Radical Prostatectomy Gleason Score Research Articles

Prediction of biochemical recurrence after radical prostatectomy from primary tumour characteristics.

To construct and externally calibrate a predictive model for early biochemical recurrence (BCR) after radical prostatectomy (RP) incorporating clinical and modern imaging characteristics of the primary tumour. Patients who underwent RP following multiparametric magnetic resonance imaging, prostate biopsy and prostate-specific membrane antigen-positron emission tomography/computed tomography (PSMA-PET/CT), from two centres in Australia and the Netherlands. The primary outcome was biochemical recurrence-free survival (BRFS), where BCR was defined as a rising PSA level of ≥0.2 ng/mL or initiation of postoperative treatment per clinician discretion. Proportional hazards models to predict time to event were developed in the Australian sample using relevant pre- and post-surgical parameters and primary tumour maximum standardised uptake value (SUVmax) on diagnostic PSMA-PET/CT. Calibration was assessed in an external dataset from the Netherlands with the same inclusion criteria. Data from 846 patients were used to develop the models. Tumour SUVmax was associated with worse predicted 3-year BRFS for both pre- and post-surgical models. SUVmax change from 4 to 16 lessened the predicted 3-year BRFS from 66% to 42% for a patient aged 65 years with typical pre-surgical parameters (PSA level 8 ng/mL, Prostate Imaging-Reporting and Data System score 4/5 and biopsy Gleason score ≥4 + 5). Considering post-surgical variables, a patient with the same age and PSA level but pathological stage pT3a, RP Gleason score ≥4 + 5 and negative margins, SUVmax change from 4 to 16 lessened the predicted 3-year BRFS from 76% to 61%. Calibration on an external sample (n = 464) showed reasonable performance; however, a tendency to overestimate survival in patients with good prognostic factors was observed. Tumour SUVmax on diagnostic PSMA-PET/CT has utility additional to commonly recognised variables for prediction of BRFS after RP.

Enhancing Prostate Cancer Diagnosis: Artificial Intelligence–Driven Virtual Biopsy for Optimal Magnetic Resonance Imaging-Targeted Biopsy Approach and Gleason Grading Strategy

An optimal approach to magnetic resonance imaging fusion targeted prostate biopsy (PBx) remains unclear (number of cores, intercore distance, Gleason grading [GG] principle). The aim of this study was to develop a precise pixel-wise segmentation diagnostic artificial intelligence (AI) algorithm for tumor detection and GG as well as an algorithm for virtual prostate biopsy that are used together to systematically investigate and find an optimal approach to targeted PBx. Pixel-wise AI algorithms for tumor detection and GG were developed using a high-quality, manually annotated data set (slides n = 442) after fast-track annotation transfer into segmentation style. To this end, a virtual biopsy algorithm was developed that can perform random biopsies from tumor regions in whole-mount whole-slide images with predefined parameters. A cohort of 115 radical prostatectomy (RP) patient cases with clinically significant, magnetic resonance imaging-visible tumors (n = 121) was used for systematic studies of the optimal biopsy approach. Three expert genitourinary (GU) pathologists (Y.T., A.P., A.Q.) participated in the validation. The tumor detection algorithm (aware version sensitivity/specificity 0.99/0.90, balanced version 0.97/0.97) and GG algorithm (quadratic kappa range vs pathologists 0.77-0.78) perform on par with expert GU pathologists. In total, 65,340 virtual biopsies were performed to study different biopsy approaches with the following results: (1) 4 biopsy cores is the optimal number for a targeted PBx, (2) cumulative GG strategy is superior to using maximal Gleason score for single cores, (3) controlling for minimal intercore distance does not improve the predictive accuracy for the RP Gleason score, (4) using tertiary Gleason pattern principle (for AI tool) in cumulative GG strategy might allow better predictions of final RP Gleason score. The AI algorithm (based on cumulative GG strategy) predicted the RP Gleason score of the tumor better than 2 of the 3 expert GU pathologists. In this study, using an original approach of virtual prostate biopsy on the real cohort of patient cases, we find the optimal approach to the biopsy procedure and the subsequent GG of a targeted PBx. We publicly release 2 large data sets with associated expert pathologists’ GG and our virtual biopsy algorithm.

The factors impacting on Gleason score upgrading in prostate cancer with initial low Gleason scores

BackgroundThis study aims to investigate the factors contributing to the discrepancy in between biopsy Gleason score (GS) and radical prostatectomy GS in patients diagnosed with prostate cancer. Methods341 patients who underwent radical prostatectomy from 2011/04 to 2020/12 were identified. 102 Patients with initial GS of six after biopsy were enrolled. Preoperative clinical variables and pathological variables were also obtained and assessed. The optimal cut-off points for significant continuous variables were identified by the area under the receiver operating characteristic curve. ResultsUpgrading was observed in 63 patients and non-upgrading in 39 patients. In the multiple variables assessed, smaller prostate volume (PV) (p value = 0.0007), prostate specific antigen density (PSAD) (p value = 0.0055), positive surgical margins (p value = 0.0062) and pathological perineural invasion (p value = 0.0038) were significant predictors of GS upgrading. To further explore preclinical variables, a cut-off value for PV (≤ 38 ml, p value = 0.0017) and PSAD (≥ 0.26 ng/ml2, p value = 0.0013) were identified to be associated with GS upgrading. ConclusionsSmaller PV and elevated PSAD are associated with increased risk of GS upgrading, whereas lead-time bias is not. A cut-off value of PV < 38 ml and PSAD > 0.26 ng/ml2 were further identified to be associated with pathological GS upgrading.

Role of inflammatory factors in prediction of Gleason score and its upgrading in localized prostate cancer patients after radical prostatectomy.

To investigate the role of inflammatory factors including systemic immune-inflammation index (SII) and neutrophil to lymphocyte ratio (NLR) in predicting Gleason Score (GS) and Gleason Score upgrading (GSU) in localized prostate cancer (PCa) after radical prostatectomy (RP). The data of 297 patients who underwent prostate biopsy and RP in our center from January 2014 to March 2020 were retrospectively analyzed. Preoperative clinical characteristics including age, values of tPSA, total prostate volume (TPV), f/t PSA ratio, body mass index (BMI), biopsy GS and inflammatory factors including SII, NLR, lymphocyte to monocyte (LMR), neutrophil ratio (NR), platelet to lymphocyte ratio (PLR), lymphocyte ratio (LR), mean platelet volume (MPV) and red cell distribution (RDW) as well as pathological T (pT) stage were collected and compared according to the grades of RP GS (GS ≤ 6 and GS≥7), respectively. ROC curve analysis was used to confirm the discriminative ability of inflammatory factors including SII, NLR and their combination with tPSA for predicting GS and GSU. By using univariate and multivariate logistic regression analysis, the association between significant inflammatory markers and grades of GS were evaluated. Patients enrolled were divided into low (GS ≤ 6) and high (GS≥7) groups by the grades of GS. The median values of clinical factors were 66.08 ± 6.04 years for age, 36.62 ± 23.15 mL for TPV, 26.16 ± 33.59 ng/mL for tPSA and 0.15 ± 0.25 for f/t PSA ratio, 22.34 ± 3.14 kg/m2 for BMI, 15 (5.1%) were pT1, 116 (39.1%) were pT2 and 166 (55.9%) were pT3. According to the student's t test, patients in high GS group had a greater proportion of patients with pT3 (P<0.001), and higher NLR (P=0.04), SII (P=0.037) and tPSA (P=0.015) compared with low GS group, the distribution of age, TPV, f/t PSA ratio, BMI, LMR, NR, PLR, LR, MPV and RDW did not show any significantly statistical differences. The AUC for SII, NLR and tPSA was 0.732 (P=0.007), 0.649 (P=0.045) and 0.711 (P=0.015), with threshold values of 51l.08, 2.3 and 10.31ng/mL, respectively. According to the multivariable logistic regression models, NLR ≥ 2.3 (OR, 2.463; 95% CI, 0.679-10.469, P=0.042), SII ≥ 511.08 (OR, 3.519; 95% CI 0.891-12.488; P=0.003) and tPSA ≥ 10.31 ng/mL (OR, 4.146; 95% CI, 1.12-15.35; P=0.033) were all independent risk factors associated with higher GS. The AUC for combination of SII, NLR with tPSA was 0.758 (P=0.003) and 0.756 (P=0.003), respectively. GSU was observed in a total of 48 patients with GS ≤ 6 (55.17%). Then patients were divided into 2 groups (high and low) according to the threshold value of SII, NLR, tPSA, SII+tPSA and NLR+tPSA, respectively, when the GSU rates were compared with regard to these factors, GSU rate in high level group was significantly higher than that in low level group, P=0.001, 0.044, 0.017, <0.001 and <0.001, respectively. High SII, NLR and tPSA were associated with higher GS and higher GSU rate. SII was likely to be a more favorable biomarker for it had the largest AUC area compared with tPSA and NLR; the combination of SII or NLR with tPSA had greater values for predicting GS and GSU compared with NLR, SII or tPSA alone, since the AUC area of combination was much higher. SII, NLR were all useful inflammatory biomarkers for predicting GS and detecting GSU among localized PCa patients with biopsy GS ≤ 6.

Evaluation of Initial 24-core Transrectal Prostate Biopsy on the Detection of Significant Prostate Cancer and High-grade Prostatic Intraepithelial Neoplasia

Abstract Purpose: The purpose of the study was to assess the diagnostic value of an initial 24-sample transrectal ultrasound-guided (TRUS) prostate biopsy protocol compared to the 10-core technique. Materials and Methods: We retrospectively reviewed the prostate biopsy database of consecutive men undergoing prostate biopsies under local anesthesia using the 10 (Group A) and 24 (Group B) protocols. Men were stratified according to biopsy protocol and prostate-specific antigen (PSA) levels. Exclusion criteria were age = 75 years and PSA &gt;20 ng/mL. The Mann–Whitney U and Fisher’s exact test were used for statistical analysis. Results: Between November 2018 and August 2020, 169 men underwent TRUS prostate biopsies. Group A (10-cores) consisted of 105 (62.13%) men and Group B (24-cores) included 64 (37.86%) men. The overall prostate cancer detection rate was 41.05% and 36.72% in Groups A and B, respectively (P = 0.48). An overall 9.8% increase in Gleason 7 detection rate was found in Group B (P = 0.24). The high-grade prostatic intraepithelial neoplasia (HGPIN) detection rate in men with negative initial biopsies was 15.54% and 35.55% in Groups A and B, respectively (P &lt; 0.001). In patients with PSA &lt;10 ng/mL, the 24-core technique increased Gleason 7 detection rate by 13.4% (P = 0.16) and HGPIN by 23.4% (P = 0.0008), compared to the 10-core technique. The 24-core technique increased the concordance between needle biopsy and prostatectomy specimen compared to the 10-core technique (P &lt; 0.002). Conclusions: The initial 24-core prostate biopsy protocol did not show any benefit in the detection of prostate cancer compared to the 10-core technique. However, it improved the HGPIN detection and the correlation between biopsy results and radical prostatectomy Gleason score in men with lower PSA levels.

Assessment of Gleason Score Concordance Between Prostate Biopsy and Radical Prostatectomy

Introduction: Prostate cancer is being diagnosed and graded by examining needle biopsies. As needle biopsies may represent the low percentage of general tumor histology, downgrading or upgrading can cause problems in radical prostatectomy (RP) specimens. Our aim in this study was to put forth the concordance between needle biopsy and RP Gleason scores. Methods: The biopsy pathology results, and post-RP pathology results of 112 patients diagnosed as prostate cancer and underwent RP were revised and the concordance of the biopsy and RP Gleason score was analyzed by kappa statistics in addition to percentages of downgrading or upgrading rates. Results: The mean age, and PSA values of the patients were 64,4 (±6,2) years, and 11,7 (±9,2) ng/mL, respectively. There was a moderate agreement between biopsy and prostatectomy gleason scores(κ=0,452) and between Gleason groups Conclusion: It is important for the urologists to be aware of the variety of Gleason score between biopsy results and prostatectomy specimens as needle biopsies represent small areas of tumors

Concordance between Gleason score of prostate biopsies and radical prostatectomy specimens and its predictive factors.

The Gleason score is an essential factor for making decisions about prostate cancer management and its prognosis. Thus, we conducted this research to discover the histologic-grading accuracy of needle biopsy specimens, and to identify preoperative clinical and pathological factors that predict upgrading and downgrading from biopsy to radical prostatectomy specimen. This study was performed on 570 patients who were referred to the medical centers affiliated with Shiraz University of Medical Sciences and underwent radical prostatectomy from 2013 to 2017. Concordance was evaluated between the Gleason score of needle biopsy and radical prostatectomy specimens. Predictors of upgrades and downgrades were assessed in univariate and multivariate logistic regression analyses. Scores were the same in 50% of cases, downgraded in 26%, and upgraded in 24%. The variables predicting a Gleason score upgrade were higher Prostate specific antigen level, larger tumors, and older age. Lower tumor volume, lower Prostate specific antigen, and low maximum percentage of cancer in cores were predictors of downgrading from Gleason score>6 to ⩽6. Also, Body mass index>30, smaller tumor size, and negative lymph nodes were predictors of downgrading from Gleason score>7 to 7. The correlation between biopsy and Radical prostatectomy Gleason scores was only 50%. After dividing them into the new grading groups, this coordination increased by only 5.6%. Physicians need to consider possible limitations of the Gleason score of biopsy and factors that can be predictive of upgrading to high-risk prostate cancer before making treatment decisions.

Nomogram Predicting Adverse Pathology Outcome on Radical Prostatectomy in Low-Risk Prostate Cancer Men

ObjectiveTo develop and validate a prediction model to predict the risk of adverse pathology outcome on final pathology in low-risk prostate cancer (PCa) men. Materials and MethodsThis study was a monocentric retrospective analysis of 426 men who underwent radical prostatectomy (RP) for low-risk PCa. The validation cohort included 103 men from another hospital. Adverse pathology outcome was defined either by upgrading on RP Gleason Score (GS) (from GS 3+3 to GS ≥ 3+4 with Gleason pattern 4 ≥ 10%) or a non-organ confined disease (pathologic stage ≥ pT3a). Multivariable logistic regression analysis was performed to build nomogram for predicting adverse pathology outcome. Nomogram validation was performed by calculating the area under receiver operating characteristic curves (AUC) and comparing nomogram-predicted probabilities with actual rates of adverse pathology outcome in the external cohort. The Kaplan-Meier method was used to estimate and compare the biochemical recurrence-free survival rates between the two groups. ResultsOf 426 men in the development cohort, 45.7% showed adverse pathology outcome on RP. Age, body mass index, prostate specific antigen density, history of prior negative biopsy, magnetic resonance imaging prostate imaging reporting and data system score 4-5 and percentage of positive biopsies were significant predictors in multivariate analysis. A nomogram was constructed with an area under curve of 87%. There was agreement between predicted and actual rates of adverse pathology outcome in the validation cohort. The 5-year biochemical recurrence-free survival rates in patients with and without adverse pathology outcome was 70% and 98%, respectively. ConclusionThis novel nomogram would help identify low-risk PCa men at risk of adverse pathology outcome and can be relevant for treatment decision-making.

In-bore MRI-guided prostate biopsy in a patient group with PI-RADS 4 and 5 targets: A single center experience

PurposeTo determine the diagnostic yield of magnetic resonance imaging (MRI) guided in-bore biopsy in patients with high likelihood multiparametric MRI (mpMRI) findings, regarding overall and clinically significant prostate cancer (csPCa) detection rates and concordance of biopsy and radical prostatectomy (RP) Gleason scores (GS). MethodsThis retrospective study consisted of 277 Prostate Imaging Reporting and Data System (PI-RADS) assessment category 4 and 5 targets in 246 patients (mean age, 65.7 years; median prostate specific antigen value, 7.75 ng/mL) who had undergone in-bore biopsy at our institution between 2012 and 2020. Eighty-one patients who underwent RP were eligible for the concordance analysis of biopsy and RP specimen GS. ResultsOverall PCa detection rates were 80.5 % per patient (198/246) and 78 % per target (216/277) and 83.5 % and 67.4 % in primary (biopsy naive) and secondary (at least one negative prior biopsy) settings. csPCa was found in 63 % overall, 66 % of patients (132/200) in the primary, and 50 % of patients (23/46) in the secondary biopsy settings (p < 0.001). The prostate cancer detection rate was 68 % and 92 % in PI-RADS 4 and 5, respectively (p < 0.001).In the radical prostatectomy subcohort, 27.2 % of patients were upgraded, 8.6 % of patients were downgraded from needle biopsy. Significant complications occurred in 1.2 % of patients. ConclusionsMRI-guided in-bore prostate biopsy has a high detection rate of csPCa in primary and secondary biopsy cohorts. Biopsy results were satisfactory in terms of the number of positive cores, cancer percentage in positive cores, and concordance of GS in needle biopsy and RP specimen.

The Discrepancy between Needle Biopsy and Radical Prostatectomy Gleason Score in Patients with Prostate Cancer.

Gleason score (GS), as well as other prognostic and diagnostic modalities, can predict the possibility of tumor growth and metastasis during the life of patients with prostate cancer. Based on the prostate biopsy GS, clinicians choose the most appropriate therapy for managing patients. The objective of this cross-sectional study was to determine the discrepancy between needle biopsy and radical prostatectomy GS and to identify its predictive factors among the Iranian population. A total of 1147 patients who underwent radical prostatectomy from 2009 to 2019 were initially enrolled in this study. After consideration of the inclusion and exclusion criteria, 439 patients were finally included. The demographic variables and clinical data including age, PSA level, prostate volume, PSA density, GS derived from ultrasonography-guided core needle biopsy specimen, and GS derived from radical prostatectomy specimen were collected from the medical records of patients with prostate adenocarcinoma and were reviewed by a urology resident. Statistical analysis was done by using the Social Sciences Software version 21. The average age of patients was 64.5 years (range 48-84 years), and the average preoperative PSA level was 14.8 ng/mL. On histopathological examination, no changes in GS were observed in 237 (53.9%) patients, whereas GS was upgraded in 144 (32.8%) patients and downgraded in 58 (13.2%) patients at radical prostatectomy. The number of patients who had extracapsular extension, seminal vesicle invasion and positive lymph nodes was significantly higher in the upgraded group compared with the non-upgraded group. Conclusion: In this study, there was a steady decrease in GS upgrading with the prostate size extending up to 49.7 g. There was also an association between downgrading and extending prostate size. Due to the greater risk of high-grade disease in men with small prostates, smaller prostate bulks are most probably upgraded after radical prostatectomy. A higher maximum percentage of involvement per core was an independent predictive factor of upgrading from biopsy grade 1 to grade ≥ 2. Our study showed that patients' age was not predictive of upgrading, which is consistent with other studies. Also, we demonstrated a non-significant relationship between PSA level and upgraded GS. Findings in this study did not demonstrate a significant relationship between PSA level and upgrading.

Concordance Between Biopsy and Radical Prostatectomy Gleason Scores: Evaluation of Determinants in a Large-Scale Study of Patients Undergoing RARP in Belgium.

To determine whether Gleason scores were concordant between prostate biopsies (bGS) and the definitive resection specimen (pGS) excised with robot-assisted radical prostatectomy (RARP); to identify clinical and pathological factors that might predict upgrading; and to evaluate how upgrading affected outcome. Between 2009 and 2016, 25 Belgian centers participated in collecting prospective data for patients that underwent RARP. We analyzed the concordance rate between the bGS and the pGS in 8021 patients with kappa statistics, and we compared concordance rates from different centers. We assessed the effect of several clinical and pathological factors on the concordance rate with logistic regression analysis. The concordance rate for the entire population was 62.9%. Upgrading from bGS to pGS occurred in 27.3% of patients. The number of biopsies was significantly associated with concordance. Older age (>60 y), a higher clinical T stage (≥cT2), a higher PSA value at the time of biopsy (>10ng/ml), and more time between the biopsy and the radical prostatectomy were significantly associated with a higher risk of upgrading. Positive margins and PSA relapse occurred more frequently in upgraded patients. Center size did not significantly affect the concordance rate (p = 0.40).This prospective, nationwide analysis demonstrated a Gleason score concordance rate of 62.9%. Upgrading was most frequently observed in the non-concordant group. We identified clinical and pathological factors associated with (non)-concordance. Upgrading was associated with a worse oncological outcome. Center volume was not associated with pathological accuracy.

Retracted: Histopathological Correlation Between Prostatic Adenocarcinoma in Transrectal Ultrasound Guided Biopsies and Radical Prostatectomy Specimens

Introduction: Differences in Gleason grade in transrectal ultrasonography (TRUS) biopsies and radical prostatectomy (RP) specimens are well documented in literature. Keeping in view the limitations of Gleason grading system, Epstein JI grade group system was introduced. Various other parameters also have a significant role in predicting the pathological stage, extraprostatic extension, status of surgical margins and metastatic disease in regional lymph nodes. RP is performed at limited centres in Pakistan. Till date, no comparison of the histopathological findings in 12-core TRUS and RP specimens had been performed at the national level. Our study is aimed at generating local data in this context. Materials and Methods: This was a crosssectional study and non-probability consecutive sampling was performed. It was conducted at Histopathology Department, Shifa International Hospital, Islamabad, from January 2008 to December 2014. Gleason scores of 20 RP specimens were compared to Gleason scores of TRUS biopsies of same patients. Concordance in Gleason score and grade groups with laterality, perineural invasion was also studied. Results: Out of 20 RP cases, 40% (n = 8) had a Gleason score of 6, 30% (n = 6) had score 7, 20% (n = 4) had score 8 and 15% (n = 3) had score 9. Compared to the TRUS biopsy, RP Gleason score was concordant in 11 cases (55%), higher in 7 cases (35%) and lower in 2 cases (10%). TRUS involvement was unilateral in 10 cases (50%) and bilateral in 10 cases (50%). However, bilateral involvement of RP specimen was seen in 14 cases (70%) and unilateral in 6 cases (30%). Thus, better tumour yield was observed in RP specimens i.e., bilateral involvement in RP specimens was found in additional 5 cases (25%). Perineural involvement was higher in RP specimen i.e., 12 cases (60%), compared to 5 cases (25%) in TRUS biopsies. Its concordance was significantly higher in those with Gleason score of equal to or more than 7 (83%) and low in score less than score 7 (17%). Conclusion: When comparing RP to initial TRUS biopsies, Gleason score was upgraded in 35% and downgraded in 10% of cases. Bilateral involvement in 25% of cases of RP specimens was underestimated as unilateral involvement in TRUS biopsies. Perineural involvement with high Gleason score was also seen.

Outcomes of pathologically localized high-grade prostate cancer treated with radical prostatectomy.

Adjuvant radiation therapy (ART) is recommended without consideration of radical prostatectomy Gleason score (RP GS) for cases with adverse features. We compared the outcomes of pathologically localized high-grade (GS 8–10) prostate cancer (PC) with those of pT3 GS 7 PC.A total of 1585 men who underwent RP between 1995 and 2015 comprised the cohort, which was divided into group 1 (RP GS 7(3 + 4) and pT3; n = 760), group 2 (RP GS 7(4 + 3) and pT3; n = 565), and group 3 (RP GS 8–10 and pT2; n = 260). Biochemical recurrence (BCR), all-cause mortality (ACM), and PC-specific mortality (PCSM) risk were compared among groups using Cox regression and competing risk analysis.At a median follow-up of 58 months (interquartile range: 37–85), 721 men experienced BCR and 84 died (22 due to PC). BCR-free survival rates were lower in group 3 than in group 1 (P < .001); nevertheless, no difference was observed between groups 2 and 3 (P = .638). Furthermore, no difference in ACM was noted among groups. PCSM rates were higher in group 3 than in groups 1 and 2 (P = .001 and P = .005, respectively). This association persisted in multivariate models after adjustment for clinicopathological variables.Patients with RP GS 8–10 and pT2 PC had higher BCR and PCSM rates than those with RP GS 7 and pT3 PC. Localized high-grade PC should be considered in decision-making for ART.

MRI-Fusion Targeted vs. Systematic Prostate Biopsy-How Does the Biopsy Technique Affect Gleason Grade Concordance and Upgrading After Radical Prostatectomy?

Introduction: MRI-targeted biopsy (TB) increases overall prostate-cancer (PCa) detection-rates and decreases the risk of insignificant PCa detection. However, the impact of these findings on the definite pathology after radical prostatectomy (RP) is under debate.Materials and Methods: Between 01/2014 and 12/2018, 366 patients undergoing prostate biopsy and RP were retrospectively analyzed. The correlation between biopsy Gleason-score (highest Gleason-score in a core) and the RP Gleason-score in patients undergoing systematic biopsy (SB-group) (n = 221) or TB+SB (TB-group, n = 145) was tested using the ISUP Gleason-group grading (GGG, scale 1–5). Sub analyses focused on biopsy GGG 1 and GGG ≥ 2.Results: Proportions of biopsy GGG 1–5 in the SB-group and TB-group were 24.4, 37.6, 19, 10.9, 8.1% and 13.8, 43.4, 24.2, 13.8, 4.8%, respectively (p = 0.07). Biopsy and pathologic GGG were concordant in 108 of 221 (48.9%) in SB- and 74 of 145 (51.1%) in TB-group (p = 0.8). Gleason upgrading was recorded in 33.5 and 31.7% in SB- vs. TB-group (p = 0.8). Patients with biopsy GGG 1 undergoing RP showed an upgrading in 68.5%(37/54) in SB- and 75%(15/20) in TB-group (p = 0.8). In patients with biopsy GGG ≥ 2 concordance increased for both biopsy approaches (54.5 vs. 55.2% for SB- vs. TB-group, p = 0.9).Discussion: Irrespective of differences in PCa detection-rates between TB- and SB-groups, no significant differences in GGG concordance and upgrading between patients of both groups undergoing biopsy, followed by RP, were recorded. Concordance rates increased in men with biopsy GGG ≥ 2. TB seems to detect more patients with PCa without a difference in concordance with final pathology.

The prognostic impact of downgrading and upgrading from biopsy to radical prostatectomy among men with Gleason score 7 prostate cancer.

Recently, a new prostate cancer (PC) grading system was introduced, where Gleason score (GS) 7 was divided into 3 + 4 = 7 and 4 + 3 = 7 due to the different prognoses associated with each tumor type. However, whether downgrading or upgrading from needle biopsy (NB) to radical prostatectomy (RP) affects oncologic outcomes is currently unknown. Herein, we investigated the prognostic impact of downgrading and upgrading from NB to RP among men with GS 7 PC. We retrospectively reviewed the medical records of 3003 patients with localized PC who underwent RP between 2005 and 2014. We included 692 patients with GS 7 PC on both NB and RP specimens. We analyzed the data using Kaplan-Meier methods and Cox proportional hazard models. Of the 692 patients enrolled in this study, 389 (56.2%) and 303 (43.8%) patients had RP GS 3 + 4 = 7 and RP GS 4 + 3 = 7 PC, respectively. On the basis of NB and RP GS, 264 (38.1%), 125 (18.1%), 142 (20.5%), and 161 (23.3%) patients were classified as 3 + 4/3 + 4, 4 + 3/3 + 4, 3 + 4/4 + 3, and 4 + 3/4 + 3, respectively. Kaplan-Meier curves showed significant differences in biochemical recurrence (BCR)-free survival across the groups (P < .001). In the multivariate analyses, these groups were significantly associated with BCR (4 + 3/3 + 4: hazard ratio [HR], 1.675; 3 + 4/4 + 3: HR, 1.908; and 4 + 3/4 + 3: HR, 2.699). Downgrading and upgrading from NB to RP was an independent predictor of BCR in men with GS 7 PC, which could be due to the amount of Gleason pattern 4.

Periprostatic fat adipokine expression is correlated with prostate cancer aggressiveness in men undergoing radical prostatectomy for clinically localized disease.

To investigate the relationship between periprostatic adipose tissue (PPAT) adipokine expression and prostate cancer (PCa) aggressiveness using both pathological features of radical prostatectomy (RP) and multiparametric magnetic resonance imaging ( MRI) variables. Sixty-nine men were recruited to assess immunohistochemical expression of tumour necrosis factor (TNF)α and vascular endothelial growth factor (VEGF) of periprostatic fat of RP specimens. Per cent immunopositivity was quantified on scanned slides using the Aperio Positive Pixel Count algorithm for PPAT TNFα, VEGF and androgen receptors. Periprostatic fat volume (PFV) was segmented on contiguous T1 -weighted axial MRI slices from the level of the prostate base to apex. PFV was normalized to prostate volume (PV) to account for variations in PV (normalized PFV = PFV/PV). MRI quantitative values (Kep , Ktrans and apparent diffusion coefficient) were measured from the PCa primary lesion using Olea Sphere software. Patients were stratified into three groups according to RP Gleason score (GS): ≤6, 7(3 + 4) and ≥7(4 + 3). The mean rank of VEGF and TNFα was significantly different between the groups [H(2) = 11.038, P = 0.004] and [H(2) = 13.086, P = 0.001], respectively. Patients with stage pT3 had higher TNFα (18.2 ± 8.95) positivity than patients with stage pT2 (13.27 ± 10.66; t [67] = -2.03, P = 0.047). TNFα expression significantly correlated with Ktrans (ρ = 0.327, P = 0.023). TNFα (P = 0.043), and VEGF (P = 0.02) correlated with high grade PCa (GS ≥ 7) in RP specimens and also correlated significantly with upgrading of GS from biopsy to RP histology. The expression levels of TNFα and VEGF on immunostaining significantly correlated with aggressivity of PCa. As biomarkers, these indicate the risk of having high grade PCa in men undergoing RP.

Abstract B083: Disease marker-specific disseminated tumor cells in bone are rare at the time of radical prostatectomy

Abstract Introduction: In prostate cancer (PCa), DTCs are cells that have escaped the primary lesion and enter the metastatic site, most commonly the bone marrow (BM). The pelvis is a common metastatic site for prostate cancer metastases. However, it is unclear when PCa cells leave the prostate and travel to bone in clinically localized disease. Thus, we studied whether PCa DTCs can be detected at the time of radical prostatectomy (RP) by performing a bone marrow aspiration (BMA) from the anterior iliac crest (AIC) at the time of surgery. Methods: The study protocol was approved by the institutional review board at the Johns Hopkins Medical Institutions. Informed consent to perform BMA was obtained from 94 clinically localized PCa patients undergoing a robotic-assisted laparoscopic prostatectomy (RALP). In the supine position, patients underwent general anesthesia and were prepped and draped in a normal sterile fashion. Aspiration was performed by the attending surgeon prior to first incision and obtained percutaneously from the AIC using a BM biopsy needle (11G x 100 mm Hospital Trapsystem, HS Hospital Service S.p.A.). 8-20 mL of BM were aspirated into 1 or 2 10-mL syringes (BD) and transferred into collection tubes through an 18-gauge needle (PrecisionGlide, BD). Samples were distributed among 7 different principal investigators within 24 hours of collection for DTC analyses. One type of analysis included the AdnaTest, which first involved collecting 8 mL of BM from 43/77 (56%) patients. 5 mL of whole cell extract was then assayed with the AdnaTest ProstateCancerSelect kit (Qiagen) to enrich for epithelial-marker, EpCAM, positive cells using immunomagnetic beads. Reverse transcription (SensiScript RT kit, Qiagen) and real-time qPCR quantified the expression of RPL13A (control, ribosomal protein), EPCAM (epithelial), NKX3.1, prostate-specific antigen (PSA), androgen receptor full length (AR), and HOXB13 (prostate-specific). DTC detection was defined as positive prostate-specific marker expression in the BM. Quality control was performed with Sanger sequencing. Results: BM was successfully obtained from 77/94 (82%) patients. The median (range) age was 62 (43-76) years and the median (range) preoperative PSA was 6 (1.3-62.6) ng/mL. 8/77 (10%) patients had RP Gleason Score 6 disease, 37/77 (48%) were Gleason 3+4, 18/77 (23%) were 4+3, and 13/77 (17%) were Gleason 8-10. One patient had an undetermined RP Gleason due to effects from neoadjuvant chemotherapy. 65/77 (85%) had PSA &amp;lt;10, 8/77 (10%) had PSA 10-20, and 4/77 (5%) had PSA &amp;gt;20. 50/77 (65%) had pT2, 21/77 (27%) had pT3a, and 6/77 (8%) had pT3b diseases. 3/77 (4%) had lymph node metastasis as confirmed in their pathology. The average time to collect BM and transfer into tubes was 2.5 minutes. The median volume collected was 10.5 mL. RALP was performed without BMA-associated complication and there were no reports of BMA-induced postoperative complications including discomfort at the BMA site. Patients were discharged on postoperative day one. For the AdnaTest, 1/43 (2%) BM expressed PSA and 43/43 (100%) expressed EpCAM. Conclusions: We demonstrated an efficient percutaneous approach to BMA from the AIC with 77/94 (82%) successful attempts to obtain BMA and an average collection time of 2.5 minutes. This technique is feasible and safe with no BMA-associated surgical complications or patient discomfort postoperatively. Samples are utilized to study PCa dissemination to bone. Putative PSA positive DTCs can be identified at the time of RP. Citation Format: Emily A. Caruso, Stephanie Glavaris, Heather J. Chalfin, Kenneth C. Valkenburg, Mohamad E. Allaf, Misop Han, Kenneth Pienta. Disease marker-specific disseminated tumor cells in bone are rare at the time of radical prostatectomy [abstract]. In: Proceedings of the AACR Special Conference: Prostate Cancer: Advances in Basic, Translational, and Clinical Research; 2017 Dec 2-5; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(16 Suppl):Abstract nr B083.

Elevated preoperative neutrophil-lymphocyte ratio predicts upgrading at radical prostatectomy.

Neutrophil-lymphocyte ratio (NLR) is a widely used, representative marker of systemic inflammatory response within the body. NLR can be calculated from simple, inexpensive peripheral blood samples. High NLR is a negative prognostic factor in a variety of malignancies including urological tumors. In this study, we aim to assess the prognostic value of preoperative neutrophil- lymphocyte ratio (NLR) in patients treated with radical prostatectomy (RP) for localized prostate cancer (PCa). Records of 7426 patients were retrospectively analyzed from prospectively collected datasets. A cut-off point of 3 was taken for NLR based on ROC analyses and previous literature. 23% (n = 1707) of patients had an NLR of ≥3. Patients with NLR ≥3 were more likely to harbor unfavorable pathological features such as higher biopsy Gleason score (GS), higher RP GS, higher rates of extra capsular extension, nodal involvement (all p < 0.001) and positive surgical margins (p = 0.002). On multivariable analyses, NLR ≥ 3 was associated with higher RP GS (OR 2.32; p < 0.001), seminal vesicle invasion (OR 1.60; p < 0.001) and nodal involvement (OR 1.43; p < 0.001). On multivariable analyses, NLR ≥ 3 was significantly associated with GS upgrading at RP (OR 1.39 p < 0.001). During a median follow up of 45 months, NLR ≥ 3 was associated with higher risk of BCR (p = 0.001). However, on multivariable Cox regression analysis such association was not shown (HR 0.86; p = 0.4). Preoperative NLR ≥ 3 was associated with aggressive PCa, such as upgrading at RP. Even though its effect on clinical-decision making seems to be limited when all clinical and pathological confounders are taken into account, preoperative NLR may still be useful in selected patients to identify aggressive PCa helping patient selection for active surveillance protocols. Conversely, it does not predict BCR when adjusted for the effect of pathological features.

Pathological and 3 Tesla Volumetric Magnetic Resonance Imaging Predictors of Biochemical Recurrence after Robotic Assisted Radical Prostatectomy: Correlation with Whole Mount Histopathology

We sought to identify the clinical and magnetic resonance imaging variables predictive of biochemical recurrence after robotic assisted radical prostatectomy in patients who underwent multiparametric 3 Tesla prostate magnetic resonance imaging. We performed an institutional review board approved, HIPAA (Health Insurance Portability and Accountability Act) compliant, single arm observational study of 3 Tesla multiparametric magnetic resonance imaging prior to robotic assisted radical prostatectomy from December 2009 to March 2016. Clinical, magnetic resonance imaging and pathological information, and clinical outcomes were compiled. Biochemical recurrence was defined as prostate specific antigen 0.2 ng/cc or greater. Univariate and multivariate regression analysis was performed. Biochemical recurrence had developed in 62 of the 255 men (24.3%) included in the study at a median followup of 23.5 months. Compared to the subcohort without biochemical recurrence the subcohort with biochemical recurrence had a greater proportion of patients with a high grade biopsy Gleason score, higher preoperative prostate specific antigen (7.4 vs 5.6 ng/ml), intermediate and high D'Amico classifications, larger tumor volume on magnetic resonance imaging (0.66 vs 0.30 ml), higher PI-RADS® (Prostate Imaging-Reporting and Data System) version 2 category lesions, a greater proportion of intermediate and high grade radical prostatectomy Gleason score lesions, higher pathological T3 stage (all p <0.01) and a higher positive surgical margin rate (19.3% vs 7.8%, p = 0.016). On multivariable analysis only tumor volume on magnetic resonance imaging (adjusted OR 1.57, p = 0.016), pathological T stage (adjusted OR 2.26, p = 0.02), positive surgical margin (adjusted OR 5.0, p = 0.004) and radical prostatectomy Gleason score (adjusted OR 2.29, p = 0.004) predicted biochemical recurrence. In this cohort tumor volume on magnetic resonance imaging and pathological variables, including Gleason score, staging and positive surgical margins, significantly predicted biochemical recurrence. This suggests an important new imaging biomarker.

Does index tumor predominant location influence prognostic factors in radical prostatectomies?

ABSTRACTPurpose To find any influence on prognostic factors of index tumor according to predominant location.Materials and Methods Prostate surgical specimens from 499 patients submitted to radical retropubic prostatectomy were step-sectioned. Each transverse section was subdivided into 2 anterolateral and 2 posterolateral quadrants. Tumor extent was evaluated by a semi-quantitative point-count method. The index tumor (dominant nodule) was recorded as the maximal number of positive points of the most extensive tumor area from the quadrants and the predominant location was considered anterior (anterolateral quadrants), posterior (posterolateral quadrants), basal (quadrants in upper half of the prostate), apical (quadrants in lower half of the prostate), left (left quadrants) or right (right quadrants). Time to biochemical recurrence was analyzed by Kaplan-Meier product-limit analysis and prediction of shorter time to biochemical recurrence using univariate and multivariate Cox proportional hazards model.Results Index tumors with predominant posterior location were significantly associated with higher total tumor extent, needle and radical prostatectomy Gleason score, positive lymph nodes and preoperative prostate-specific antigen. Index tumors with predominant basal location were significantly associated with higher preoperative prostate-specific antigen, pathological stage higher than pT2, extra-prostatic extension, and seminal vesicle invasion. Index tumors with predominant basal location were significantly associated with time to biochemical recurrence in Kaplan-Meier estimates and significantly predicted shorter time to biochemical recurrence on univariate analysis but not on multivariate analysis.Conclusions The study suggests that index tumor predominant location is associated with prognosis in radical prostatectomies, however, in multivariate analysis do not offer advantage over other well-established prognostic factors.