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Purpose: Longitudinal cohort studies and guidelines demonstrate that prostate specific antigen 1 ng/ml or greater in younger patients confers an increased risk of delayed prostate cancer death. At our institution we have used an aggressive biopsy strategy in younger patients with prostate specific antigen 1 ng/ml or greater. Our objective was to determine the proportion of detected cancer and specifically clinically significant cancer by this strategy., Materials and Methods: The prostate biopsy database at Princess Margaret Cancer Centre was queried for patients younger than 50 years who underwent a first prostate biopsy between 2000 and 2016. We included only patients who underwent prostate biopsy due to prostate specific antigen 1 ng/ml or greater and those with a suspicious digital rectal examination, a positive family history or a suspicious lesion on transrectal ultrasound. All clinical and pathological parameters were analyzed. Patients were stratified according to specific prostate specific antigen values. Multivariable logistic regression was performed to ascertain predictors of any prostate cancer diagnosis and of clinically significant prostate cancer., Results: Of the 199 patients who met study inclusion criteria 37 (19%) were diagnosed with prostate cancer and 8 (22%) had a Gleason score of 7 or greater. Of those diagnosed with prostate cancer 25 (68%) had prostate specific antigen 1.5 ng/ml or greater and all men with a Gleason score of 7 or greater had prostate specific antigen 1.5 ng/ml or greater. Notably 19 patients (51%) had prostate cancer exceeding the Epstein criteria for active surveillance. Factors predicting prostate cancer included a positive family history, rising prostate specific antigen and lower prostate volume., Conclusions: Our results justify adopting an aggressive prostate biopsy strategy in men younger than 50 years with prostate specific antigen 1.5 ng/ml or greater while patients with prostate specific antigen less than 1.5 ng/ml are unlikely to have significant cancer. Special attention should be given to patients with a smaller prostate and a positive family history., (Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Introduction: Complex statistical models utilizing multiple inputs to derive a risk assessment may benefit prostate cancer (PC) detection where focus has been on prostate-specific antigen (PSA). This study develops a polychotomous logistic regression (PR) model and an artificial neural network (ANN) for predicting biopsy results, particularly for clinically significant PC., Methods: There were 3,025 men undergoing TRUS-guided biopsy (BX) with PSA <10 ng/ml selected. BX outcome classified as benign, atypical small acinar proliferation or high-grade prostatic intraepithelial neoplasia (ASAP/PIN), non-significant (NSPC) or clinically significant PC (CSPC). PR and ANN models were developed to distinguish between BX categories. Predictors were age, PSA, abnormal digital rectal examination (DRE), positive transrectal ultrasound (TRUS) and prostate volume., Results: Among the BXs, 44% were benign, 14% ASAP/PIN, 16% NSPC and 25% CSPC. Median age, PSA and volume were 64 years, 5.7 ng/ml and 50 cc. TRUS lesion was present in 47%, and DRE was abnormal in 39%. PR and ANN models did not differ on percentage BX outcomes correctly predicted (55, 57%, respectively) and were equally poor for both ASAP/PIN (0%) and NSPC (2%). For PR and ANN, 74-78% ASAP/PIN predicted benign, 2% NSPC and 20-24% CSPC. For NSPC, 69-71% predicted benign, 27-29% CSPC. Benign outcomes were well identified (86-88%), although 12-13% classified CSPC. CSPC was correctly identified in 65-66% with misclassifications largely benign (33% for PR and ANN)., Conclusions: Neither PR nor ANN was able to distinguish between the four biopsy outcomes: ASAP/PIN and NSPC were not distinguished from benign or CSPC. ANN did not perform better than PR. Inclusion of additional predictors may increase the performance of statistical models in predicting BX outcome.

Accurate Gleason score, pathologic stage, and surgical margin (SM) information is critical for the planning of post-radical prostatectomy management in patients with prostate cancer. Although interobserver variability for Gleason score among urologic pathologists has been well documented, such data for pathologic stage and SM assessment are limited. We report the first study to address interobserver variability in a group of expert pathologists concerning extraprostatic soft tissue (EPE) and SM interpretation for radical prostatectomy specimens. A panel of 3 urologic pathologists selected 6 groups of 10 slides designated as being positive, negative, or equivocal for either EPE or SM based on unanimous agreement. Twelve expert urologic pathologists, who were blinded to the panel diagnoses, reviewed 40x whole-slide scans and provided diagnoses for EPE and SM on each slide. On the basis of panel diagnoses, as the gold standard, specificity, sensitivity, and accuracy values were high for both EPE (87.5%, 95.0%, and 91.2%) and SM (97.5%, 83.3%, and 90.4%). Overall kappa values for all 60 slides were 0.74 for SM and 0.63 for EPE. The kappa values were higher for slides with definitive gold standard EPE (kappa=0.81) and SM (kappa=0.73) diagnoses when compared with the EPE (kappa=0.29) and SM (kappa=0.62) equivocal slides. This difference was markedly pronounced for EPE. Urologic pathologists show good to excellent agreement when evaluating EPE and SM. Interobserver variability for EPE and SM interpretation was principally related to the lack of a clearly definable prostatic capsule and crush/thermal artifact along the edge of the gland, respectively.

Purpose: To compare the value of diffusion-weighted MRI (DWI), dynamic contrast-enhanced (DCE) MRI, and microbubble contrast-enhanced ultrasound (CEUS) for assessment of the thermal lesion created by interstitial microwave heating of the normal canine prostate., Materials and Methods: A microwave antenna was inserted into each lobe of the prostate in seven dogs to induce coagulation necrosis. Immediately after therapy the lesion was assessed using CEUS, DCE-MRI, and DWI. The prostates were excised, photographed, and prepared for hematoxylin and eosin staining. Results from posttreatment MRI and ultrasound were compared to histology., Results: The apparent diffusion coefficient (ADC) was slightly lowered within the thermal lesion but was drastically reduced in a ring-like region that corresponds to a grossly appearing red thermal damage zone immediately peripheral to the central coagulum. Both DCE-MRI and CEUS delineated a smaller area of vascular damage, for which the borders lie within the red zone., Conclusion: The red zone encompasses a range of vascular responses, including hyperemia and hemostasis, and is known to progress to necrosis and tissue nonviability. DWI clearly depicts this zone as a region of sharply reduced ADC, and may be better than contrast-enhanced imaging for accurate assessment of the eventual full extent of thermal damage., ((c) 2008 Wiley-Liss, Inc.)

Purpose: Serum prostate specific antigen screening has increased the number of prostate biopsies performed increasing the number of patients with high grade prostatic intraepithelial neoplasia. The criteria for re-biopsy are not standardized but may be refined by the identification of novel biomarkers demonstrating prognostic significance. Alpha-methylacyl-CoA racemase is a robust marker of prostate cancer and is expressed in a subset of high grade prostatic intraepithelial neoplasia. This study evaluates the prognostic significance of alpha-methylacyl-coA racemase positive high grade prostatic intraepithelial neoplasia glands in prostate biopsies., Materials and Methods: Immunohistochemical staining with alpha-methylacyl-coA racemase and p63 was examined in a selected group of 62 patients with a diagnosis of high grade prostatic intraepithelial neoplasia on initial prostate biopsy, of which on repeat biopsy 32 had no carcinoma and 30 had prostate cancer. There was no significant difference in age, number of cores sampled or prostate specific antigen history between the 2 outcome groups (ANOVA p >0.9). High grade prostatic intraepithelial neoplasia glands in each case were evaluated for alpha-methylacyl-coA racemase and p63., Results: Reactivity for alpha-methylacyl-coA racemase was found in 27 of the 62 cases examined. Fisher's exact analysis revealed that patients with at least 1 alpha-methylacyl-coA racemase positive high grade prostatic intraepithelial neoplasia gland were 5.2 times more likely to have a subsequent diagnosis of prostate cancer on repeat biopsy than those without any alpha-methylacyl-coA racemase positive high grade prostatic intraepithelial neoplasia glands (p = 0.0044). No correlation was found between alpha-methylacyl-coA racemase positivity and any other clinical variable., Conclusions: This is the first study to our knowledge to illustrate that alpha-methylacyl-coA racemase reactivity in high grade prostatic intraepithelial neoplasia may be useful to refine re-biopsy criteria and assist in clinical management decisions.

Objective: To determine the practice pattern of repeat prostate biopsies to detect prostate cancer, as there is growing evidence to support the recommendation that a repeat prostate biopsy should be taken after an initially negative prostate biopsy, the rate of cancer detection then being approximately 30%., Patients and Methods: We examined the practice patterns of taking a repeat prostate biopsy after an initial negative biopsy and the predictors for cancer at repeat biopsy among 1536 patients who had an initial prostate biopsy because of an elevated prostate-specific antigen (PSA) level (>4.0 ng/mL) or abnormal digital rectal examination., Results: Of the 1536 men, 712 (46.4%) had cancer detected on the first biopsy; of the remaining 824 with no cancer detected, 268 (32.5%) had a repeat biopsy within a year, and 68 of these (25.4%) had cancer detected. Of the cancers detected at repeat biopsy, 31% were high-grade. Men with abnormal histology (prostatic intraepithelial neoplasia or atypia) had an odds ratio of 3.2 (P < 0.001) for having a repeat biopsy. For men with normal initial prostate histology, those with an initial PSA of 10.0-20.0 and >20.0 ng/mL had an odds ratio of 3.6 and 4.5 (both P < 0.001), respectively, for a repeat prostate biopsy, compared with patients with a PSA of <10.0 ng/mL. However, the PSA level was not predictive of prostate cancer at repeat biopsy, but age and prostate volume were., Conclusions: A third of patients had a repeat biopsy after a negative biopsy. The most important factors influencing whether a patient was to have a repeat biopsy were initial biopsy histology and PSA level. However, the latter was not an important factor for predicting prostate cancer at repeat biopsy.

Purpose: In light of a recent tendency toward systematic nontargeted biopsy we reassessed whether identification and biopsy of ultrasonographically suspicious lesions contribute to the detection of prostate cancer. Materials and Methods: We reviewed prospectively gathered data on 7,426 transrectal ultrasound directed prostatic biopsies performed at our institution between June 16, 2000 and September 1, 2005. Patients underwent systematic biopsy (6 to 10 cores on initial biopsy and 13 to 15 on rebiopsy) with additional sampling of visible suspicious lesions. The RR for finding cancer in transrectal ultrasound positive and negative patients was calculated for likely independent prognostic variables. Results: A total of 3,828 biopsies (51.5%) were transrectal ultrasound negative and 3,598 (48.5%) were transrectal ultrasound positive. Prostate cancer was detected in 3,258 biopsies (43.9%). For each independent variable the RR for prostate cancer was higher if a sonographic lesion was present. A lesion increased the likelihood of cancer detection (57.8% vs 30.8%, RR 1.8). Biopsies from lesions identified by transrectal ultrasound had a greater median percent of the core involved with cancer (50% vs 10%, p <0.001) and they were more likely to have Gleason score 7 or greater (69.3% vs 28.3%, p <0.001). Conclusions: Biopsies taken when a prostatic lesion is identified by transrectal ultrasound are almost twice as likely to show cancer than when no lesion is visible. These cancers are of higher grade and volume and, therefore, they are more clinically significant. The search for and targeted biopsy of suspicious lesions seen on transrectal ultrasound remains important for prostate cancer diagnosis. [Copyright &y& Elsevier]

Purpose: Differentiation between Gleason score 6 and 7 in prostate biopsy is important for treatment decision making. Nevertheless, under grading errors compared with the actual pathological grade at radical prostatectomy are common. We compared the characteristics and outcomes of tumors that were scored 6 on prostate biopsy but were 7 on subsequent radical prostatectomy pathological evaluation to those in tumors with a consistent rating of Gleason score 6 or 7 at biopsy and surgery. Materials and Methods: We performed a retrospective database analysis from our referral center (1989 to 2004). We compared pre-prostatectomy characteristics, radical prostatectomy pathological features and the post-radical prostatectomy prostate specific antigen failure rate, defined as any 2 consecutive detectable prostate specific antigen measurements, in 3 subgroups of patients, including 156 with matched Gleason score 6 in the prostate biopsy and radical prostatectomy, 205 with upgraded Gleason score 6/7, that is prostate biopsy Gleason score 6 and radical prostatectomy Gleason score 7, and 412 with matched Gleason score 7 in the prostate biopsy and radical prostatectomy. Results: Radical prostatectomy Gleason score matched the prostate biopsy score in 38.2% of biopsy Gleason score 6 and 81.4% of biopsy Gleason score 7 cases. Higher prostate specific antigen was associated and an increased percent of cancer in the prostate biopsy was predictive of discordance between the prostate biopsy and radical prostatectomy Gleason scores (p <0.001). Margin (p = 0.0075) or seminal vesicle involvement (p = 0.0002), cancer volume (p <0.001) and the prostate specific antigen failures rate (p = 0.014) were significantly higher in under graded Gleason score 7 cancer compared to those in matched Gleason score 6 cases. However, they were comparable to those with a matched Gleason score 7 tumor grade (p = 0.66). Conclusions: Almost half of tumors graded Gleason score 6 at biopsy are Gleason score 7 at surgery. Upgraded Gleason score 6 to 7 tumors have outcomes similar to those of genuine Gleason score 7 cancer. For prostate biopsy Gleason score 6 tumors clinicians should consider the overall likelihood of tumor upgrading as well as specific patient characteristics, such as prostate specific antigen and the percent of tumor in the prostate biopsy, when contemplating treatments that are optimized for low grade tumors, including watchful waiting or brachytherapy. [Copyright &y& Elsevier]

Purpose: The clinical usefulness of PSA for prostate cancer screening is unclear, although the test remains in common use. New methods to interpret PSA are needed. Materials and Methods: We examined a cohort of 2,637 men who underwent prostate biopsies for abnormal DRE or PSA between 1999 and 2004. Using risk factors for prostate cancer, including patient age, ethnicity, family history of prostate cancer, previous negative biopsy, voiding symptoms and prostate volume, we developed risk groups for prostate cancer using recursive partitioning modeling independent of PSA or DRE. We then compared prostate cancer probabilities by PSA ranges by risk group. Results: Of the 2,637 men 1,282 (48.6%) had prostate cancer. Age, ethnicity, family history, previous negative biopsy and prostate volume were predictive for cancer. We constructed 6 risk groups by combining these factors and created tables to assign patients to these groups. Independent of PSA and DRE the probability of cancer ranged from 15% in patients in group 1 to 78% in patients in group 6 (p <0.0001). By adding PSA and DRE to each risk group prostate cancer probabilities were refined from 0% to 100%. Patients in the higher risk groups also had higher grade cancer (p <0.0001). Conclusions: We generated 6 risk groups based on simple risk factors for prostate cancer. When used in the right context and patient, PSA is highly accurate for predicting prostate cancer and permitting rational decision making in patients with abnormal PSA. [Copyright &y& Elsevier]