SVs were classified as abnormal by a variation of the body anterior-posterior diameter, asymmetry of the volume, parietal thickness, distance between the SVs and the rectal surface, and altered echogenicity of SVs and the base of the prostate. Of the 137 biopsies performed in SVs, the SVI by PCa was diagnosed in 66.5% of candidate patients. The overall prevalence of SVI was 28.5%. No significant difference was noted between the patients with SVI and without SVI, when comparing age, prostate volume, and total core length, except for preoperative PSA serum levels. The sensitivity of any abnormal finding on transrectal ultrasound for the presence of SVI by PCa is 90.8%, whereas the specificity is 96%. We believe that an extended prostate biopsy protocol to provide the possibility of taking one biopsy core of each SV when SVI is suspected should be considered a complementary procedure for PCa staging.

High serum dihydrotestosterone examined by ultrasensitive LC-MS/MS as a predictor of benign prostatic hyperplasia or Gleason score 6 cancer in men with prostate-specific antigen levels of 3-10ng/mL.

There has been no consensus on the role of serum androgen concentrations in prostate cancer detection in men with prostate-specific antigen levels of 3-10ng/mL. In this study, testosterone and dihydrotestosterone concentrations in blood were examined by a newly developed method using ultrasensitive liquid chromatography with two serially linked mass spectrometers (LC-MS/MS). We investigated the correlation between serum androgen levels and Gleason scores at biopsy. We analyzed data of 157 men with a total prostate-specific antigen range of 3-10ng/mL who underwent initial systematic prostate needle biopsy for suspected prostate cancer between April 2000 and July 2003. Peripheral blood testosterone and dihydrotestosterone concentrations were determined by LC-MS/MS. Blood levels of testosterone and dihydrotestosterone were compared with pathological findings by multivariate analyses. Median values of prostate-specific antigen and prostate volume measured by ultrasound were 5.7ng/mL and 31.4cm3 , respectively. Benign prostatic hyperplasia was diagnosed in 97 patients (61.8%), and prostate cancer was diagnosed in 60 (38.2%) patients, including 31 (19.7%) patients with a Gleason score of 6 and 29 (18.5%) patients with a Gleason score of 7-10. Median values of testosterone and dihydrotestosterone in blood were 3798.7 and 371.7pg/mL, respectively. There was a strong correlation between serum testosterone and dihydrotestosterone. In multivariate analysis, age, prostate volume, and serum dihydrotestosterone were significant predictors of benign prostatic hyperplasia or prostate cancer with a Gleason score of 6. The area under the receiver operating characteristics curve for age, prostate volume, and serum dihydrotestosterone were 0.67, 0.67, and 0.67, respectively . We confirmed that high dihydrotestosterone blood levels can predict benign prostatic hyperplasia or prostate cancer with a Gleason score of 6 in men with prostate-specific antigen levels of 3-10ng/mL.

Effects of ω-3 Fatty Acids and Catechins on Fatty Acid Synthase in the Prostate: A Randomized Controlled Trial

ABSTRACTAnimal and human studies suggest fish oil and green tea may have protective effect on prostate cancer. Fatty acid synthase (FAS) has been hypothesized to be linked to chemoprotective effects of both compounds. This study evaluated the independent and joint effects of fish oil (FO) and green tea supplement (epigallocatechin-3-gallate, EGCG) on FAS and Ki-67 levels in prostate tissue. Through a double-blinded, randomized controlled trial with 2 × 2 factorial design, 89 men scheduled for repeat prostate biopsy following an initial negative prostate biopsy were randomized into either FO alone (1.9 g DHA + EPA/day), EGCG alone (600 mg/day), a combination of FO and EGCG, or placebo. We used linear mixed-effects models to test the differences of prostate tissue FAS and Ki-67 by immunohistochemistry between pre- and post-intervention within each group, as well as between treatment groups. Results did not show significant difference among treatment groups in pre-to-post-intervention changes of FAS (P = 0.69) or Ki-67 (P = 0.26). Comparing placebo group with any of the treatment groups, we did not find significant difference in FAS or Ki-67 changes (all P > 0.05). Results indicate FO or EGCG supplementation for a short duration may not be sufficient to produce biologically meaningful changes in FAS or Ki-67 levels in prostate tissue.

A nomogram for prediction of prostate cancer on multi‐core biopsy using age, serum prostate‐specific antigen, prostate volume and digital rectal examination in Singapore

To develop and internally validate two nomograms for predicting the probability of overall and clinically-significant prostate cancer on initial biopsy in a Singaporean population. Data were collected from men undergoing initial prostate biopsy at a single center. The indications for biopsy were serum prostate-specific antigen (PSA) ≥4.0 ng/mL or suspicious digital rectal examination (DRE) findings. Men with PSA >30 ng/mL were excluded. Age, PSA, prostate volume (PV) and DRE were predictors included in our logistic regression model and used to construct two nomograms for overall prostate cancer and clinically-significant (Gleason sum ≥7) cancer detection. Predictive accuracies of our nomograms were assessed using area under curve (AUC) of their receiver-operator characteristic curves. Internal validation was performed using the bootstrap method. Our nomograms were compared to a model based on PSA alone using AUC and decision curve analysis (DCA). Out of 672 men analyzed, our positive biopsy rate was 26.2% (n = 176), of which 63.6% (n = 112) had clinically significant disease. Age, PSA, PV and DRE status were all independent risk factors for both overall prostate cancer detection as well as clinically-significant cancer detection (all P < 0.05). Our nomogram outperformed serum PSA for both overall and clinically-significant cancer detection (0.736 vs 0.642, P < 0.001 and 0.793 vs 0.696, P < 0.001, respectively). Using DCA, our nomograms had superior net benefit and net reduction in biopsy rate compared to PSA alone. Our nomograms have been shown to be superior to PSA alone, on both AUC and DCA. However, it warrants external validation.

Targeted Biopsy to Detect Gleason Score Upgrading during Active Surveillance for Men with Low versus Intermediate Risk Prostate Cancer

We sought to determine the rate of upgrading to Gleason score 4 + 3 or greater using targeted biopsy for diagnosis and monitoring in men undergoing active surveillance of prostate cancer. Study subjects comprised all 259 men, including 196 with Gleason score 3 + 3 and 63 with Gleason score 3 + 4, who were diagnosed by magnetic resonance imaging/ultrasound fusion guided biopsy from 2009 to 2015 and underwent subsequent fusion biopsy for as long as 4 years of active surveillance. The primary end point was the discovery of Gleason score 4 + 3 or greater prostate cancer. Followup biopsies included targeting of positive sites, which were tracked in an Artemis™ device. Kaplan-Meier curves were generated to determine upgrading rates, stratified by initial Gleason score and prostate specific antigen density. Based on a Cox proportional hazard model, men with Gleason score 3 + 4 were 4.65 times more likely to have upgrading than men with an initial Gleason score of 3 + 3 at 3 years (p <0.01). By the third surveillance year 63% of men with Gleason score 3 + 4 had been upgraded compared with 18.0% who started with Gleason score 3 + 3 (p <0.01). Of all 33 upgrades 32 (97%) occurred at a magnetic resonance imaging visible or a tracked site of tumor, rather than at a previously negative systematic site. Independent predictors of upgrading were Gleason score 3 + 4, prostate specific antigen density 0.15 ng/ml/cm3 or greater and a grade 5 lesion on magnetic resonance imaging. The incidence rate ratio of upgrading (Gleason score 3 + 4 vs 3 + 3) was 4.25 per year of patient followup (p<0.01). During active surveillance of prostate cancer, targeting of tracked tumor foci by magnetic resonance imaging/ultrasound fusion biopsy allows for heightened detection of Gleason score 4 + 3 or greater cancers. Baseline variables directly related to important upgrading that warrant increased vigilance include Gleason score 3 + 4, prostate specific antigen density 0.15 ng/ml/cm3 or greater and grade 5 lesions on magnetic resonance imaging.

Comparison Between a Combined Transrectal and Transperineal Approach and a Transrectal Approach for Prostate Rebiopsy.

To evaluate whether a combination method involving the transrectal (TR) and transperineal (TP) approach can increase the cancer detection rate relative to the TR approach regarding repeat prostate biopsy. One thousand and nineteen patients underwent initial prostate biopsies and 298 repeat prostate biopsies. All initial biopsies were conducted transrectally. Of the repeat biopsies, 179 (60.1%) were performed using the combined transrectal and transperineal (TR+TP) approach; 113 (37.9%) were carried out transrectally. All biopsies were performed under ultrasound guidance using a 16-gauge core biopsy needle; 651 were diagnosed as prostate cancer; 224 patients underwent radical prostatectomies (RPs). We evaluated the cancer detection rates between the biopsy methods in the repeat biopsy cohort and compared the clinical and pathological features of the RP specimens between the initial and repeat biopsy groups. A median of 12 and 20 cores were obtained in the initial and repeat biopsy patients, respectively. Cancer detection rates regarding biopsies 1, 2, 3, 4 and 5 were 49.2% (551/1,119), 34.7% (75/216), 33.3% (20/60), 26.7% (4/15) and 14.3% (1/7), respectively. There were no significant differences between the TR and the TR+TP approach (32.7% vs. 33.5%). RP specimens diagnosed using repeat biopsies showed more anterior dominant tumors relative to those diagnosed using the initial biopsies (59.5% vs. 35.9%; p<0.001). The TR+TP combination approach could not increase cancer detection rates relative to the TR approach in the repeat biopsy cohort. However, 16-gauge needle biopsy demonstrated acceptable cancer detection rates in the comparatively small number of biopsy cores.

A Novel Pain Alternative for Patients with Anorectal Pathologies: The Comparison of Transperineal Prostatic Blockage Technique with Periprostatic Nerve Blockage and Rectal Gel Technique in Initial Transrectal Ultrasound-Guided Prostate Biopsy - A Prospective, Randomized Trial

Introduction: The study aimed to compare the efficiency of periprostatic nerve blockage (PPNB) and intrarectal lidocaine gel (PPNB + gel) with a transperineal prostatic block (TPPB) technique during transrectal ultrasound-guided prostate biopsy (TRUS-PBx) in patients with anorectal pathologies. Materials and Methods: A total of 376 patients who underwent TRUS-PBx were randomized into 2 groups. Group-I (n = 198) received TPPB with 10 ml 2% prilocaine, and group-II (n = 178) received intrarectal administration of 10 ml 2% lidocaine gel followed by PPNB with 10 ml 2% prilocaine. A 10-point linear visual analogue scale (VAS) was used to assess the pain arising from probe insertion (VAS-1) and prostate sampling (VAS-2). Results: VAS-1 scores were significantly lower in group-I than group-II (1.7 ± 1.9 vs. 3.9 ± 1.5; p < 0.001). Combining local anesthesia produced superior pain control to TPPB during sampling (2.0 ± 1.2 vs. 2.5 ± 2.4; p = 0.015). Following subgroup analyses with reference to concomitant anorectal pathologies, VAS-1 scores were significantly lower in group-I than group-II (2.0 ± 1.8 vs. 5.5 ± 1.7; p < 0.001). VAS-2 scores were lower in group-II than group-I; however, the difference was not considered significant (2.4 ± 1.3 vs. 3.1 ± 2.8; p = 0.303). Conclusions: In all patients referred for TRUS-PBx, TPPB is a good alternative to PPNB + gel. TPPB can be particularly useful for patients with anorectal pathologies due to its improved pain reduction during probe insertion.

Prostate Specific Antigen and Prostate Cancer in Chinese Men Undergoing Initial Prostate Biopsies Compared with Western Cohorts

We determined the characteristics of Chinese men undergoing initial prostate biopsy and evaluated the relationship between prostate specific antigen levels and prostate cancer/high grade prostate cancer detection in a large Chinese multicenter cohort. This retrospective study included 13,904 urology outpatients who had undergone biopsy for the indications of prostate specific antigen greater than 4.0 ng/ml or prostate specific antigen less than 4.0 ng/ml but with abnormal digital rectal examination results. The prostate specific antigen measurements were performed in accordance with the standard procedures at the respective institutions. The type of assay used was documented and recalibrated to the WHO standard. The incidence of prostate cancer and high grade prostate cancer was lower in the Chinese cohort than the Western cohorts at any given prostate specific antigen level. Around 25% of patients with a prostate specific antigen of 4.0 to 10.0 ng/ml were found to have prostate cancer compared to approximately 40% in U.S. clinical practice. Moreover, the risk curves were generally flatter than those of the Western cohorts, that is risk did not increase as rapidly with higher prostate specific antigen. The relationship between prostate specific antigen and prostate cancer risk differs importantly between Chinese and Western populations, with an overall lower risk in the Chinese cohort. Further research should explore whether environmental or genetic differences explain these findings or whether they result from unmeasured differences in screening or benign prostate disease. Caution is required for the implementation of prostate cancer clinical decision rules or prediction models for men in China or other Asian countries with similar genetic and environmental backgrounds.

Beyond prostate-specific antigen: utilizing novel strategies to screen men for prostate cancer.

The purpose of this article is to review blood and urine tests that are currently available and under investigation for a role in prostate cancer screening and detection. Compared with total prostate-specific antigen (PSA) alone, its combination with percentage free-to-total PSA contributes greater specificity for prostate cancer, and is a component of two newer blood tests called the 4kScore and Prostate Health Index. All three tests improve the prediction of high-grade disease and are commercially available options to aid in initial or repeat prostate biopsy decisions. PCA3 is a urinary marker that is currently available for repeat prostate biopsy decisions. Although PCA3 alone has inferior prediction of clinically significant disease and requires collection of urine after digital rectal examination, it may be combined with other clinical variables or other urine markers like TMPRSS2:ERG to improve performance. Little data are available to support a role for single nucleotide polymorphisms or other investigational markers in early detection. Several commercially available blood and urine tests have been shown to improve specificity of PSA for high-grade prostate cancer. Use of such tests would decrease unnecessary biopsy and overdiagnosis of indolent disease. Biopsy of men with moderately elevated PSA without use of such a reflex test should be discouraged.

Outcomes of Active Surveillance after Initial Surveillance Prostate Biopsy

We analyzed the rates of disease reclassification at initial and subsequent surveillance prostate biopsy as well as the treatment outcomes of deferred therapy among men on active surveillance for prostate cancer. From a prospective database we identified 300 men on active surveillance who had undergone initial surveillance prostate biopsy, with or without confirmatory biopsy, within 1 year of diagnosis. Of these men 261 (87%) were classified as having NCCN very low or low risk disease at diagnosis. Disease reclassification on active surveillance was defined as the presence of 50% or more positive cores and/or surveillance prostate biopsy Gleason score upgrading. Patients with type I disease reclassification included those with any surveillance prostate biopsy Gleason score upgrading, while patients with type II reclassification had to have primary Gleason pattern 4-5 disease on surveillance prostate biopsy. Outcomes after initial surveillance prostate biopsy were evaluated using actuarial analyses. At the time of initial surveillance prostate biopsy 49 (16%) and 19 (6%) patients had type I and type II disease reclassification, respectively. Those who underwent confirmatory biopsy had significantly reduced rates of type I (9% vs 23%, p=0.001) and type II (3% vs 9%, p=0.01) reclassification at initial surveillance prostate biopsy. For the 251 patients without disease reclassification at initial surveillance prostate biopsy the 2-year rates of subsequent type I and II reclassification were 17% (95% CI 0-24) and 3% (95% CI 0.1-7), respectively. For the 93 patients who received deferred therapy the 5-year biochemical progression-free probability was 89% (95% CI 79-98), including 95%, 82% and 70% among those without, and those with type I and type II disease reclassification, respectively. Patients on active surveillance with stable disease at the time of initial surveillance prostate biopsy may be appropriate candidates for less intensive surveillance prostate biopsy schedules.