Percentage Of Gleason Pattern Research Articles

The present and future of prostate cancer histopathology.

The present review describes recent changes in the histologic grading of prostatic adenocarcinoma and emerging data suggesting areas for further grade optimization. The grading of prostatic adenocarcinoma has evolved over time, and optimization for active surveillance management has been one major driving force. Recent changes include adoption of the Grade Group system, which stratifies patients into one of five prognostic groups. Although it provides clearer labels for patient understanding and defines a more homogenous low-risk group (i.e. Grade Group 1 of 5), emerging data suggest that further prognostic stratification may be achieved by incorporating other histologic findings. The impact of 'cribriform histology' and intraductal carcinoma as aggressive features of prostate cancer has gained significant recognition. Furthermore, quantifying the fraction of each individual Gleason pattern component may also add prognostic stratification. In addition to Gleason score and Grade Group, some institutions now identify and report high-risk histologic patterns (e.g. 'cribriform histology') and the percentage of Gleason pattern 4 on biopsies. While early in adoption, these additional features are being used to further stratify patients beyond the Grade Group system, particularly for patients with Grade Group 2 carcinomas. These histologic findings will likely be incorporated into future modifications of the grading system to further optimize patient stratification and ensure reporting consistency. The histologic evaluation of prostatic adenocarcinoma provides strong prognostic information for clinical management. The recent Grade Group system offers many improvements, but further optimization based on specific histologic patterns may evolve.

Pathological characteristics according to age at diagnosis in 2 929 men with prostate cancer

Objective To compare pathological grading characteristics according to age at diagnosis in men with prostate cancer. Methods A single institutional review of 2 929 records of patients diagnosed with prostate cancer from January 2000 to June 2016 was conducted. Patients [age from 33 to 91 years old, averaged (70.0±8.0) years old] were stratified by age: only 133 cases (4.5%) were in young group (≤55 years old), 2 033 cases(69.5%) in middle-aged group (56-75 years old ), and 763 cases (26.0%) in senile group (76-91 years old). The pathological grading characteristics (Gleason sum, primary Gleason score, the second primary Gleason score, the percent of Gleason pattern 5) were compared among the three groups. Results The median Gleason sum of the three groups were 8 (6-10), 7 (3-10), and 8 (3-10), respectively. Gleason sum, primary Gleason score, the second primary Gleason score were different among the three groups (H=12.975, P=0.002; H=9.264, P=0.010; H=6.692, P=0.035). The percentage of Gleason pattern 5 were 44.4%, 32.3% and 36.8% respectively, with significant difference(χ2=11.641, P=0.003) among the three groups. The difference between young group and middle-aged group, and the difference between middle-aged group and senile group were all significant(χ2=8.183, P=0.004; χ2=5.065, P=0.024). Conclusions Gleason sum was different based on age groups. The percentage of Gleason pattern 5 in young group and senile group are much higher than that in middle-aged group. The prostate cancer was more aggressive in young or senile men than in middle-aged men. Key words: Prostatic neoplasms; Gleason score; Age; Prognosis

Accuracy of Grading Gleason Score 7 Prostatic Adenocarcinoma on Needle Biopsy: Influence of Percent Pattern 4 and Other Histological Factors

Recognition of Gleason pattern 4 in prostatic needle biopsies is crucial for both prognosis and therapy. Recently, it has been recommended to record percent pattern 4 when Gleason score 7 cancer is the highest grade in a case. Four hundred and five prostate needle core biopsies received for a second opinion at our institution from February-June, 2015 were prospectively diagnosed with prostatic adenocarcinoma Gleason score 7 as the highest score on review by a consultant urological pathologist. Percentage of core involvement by cancer, percentage of Gleason pattern 4 per core, distribution of Gleason pattern 4 (clustered, scattered), morphology of pattern 4 (cribriform, non-cribriform), and whether the cancer was continuous or discontinuous were recorded. Better agreement was noted between the consultant and referring pathologists when pattern 4 was clustered as opposed to dispersed in biopsies (P = 0.009). The percentage of core involvement by cancer, morphology of pattern 4, and continuity of cancer did not affect the agreement between the consultant and referring pathologists. There was a trend (P = 0.06) for better agreement based on the percent of pattern 4. When pattern 4 is scattered amongst pattern 3 as opposed to being discrete foci, there is less interobserver reproducibility in grading Gleason score 7 cancer, and in this setting pathologists should consider obtaining second opinions either internally within their group or externally. Prostate 77: 681-685, 2017. © 2017 Wiley Periodicals, Inc.

Diffusion-weighted endorectal MR imaging at 3T for prostate cancer: correlation with tumor cell density and percentage Gleason pattern on whole mount pathology.

To determine if tumor cell density and percentage of Gleason pattern within an outlined volumetric tumor region of interest (TROI) on whole-mount pathology (WMP) correlate with apparent diffusion coefficient (ADC) values on corresponding TROIs outlined on pre-operative MRI. Men with biopsy-proven prostate adenocarcinoma undergoing multiparametric MRI (mpMRI) prior to prostatectomy were consented to this prospective study. WMP and mpMRI images were viewed using 3D Slicer and each TROI from WMP was contoured on the high b-value ADC maps (b0, 1400). For each TROI outlined on WMP, TCD (tumor cell density) and the percentage of Gleason pattern 3, 4, and 5 were recorded. The ADCmean, ADC10th percentile, ADC90th percentile, and ADCratio were also calculated in each case from the ADC maps using 3D Slicer. Nineteen patients with 21 tumors were included in this study. ADCmean values for TROIs were 944.8±327.4 vs. 1329.9±201.6mm2/s for adjacent non-neoplastic prostate tissue (p<0.001). ADCmean, ADC10th percentile, and ADCratio values for higher grade tumors were lower than those of lower grade tumors (mean 809.71 and 1176.34mm2/s, p=0.014; 10th percentile 613.83 and 1018.14mm2/s, p=0.009; ratio 0.60 and 0.94, p=0.005). TCD and ADCmean (ρ=-0.61, p=0.005) and TCD and ADC10th percentile (ρ=-0.56, p=0.01) were negatively correlated. No correlation was observed between percentage of Gleason pattern and ADC values. DWI MRI can characterize focal prostate cancer using ADCratio, ADC10th percentile, and ADCmean, which correlate with pathological tumor cell density.

Prognostic Significance of Percentage and Architectural Types of Contemporary Gleason Pattern 4 Prostate Cancer in Radical Prostatectomy.

The International Society of Urological Pathology (ISUP) 2014 consensus meeting recommended a novel grade grouping for prostate cancer that included dividing Gleason score (GS) 7 into grade groups 2 (GS 3+4) and 3 (GS 4+3). This division of GS 7, essentially determined by the percent of Gleason pattern (GP) 4 (< or >50%), raises the question of whether a more exact quantification of the percent GP 4 within GS 7 will yield additional prognostic information. Modifications were also made by ISUP regarding the definition of GP 4, now including 4 main architectural types: cribriform, glomeruloid, poorly formed, and fused glands. This study was conducted to analyze the prognostic significance of the percent GP 4 and main architectural types of GP 4 according to the 2014 ISUP grading criteria in radical prostatectomies (RPs). The cohort included 585 RP cases of GS 6 (40.2%), 3+4 (49.0%), and 4+3 (10.8%) prostate cancers. Significantly different 5-year biochemical recurrence (BCR)-free survival rates were observed among GS 6 (99%, 95% confidence interval [CI]: 97%-100%), 3+4 (81%, 95% CI: 76%-86%), and 4+3 (60%, 95% CI: 45%-71%) cancers (P<0.01). Dividing the GP 4 percent into quartiles showed a 5-year BCR-free survival of 84% (95% CI: 78%-89%) for 1% to 20%, 74% (95% CI: 62%-83%) for 21% to 50%, 66% (95% CI: 50%-78%) for 51% to 70%, and 32% (95% CI: 9%-59%) for >70% (P<0.001). Among the GP 4 architectures, cribriform was the most prevalent (43.7%), and combination of architectures with cribriform present was more frequently observed in GS 4+3 (60.3%). Glomeruloid was mostly (67.1%) seen combined with other GP 4 architectures. Unlike the other GP 4 architectures, glomeruloid as the sole GP 4 was observed only as a secondary pattern (ie, 3+4). Among patients with GS 7 cancer, the presence of cribriform architecture was associated with decreased 5-year BCR-free survival when compared with GS 7 cancers without this architecture (68% vs. 85%, P<0.01), whereas the presence of glomeruloid architecture was associated with improved 5-year BCR-free survival when compared with GS 7 cancers without this architecture (87% vs. 75%, P=0.01). However, GS 7 disease having only the glomeruloid architecture had significantly lower 5-year BCR-free survival than GS 6 cancers (86% vs. 99%, P<0.01). Multivariable Cox proportional hazards regression model for factors associated with BCR among GS 7 cancers identified age (hazard ratio [HR] 0.95, P<0.01), preoperative prostate-specific antigen (HR 1.07, P<0.01), positive surgical margin (HR 2.70, P<0.01), percent of GP 4 (21% to 50% [HR 2.21], 51% to 70% [HR 2.59], >70% [HR 6.57], all P<0.01), presence of cribriform glands (HR 1.78, P=0.02), and presence of glomeruloid glands (HR 0.43, P=0.03) as independent predictors. In conclusion, our study shows that increments in percent of GP 4 correlate with increased risk for BCR supporting the ISUP recommendation of recording the percent of GP 4 in GS 7 prostate cancers at RP. However, additional larger studies are needed to establish the optimal interval for reporting percent GP 4 in GS 7 cancers. Among the GP 4 architectures, cribriform independently predicts BCR, whereas glomeruloid reduces the risk of BCR. Distinction should be made between cribriform and glomeruloid architectures, despite glomeruloid being considered as an early stage of cribriform, as cribriform confers a higher risk for poorer outcome.

PD42-12 EXTRA-PROSTATIC EXTENSION AND SEMINAL VESICLE INVASION ARE EXCEEDINGLY RARE AT RADICAL PROSTATECTOMY FOR GLEASON 6 PROSTATE CANCER USING ISUP MODIFIED SCORING CRITERIA

You have accessJournal of UrologyProstate Cancer: Staging I1 Apr 2016PD42-12 EXTRA-PROSTATIC EXTENSION AND SEMINAL VESICLE INVASION ARE EXCEEDINGLY RARE AT RADICAL PROSTATECTOMY FOR GLEASON 6 PROSTATE CANCER USING ISUP MODIFIED SCORING CRITERIA Blake Anderson, Aria Razmaria, Bonnie Choy, Gregory Zagaja, Arieh Shalhav, Gladell Paner, and Scott Eggener Blake AndersonBlake Anderson More articles by this author , Aria RazmariaAria Razmaria More articles by this author , Bonnie ChoyBonnie Choy More articles by this author , Gregory ZagajaGregory Zagaja More articles by this author , Arieh ShalhavArieh Shalhav More articles by this author , Gladell PanerGladell Paner More articles by this author , and Scott EggenerScott Eggener More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.1764AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Recent studies employing contemporary Gleason grading have demonstrated Gleason score 6 (GS6) prostate cancers lack the ability to metastasize. The goal of this study was to assess the pathologic stage following radical prostatectomy of true GS6 prostate cancers in a large institutional series. METHODS From 2003 to 2013, 3731 patients underwent robotic radical prostatectomy at a single academic institution. Out of 1106 patients with GS6 identified at surgery, 38 (3.4%) were identified as GS6 with stage pT3a/b on initial pathologic review, 34 with pT3a (extra-prostatic extension; EPE) and 4 with pT3b disease (seminal vesicle invasion; SVI). All cases underwent repeat pathologic evaluation by a single expert genitourinary pathologist (GPP) for Gleason grade, pathological stage, extent of EPE, percent of prostate volume with tumor, percent of Gleason pattern 4 and type of Gleason pattern 4 (e.g. cribriform, fused, ill-formed, glomeruloid, variant patterns). Additionally, all Gleason score 7-9 (GS7-9) pT3b cases from our database, in total 153, were re-reviewed. The 2014 International Society of Urological Pathology (ISUP) modified Gleason grading criteria were applied. RESULTS Of the 38 GS6 pT3a/b cases, 34 (90%) were upgraded to Gleason 3+4 (32), 4+3 (1) or 4+4 (1). Of the upgraded cases, 8 (24%) had minor (< 5%) components of pattern 4, which under the 2004 ISUP Gleason grading consensus was not established as a secondary grade. Six (16%) were down-staged to pT2 since only capsular incision was present or tumor invaded capsule but not beyond. After re-review, only 2 cases (0.2% of entire GS6 cohort) with pT3a were observed, both with focal EPE (non-established). Among the re-examined cohort, no cases with pure GS6 and stage pT3b were observed. Ill-formed glands were the most common type of pattern 4 present in 91% of upgraded cases, followed by fused (82%) and cribriform (35%) glands. Ductal (6%) and mucinous (3%) variants were rare reasons for upgrading. Lastly, none of the 153 GS7-9 pT3b cases were downgraded to Gleason 6. CONCLUSIONS In this large contemporary study, Gleason 6 prostate cancer never had seminal vesicle invasion (0%) and was only rarely (0.2%) associated with extra-prostatic extension. Our data further supports active surveillance as an optimal management strategy for most men with Gleason 6 prostate cancer. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e992 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Blake Anderson More articles by this author Aria Razmaria More articles by this author Bonnie Choy More articles by this author Gregory Zagaja More articles by this author Arieh Shalhav More articles by this author Gladell Paner More articles by this author Scott Eggener More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

MP79-13 TESTOSTERONE LEVELS AS A PREDICTOR FACTOR OF AGRESSIVE DISEASE IN PATIENTS WITH PROSTATE CANCER SUBMITTED TO RADICAL PROSTATECTOMY

INTRODUCTION AND OBJECTIVES: We sought to determine the prognostic value of percentage Gleason pattern 4 in radical prostatectomy specimens. METHODS: We selected 400 patients who underwent robotic radical prostatectomy (RRP) between 2010 and 2011 with Gleason score 7. Data collected included pT stage, tumor volume, margin status, angiolymphatic invasion, lymph node involvement and biochemical recurrence (BCR) at 2 years after surgery. RESULTS: Mean age of the patients was 62 years. We stratified the patients into four quartiles based on percentage of Gleason pattern 4 (GP4). Q1: percent of Gleason 4 20% 35%, Q3: >35% 65%, Q4: >65%. Table 1 shows these quartiles correlated with multiple pathological outcomes. Percentage of GP4 was associated with BCR when other pathologic features were accounted for. A percent greater than 65 (i.e. fourth quartile) was significantly different from a percent of 20 or less in providing a greater likelihood for recurrence OR1⁄46.53 (95% CI 2.43, 17.56). The other factors that were also significant were margins, positive lymph nodes and angiolymphatic invasion. These four variables yielded a c-statistic of 0.82. If percentage of GP4 is considered as a continuous measure, it is also independently related with PSA recurrence within 2 years of surgery. A unit increase in the percent of GP4 increases the likelihood of recurrence by 3 percent, OR1⁄41.03 (1.01, 1.04). CONCLUSIONS: 1. Gleason 7 prostatic adenocarcinoma represents a heterogenous group of tumors. A subgroup of tumors with Gleason score 3+41⁄47 and low percentage of GP4 ( 20%) of pattern 4. 2. Percentage of GP4 is an important parameter that should be reported on all radical prostatectomies with Gleason score 7, given its independent prognostic value. 3. Additional studies are needed to determine the role of higher Gleason pattern percentages in tumors other than Gleason score 7. Source of Funding: None

MP46-17 THE IMPACT OF PATHOLOGICAL GLEASON SCORE ON BIOCHEMICAL RECURRENCE IN PATIENTS WITH PATHOLOGICALLY ORGAN-CONFINED T2 PROSTATE CANCER AND POSITIVE SURGICAL MARGINS: CAN WE JUSTIFY EXPECTANT MANAGEMENT OR IS ADJUVANT RADIATION THERAPY INDICATED? RESULTS OF A MULTICENTER EUROPEAN EVALUATION

Alexander Karl*, Alexander Buchner, Christian Stief, Christiane Tympner, Thomas Kirchner, Ute Ganswindt, Claus Belka, Munich, Germany; Roman Ganzer, Wolf Wieland, Fabian Eder, Ferdinand Hofst€ adter, Regensburg, Germany; David Schilling, Karl-Dietrich Sievert, Arnulf Stenzl, Marcus Scharpf, Falko Fend, T€ ubingen, Germany; Frank vom Dorp, Jochen Hess, Herbert R€ ubben, Kurt Werner Schmid, Essen, Germany; Daniel Porres-Knoblauch, Axel Heidenreich, Birgit Hangarter, Ruth Kn€ uchel-Clarke, Aachen, Germany; Michael Rogenhofer, Bernd Wullich, Arndt Hartmann, Erlangen, Germany; Evi Comploj, Armin Pycha, Esther Hanspeter, Bozen, Italy; Dirk Pehrke, Guido Sauter, Markus Greafen, Alexander Haese, Hamburg, Germany

Tertiary Gleason Pattern 5 and Oncological Outcomes after Radical Prostatectomy

This study examined the rate of Gleason pattern 5 and the influence of tertiary Gleason pattern 5 on oncological outcomes. Four hundred sixty-six patients underwent a radical prostatectomy between 1993 and 2008. Each surgical specimen was reviewed and assessed for the tumor diameter, Gleason score (which was based on the 2005 International Society of Urological Pathology Consensus Conference criteria) and the percentage of Gleason pattern 5. The median patient age was 68.0 years old and the median prostate-specific antigen level was 9.28 ng/ml. A tertiary Gleason pattern 5 was present in 24.2% of patients with a Gleason score of <9; in 12.2% of patients with a Gleason score of 3 + 4 and in 45.9% of patients with a Gleason score of 4 + 3. A multivariate analysis showed that a tertiary Gleason pattern 5 was not independently associated with biochemical recurrence-free survival among patients in the Gleason score of 7 and 8 pN0 groups. One hundred eighty-seven patients had any rate of Gleason pattern 5 and significantly worse pathological factors, compared with patients who did not have this pattern. A multivariate analysis of all patients showed that the surgical margin, Gleason score, prostate-specific antigen level and pathological stage were all independent predictors of biochemical recurrence. However, the rate of Gleason pattern 5 was not an independent factor. Tertiary Gleason pattern 5 was not a significant predictive factor for biochemical recurrence. The rate of Gleason pattern 5 was associated with adverse pathological factors.

An Exploratory Study of Endorectal Magnetic Resonance Imaging and Spectroscopy of the Prostate as Preoperative Predictive Biomarkers of Biochemical Relapse After Radical Prostatectomy

Radical prostatectomy has significant side effects. Preoperative information predicting its long-term outcome would be valuable to patients and physicians. We determined whether pretreatment endorectal magnetic resonance imaging/magnetic resonance spectroscopic imaging predicts biochemical recurrence after radical prostatectomy. Of 202 patients who underwent endorectal magnetic resonance imaging/magnetic resonance spectroscopic imaging from January 2000 to December 2002 before radical prostatectomy 130 satisfied study inclusion criteria and were included in analysis. We compared imaging factors with potential predictive capability to biochemical recurrence data, including magnetic resonance imaging risk score based on local disease extent and magnetic resonance spectroscopic imaging index lesion characteristics, such as the number of voxels and degree of metabolic abnormality (magnetic resonance spectroscopic imaging grade). We evaluated associations of these imaging variables with time to biochemical recurrence by Cox proportional hazards regression adjusted for known predictors of biochemical recurrence, such as stage, grade and prostate specific antigen. At a median 68-month followup there were 26 biochemical failures. Risk score, lesion volume and high grade voxels each correlated with time to biochemical recurrence. In a model combining clinical parameters risk score, lesion volume and at least 1 high grade voxel the magnetic resonance spectroscopic imaging variables remained significant but the magnetic resonance imaging score dropped out. Index lesion volume on magnetic resonance spectroscopic imaging and high grade magnetic resonance spectroscopic imaging voxels correlate with time to biochemical recurrence after radical prostatectomy even when adjusted for clinical data. Results suggest the preoperative predictive usefulness of endorectal magnetic resonance imaging/magnetic resonance spectroscopic imaging in patients considering radical prostatectomy.

Impact of disseminated tumor cells in bone marrow at diagnosis in patients with nonmetastatic prostate cancer treated by definitive radiotherapy

The purpose of this study was to explore whether detection of disseminated tumor cells (DTCs) in bone marrow (BM) of nonmetastatic prostate cancer (PC) was associated with other clinical or histopathological factors at diagnoses or clinical outcome subsequent to definitive radiotherapy (RT). We evaluated BM aspirates from 272 cT(1-4)pN(0)M(0) PC patients by immunocytochemistry employing anticytokeratin antibodies (AE1/AE3). BM-status was compared with clinical and histopathological parameters. Long-term clinical outcome was assessed in 131 of the patients who all had completed definitive RT with or without androgen deprivation (AD), initiating treatment >5 years before cut-off date June 1, 2005. They had at least 1 unfavorable prognostic feature defined as cT(3-4) or Gleason score (GS) >or= 7B or PSA >or= 10 microg/l. Overall death, cause-specific death, distant metastases (DM) as first clinical relapse, local failure as first clinical relapse and biochemical failure were defined as end-points. DTCs were detected in 18% of the patients and were associated with increasing GS (p = 0.04) and percentage of Gleason pattern 4/5 (p = 0.04). The 7-year cumulative risk of DM was 21% for BM-positive patients vs. 6% for BM-negative patients (p = 0.07). In patients receiving RT without AD (n = 75), the 7-year cumulative risk of DM for BM-positive patients was 28% vs. 9% for BM-negative patients (p = 0.03). BM-status did not have impact on other end-points. In conclusion our study shows that presence of DTCs in BM at diagnosis was associated with the histological differentiation of the primary tumor and an increased risk of developing distant metastases after RT.

O padrão 4 de Gleason e o volume tumoral no prognóstico do carcinoma da próstata

Early introduction of adjuvant radiation or hormone therapy after radical prostatectomy has been advocated in recent literature aiming to improve survival rates in high risk prostate cancer. Traditional prognostic parameters such as serum PSA, Gleason score and clinical stage have been used to identify these cases however accuracy is far from ideal. Recently, tumor volume and presence and percentage of a tertiary less differentiated Gleason pattern have been considered better indicators of prostate cancer behavior. The purpose of this study was to evaluate the importance of presence and percentage of a Gleason pattern 4 and of tumor volume in the outcome of patients treated for well-differentiated prostate adenocarcinoma. Seventy seven patients submitted to radical prostatectomy for well-differentiated prostate carcinoma, Gleason score 6 or less, and followed up for at least 5 years were selected. Thirty seven experienced biochemical recurrence while 40 did not. The percentage of Gleason pattern 4, the percentage of the gland involvement (considered as "tumor volume"), capsular invasion and extraprostatic extension were submitted to univariate and multivariate analyses for the evaluation of possible associations with biochemical recurrence. Tumor volume was the most important parameter to predict biochemical recurrence by univariate and multivariate analysis. The median of tumor volume was 25.0% for patients who suffered recurrence, and 11.5% for those with no recurrence (p=0.003). The percentage of Gleason pattern 4 was predictive of recurrence in univariate analysis only. The median percentage of Gleason pattern 4 was 7.5% for patients without recurrence and 19.0% for those who presented recurrence (p=0.046). Tumor volume is very objective, easy to evaluate and the most important parameter to predict biochemical recurrence in well-differentiated adenocarcinoma of the prostate. On the other hand, presence and percentage of a tertiary less differentiated Gleason pattern correlated with systemic relapse. Both parameters should be included in future studies to evaluate the role of adjuvant therapy in high risk prostate cancer.

PREDICTORS OF GLEASON PATTERN 4/5 PROSTATE CANCER ON PROSTATECTOMY SPECIMENS: CAN HIGH GRADE TUMOR BE PREDICTED PREOPERATIVELY?

Radical prostatectomy provides excellent cancer control in men with clinically localized prostate carcinoma. However, to our knowledge preoperative parameters for distinguishing indolent from clinically significant cancer are not well characterized. In fact, recent evidence suggests that the percent of Gleason pattern 4/5 carcinoma in the complete radical prostatectomy specimen is one of the strongest predictors of prostate cancer progression and a valid measure of cancer severity. However, it is unclear whether preoperative parameters, including biopsy Gleason pattern 4/5 carcinoma, may predict radical prostatectomy Gleason pattern 4/5 disease and, thereby, distinguish indolent from clinically significant cancer. We prospectively obtained 101 consecutive radical prostatectomy specimens and processed them in whole mount fashion. In addition to total tumor volume, we determined tumor volume for each Gleason pattern. Biopsy tumor area was measured in a similar fashion. Univariate and multivariate analyses were performed to identify preoperative clinical and pathology parameters for predicting Gleason pattern 4/5 carcinoma on prostatectomy specimens. Biopsy Gleason score 7 or greater, Gleason pattern 4/5 carcinoma, perineural invasion and biopsy tumor area had statistically significant associations for identifying Gleason pattern 4/5 carcinoma on prostatectomy specimens. Logistic regression models for predicting any or greater than 10% Gleason pattern 4/5 carcinoma on prostatectomy specimens revealed that an area of pattern 4/5 disease of greater than 0.01 cm.2 on biopsy was the best single predictor with odds ratios of 15.0 (95% confidence interval 3.3 to 69.0, p = 0.0005) and 3.9 (95% confidence interval 1. 4 to 10.9, p = 0.009), respectively. For predicting any pattern 4/5 carcinoma on prostatectomy specimens a biopsy area of pattern 4/5 disease of greater than 0.01 cm.2 had only 38% sensitivity but 96% specificity. Similarly for predicting significant pattern 4/5 disease on prostatectomy specimens, defined as 10% or greater pattern 4/5, sensitivity and specificity for a biopsy area of greater than 0.01 cm.2 were 34% and 88%, respectively. Therefore, due to high false-negative rates these models had limited predictive value on an individual basis. Biopsy parameters such as Gleason pattern 4/5 carcinoma may provide adequate specificity for predicting clinically significant cancer, as defined by high grade Gleason patterns in the corresponding radical prostatectomy specimen. However, the accuracy of these parameters for predicting indolent cancer is limited by a prohibitive rate of false-negative findings.

Adenocarcinoma of the prostate invading the seminal vesicle: prognostic stratification based on pathologic parameters

Objectives. To stratify the prognosis of lymph node-negative, seminal vesicle-positive tumors in men with prostate cancer after radical retropubic prostatectomy. Methods. Sixty cases were analyzed for multiple parameters and correlated with postoperative biochemical (prostate-specific antigen) progression. Variables included Gleason score, primary Gleason pattern, percentage of Gleason pattern 4, any presence of Gleason pattern 5, method of seminal vesicle invasion (SVI), margin positivity, SVI extent, SVI bilaterality, vascular invasion, extent of extraprostatic extension, length of tumor extending along the seminal vesicles, presence of intraductal carcinoma within the prostate, bladder neck margin positivity, and tumor volume. Results. We were able to stratify the prognosis based on the combination of a variation of the Gleason score and margin status and vascular invasion status. Using this stratification, a few patients had an excellent long-term prognosis, with most patients split into two groups, one experiencing rapid and the other slower progression. Conclusions. SVI is not associated with a uniformly poor prognosis. Rather, tumors can be substratified by pathologic parameters into groups with differing prognoses based on routine histologic examination.

Significance of small foci of Gleason score 7 or greater prostate cancer on needle biopsy

Objectives. With increased screening for prostate cancer, we have noted a greater number of patients with small foci of Gleason score 7 or greater prostate cancer on needle biopsy. The significance of these findings is unknown. Methods. We studied 57 men with small foci of Gleason score 7 or greater on needle biopsy. Tumor length was less than 1.5 mm in all but 2 cases. In those 2 cases, there were two minute (less than 0.5 mm) foci of cancer separated by 1.8 mm. The length of cancer ranged from 0.2 to 1.8 mm (mean 0.63 mm). In all cases, only one core was involved. Results. Thirty-three men underwent radical prostatectomy (RP), 14 received radiation, 8 underwent surveillance, and 2 received hormonal therapy. Men who underwent RP were younger (62 years) than those who had radiotherapy (69.1 years), who were younger than those who underwent surveillance (74.5 years). The mean prostate-specific antigen (PSA) for men undergoing RP was 8.0 ng/mL (range 1.4 to 22). Preoperative serum PSA values did not predict organ-confined status. Needle biopsy grades were as follows: 3 + 4 = 7 (n = 30); 4 + 3 = 7 (n = 17); 4 + 4 = 8 (n = 7); 5 + 4 = 9 (n = 1); and 5 + 5 = 10 (n = 2). We were able to review slides in 27 of the RP specimens, of which 24 were well sampled. Of these 24 cases, 33% had positive margins and 33% were not organ confined; the median tumor volume was 0.5 cc (mean 1.04). No difference in RP tumor volume was found between tumors with needle biopsy Gleason primary grade 3 and those with 4 or greater. The percentage of Gleason pattern 4 on needle biopsy weakly correlated with the percentage of Gleason pattern 4 in the RP specimen ( P = 0.04). However, the percentage of Gleason pattern 4 only in the RP specimen, but not in the biopsy, correlated with whether the tumor was organ confined. Conclusions. The likelihood of having organ-confined disease with small foci of Gleason score 7 or greater on needle biopsy appears to be equivalent to that calculated from the Partin Tables for greater amounts of Gleason score 6 cancer on needle biopsy. In men who are considering RP, small foci of Gleason score 7 or greater adenocarcinoma on needle biopsy should not necessarily be considered an adverse finding.

Neuroendocrine differentiation in prostatic intraepithelial neoplasia and adenocarcinoma.

Neuroendocrine cells are thought to have a regulatory role in prostatic epithelial growth and may be prognostically useful in prostatic adenocarcinoma. To determine the extent of neuroendocrine differentiation in high-grade prostatic intraepithelial neoplasia (PIN), a putative precursor of cancer, we studied the immunohistochemical expression of 10 markers in 26 radical prostatectomy specimens with PIN and adenocarcinoma. Expression was measured as mean percent of positive cases and positive high-power (x40) fields. The highest percentage of cases showed immunoreactivity for serotonin (73%, PIN; 54%, carcinoma), neuron-specific enolase (NSE) (67%, PIN; 46%, carcinoma), chromogranin (62%, PIN; 65%, carcinoma), and human chorionic gonadotropin (hCG) (30%, PIN; 22%, carcinoma); the remaining markers showed immunoreactivity in fewer than 5% of cases (somatostatin, calcitonin, corticotropin) or in no cases (thyrotropin, prolactin, and glucagon). At least one of the markers was present in 88% of cases of PIN and 92% of carcinoma. Non-neoplastic epithelial cells expressed serotonin, NSE, chromogranin, and hCG in every case, and the expression was significantly greater than in PIN and cancer. Stepwise regression analysis revealed the following positive correlations: chromogranin expression in PIN and patient age, NSE expression in cancer and number of lymph node metastases, and hCG expression in cancer and percentage of Gleason pattern 5; serotonin expression in PIN and cancer did not correlate with any of the clinical and pathologic factors. Neuroendocrine differentiation is downregulated in prostatic carcinogenesis, with intermediate levels of expression in PIN compared with normal cells and carcinoma.