Prostatectomy Gleason Score Research Articles

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.

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.

A multidisciplinary approach to optimize primary prostate cancer biobanking.

Biobanking tissue of high quality and fidelity is imperative for cancer genomics research. Since it is a challenging process, we sought to develop a protocol that improves the fidelity and quantity of biobanked primary prostate cancer (CaP) tissue. We conducted a pilot study evaluating pathologic concordance of biobanked tissue and the radical prostatectomy specimen using either standard protocol (SP) vs. next-generation protocol (NGP). There were no significant differences in clinical and pathologic characteristics (age, BMI, preoperative PSA, prostate weight, race, final prostatectomy Gleason score, or pathologic tumor and nodal stages) between the two protocol arms. Utilization of the NGP compared to the standard protocol resulted in a significantly higher rate of pathologic concordance between the biobanked and RP specimens (61.8% vs. 37.9%, P = 0.0231) as well as a nearly two-fold increase in the amount of biobanked tumor tissue (330 mm3 vs. 174 mm3, P < 0.001). When looking at relevant clinical and pathologic characteristics, NGP was associated with pathologic concordance on both univariate [OR 2.65 (95% CI 1.13-6.21), P = 0.025] and multivariate analysis [OR 3.11 (95% CI 1.09-8.88), P = 0.034]. Our study validates the NGP as a multidisciplinary approach for improving the fidelity and amount of biobanked primary CaP tissue for future studies. Given the challenges to banking tissue from primary CaP as tumors are often difficult to visualize grossly and are frequently multifocal, optimizing the fidelity and volume of biobanked tissue is an important step forward to improve the generalizability of genomic data as we move towards precision medicine.

The addition of androgen deprivation therapy and pelvic lymph node treatment to prostate bed salvage radiotherapy (NRG Oncology/RTOG 0534 SPPORT): an international, multicentre, randomised phase 3 trial

In men with a detectable prostate-specific antigen (PSA) level after prostatectomy for prostate cancer, salvage prostate bed radiotherapy (PBRT) results in about 70% of patients being free of progression at 5 years. A three-group randomised trial was designed to determine whether incremental gains in patient outcomes can be achieved by adding either 4-6 months of short-term androgen deprivation therapy (ADT) to PBRT, or both short-term ADT and pelvic lymph node radiotherapy (PLNRT) to PBRT. The international, multicentre, randomised, controlled SPPORT trial was done at 283 radiation oncology cancer treatment centres in the USA, Canada, and Israel. Eligible patients (aged ≥18 years) were those who after prostatectomy for adenocarcinoma of the prostate had a persistently detectable or an initially undetectable and rising PSA of between 0·1 and 2·0 ng/mL. Patients with and without lymphadenectomy (N0/Nx) were eligible if there was no clinical or pathological evidence of lymph node involvement. Other eligibility criteria included pT2 or pT3 disease, prostatectomy Gleason score of 9 or less, and a Zubrod performance status of 0-1. Eligible patients were randomly assigned to receive PBRT alone at a dose of 64·8-70·2 Gy at 1·8 Gy per fraction daily (group 1), PBRT plus short-term ADT (group 2), or PLNRT (45 Gy at 1·8 Gy per fraction, and then a volume reduction made to the planning target volume for the remaining 19·8-25 ·2 Gy) plus PBRT plus short-term ADT (group 3). The primary endpoint was freedom from progression, in which progression was defined as biochemical failure according to the Phoenix definition (PSA ≥2 ng/mL over the nadir PSA), clinical failure (local, regional, or distant), or death from any cause. A planned interim analysis of 1191 patents with minimum potential follow-up time of 5 years applied a Haybittle-Peto boundary of p<0·001 (one sided) for comparison of 5-year freedom from progression rates between the treatment groups. This trial is registered with ClinicalTrials.gov, NCT00567580. The primary objectives of the trial have been completed, although long-term follow-up is continuing. Between March 31, 2008, and March 30, 2015, 1792 eligible patients were enrolled and randomly assigned to the three treatment groups (592 to group 1 [PBRT alone], 602 to group 2 [PBRT plus short-term ADT], and 598 to group 3 [PLNRT plus PBRT plus short-term ADT]). 76 patients subsequently found to be ineligible were excluded from the analyses; thus, the evaluable patient population comprised 1716 patients. At the interim analysis (n=1191 patients; data cutoff May 23, 2018), the Haybittle-Peto boundary for 5-year freedom from progression was exceeded when group 1 was compared with group 3 (difference 17·9%, SE 2·9%; p<0·0001). The difference between groups 2 and 3 did not exceed the boundary (p=0·0063). With additional follow-up beyond the interim analysis (the final planned analysis; data cutoff May 26, 2021), at a median follow-up among survivors of 8·2 years (IQR 6·6-9·4), the 5-year freedom from progression rates in all 1716 eligible patients were 70·9% (95% CI 67·0-74·9) in group 1, 81·3% (78·0-84·6) in group 2, and 87·4% (84·7-90·2) in group 3. Per protocol criteria, freedom from progression in group 3 was superior to groups 1 and 2. Acute (≤3 months after radiotherapy) grade 2 or worse adverse events were significantly more common in group 3 (246 [44%] of 563 patients) than in group 2 (201 [36%] of 563; p=0·0034), which, in turn, were more common than in group 1 (98 [18%] of 547; p<0·0001). Similar findings were observed for grade 3 or worse adverse events. However, late toxicity (>3 months after radiotherapy) did not differ significantly between the groups, apart from more late grade 2 or worse blood or bone marrow events in group 3 versus group 2 (one-sided p=0·0060) attributable to the addition of PLNRT in this group. The results of this randomised trial establish the benefit of adding short-term ADT to PBRT to prevent progression in prostate cancer. To our knowledge, these are the first such findings to show that extending salvage radiotherapy to treat the pelvic lymph nodes when combined with short-term ADT results in meaningful reductions in progression after prostatectomy in patients with prostate cancer. National Cancer Institute.

TRUS-Guided Target Biopsy for a PI-RADS 3-5 Index Lesion to Reduce Gleason Score Underestimation: A Propensity Score Matching Analysis.

BackgroundMagnetic resonance imaging (MRI) and transrectal ultrasound (TRUS)-guided cognitive or image fusion biopsy is performed to target a prostate imaging reporting and data system (PI-RADS) 3–5 lesion. Biopsy Gleason score (GS) is frequently underestimated compared to prostatectomy GS. However, it is still unclear about how many cores on target are necessary to reduce undergrading and if additional cores around the target may improve grade prediction on surgical specimen.PurposeTo determine the number of target cores and targeting strategy to reduce GS underestimation.Materials and MethodsBetween May 2017 and April 2020, a total of 385 patients undergoing target cognitive or image fusion biopsy of PI-RADS 3–5 index lesions and radical prostatectomies (RP) were 2:1 matched with propensity score using multiple variables and divided into the 1–4 core (n = 242) and 5–6 core (n = 143) groups, which were obtained with multiple logistic regression with restricted cubic spline curve. Target cores of 1–3 and 4–6 were sampled from central and peripheral areas, respectively. Pathologic outcomes and target cores were retrospectively assessed to analyze the GS difference or changes between biopsy and RP with Wilcoxon signed-rank test.ResultsThe median of target cores was 3 and 6 in the 1–4 core and 5–6 core groups, respectively (p < 0.001). Restricted cubic spline curve showed that GS upgrade was significantly reduced from the 5th core and there was no difference between 5th and 6th cores. Among the matched patients, 35.4% (136/385; 95% confidence interval, 0.305–0.403) had a GS upgrade after RP. The GS upgrades in the 1–4 core and 5–6 core groups were observed in 40.6% (98/242, 0.343–0.470) and 26.6% (38/143, 0.195–0.346), respectively (p = 0.023). Although there was no statistical difference between the matched groups in terms of RP GS (p = 0.092), the 5–6 core group had significantly higher biopsy GS (p = 0.006) and lower GS change from biopsy to RP (p = 0.027).ConclusionFive or more target cores sampling from both periphery and center of an index tumor contribute to reduce GS upgrade.

Prediction of clinically significant prostate cancer using polygenic risk models in Asians

PurposeTo develop and evaluate the performance of a polygenic risk score (PRS) constructed in a Korean male population to predict clinically significant prostate cancer (csPCa).Materials and MethodsTotal 2,702 PCa samples and 7,485 controls were used to discover csPCa susceptible single nucleotide polymorphisms (SNPs). Males with biopsy-proven or post-radical prostatectomy Gleason score 7 or higher were included for analysis. After genotype imputation for quality control, logistic regression models were applied to test association and calculate effect size. Extracted candidate SNPs were further tested to compare predictive performance according to number of SNPs included in the PRS. The best-fit model was validated in an independent cohort of 311 cases and 822 controls.ResultsOf the 83 candidate SNPs with significant PCa association reported in previous literature, rs72725879 located in PRNCR1 showed the highest significance for PCa risk (odds ratio, 0.597; 95% confidence interval [CI], 0.555–0.641; p=4.3×10-45). Thirty-two SNPs within 26 distinct loci were further selected for PRS construction. Best performance was found with the top 29 SNPs, with AUC found to be 0.700 (95% CI, 0.667–0.734). Males with very-high PRS (above the 95th percentile) had a 4.92-fold increased risk for csPCa.ConclusionsEthnic-specific PRS was developed and validated in Korean males to predict csPCa susceptibility using the largest csPCa sample size in Asia. PRS can be a potential biomarker to predict individual risk. Future multi-ethnic trials are required to further validate our results.

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 predictive factor for pathological downgrading after prostatectomy in patients with biopsy Gleason score 4+3 or 4+4 prostate cancer.

The proportion of Gleason pattern (GP) 4 prostate cancers at prostate biopsy has a clinically significant impact on risk stratification for patients with prostate cancer. In pathological diagnosis including GP 4, a biopsy Gleason score (GS) of 3+4 has a more favorable prognosis than a GS of 4+3 and 4+4. However, the discrepancy between biopsy and prostatectomy specimens is well known. The current study investigated the clinical parameters and biopsy specimens associated with pathological downgrading after prostatectomy in biopsies with a GS of 4+3 or 4+4 prostate cancer. A total of 302 patients with prostate cancer who underwent robot-assisted radical prostatectomy between August 2013 and May 2019 were retrospectively reviewed. A total of 103 patients had biopsies with GSs of 4+3 and GS 4+4 (unfavorable pathology). The proportion of patients who were downgraded from unfavorable disease to GS ≤3+4 (favorable pathology) in prostatectomy specimens was investigated. Logistic regression analysis was used to explore the association between clinical parameters and downgrading in prostatectomy specimens. A total of 43 patients (41.7%) were downgraded from biopsy GS to prostatectomy GS. The proportions of downgrade in biopsy GS 4+4 and 4+3 were 14.6 and 27.1%, respectively. The percentage of highest GS out of positive biopsy cores and the maximum percentage of cancer involvement within a positive core with the highest GS were lower in the downgrade group than in the no downgrade group (45 vs. 66.7%, P=0.025; 20 vs. 30%, P=0.048, respectively). When performing multivariate logistic regression analysis, the only significant predictor for downgrade was lower percentage of highest GS cores out of positive biopsy cores (odds ratio, 2.469; 95% confidence interval, 1.029-5.925 P=0.043). In conclusion, patients with biopsy GS 4+4 and 4+3 often exhibit a downgrade to GS 3+4 or less in prostatectomy specimens. The lower percentage of highest GS cores out of positive biopsy cores was associated with downgrade.

Prognostic capabilities and clinical utility of cell cycle progression testing, prostate imaging reporting and data system, version 2, and clinicopathologic data in management of localized prostate cancer

ObjectivesTo compare the prognostic capabilities and clinical utility of the cell cycle progression (CCP) gene expression classifier test, multiparametric magnetic resonance imaging (mpMRI) with Prostate Imaging Reporting and Data System (PI-RADS) scoring, and clinicopathologic data in select prostate cancer (PCa) medical management scenarios. Patients and methodsRetrospective, observational analysis of patients (N = 222) ascertained sequentially from a single urology practice from January 2015 to June 2018. Men were included if they had localized PCa, a CCP score, and an mpMRI PI-RADS v2 score. Cohort 1 (n = 156): men with newly diagnosed PCa, with or without a previous negative biopsy. Cohort 2 (n = 66): men who initiated active surveillance (AS) without CCP testing, but who received the test during AS. CCP was combined with the UCSF Cancer of the Prostate Risk Assessment (CAPRA) score to produce a clinical cell-cycle risk (CCR) score, which was reported in the context of a validated AS threshold. Spearman's rank correlation test was used to evaluate correlations between variables. Generalized linear models were used to predict binary Gleason score category and medical management selection (AS or curative therapy). Likelihood-ratio tests were used to determine predictor significance in both univariable and multivariable models. ResultsIn the combined cohorts, modest but significant correlations were observed between PI-RADS score and CCP (rs = 0.22, P = 8.1 × 10−4), CAPRA (rs= 0.36, P = 4.8 × 10−8), or CCR (rs = 0.37, P = 2.0 × 10−8), suggesting that much of the prognostic information captured by these measures is independent. When accounting for CAPRA and PI-RADS score, CCP was a significant predictor of higher-grade tumor after radical prostatectomy, with the resected tumor approximately 4 times more likely to harbor Gleason ≥4+3 per 1-unit increase in CCP in Cohort 1 (Odds Ratio [OR], 4.10 [95% confidence interval [CI], 1.46, 14.12], P = 0.006) and in the combined cohorts (OR, 3.72 [95% CI, 1.39, 11.88], P = 0.008). On multivariable analysis, PI-RADS score was not a significant predictor of post-radical prostatectomy Gleason score. Both CCP and CCR were significant and independent predictors of AS versus curative therapy in Cohort 1 on multivariable analysis, with each 1-unit increase in score corresponding to an approximately 2-fold greater likelihood of selecting curative therapy (CCP OR, 2.08 [95% CI, 1.16, 3.94], P = 0.014) (CCR OR, 2.33 [95% CI, 1.48, 3.87], P = 1.5 × 10−4). CCR at or below the AS threshold significantly reduced the probability of selecting curative therapy over AS (OR, 0.28 [95% CI, 0.13, 0.57], P = 4.4 × 10−4), further validating the clinical utility of the AS threshold. ConclusionCCP was a better predictor of both tumor grade and subsequent patient management than was PI-RADS. Even in the context of targeted biopsy, molecular information remains essential to ensure precise risk assessment for men with newly diagnosed PCa.

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.

Metabolically Abnormal Obesity Increases the Risk of Advanced Prostate Cancer in Chinese Patients Undergoing Radical Prostatectomy.

BackgroundTo investigate the pathological risk of prostate cancer (PCa) according to the obesity and metabolic status of Chinese patients undergoing radical prostatectomy.Materials and MethodsWe performed a retrospective cross-sectional study of 1016 patients with PCa who underwent radical prostatectomy and whose metabolic status and body mass index were examined. Multivariate logistic regression analysis was performed to examine the relationship between different metabolic obesity phenotypes and the pathological outcomes of PCa.ResultsAmong 1016 men, 551 (54.2%), 106 (10.4%), 238 (23.4%), and 121 (11.9%) were assigned to the metabolically healthy and normal weight (MHNW) group, metabolically abnormal but normal weight (MANW) group, metabolically healthy but overweight or obese (MHO) group, and metabolically abnormal and overweight or obese (MAO) group, respectively. Compared with the MHNW group, the MAO group had a significantly greater risk of a higher prostatectomy Gleason score [odds ratio (OR), 1.907; 95% confidence interval (95% CI), 1.144–3.182], pathological stage (OR, 1.606; 95% CI, 1.035–2.493), and seminal vesicle invasion (OR, 1.673; 95% CI, 1.041–2.687). In contrast, the ORs were not increased in the MHO or MANW group. In the context of normal weight, metabolic disorders were associated with lymph node involvement. The metabolic status and body mass index were not associated with extracapsular extension or surgical margins in any of the four groups.ConclusionThe MAO phenotype is associated with aggressive PCa, including a higher prostatectomy Gleason score, pathological stage, and seminal vesicle invasion and might also be associated with disease progression. Obesity and metabolic disorders act synergistically to increase the pathological risk of PCa.

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.

Impact of Prostate Specific Antigen Level on Oncological Outcomes after Open Radical Prostatectomy

To compare the impact of prostate specific antigen (PSA) on oncological outcomes in the patients with 4-10 and 10.01-20 ng/ml PSA level. Retrospective comparative study. Hitit University, Çorum Erol Olçok Training and Research Hospital, Çorum, Turkey, between February 2010 and January 2018. Patients who underwent open radical prostatectomy in our department were reviewed retrospectively. The patients were divided into two groups according to the PSA level at diagnosis between 4 and 20 ng/ml. The patients with PSA level of 4-10 ng/ml was in group 1 and 10.01-20 ng/ml was in group 2. Preoperative data including age, biopsy Gleason score (GS), PSA level, postoperative pathological reports, T stage, GS, positive surgical margin, upgrading and downgrading, were compared between groups. There were 109 (71.24%) and 44 patients (28.75%) in group 1 and group 2, respectively. The median age and PSA level of the patients was 67 and 64.5 years; 6.12 and 12.45 ng/ml in both groups, respectively. There was no significant difference for age, GS, number of positive biopsy cores except the PSA level (p<0.001). The difference did not reach statistical significance for stage, upgrading, downgrading, positive surgical margin, and prostatectomy GS between groups. Serum high PSA level at the time of the diagnosis was unrelated to final pathology. The proportion of local advanced disease and positive surgical margin was higher in patients with low PSA values than high levels without statistically significance.

Circulating miRNAs in localized/locally advanced prostate cancer patients after radical prostatectomy and radiotherapy.

BackgroundOvertreatment is a well‐known clinical challenge in local prostate cancer (PCa). Although risk assessment models have contributed to a better stratification of patients with local PCa, a tailored management is still in its infancy. Over the last few decades, microRNAs (miRNAs) have shown promising results as biomarkers in PCa. The aim of this study was to investigate circulating miRNAs after management of local PCa.MethodsThe relative expression of four miRNAs (miRNA‐21, ‐93, ‐125b, and miRNA‐221) was assessed in plasma from 149 newly diagnosed patients with local or locally advanced PCa. Real‐time polymerase chain reaction was used for analysis. A baseline sample at time of diagnosis and a follow‐up sample after 6 months were assessed. The patients were grouped in an interventional cohort (radical prostatectomy, curative intent radiotherapy, or androgen‐deprivation therapy alone) and an observational cohort (watchful waiting or active surveillance).ResultsIn the interventional cohort, levels of both miRNA‐93 and miRNA‐221 were significantly lower in the follow‐up samples compared to baseline z = −2.738, P = 0.006, and z = −4.498, P < 0.001, respectively. The same observation was recorded for miRNA‐125b in the observational cohort (z = −2.656, P = 0.008). Both miRNA‐125b and miRNA‐221 were correlated with risk assessment r = 0.23, P = 0.015, and r = 0.203, P = 0.016 respectively, while miRNA‐93 showed tendency to significant correlation with the prostatectomy Gleason score (r = 0.276, P = 0.0576).ConclusionsThe current results indicate a possible role of miRNA‐93 and miRNA‐221 in disease monitoring in localized and locally advanced PCa. Larger studies are warranted to assess the clinical impact of these biomarkers.

Optimizing the Number of Cores Targeted During Prostate Magnetic Resonance Imaging Fusion Target Biopsy

BackgroundThe number of prostate biopsy cores that need to be taken from each magnetic resonance imaging (MRI) region of interest (ROI) to optimize sampling while minimizing overdetection has not yet been clearly elucidated. ObjectiveTo characterize the incremental value of additional MRI-ultrasound (US) fusion targeted biopsy cores in defining the optimal number when planning biopsy and to predict men who might benefit from more than two targeted cores. Design, setting, and participantsThis was a retrospective cohort study of MRI-US fusion targeted biopsies between 2015 and 2017. InterventionMRI-US fusion targeted biopsy in which four biopsy cores were directed to each MRI-targeted ROI. Outcomes measurements and statistical analysisThe MRI-targeted cores representing the first highest Gleason core (FHGC) and first clinically significant cancer core (FCSC; GS≥3+4) were evaluated. We analyzed the frequency of FHGC and FCSC among cores 1–4 and created a logistic regression model to predict FHGC >2. The number of unnecessary cores avoided and the number of malignancies missed for each Gleason grade were calculated via clinical utility analysis. The level of agreement between biopsy and prostatectomy Gleason scores was evaluated using Cohen's κ. Results and limitationsA total of 479 patients underwent fusion targeted biopsy with four individual cores, with 615 ROIs biopsied. Among those, FHGC was core 1 in 477 (76.8%), core 2 in 69 (11.6%), core 3 in 48 (7.6%), and core 4 in 24 men (4.0%) with any cancer. Among men with clinically significant cancer, FCSC was core 1 in 191 (77.8%), core 2 in 26 (11.1%), core 3 in 17 (6.2%), and core 4 in 11 samples (4.9%). In comparison to men with a Prostate Imaging-Reporting and Data System (PI-RADS) score of 5, patients were significantly less likely to have FHGS >2 if they had PI-RADS 4 (odds ratio [OR] 0.287; p=0.006), PI-RADS 3 (OR 0.284; p=0.006), or PI-RADS 2 (OR 0.343; p=0.015). Study limitations include a single-institution experience and the retrospective nature. ConclusionsCores 1–2 represented FHGC 88.4% and FCSC 88.9% of the time. A PI-RADS score of 5 independently predicted FHGC >2. Although the majority of cancers in our study were appropriately characterized in the first two biopsy cores, there remains a proportion of men who would benefit from additional cores. Patient summaryIn men who undergo magnetic resonance imaging-ultrasound fusion targeted biopsy, the first two biopsy cores diagnose the majority of clinically significant cancers. However, there remains a proportion of men who would benefit from additional cores.

Prostate Cancers Detected by Magnetic Resonance Imaging-Targeted Biopsies Have a Higher Percentage of Gleason Pattern 4 Component and Are Less Likely to Be Upgraded in Radical Prostatectomies.

In Gleason score (GS) 7 prostate cancers, the quantity of Gleason pattern 4 (GP 4) is an important prognostic factor and influences treatment decisions. Magnetic resonance imaging (MRI)-targeted biopsy has been increasingly used in clinical practice. To investigate whether MRI-targeted biopsy may detect GS 7 prostate cancer with greater GP 4 quantity, and whether it improves biopsy/radical prostatectomy GS concordance. A total of 243 patients with paired standard and MRI-targeted biopsies with cancer in either standard or targeted or both were studied, 65 of whom had subsequent radical prostatectomy. The biopsy findings, including GS and tumor volume, were correlated with the radical prostatectomy findings. More prostate cancers detected by MRI-targeted biopsy were GS 7 or higher. Mean GP 4 percentage in GS 7 cancers was 31.0% ± 29.3% by MRI-targeted biopsy versus 25.1% ± 29.5% by standard biopsy. A total of 122 of 218 (56.0%) and 96 of 217 (44.2%) prostate cancers diagnosed on targeted biopsy and standard biopsy, respectively, had a GP 4 of 10% or greater ( P = .01). Gleason upgrading was seen in 12 of 59 cases (20.3%) from MRI-targeted biopsy and in 24 of 57 cases (42.1%) from standard biopsy ( P = .01). Gleason upgrading correlated with the biopsy cancer volume inversely and GP 4 of 30% or less in standard biopsy. Such correlation was not found in MRI-targeted biopsy. Magnetic resonance imaging-targeted biopsy may detect more aggressive prostate cancers and reduce the risk of Gleason upgrading in radical prostatectomy. This study supports a potential role for MRI-targeted biopsy in the workup of prostate cancer and inclusion of percentage of GP 4 in prostate biopsy reports.

An Automated Multiparametric MRI Quantitative Imaging Prostate Habitat Risk Scoring System for Defining External Beam Radiation Therapy Boost Volumes

To develop a prostate tumor habitat risk scoring (HRS) system based on multiparametric magnetic resonance imaging (mpMRI) referenced to prostatectomy Gleason score (GS) for automatic delineation of gross tumor volumes. A workflow for integration of HRS into radiation therapy boost volume dose escalation was developed in the framework of a phase 2 randomized clinical trial (BLaStM). An automated quantitative mpMRI-based 10-point pixel-by-pixel method was optimized to prostatectomy GSs and volumes using referenced dynamic contrast-enhanced and apparent diffusion coefficient sequences. The HRS contours were migrated to the planning computed tomography scan for boost volume generation. There were 51 regions of interest in 12 patients who underwent radical prostatectomy (26 with GS ≥7 and 25 with GS 6). The resultant heat maps showed inter- and intratumoral heterogeneity. The HRS6 level was significantly associated with radical prostatectomy regions of interest (slope 1.09, r = 0.767; P < .0001). For predicting the likelihood of cancer, GS ≥7 and GS ≥8 HRS6 area under the curve was 0.718, 0.802, and 0.897, respectively. HRS was superior to the Prostate Imaging, Reporting and Diagnosis System 4/5 classification, wherein the area under the curve was 0.62, 0.64, and 0.617, respectively (difference with HR6, P < .0001). HRS maps were created for the first 37 assessable patients on the BLaStM trial. There were an average of 1.38 habitat boost volumes per patient at a total boost volume average of 3.6 cm3. An automated quantitative mpMRI-based method was developed to objectively guide dose escalation to high-risk habitat volumes based on prostatectomy GS.