Role of PI-RADS Version 2 for Prediction of Upgrading in Biopsy-Proven Prostate Cancer With Gleason Score 6

Introduction

The objective of this study was to investigate the effect of Prostate Imaging Reporting and Data System version 2 (PI-RADSv2) on prediction of postoperative Gleason score (GS) upgrading for patients with biopsy GS 6 prostate cancer.

Targeted and Systematic Prostate Biopsy in Biopsy-naive Men With Positive Multiparameter Magnetic Resonance Imaging Findings: A Meta-analysis

We assessed the difference in the detection rate of prostate cancer, specifically clinically significant prostate cancer, using targeted biopsy (TB), systematic biopsy (SB), and the combination of these 2 (CB) in biopsy-naive men with positive multiparameter magnetic resonance imaging results. We performed a literature review in September 2018 using PubMed and the Web of Science. Relevant studies acquired from specific articles’ references were also reviewed. Only those studies that had provided the detection rate of TB, SB, and CB in biopsy-naive men with positive multiparameter magnetic resonance imaging findings were included for a total of 11 studies with 2099 patients. The combined strategy was better than TB or SB alone, with an odds ratio (OR) of 1.47 (95% confidence interval [CI], 1.30-1.67; P < .001) and 1.45 (95% CI, 1.28-1.65; P < .001), respectively, in the overall detection rate. Also, TB was not better than SB, with an OR of 0.99 (95% CI, 0.87-1.12; P = .825). For the clinically significant prostate cancer detection rate, CB was still better than TB or SB alone, with an OR of 1.25 (95% CI, 1.11-1.42; P < .001) and an OR of 1.23 (95% CI, 1.08-1.40; P = .002), respectively. Again, TB was not better than SB, with an OR of 0.98 (95% CI, 0.86-1.12; P = .768). In conclusion, CB resulted in a better detection rate than TB or SB alone for both the overall prostate cancer detection rate and the clinically significant prostate cancer detection rate.     

Rates of Positive Surgical Margins and Their Effect on Cancer-specific Mortality at Radical Prostatectomy for Patients With Clinically Localized Prostate Cancer

Background

The objective of this study was to investigate positive surgical margin (PSM) rates in patients with prostate cancer treated with radical prostatectomy (RP) and assess PSM impact on cancer-specific mortality (CSM).

Evaluation of Biochemical Recurrence-free Survival after Radical Prostatectomy by Cancer of the Prostate Risk Assessment Post-Surgical (CAPRA-S) Score

Background: The cancer of the prostate risk assessment (CAPRA) score has been defined to predict prostatecancer recurrence based on the pre-clinical data, then pathological data have also been incorporated. Thus,CAPRA post-surgical (CAPRA-S) score has been developed based on six criteria (prostate specific antigen(PSA) at diagnosis, pathological Gleason score, and information on surgical margin, seminal vesicle invasion,extracapsular extension and lymph node involvement) for the prediction of post-surgical recurrences. In thepresent study, biochemical recurrence (BCR)-free probabilities after open retropubic radical prostatectomy (RP)were evaluated by the CAPRA-S scoring system and its three-risk level model. Materials and Methods: CAPRA-Sscores (0-12) of our 240 radical prostatectomies performed between January 2000-May 2011 were calculated.Patients were distributed into CAPRA-S score groups and also into three-risk groups as low, intermediate andhigh. BCR-free probabilities were assessed and compared using Kaplan-Meier analysis and Cox proportionalhazards regression. Ability of CAPRA-S in BCR detection was evaluated by concordance index (c-index). Results:BCR was present in 41 of total 240 patients (17.1%) and the mean follow-up time was 51.7 ± 33.0 months. MeanBCR-free survival time was 98.3 months (95% CI: 92.3-104.2). Of the patients in low, intermediate and highrisk groups, 5.4%, 22.0% and 58.8% had BCR, respectively and the difference among the three groups wassignificant (P = 0.0001). C-indices of CAPRA-S score and three-risk groups for detecting BCR-free probabilitiesin 5-yr were 0.87 and 0.81, respectively. Conclusions: Both CAPRA-S score and its three-risk level model wellpredicted BCR after RP with high c-index levels in our center. Therefore, it is a clinically reliable post-operativerisk stratifier and disease recurrence predictor for prostate cancer.     

Prognostic Value of Gleason Score at Positive Surgical Margin in Prostate Cancer: A Systematic Review and Meta-analysis

The individual clinical significance of a positive surgical margin (PSM) after radical prostatectomy has remained controversial. Studies have suggested that the Gleason grade (GG) at the PSM could improve predictive accuracy and decision making. Our objective was to systematically review the reported data to determine the effect of the GG at the PSM on the prognosis after radical prostatectomy. A systematic review was conducted by searching MEDLINE/PubMed for studies reported by June 2019 in accordance with the Preferred Reporting Items for Systematic Review statement. The keywords used included prostate cancer, radical prostatectomy, positive surgical margin, Gleason score, and/or Gleason grade. After a systematic literature review, 10 studies were included, comprising 14,108 patients, of whom 2454 (17.4%) had a PSM and 428 (14%) eventually experienced biochemical recurrence (BCR) within a median follow-up of 18 to 156 months. Data on neoadjuvant or adjuvant therapy were not estimable. In a meta-analysis, GG4 at PSM was significantly associated with BCR compared with GG3 (pooled hazard ratio, 1.87; 95% confidence interval, 1.53-2.28; z = 6.16). The Cochrane Q test (χ² = 5.88; P = .318) and I² test (I² = 15.0%) showed that no significant heterogeneity was present. GG4 at a PSM is a feature of biologically and clinically aggressive prostate cancer that is associated with a significant increase risk of BCR. GG at PSM should be recorded in each pathological report. Given this adverse prognostic value patients with GG4 at the PSM should be considered for multimodal therapy such as radiotherapy.     

The Effect of Differing Gleason Scores at Biopsy on the Odds of Upgrading and the Risk of Death From Prostate Cancer

Introduction/BackgroundThe GS is an established prostate cancer prognostic factor. Whether the presence of differing GSs at biopsy (eg, 4+3 and 3+3), which we term ComboGS, improves the prognosis that would be predicted based on the highest GS (eg, 4+3) because of decreased upgrading is unknown. Therefore, we evaluated the odds of upgrading at time of radical prostatectomy (RP) and the risk of PCSM when ComboGS was present versus absent.Patients and MethodsLogistic and competing risks regression were performed to assess the effect that ComboGS had on the odds of upgrading at time of RP in the index (n = 134) and validation cohorts (n = 356) and the risk of PCSM after definitive therapy in a long-term cohort (n = 666), adjusting for known predictors of these end points. We calculated and compared the area under the curve using a receiver operating characteristic analysis when ComboGS was included versus excluded from the upgrading models.ResultsComboGS was associated with decreased odds of upgrading (index: adjusted odds ratio [AOR], 0.14; 95% confidence interval [CI], 0.04-0.50; P = .003; validation: AOR, 0.24; 95% CI, 0.11-0.51; P < .001) and added significantly to the predictive value of upgrading for the in-sample index (P = .02), validation (P = .003), and out-of-sample prediction models (P = .002). ComboGS was also associated with a decreased risk of PCSM (adjusted hazard ratio, 0.40; 95% CI, 0.19-0.85; P = .02).ConclusionDiffering biopsy GSs are associated with a lower odds of upgrading and risk of PCSM. If validated, future randomized noninferiority studies evaluating deescalated treatment approaches in men with ComboGS could be considered.     

Fourteen-Core Systematic Biopsy That Includes Two Anterior Cores in Men With PI-RADS Lesion ≥ 3 is Comparable With Magnetic Resonance Imaging-ultrasound Fusion Biopsy in Detecting Clinically Significant Prostate Cancer: A Single-institution Experience

IntroductionMagnetic resonance imaging (MRI)-ultrasound fusion targeted prostate biopsy (FB) has been advocated by many experts as a replacement for the standard template biopsy. Herein, we compared pathology results and cancer detection rates of FB with our standard 14-core systematic prostate biopsy (SB) that includes 2 anterior cores.Materials and MethodsOne hundred two men with elevated prostate-specific antigen and suspicious lesions on multiparametric MRI, Prostate Imaging Reporting And Data System (PI-RADS) v2 score ≥ 3, underwent FB. Each target lesion was biopsied 3 times; our SB was performed concurrently. Biopsy results were compared for overall and clinically significant (cs), defined as Gleason score ≥ 7, cancer detection.ResultsFifty-two percent of patients had positive biopsy results, and of those, 44 had cs prostate cancer (PCa). The overall detection rates for FB and SB were 39% and 50%, respectively, and there was no statistical difference in the detection rate of csPCa detection rate (P = .42). Of 17 patients diagnosed with a high-risk PCa, defined as Gleason score ≥ 8, SB identified 15, whereas FB identified 10. Within the SB group, 21 had positive anterior core biopsies, of which 11 were cs.ConclusionExpanding the standard template prostate biopsies to include 2 anterior horn sampling may be just as effective as FB in men with PI-RADS lesion ≥ 3, thereby mitigating the increased cost associated with FB.     

Apparent Diffusion Coefficient and Other Preoperative Magnetic Resonance Imaging Features for the Prediction of Positive Surgical Margins in Prostate Cancer Patients Undergoing Radical Prostatectomy

PurposeTo investigate the use of apparent diffusion coefficient (ADC) values and other MRI features for predicting positive surgical margins (PSMs) in patients undergoing radical prostatectomy.Materials and MethodsWe retrospectively identified 400 consecutive patients who underwent surgery for prostate cancer between January 2015 and June 2016. ADC values of the index lesion and other preoperative magnetic resonance imaging features, including tumor site, laterality, level, Prostate Imaging Reporting and Data System category, European Society of Urogenital Radiology extracapsular extension score, and prostate volume, were assessed. Univariate and multivariable logistic regression were performed. Performance in predicting the occurrence of PSMs was measured using the area under the curve (AUC). AUC differences were evaluated with the DeLong method. The Youden index was calculated to identify the ADC threshold to best discriminate patients with PSMs.ResultsOf the 400 patients, 105 (26.2%) had PSMs after radical prostatectomy. ADC values, Prostate Imaging Reporting and Data System category, extracapsular extension score, tumor site, and laterality were significantly associated with PSMs (P < .001) in univariate analysis. The AUC of the predictive model based on ADC alone was 68.2% (95% confidence interval, 62.2-74.2%) and did not significantly differ from the best multivariable predictive model which combined laterality, and site with ADC to attain an AUC of 70.0% (95% confidence interval, 64.2-75.8%; DeLong P = .318). The ADC threshold that maximized the Youden index was 960.3 µm²/s.ConclusionADC values and preoperative magnetic resonance imaging features can help estimate the risk of PSMs after radical prostatectomy.     

Comparison of the Formula of PSA,Age, Prostate Volume and Race Versus PSA Density and the Detection of Primary Malignant Circulating Prostate Cells in Predicting a Positive Initial Prostate Biopsy in Chilean Men with Suspicion of Prostate Cancer

Background: Combining risk factors for prostate cancer into a predictive tool may improve the detection ofprostate cancer while decreasing the number of benign biopsies. We compare one such tool, age multiplied byprostate volume divided by total serum PSA (PSA-AV) with PSA density and detection of primary malignantcirculating prostate cells (CPCs) in a Chilean prostate cancer screening program. The objectives were not only todetermine the predictive values of each, but to determine the number of clinically significant cancers that wouldhave been detected or missed. Materials and Methods: A prospective study was conducted of all men undergoing12 core ultrasound guided prostate biopsy for suspicion of cancer attending the Hospital DIPRECA and Hospitalde Carabineros de Chile. Total serum PSA was registered, prostate volumecalculated at the moment of biopsy,and an 8ml blood simple taken immediately before the biopsy procedure. Mononuclear cells were obtained fromthe blood simple using differential gel centrifugation and CPCs identified using immunocytchemistry with anti-PSA and anti-P504S. Biopsy results were classed as positive or negative for cancer and if positive the Gleasonscore, number of positive cores and percent infiltration recorded. Results: A total of 664 men participated, ofwhom 234 (35.2%) had cancer detected. They were older, had higher mean PSA, PSA density and lower PSA-AV.Detection of CPCs had high predictive score, sensitivity, sensibility and positive and negative predictive values,PSA-AV was not significantly different from PSA density in this population. The use of CPC detection avoidedmore biopsies and missed fewer significant cancers.Conclusions: In this screening population the use of CPCdetection predicted the presence of clinically significant prostate cancer better than the other parameters. Thehigh negative predictive value would allow men CPC negative to avoid biopsy but remain in follow up. Theformula PSA-AV did not add to the predictive performance using PSA density.     

bc1-2、P~(53)和c-erb-B_2基因在前列腺癌中的表达

探讨癌基因在前列腺癌发生发展中意义，应用免疫组化S－P（过氧化物酶—链霉卵白素）法对50例前列腺癌组织中bcl－2、P53和c－erb－B2的表达产物进行检测。结果bcl－2、P53和c－erb－B2的表达率为42％、48％和44％，bcl－2、P53和c－erb－B2的表达与肿瘤的分级、分期皆相关。66％肿瘤有癌基因表达异常，26％的肿瘤同时有多个癌基因表达异常，多个癌基因表达异常与分级、分期相关，bcl－2的表达与P53的表达呈负相关：（γ＝-0．51，P<0．05）。结论：上述癌基因参与了前列腺癌发生发展过程，肿瘤多个基因分析比单个分析更有价值。     

Increasing Immune Dysfunction is Associated with Increasing Matrix-Metalloproteinase-2 Expression and Predicts Biochemical Failure in Men with Bone Marrow Micro-Metastasis Positive Localized Prostate Cancer

Introduction: To determine if there was an association of the ALC (absolute lymphocyte count) and LCP (lymphocytopenia) with the expression of MMP-2 in bone marrow micro-metastasis, the changes occurring during follow-up and association with biochemical failure. Methods and patients: One month after surgery blood and bone marrow samples were taken to determine the presence of micro-metastasis, the presence of circulating prostate cells (CPCs) and ALC. CPCs and micro-metastasis were detected using immunocytochemistry and MMP-2 expression determined in micro-metastasis. Only men positive for micro-metastasis participated in the study. At end follow blood was taken for serum PSA, ALC and CPCs, if the ALC decreased by more than 10% bone marrow sampling was repeated and MMP-2 expression determined, similarly for men with BF. Men who had stable ALCs had an end of study evaluation of the bone marrow. Results: 402 men underwent radical prostatectomy, one month post surgery 79 men were positive for only bone marrow micro-metastasis and formed the study group; of whom 36/79 (45%) underwent BF. Clinical pathological findings were not significantly different between men with or without BF. In men with BF the ALC was significantly lower one-month post surgery. The 5 and 10 year Kaplan-Meier survival was 100% at 5-years and 65% at 10-years for the whole cohort. Men without BF had stable ALCs. A decrease of >10% in the ALC was associated with increasing MMP-2 expression in the micro-metastasis and surrounding stromal tissue, the appearance of CPCs 6-12 months later and BF. Conclusions: the immune host-tumour cell interaction in the microenvironment is dynamic and changes with time. A decreasing ALC may be a valuable marker in identifying men with high risk of BF and changes in immune mediated dormancy before the PSA rises.     

Diagnostic Performance of PI-RADS v2, Proposed Adjusted PI-RADS v2 and Biparametric Magnetic Resonance Imaging for Prostate Cancer Detection: A Preliminary Study

Purpose: To evaluate the diagnostic performance of PI-RADS v2, proposed adjustments to PI-RADS v2 (PA PI-RADS v2) and biparametric magnetic resonance imaging (MRI) for prostate cancer detection. Methods: A retrospective cohort of 224 patients with suspected prostate cancer was included from January 2016 to November 2018. All the patients underwent a multi-parametric MR scan before biopsy. Two radiologists independently evaluated the MR examinations using PI-RADS v2, PA PI-RADS v2, and a biparametric MRI protocol, respectively. Receiver operating characteristic (ROC) curves for the three different protocols were drawn. Results: In total, 90 out of 224 cases (40.18%) were pathologically diagnosed as prostate cancer. The area under the ROC curves (AUC) for diagnosing prostate cancers by biparametric MRI, PI-RADS v2, and PA PI-RADS v2 were 0.938, 0.935, and 0.934, respectively. For cancers in the peripheral zone (PZ), the diagnostic sensitivity was 97.1% for PI-RADS v2/PA PI-RADS v2 and 96.2% for biparametric MRI. Moreover, the specificity was 84.0% for biparametric MRI and 58.0% for PI-RADS v2/PA PI-RADS v2. For cancers in the transition zone (TZ), the diagnostic sensitivity was 93.4% for PA PI-RADS v2 and 88.2% for biparametric MRI/PI-RADS v2. Furthermore, the specificity was 95.4% for biparametric MRI/PI-RADS v2 and 78.0% for PA PI-RADS v2. Conclusions: The overall diagnostic performance of the three protocols showed minimal differences. For lesions assessed as being category 3 using the biparametric MRI protocol, PI-RADS v2, or PA PI-RADS v2, it was thought prostate cancer detection could be improved. Attention should be paid to false positive results when PI-RADS v2 or PA PI-RADS v2 are used.     

bc1-2、P53和c-erb-B2基因在前列腺癌中的表达

 探讨癌基因在前列腺癌发生发展中意义,应用免疫组化S－P(过氧化物酶—链霉卵白素)法对50例前列腺癌组织中bcl－2、P53和c－erb－B2的表达产物进行检测。结果bcl－2、P53和c－erb－B2的表达率为42％、48％和44％,bcl－2、P53和c－erb－B2的表达与肿瘤的分级、分期皆相关。66％肿瘤有癌基因表达异常,26％的肿瘤同时有多个癌基因表达异常,多个癌基因表达异常与分级、分期相关,bcl－2的表达与P53的表达呈负相关:(γ＝-0.51,P<0.05)。结论:上述癌基因参与了前列腺癌发生发展过程,肿瘤多个基因分析比单个分析更有价值。     

Predictive Value of Neutrophil to Lymphocyte Ratio in the Diagnosis of Significant Prostate Cancer at Initial Biopsy: A Comparison with Free Percent Prostate Specific Antigen,Prostate Specific Antigen Density and Primary Circulating Prostate Cells

Introduction: An elevated serum PSA is the only biomarker routinely used in screening for prostate cancer to indicate a prostate biopsy. However, it is not specific for prostate cancer and the neutrophil/lymphocyte ratio has been suggested as an alternative. We present a prospective study of men with an elevated PSA and compare the neutrophil/lymphocyte ratio, free percent PSA, PSA density and the presence of circulating prostate cells to detect clinically significant prostate cancer at first biopsy. Patients and Methods: Prospective study of consecutive men with a PSA 4-10 ng/ml referred for initial prostate biopsy, the results were compared with the neutrophil/lymphocyte ratio, free percent PSA and PSA density. Circulating prostate cells (CPCs) were detected using immunocytochemistry. The blood sample was taken immediately before the prostate biopsy. Results: 1,223 men participated, 38% (467) of whom had prostate cancer detected, of these 322 were clinically significant. The area under the curves were for neutrophil/lymphocyte ratio, free percent PSA, PSA density and CPC detection were 0.570, 0.785, 0,620 and 0.844 respectively. Sensitivity/specificity were 0.388/0.685, 0.419/0.897, 0.598/0.624 and 0.966/0.786 respectively. The neutrophil/lymphocyte ratio did not differentiate between benign and malignant disease. Conclusions: The neutrophil/lymphocyte ratio did not discriminate between benign and malignant prostatic disease in patients with a PSA between 4-10ng/ml.     

The Utility of Combined Target and Systematic Prostate Biopsies in the Diagnosis of Clinically Significant Prostate Cancer Using Prostate Imaging Reporting and Data System Version 2 Based on Biparametric Magnetic Resonance Imaging

This study aimed to determine the predictive value of the Prostate Imaging Reporting and Data System version 2 (PI-RADS v2) based on biparametric magnetic resonance imaging (bpMRI) with combined target biopsy (TBx) and systematic biopsy (SBx) in patients with suspicion of having clinically significant prostate cancer (csPCa). In this retrospective study, we reviewed the clinical and pathological records of 184 consecutive patients who underwent bpMRI before prostate biopsy. We focused on patients with PI-RADS v2 scores ≥ 3. MRI was performed using a 3-Tesla clinical scanner with a 32-channel phased-array receiver coil. PI-RADS v2 was used to describe bpMRI findings based on T2-weighted imaging and diffusion-weighted imaging scores. The primary endpoint was the diagnostic accuracy rate of PI-RADS v2 based on bpMRI for patients with prostate cancer (PCa) who underwent combined TBx and SBx. A total of 104 patients were enrolled in this study. Combined TBx and SBx was significantly superior to either method alone for PCa detection in patients with suspicious lesions according to PI-RADS v2. TBx and SBx detected concordant csPCa in only 24.1% of the patients. In addition, the rate of increase in the Gleason score was similar between SBx (41.5%) and TBx (34.1%). The diagnostic accuracy of bpMRI is comparable to that of standard multiparametric MRI for the detection of csPCa. Moreover, combined TBx and SBx may be optimal for the accurate determination of csPCa diagnosis, the International Society of Urological Pathology grade, and risk classification.