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Purpose: We assessed whether the visibility of Grade Group (GG) 1 prostate cancer on baseline multiparametric magnetic resonance imaging affects clinical outcomes., Materials and Methods: We evaluated 454 men who underwent multiparametric magnetic resonance imaging between 2006 and 2018 with maximum GG1 prostate cancer inclusive of magnetic resonance imaging targeted biopsy. Multiparametric magnetic resonance imaging was graded as negative, equivocal or positive. Assessed outcomes were treatment-free survival, biopsy upgrade-free survival and unfavorable disease at radical prostatectomy (pT 3 or greater and/or GG3 or greater). Kaplan-Meier and multivariable Cox proportional hazard analyses were used to estimate the impact of multiparametric magnetic resonance imaging and clinicopathological variables (age, year, prostate specific antigen density and measures of tumor volume on biopsy) on outcomes., Results: During followup (median 45.2 months) 61 men had disease upgraded on followup biopsy and 139 underwent definitive treatment. In men with negative, equivocal and positive baseline multiparametric magnetic resonance imaging at 5 years, treatment-free survival was 79%, 73% and 49% (p <0.0001), treatment-free survival was 89%, 82% and 70% (p=0.002), and survival without unfavorable disease at radical prostatectomy was 98%, 98% and 86% (p=0.007), respectively. At multivariable analysis positive (HR 1.93, 95% CI 1.21-3.09, p=0.006) and equivocal multiparametric magnetic resonance imaging (HR 2.02, 95% CI 1.11-3.68, p=0.02) were associated with shorter treatment-free survival, and positive multiparametric magnetic resonance imaging was a significant prognostic factor for upgrade-free survival (HR 2.03, 95% CI 1.06-3.86, p=0.03) and unfavorable disease at radical prostatectomy (HR 4.45, 95% CI 1.39-18.17, p=0.01)., Conclusions: Men with positive multiparametric magnetic resonance imaging and GG1 prostate cancer on magnetic resonance imaging targeted biopsy are at increased risk for intervention, upgrading and unfavorable disease at radical prostatectomy compared to those with multiparametric magnetic resonance imaging invisible GG1 prostate cancer.

Objectives: To develop and externally validate a nomogram that predicts risk of side-specific extraprostatic extension (EPE) at time of surgery, using commonly available preoperative markers., Materials and Methods: A consecutive sample of 753 men treated by radical prostatectomy (RP) at the University Health Network, Toronto, between 2009 and 2015, was used to develop the nomogram. The validation cohort consisted of 311 men treated by RP at Ottawa Hospital Research Institute, between 1992 and 2014. The study outcome was presence of ipsilateral EPE. The association between predictors considered and EPE was tested using univariate and multivariate logistic regression analyses. The predictive accuracy of the nomogram was determined using the area under the receiver-operating characteristic curve., Results: The overall rate of EPE was 19.8% of all lobes in the developmental cohort and 28.9% in the validation cohort. Significant variables in the models were age, prostate-specific antigen and ipsilateral Gleason score, percentage of positive cores and highest core involvement (all P < 0.05). The nomogram predicting risk of EPE had a predictive accuracy of 0.74 in the external validation cohort., Conclusion: We developed and externally validated a nomogram that predicts the risk of ipsilateral EPE based on commonly used preoperative markers. This nomogram may be used to assist surgical decision-making prior to RP., (© 2016 The Authors BJU International © 2016 BJU International Published by John Wiley & Sons Ltd.)

Purpose: While prostate cancer is primarily a disease of older men, young age prostate cancer represents an important clinical subgroup which has not been adequately studied. We evaluated the histopathological features and associated clinical behavior of prostate cancer in a cohort of younger men treated with radical prostatectomy., Materials and Methods: The study included 171 men younger than 50 years with prostate cancer who were treated with radical prostatectomy at an academic institution between 2001 and 2015. Comprehensive pathology review was performed. Clinical and followup data were obtained from a prospectively maintained institutional database., Results: Median age was 43 years (range 38 to 49). Of the tumors 42% were Gleason score 3 + 3 and 45% were 3 + 4 while Gleason score 4 + 3, 4 + 4 and 4 + 5 disease comprised 10.5%, 0.5% and 1% of cases, respectively. Mucinous carcinoma (greater than 25% extracellular mucin), an uncommon histological variant which comprises 0.2% of prostate cancers, was noted in 11 of our cases (6%). A further 21 cases (12%) of acinar adenocarcinoma had a less than 25% mucinous component. Followup data were available on 156 men (91%). Biochemical recurrence developed in 12 patients (19%) but there was no documented postoperative metastasis or death from disease in the cohort. All cases of mucinous carcinoma were associated with favorable clinicopathological characteristics., Conclusions: Our findings provide additional evidence that younger men with prostate cancer who are treated with radical prostatectomy mostly have favorable disease characteristics and outcomes. While the histopathological features in our series were generally comparable to those of older onset carcinoma, our cohort was enriched for tumors with a mucinous phenotype. Correlation with molecular-genetic analysis in this subset of tumors may be valuable., (Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

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 1,255 patients biopsy Gleason score 7 (3 + 4) was associated with T3 or greater disease at radical prostatectomy in 35.0% compared with Gleason score 6 (3 + 3) in 19.0% (p <0.001). On multivariate analysis for each quantitative percent of Gleason pattern 4 increase there were 2% higher odds of T3 or greater disease (OR 1.02, 95% CI 1.01-1.04, p <0.001). When stratified, patients with Gleason score 7 (3 + 4) only approximated the pT3 rates of Gleason score 6 (3 + 3) when prostate specific antigen was less than 8 ng/ml and the percent of prostate cancer was less than 15%. In those cases the quantitative percent of Gleason pattern 4 had less effect. Time to failure after radical prostatectomy was worse in Gleason score 7 (3 + 4) than 6 (3 + 3) cases., Conclusions: The quantitative percent of Gleason pattern 4 helps predict advanced disease and Gleason score 7 (3 + 4) is associated with worse outcomes. However, the impact of the quantitative percent of Gleason pattern 4 on adverse pathological and clinical outcomes is best used in combination with prostate specific antigen, age and disease volume since each has a greater impact on predicting nonorgan confined disease. The calculated absolute risk of T3 or greater can be used in shared decision making on prostate cancer treatment by patients and clinicians., (Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: Metabolic syndrome (MetS) is associated with an increased risk of finding prostate cancer overall and high-grade disease on biopsy. This study sought to determine if MetS is associated with adverse final pathology and risk of overall recurrence in men undergoing radical prostatectomy (RP)., Methods: Men undergoing RP (2004-2013) were identified using our prospectively maintained institutional database. MetS was defined by ≥3 of 5 components (obesity, dysglycemia, hypertension, low high-density lipoprotein-cholesterol, and high triglycerides). Multivariable logistic regression models were created for prostate cancer grade and stage on final pathology. Kaplan-Meier and multivariable Cox regression analyses were performed to model overall recurrence, defined by biochemical recurrence (postoperative serum prostate-specific antigen ≥0.2 ng/mL) or use of salvage therapies., Results: Of 1939 men, 439 (22.6%) had MetS. MetS (≥3 vs. 0 components) was associated with an increased odds of Gleason 8-10 disease (odds ratio [OR] = 2.49, 95% confidence interval [CI] = 1.32-4.67, P = .005) and extraprostatic disease (OR = 1.35, 95% CI = 1.02-1.80, P = .04). Decreased use of nerve-sparing in men with MetS was noted. In unadjusted analyses, MetS was associated with a significantly increased risk of receiving salvage therapy (hazard ratio [HR] = 1.38, 95% CI = 1.04-1.83, P = .03) and a near-significant increased overall recurrence risk (HR = 1.20, 95% CI = 0.94-1.53, P = .15). These associations were attenuated upon adjusting for disease-specific parameters (salvage therapy: HR = 1.03, 95% CI = 0.76-1.40, P = .87; overall recurrence: HR = 0.94, 95% CI = 0.72-1.21, P = .62)., Conclusion: MetS is associated with an increased odds of extraprostatic and high-grade disease on final RP pathology, which appears to drive an increased risk of needing salvage therapy after RP. However, with more aggressive resection, differences in failure-free outcomes were attenuated, suggesting that men with MetS should not be precluded from RP., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: To investigate whether the amount of striated muscle (SM) removed with the apical aspect of the prostate at prostatectomy can be predictive of postprostatectomy urinary incontinence (UI)., Methods: The records of 61 consecutive patients seen in follow-up after prostatectomy were reviewed. Complete clinical data were collected. Two uropathologists reviewed the hematoxylin and eosin sections of the apical margin to semiquantitatively assess the amount of SM according to the following scheme: 0 = no SM, 1 = 1%-10% SM (of total tissue), 2 = 11%-30% SM, and 3 = >30% SM. Continence status was determined based on the last clinical visit, with UI considered as any reported leakage., Results: Patients had a median age of 62 years at surgery (interquartile range, 58-66 years) and had a median follow-up after surgery of 100 weeks (interquartile range, 50-176 weeks). Both prostate weight and SM score (P = .045 for both) were statistically significant predictors of incontinence on multivariate analysis. The odds of a patient with an average SM score of ≥2 being incontinent was 11.7 times that of a patient with an average score of <2. Using an SM score of ≥2 had a specificity of 98% and a sensitivity of 19% for detecting incontinence in patients after radical prostatectomy., Conclusion: The amount of SM seen in the pathology specimen after radical prostatectomy has a significant effect on postoperative UI., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Introduction: The clinical significance of perineural invasion (PNI) on prostate needle biopsy is controversial. The aim of this present study is to determine the role of PNI on prostate biopsy in predicting adverse findings at radical prostatectomy in a recent cohort of screen detected prostate cancer., Materials and Methods: We analyzed 470 patients diagnosed with prostate cancer from a prospectively maintained database at Princess Margaret Hospital. Out of the 470 patients diagnosed with prostate cancer, 139 underwent radical prostatectomy. Pathological specimens were examined, and perineural invasion was identified as carcinoma tracking along or around a nerve in the perineural space. We investigated the predictive value of PNI on biopsy with PNI on radical prostatectomy as well as the ability of PNI on prostate biopsy to predict adverse findings at radical prostatectomy., Results: Perineural invasion was present in 124 (26%) of biopsy specimens diagnosed with prostate cancer and 94 (68%) of those who chose radical prostatectomy. Perineural invasion on prostate needle biopsy was not predictive of radical prostatectomy Gleason score (p = .377), pathological stage (p = .852), extraprostatic extension (p = .258), surgical margin (p = .079), lymphovascular invasion (p = .499), and upgrading (p = .514) or downgrading (p = .208) at radical prostatectomy. The sensitivity, specificity, positive predictive value, and negative predictive value of PNI on biopsy for PNI on radical prostatectomy were 32%, 82%, 79%, and 37% respectively. The Cohen's Kappa correlation coefficient was .11., Conclusions: Perineural invasion on prostate needle biopsy is not predictive of radical prostatectomy outcome. Furthermore, perineural invasion on biopsy has limited predictive value for perineural invasion at radical prostatectomy.

The International Society of Urological Pathology Consensus Conference on Handling and Staging of Radical Prostatectomy Specimens in Boston made recommendations regarding the standardization of pathology reporting of radical prostatectomy specimens. Issues relating to extraprostatic extension (pT3a disease), bladder neck invasion, lymphovascular invasion and the definition of pT4 were coordinated by working group 3. It was agreed that prostate cancer can be categorized as pT3a in the absence of adipose tissue involvement when cancer bulges beyond the contour of the gland or beyond the condensed smooth muscle of the prostate at posterior and posterolateral sites. Extraprostatic extension can also be identified anteriorly. It was agreed that the location of extraprostatic extension should be reported. Although there was consensus that the amount of extraprostatic extension should be quantitated, there was no agreement as to which method of quantitation should be employed. There was overwhelming consensus that microscopic urinary bladder neck invasion by carcinoma should be reported as stage pT3a and that lymphovascular invasion by carcinoma should be reported. It is recommended that these elements are considered in the development of practice guidelines and in the daily practice of urological surgical pathology.

Objective: To review our experience and delineate the role of magnetic resonance imaging (MRI) in identifying patients presenting with a raised prostate-specific antigen (PSA) level and clinical findings suggestive of anterior predominant tumours, which appear to be significant, particularly in those with a previous negative biopsy or low-volume disease undergoing active surveillance., Patients and Methods: We retrospectively reviewed our database to identify patients with anteriorly predominant tumours on MRI whom had undergone prostate biopsy., Results: In all, 31 patients with anterior predominant tumours on MRI also had a positive biopsy (14 on active surveillance and 17 with previous negative biopsies). MRI was usually invoked by the presenting PSA level or PSA velocity. MRI had a positive predictive value for anterior tumours of 87% (27/31). The Gleason score distribution for the 27 men with cancer was 6 in 15; 3 + 4 in three, 4 + 3 in six and 8/9 in three. For prostatic cores, 44/85 (52%) samples from the anterior prostate had cancer. Thirteen patients had a radical prostatectomy (pT2 in three, pT3 in seven and pT4 in three); seven of the 13 had positive surgical margins and a third of them had a biochemical recurrence at the 1-year follow-up., Conclusion: There is a subset of patients either having a negative biopsy or low-volume disease and who are on active surveillance who should be considered for MRI and further biopsy, as their pathology might be aggressive. An entity might be emerging with anterior predominant tumours that are impalpable, and we believe the term 'prostate evasive anterior tumour syndrome' to be appropriate. This requires further analysis in a large prospective database with consideration for triggers for MRI and targeted biopsies.

Prostate cancer remains a challenge due to its incidence and radical prostatectomy continues to be a major treatment option for men with potentially curable disease who have a life expectancy over a decade. This article will address the common problem of positive surgical margins and the impact of them on patient outcome. Through these we can examine relevant clinical trials that have attempted to address this issue and offer some guided to therapy among men with this clinical problem. Close margins are probably of no significance and will not be addressed. Our recommendations take into account the current level of medical evidence, and are balanced with anticipated adverse effects of treatment. They may change over time once definitive clinical trials are completed. In brief we believe those with positive margins and PT2 we advocate close observation with the aim of early salvage radiotherapy if necessary. Those with PT3a and focally positive margins with low/intermediate grade tumors are at moderate risk of biochemical failure so should be managed like PT2 patients. However those with high-grade disease should be offered adjuvant radiotherapy. Similarly those with PT3a margin positive extensive or multiple site disease should have adjuvant radiotherapy. PT3B margin positive patients should be offered radiotherapy. PT4 with bladder neck only margin positive can probably be observed., (Copyright 2010. Published by Elsevier Inc.)

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: 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.

Objectives: To correlate the primary Gleason pattern among patients with biopsy-derived Gleason 7 tumors with the radical prostatectomy specimen Gleason grading and other clinical and pathologic outcomes., Methods and Materials: Among 474 patients who underwent radical prostatectomy for clinically localized prostate cancer between 1997-2001, 205 (43%) had Gleason 7/10 tumors on pre-operative needle biopsy. Among theses patients, 148 (72.2%) were assigned a primary Gleason 3 pattern (3+4 = 7) and 57 (27.8%) were assigned a primary Gleason 4 pattern (4+3 = 7). The two groups were compared with respect to age, serum PSA levels, Gleason grade in the radical prostatectomy specimen, pathological stage and surgical margin status., Results: Among patients with 3+4 tumors on needle biopsy, 64% remained primary Gleason grade 3 while 35% were up-graded to a primary pattern 4 following analysis of the radical prostatectomy specimen. Patients with 4+3 tumors on needle biopsy remained primary Gleason grade 4 in 51% of patients, while 49% of patients had their tumors down-graded to a primary 3 pattern (p = 0.09). There were no differences between patients with needle biopsy 3+4 and 4+3 patterns with respect to total Gleason score in the radical prostatectomy specimen (p = 0.42), pTNM stage (p = 0.36), extra-prostatic extension (p = 0.88), surgical margin involvement (p = 0.16), and seminal vesicle invasion (p = 0.19). In contrast, the primary Gleason pattern in the radical prostatectomy specimen correlated significantly with pTNM stage (p = 0.02) and seminal vesicle invasion (p= 0.003), but not with extra-prostatic extension (p = 0.32) and surgical margin involvement (p = 0.17)., Conclusions: Among patients with Gleason 7 adenocarcinoma of the prostate, the biopsy-derived primary Gleason pattern does not appear to correlate with important clinical and pathologic outcomes. The utility of distinguishing a primary Gleason pattern on needle biopsy among patients with Gleason 7 tumors remains unclear given the limited and conflicting literature addressing this issue.

Background: In Canada, waiting times for cancer care have been increasing, particularly for patients with genitourinary malignancies. We examined whether delay from diagnosis for patients undergoing surgery for clinically localized prostate cancer affects cancer cure rates., Methods: We conducted a historical cohort study among 645 patients who underwent radical prostatectomy between 1987 and 1997, using biochemical recurrence (PSA elevation) and metastasis as endpoints. We examined whether patients who underwent surgery >/= months (delayed surgery group) from the date of diagnosis had reduced recurrence-free survival, compared to patients who had surgery <3 months (early surgery group) from the date of diagnosis, adjusting for grade, stage and PSA level at diagnosis., Results: The crude 10-year recurrence-free and metastasis-free survival rates for all patients were 71.1% (95% C.I.: 64.9% - 77.3%) and 95.3% (95% C.I.: 91.3% - 99.3%), respectively. Of the 645 patients, 189 (29.3%) had surgery >/= months after diagnosis. The median time from the date of diagnosis to surgery was 68 days (range 15 to 951 days). The 10-year recurrence-free survival was higher for patients who underwent early surgery (74.6%, 95% C.I.: 67.9% - 81.4%) compared to patients in the delayed surgery group (61.3%, 95% C.I.: 46.7% - 76.0%, p=0.05). The crude and adjusted hazard ratios for developing biochemical recurrence for patients in the delayed surgery group were 1.58 (95% C.I.: 1.0 - 2.4, p=0.04) and 1.46 (95% C.I.: 0.9 - 2.3, p=0.09), respectively, compared to patients who underwent early surgery., Conclusions: There may exist a possible relationship between delays from diagnosis for radical prostatectomy and prostate cancer cure rates. These findings may have many biases that could not be properly accounted in this retrospective analysis and larger cohort analyses will be required to confirm these findings.

Aims: Intraductal and cribriform carcinoma of the prostate are increasingly recognised as independent prognosticators of poor outcome, both in prostate biopsies and surgical specimens. We studied the concordance of biopsy and prostatectomy diagnosis for these two subpathologies in relationship with pathological stage. Methods and results: Mandatory synoptic reporting of intraductal and cribriform carcinoma in prostate biopsies and prostatectomy specimens was adopted by two academic institutions in November 2015. Synoptic reports of 245 biopsy and corresponding prostatectomy specimens were interrogated to determine the prevalence of intraductal and cribriform carcinoma. Sensitivity and specificity were determined, with prostatectomy diagnosis as the gold standard. Associations with pathological stage as primary outcome parameter were determined using univariable and multivariable logistic regression analysis. Prevalence of the combination of intraductal and cribriform carcinoma was 26.9% in biopsies and 51.8% in prostatectomy specimens. Sensitivity and specificity at biopsy were 47.2% and 94.9%, respectively. Intraductal and cribriform carcinoma at biopsy were associated with advanced pathological stage independent of grade (P = 0.013). Among patients with grade group 2 prostate cancer at biopsy, the more advanced pathological stage distribution was similar for those with a false negative and a true positive biopsy diagnosis of intraductal and cribriform carcinoma (P = 0.29). Conclusion: In spite of low sensitivity, intraductal and cribriform carcinoma at biopsy was associated strongly with advanced stage at radical prostatectomy. As a false negative biopsy diagnosis was equally associated with advanced pathological stage, efforts should be undertaken to improve the sensitivity of biopsy diagnosis for intraductal and cribriform carcinoma. [ABSTRACT FROM AUTHOR]

Aims Ductal adenocarcinoma of the prostate ( DAC) is clinically important, because its behaviour may differ from that of acinar adenocarcinoma. Our aims were to investigate the interobserver variability of this diagnosis among experts in uropathology and to define diagnostic criteria. Methods and results Photomicrographs of 21 carcinomas with ductal features were distributed among 20 genitourinary pathologists from eight countries. DAC was diagnosed by 18 observers (mean 13.2 cases, range 6-19). In 11 (52%) cases, a 2/3 consensus was reached for a diagnosis of DAC, and in five (24%) there was consensus against. In DAC, the respondents reported papillary architecture (86%), stratification of nuclei (82%), high-grade nuclear features (54%), tall columnar epithelium (53%), elongated nuclei (52%), cribriform architecture (40%), and necrosis (7%). The most important diagnostic feature reported for DAC was papillary architecture (59%), whereas nuclear and cellular features were considered to be most important in only 2-11% of cases. The most common differential diagnoses were intraductal prostate cancer (52%), high-grade PIN (37%), and acinar adenocarcinoma (17%). The most common reason for not diagnosing DAC was lack of typical architecture (33%). Conclusions Papillary architecture was the most useful diagnostic feature of DAC, and nuclear and cellular features were considered to be less important. [ABSTRACT FROM AUTHOR]

Aims To assess the frequency and possible causes of downgrading from a Gleason score (GS) 7 at biopsy to a GS ⩽6 at radical prostatectomy (RP) in a Canadian referral centre. Methods Data were extracted from diagnostic reports of inhouse biopsies and matching prostatectomy specimens from 2008 to 2011 with a GS 7 at biopsy. Biopsies and corresponding prostatectomy specimens of downgraded cases were reviewed. Pathological features were assessed and possible predictors for downgrading were identified. Results Based on pathology reports, 29 (8.9%, 95% CI 5.8% to 11.9%) of the 327 eligible cases were downgraded from biopsy GS 7 to RP GS 6, 72% of them representing a GS ⩽6 with tertiary grade 4 at RP. Agreement at review of downgraded RP specimens for Gleason grading was fair and of borderline significance (?=0.34, 95% CI -0.01 to 0.68, p=0.055) with 65% agreement for tertiary grade. The predominant Gleason grade 4 pattern found in the downgraded biopsies was ill-formed glands. The number of cores with Gleason grade 4 component was found to be the strongest negative predictor of downgrading (prereview OR=0.56 (95% CI 0.39 to 0.80, p=0.002), postreview OR=0.19 (95% CI 0.07 to 0.52, p=0.001)). Conclusions The frequency of GS 7 in biopsies subsequently downgraded in RP is low and is associated with International Society of Urological Pathology modified Gleason grade 4 patterns. Downgrading could be attributed in most cases to the presence of a tertiary Gleason grade 4 pattern in the RP specimen. Interobserver agreement for the presence of tertiary grade 4 in RP specimens is moderate. [ABSTRACT FROM AUTHOR]

Delahunt B, Miller R J, Srigley J R, Evans A J & Samaratunga H (2012) Histopathology 60, 75-86 Gleason grading: past, present and future In 1966 Donald Gleason developed his grading and scoring system for prostatic adenocarcinoma. This classification was refined in 1974 and gained almost universal acceptance, being classified as a category 1 prognostic parameter by the College of American Pathologists. Modifications to the classification were recommended at a conference convened by the International Society of Urological Pathology (ISUP) in 2005. This modified classification has resulted in a significant upgrading of tumours, although some studies have shown a greater concordance between needle biopsy and radical prostatectomy scores when compared to classical Gleason (CG) grading. The ISUP consensus conference recommended that for needle biopsies higher tertiary patterns should be incorporated into the final Gleason score, and this has been correlated with biochemical failure, tumour volume and mortality. Recently the validity of including cribriform glands as a component of Gleason pattern 3 has been questioned and it has been recommended that all tumours showing cribriform architecture should be classified as Gleason pattern 4. The recommendations arising from the 2005 Consensus Conference were largely unsupported by validating data, yet this new grading system has achieved widespread usage. It is unfortunate that recent suggestions for further modification are similarly lacking in supporting evidence. In view of this it is recommended that the Modified Gleason Scoring Classification should continue to be utilized in its original (2005) format and that any future alterations should be implemented only when mandated by tumour-related outcome studies. [ABSTRACT FROM AUTHOR]

Background: Following prostate cancer surgery, positive surgical margin (PSM) status varies among institutions and there is evidence that high-volume surgeons and centres obtain better oncological results. However, larger studies recording PSM for radical prostatectomy (RP) are from large "centres of excellence" and not population-based. Cancer Care Ontario undertook an audit of pathology reports to determine the province-wide PSM rate for pathological stage T2 (pT2) disease prostate cancer and to assess the overall and regional-based PSM rates based on surgical volume to understand gaps in quality of care prior to undertaking quality improvement initiatives. Methods: Data were extracted as part of the Pathology Project Audit data output (2005, 2006). Pathology reports were submitted to Cancer Care Ontario by Ontario hospitals electronically via the Pathology Information Management System. An experienced cancer pathology coder extracted the PSM data from eligible RP cancer specimen pathology reports. Only reports that provided a pathological stage were included in the analysis. Biopsy and transurethral resection of the prostate reports were excluded. A convenience sample of 1346 reports from 2006 and 728 from 2005 were analyzed. Regression analysis was performed to assess volume-margin associations. Results: The median province-wide surgical PSM rate for pT2 disease was 33%, ranging 0-100% among 43 hospitals where RP volumes ranged 12-625. There was no significant correlation (p > 0.05) between volume and PSM by logistic regression with variable odds ratios (95% confidence interval [CI]) for PSM by quartile (1st = 1.66 [0.93-2.96]; 2nd = 0.97 [0.58-1.62]; 3rd = 1.44[0.91- 2.29]) compared to the highest volume last quartile. Mean PSM rates between community and teaching hospitals were not significantly different. Conclusions: The province-wide PSM rate for pT2 disease prostate cancer undergoing RP is higher than those published from "centres of excellence." Results from larger volume centres were not statistically significantly better, which contradicts previously published data. Factors, such as individual surgeon, patient selection, pathological processing and interpretation, may explain the differences. [ABSTRACT FROM AUTHOR]

The article deals with a study that identified clinical predictors of upgrading of biopsy-derived low-risk prostate cancer by using radical prostatectomy specimens as the gold standard. The researchers examined 175 cases of low-risk prostate cancer treated with radical prostatectomy and applied logistic regression analysis to evaluate preoperative risk factors for their ability to predict Gleason score upgrading. They also developed a nomogram which could aid in clinical decision-making.

For prostate cancer patients, the Gleason score is one of the most important prognostic factors, potentially determining treatment independent of the stage. However, Gleason scoring is based on subjective microscopic examination of tumor morphology and suffers from poor reproducibility. Here we present a deep learning system (DLS) for Gleason scoring whole-slide images of prostatectomies. Our system was developed using 112 million pathologist-annotated image patches from 1226 slides, and evaluated on an independent validation dataset of 331 slides. Compared to a reference standard provided by genitourinary pathology experts, the mean accuracy among 29 general pathologists was 0.61 on the validation set. The DLS achieved a significantly higher diagnostic accuracy of 0.70 (p = 0.002) and trended towards better patient risk stratification in correlations to clinical follow-up data. Our approach could improve the accuracy of Gleason scoring and subsequent therapy decisions, particularly where specialist expertise is unavailable. The DLS also goes beyond the current Gleason system to more finely characterize and quantitate tumor morphology, providing opportunities for refinement of the Gleason system itself. [ABSTRACT FROM AUTHOR]

Objective: To examine a 2-year cohort of patients treated with brachytherapy to determine the likelihood of unfavorable pathologic features using a nomogram recently developed at our center to estimate the likelihood of Gleason score upgrading for patients with favorable prostate cancer undergoing radical prostatectomy. The brachytherapy outcomes for patients with a high likelihood of upgrading were compared with those with a lower likelihood to affirm the effectiveness of brachytherapy in this setting. Information on the likelihood of upgrading could help in the selection between active treatment and surveillance for patients with favorable-risk prostate cancer. Methods: The records were examined for 259 men undergoing prostate brachytherapy in 2006 to 2007, of whom 217 had favorable risk cancer. The likelihood of Gleason score upgrading (GSU) was predicted using the radical prostatectomy-derived nomogram. Results: The median age was 62 years (range 44-77), and the median prostate-specific antigen level was 4.71 ng/mL (range 0.56-9.87). Central pathology review was available for 88%, and 83% had undergone extended biopsies. Two men had received androgen deprivation therapy for prostate downsizing. The median predicted likelihood of GSU was 51.2%. The median prostate-specific antigen level for 199 patients without treatment failure after a median follow-up of 4.2 years in this cohort was 0.07 ng/mL (interquartile range undetectable to 0.23). Conclusion: In the present cohort of patients with favorable-risk prostate cancer treated with brachytherapy, the estimated likelihood of GSU using the surgically derived nomogram was substantial. Follow-up with prostate-specific antigen measurement has indicated that brachytherapy is a highly effective treatment option despite less favorable clinical and pathologic factors. Patients should not be discouraged from brachytherapy on the basis of a high likelihood of GSU. [ABSTRACT FROM AUTHOR]

Background: The objective is to provide surgical and pathological guidelines for radical prostatectomy (RP) with or without concurrent pelvic lymph node dissection (PLND) to achieve optimal benefit for patients, with minimal risk of harm. Methods: For surgical questions, a literature search of MEDLINE, EMBASE and the Cochrane database was performed. A literature search for the pathological questions was not conducted since the protocol for invasive carcinomas of the prostate gland developed by the College of American Pathologists (CAP) was endorsed. Urologists and pathologists were consulted for their assessment of the surgical and pathological recommendations. Results: Limited high-quality evidence from 95 primary studies was available and, therefore, the expert panel developed recommendations on the basis of a consensus of the expert opinion of the working group and through a consultation with urologists and pathologists. In addition to the CAP protocol, some technical recommendations related to the handling and processing of the specimen were made. Conclusion: Radical prostatectomy is recommended for the surgical treatment of prostate cancer, depending on a patient's preoperative risk profile. The panel unanimously determined that the goals for RP are to attain a positive margin rate of <25% for pT2 disease, a mortality rate of <1%, rates of rectal injury of <1% and blood transfusion rates of <10% in non-anemic patients. Standard PLND should be mandatory in high-risk patients, should be recommended for intermediate-risk patients and should be optional for low-risk patients. The quality and effectiveness of this treatment and of subsequent patient care depend on good management, effective communication and reporting between surgeons and pathologists working together as part of a multidisciplinary team. The complete guideline document is posted on the Cancer Care Ontario website (www.cancercare.on.ca); search in their Toolbox, Quality Guidelines & Standards, Clinical Program category under "surgery." [ABSTRACT FROM AUTHOR]