Accurate diagnosis of prostate cancer by combining Proclarix with magnetic resonance imaging.

OBJECTIVES: To assess of the clinical performance of Proclarix® (a novel Conformité Européenne [CE]-marked biomarker test aiding in the identification of clinically significant prostate cancer [csPCa]) alone or in combination with multiparametric magnetic resonance imaging (mpMRI) to predict csPCa (International Society of Urological Pathology Grade Group ≥2). PATIENTS AND METHODS: The study included blood samples from 721 men undergoing mpMRI followed by biopsy at University College London, London, and Vall d'Hebron University Hospital, Barcelona. Samples were tested blindly. The Proclarix-MRI model combining prostate volume, Proclarix and mpMRI results was trained using the UCL cohort (n = 159) and validated in the Vall d'Hebron cohort (n = 562). Its diagnostic performance was established in correlation to biopsy outcome and compared to available clinical parameters and risk calculators. RESULTS: Clinical performance of the Proclarix-MRI model in the validation cohort did not significantly differ from the training cohort and resulted in a sensitivity for csPCa of 90%, 90% negative predictive value and 66% positive predictive value. The Proclarix-MRI score's specificity (68%) was significantly (P < 0.001) better than the MRI-European Randomized study of Screening for Prostate Cancer risk score (51%), Proclarix (27%) or mpMRI (28%) alone. In addition, Proclarix by itself was found to be useful in the MRI Prostate Imaging-Reporting and Data System (PI-RADS) score 3 subgroup by outperforming prostate-specific antigen density in terms of specificity (25% vs 13%, P = 0.004) at 100% sensitivity. CONCLUSION: When combined with mpMRI and prostate volume, Proclarix reliably predicted csPCa and ruled out men with no or indolent cancer. A large reduction of two thirds of unneeded biopsies was achieved. Proclarix can further be used with high confidence to reliably detect csPCa in men with an indeterminate PI-RADS score 3 mpMRI. Despite these encouraging results, further validation is needed.

The current recommendation for the management of isolated high-grade prostatic intraepithelial neoplasia.

OBJECTIVE: To analyse the current predictive value of isolated high-grade prostatic intraepithelial neoplasia (HGPIN) for clinically significant prostate cancer (csPCa) detection in repeat biopsies. PATIENTS AND METHODS: A cohort of 293 men with isolated HGPIN detected in previous biopsies performed without multiparametric magnetic resonance imaging (mpMRI), and who underwent repeat biopsy within 1 to 3 years, was analysed. Pre-repeat biopsy mpMRI and guided biopsies to suspicious lesions (Prostate Imaging - Reporting and Data System [PI-RADS] ≥3) and/or and systematic biopsies were performed. Persistent prostate cancer (PCa) suspicion, defined as sustained serum prostate-specific antigen level >4 ng/mL and/or abnormal digital rectal examination, was present in 248 men (84.6%), and was absent in 45 men (15.4%). A control group of 190 men who had no previous HGPIN, atypical small acinar proliferation or HGPIN with atypia who were scheduled to undergo repeat biopsy due to persistent PCa suspicion were also analysed. csPCa was defined as tumours of Grade Group ≥2. RESULTS: In the subset of 45 men with isolated HGPIN, in whom PCa suspicion disappeared, only one csPCa (2.2%) and one insignificant PCa (iPCa) were detected. csPCa was detected in 34.7% of men with persistent PCa suspicion and previous HGPIN, and in 28.4% of those without previous HGPIN (P =0.180). iPCa was detected in 12.1% and 6.3%, respectively (P =0.039). Logistic regression analysis showed that the risk of csPCa detection was not predicted by previous HGPIN: odds ratio (OR) 1.369 (95% confidence interval [CI] 0.894-2.095; P =0.149); however, previous HGPIN increased the risk of iPCa detection: OR 2.043 (95% CI 1.016-4.109; P =0.006). CONCLUSION: The risk of csPCa in men with isolated HGPIN, in whom PCa suspicion disappears, is extremely low. Moreover, in those men in whom PCa suspicion persists, the risk of csPCa is not influenced by the previous finding of HGPIN. However, previous HGPIN increases the risk of iPCa detection. Therefore, repeat prostate biopsy should not be recommended solely because of a previous HGPIN.

Accuracy of serum luteinizing hormone and serum testosterone measurements to assess the efficacy of medical castration in prostate cancer patients.

BACKGROUND: Luteinizing hormone-releasing hormone (LH-RH) agonists are the standard for androgen deprivation therapy (ADT) in prostate cancer (PCa) patients. Current guidelines recommend serum testosterone measurement to assess the efficacy of ADT and to define castration resistance. However, serum testosterone does not reflect the exclusive effect of castration due to its extratesticular production. The aim of this study is to analyze if serum LH reflects better than serum testosterone the activity of LH-RH agonists. METHODS: Serum LH and serum testosterone were measured with chemiluminescent immunoassay (CLIA) in a cohort study of 1091 participants: 488 PCa patients "on LH-RH agonists", 303 "off LH-RH agonist" in whom LH-RH agonists were withdrawn, and 350 men with PCa suspicion "no LH-RH agonist" who never received LH-RH agonists. In a validation cohort of 147 PCa patients, 124 on "LH-RH agonists" and 19 "off LH-RH agonists", serum testosterone was also measured with liquid chromatography and tandem mass spectrometry (LC MSMS). RESULTS: The area under the curve (AUC) to distinguish patients "on versus off LH-RH agonists" was 0.997 for serum LH and 0.740 for serum testosterone, P < 0.001. The 97.5 percentile of serum LH in patients "on LH-RH agonists" was 0.97 U/L, been the most efficient threshold 1.1 U/L. The AUCs for serum LH, testosterone measured with CLIA and with LC MSMS, in the validation cohort, were respectively 1.000, 0.646 and 0.814, P < 0.001. The efficacy to distinguish patients "on versus off LH-RH agonists" was 98.6%, 78.3%, and 89.5% respectively, using 1.1 U/L as threshold for serum LH and 50 ng/dL for serum testosterone regardless the method. CONCLUSIONS: Serum LH is more accurate than serum testosterone regardless the method, to distinguish patients "on versus off LH-RH agonists". The castrate level of serum LH is 1.1 U/l. These findings suggest that assessment of LH-RH agonist efficacy and castration resistance definition should be reviewed.

Role of serum cholesterol and statin use in the risk of prostate cancer detection and tumor aggressiveness.

The aim of this study was to analyze the relationship between statin use along with serum cholesterol levels and prostate cancer (PCa) detection and aggressiveness. Statin users of three years or more and serum cholesterol levels (SC) were assessed in 2408 men scheduled for prostate biopsy. SC was classified as normal (NSC: <200 mg/dL) or high (HSC: >200 mg/dL). High-grade PCa (HGPCa) was considered if the Gleason score was greater than 7. Statin users comprised 30.9% of those studied. The PCa detection rate was 31.2% of men on statins and 37% of non-statin users (p<0.006). The PCa detection rate was 26.3% in men with NSC and 40.6% in those with HSC (p<0.001). In the subset of NSC men, the PCa rate was 26.5% for statin users and 26.2% for non-users (p=0.939), while in men with HSC, the PCa rate was 36.4% for statin users and 42.0% for non-statin users (p=0.063). The HGPCa rate was 41.8% for statin users and 32.5% for non-users (p=0.012). NSC men had a 53.8% rate of HGPCa, while the rate was only 27.6% in HSC men (p<0.001). NSC men on statins had an HGPCa rate of 70.2%, while non-statin users had a rate of 41.2% (p<0.001). The HGPCa rate for HSC men on statins was 18.8%, while the rate was 30.0% (p=0.011) for non-users. Logistic regression analysis suggested that serum cholesterol levels could serve as an independent predictor of PCa risk, OR 1.87 (95% CI 1.56-2.24) and HGPCa risk, OR 0.31 (95% CI 0.23-0.44), while statin usage could not. Statin treatment may prevent PCa detection through serum cholesterol-mediated mechanisms. A disturbing increase in the HGPCa rate was observed in statin users who normalized their serum cholesterol.

Reducing the demand for magnetic resonance imaging scans and prostate biopsies during the early detection of clinically significant prostate cancer: Applying the Barcelona risk-stratified pathway in Catalonia.

PURPOSE: To analyze the reduction in multiparametric magnetic resonance imaging (mpMRI) demand and prostate biopsies after the hypothetical implementation of the Barcelona risk-stratified pathway (BCN-RSP) in a population of the clinically significant prostate cancer (csCaP) early detection program in Catalonia. MATERIALS AND METHODS: A retrospective comparation between the hypothetical application of the BCN-RSP and the current pathway, which relied on pre-biopsy mpMRI and targeted and/or systematic biopsies, was conducted. The BCN-RSP stratify men with suspected CaP based on a prostate specific antigen (PSA) level >10 ng/ml and a suspicious rectal examination (DRE), and the Barcelona-risk calculator 1 (BCN-RC1) to avoid mpMRI scans. Subsequently, candidates for prostate biopsy following mpMRI are selected based on the BCN-RC2. This comparison involved 3,557 men with serum PSA levels > 3.0 ng/ml and/or suspicious DRE. The population was recruited prospectively in 10 centers from January 2021 and December 2022. CsCaP was defined when grade group ≥ 2. RESULTS: CsCaP was detected in 1,249 men (35.1%) and insignificant CaP was overdeteced in 498 (14%). The BCN-RSP would have avoid 705 mpMRI scans (19.8%), and 697 prostate biopsies (19.6%), while 61 csCaP (4.9%) would have been undetected. The overdetection of insignificant CaP would have decrease in 130 cases (26.1%), and the performance of prostate biopsy for csCaP detection would have increase to 41.5%. CONCLUSION: The application of the BCN-RSP would reduce the demand for mpMRI scans and prostate biopsies by one fifth while less than 5% of csCaP would remain undetected. The overdetection of insignificant CaP would decrease by more than one quarter and the performance of prostate biopsy for csCaP detection would increase to higher than 40%.

Metabolic syndrome increases the risk of aggressive prostate cancer detection.

UNLABELLED: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Metabolic syndrome can identify patients at high risk of cardiovascular disease. The prevalence of metabolic syndrome is increasing worldwide and is associated with increased age, obesity and hypogonadism. The association between metabolic syndrome and prostate cancer development has not been studied comprehensively, and published studies report divergent results. This study indicates that tumours detected in men with metabolic syndrome are more aggressive than those detected in men without this condition. OBJECTIVE: To further examine the association between metabolic syndrome (MS), prostate cancer (PC) detection risk and tumour aggressiveness. PATIENTS AND METHODS: From 2006 to 2010, 2408 men not receiving 5α-reductase inhibitors were scheduled for prostatic biopsy due to PSA above 4 ng/mL and/or abnormal digital rectal examination. MS was evaluated according to the National Cholesterol Education Program Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults, Adult Treatment Panel III definition. Tumour aggressiveness was evaluated through biopsy Gleason score, clinical stage and risk of biochemical recurrence after primary treatment. RESULTS: The rates of PC detection were 34.5% and 36.4% respectively in men with and without MS, P = 0.185. High grade PC rates (Gleason score 8-10) were 35.9% and 23.9% respectively, P < 0.001. The advanced disease rates (cT3-4 N0-1 M0-1) were 17% and 12.7% respectively, P = 0.841. The high risk PC rates (cT2c-4 or Gleason score 8-10 or PSA > 20) were 38.5% and 33.0% respectively, P = 0.581. Multivariate analysis confirmed that MS was not associated with the risk of PC detection but it was associated with an increased risk of high grade tumours (odds ratio 1.75, 95% CI 1.26-2.41), P < 0.001. CONCLUSION: MS seems not be associated with an increased risk of PC detection but it is associated with an increased risk of more aggressive tumours.

Are magnetic resonance imaging and targeted biopsies needed in men with serum prostate-specific antigen over 10 ng/ml and an abnormal digital rectal examination?

The European Association of Urology currently recommends the use of risk-organized models to decrease the demand of prebiopsy magnetic resonance imaging (MRI) and unnecessary prostate biopsies in men with suspected prostate cancer (CaP). Low evidence suggests that men with prostate-specific antigen >10 ng/ml and an abnormal digital rectal examination (DRE) do not benefit from prebiopsy MRI and targeted biopsies. We aim to validate this low evidence in a sizable cohort and knowing how many clinically significant CaP (csCaP) would go undetected if only random biopsies were performed in these cases. We analyze a subset of 545 men with PSA >10 ng/ml and an abnormal DRE who met the previous criteria among 5,329 participants in a prospective trial in whom random biopsy was always performed and targeted biopsies of PI-RADS ≥3 lesions (10.2%). CsCaP (grade group ≥2) was detected in 370 men (67.9%), with 11 of 49 with negative MRI (22.5%) and 359 of 496 (72.4%) having PI-RADS ≥3. CsCaP was identified in random and targeted biopsies in 317 (88.7%) men, in targeted biopsies only in 23 (6.4%), and in random biopsies only in 19 (5.3%). If only random biopsies were performed in these men, 23 of overall 1,914 csCaP (1.2%) would go undetected in this population. Prebiopsy MRI can be saved in men with serum PSA >10 ng/ml and an abnormal DRE and only random biopsy performed. However, a close follow-up of men with negative random biopsy seems appropriate due to the high-risk of csCaP in these men.

A Diagnostic Accuracy Study of Targeted and Systematic Biopsies to Detect Clinically Significant Prostate Cancer, including a Model for the Partial Omission of Systematic Biopsies.

The primary objective of this study was to analyse the current accuracy of targeted and systematic prostate biopsies in detecting csPCa. A secondary objective was to determine whether there are factors predicting the finding of csPCa in targeted biopsies and, if so, to explore the utility of a predictive model for csPCa detection only in targeted biopsies. We analysed 2122 men with suspected PCa, serum PSA > 3 ng/mL, and/or a suspicious digital rectal examination (DRE), who underwent targeted and systematic biopsies between 2021 and 2022. CsPCa (grade group 2 or higher) was detected in 1026 men (48.4%). Discrepancies in csPCa detection in targeted and systematic biopsies were observed in 49.6%, with 13.9% of csPCa cases being detected only in systematic biopsies and 35.7% only in targeted biopsies. A predictive model for csPCa detection only in targeted biopsies was developed from the independent predictors age (years), prostate volume (mL), PI-RADS score (3 to 5), mpMRI Tesla (1.5 vs. 3.0), TRUS-MRI fusion image technique (cognitive vs. software), and prostate biopsy route (transrectal vs. transperineal). The csPCa discrimination ability of targeted biopsies showed an AUC of 0.741 (95% CI 0.721-0.762). The avoidance rate of systematic prostate biopsies went from 0.5% without missing csPCa to 18.3% missing 4.6% of csPCa cases. We conclude that the csPCa diagnostic accuracy of targeted biopsies is higher than that of systematic biopsies. However, a significant rate of csPCa remains detected only in systematic biopsies. A predictive model for the partial omission of systematic biopsies was developed.

A Randomised Controlled Trial to Assess the Benefit of Posterior Rhabdosphincter Reconstruction in Early Urinary Continence Recovery after Robot-assisted Radical Prostatectomy.

Posterior rhabdosphincter reconstruction (PRR) has been proposed to improve early urinary continence (UC) recovery after radical prostatectomy (RP). In order to generate level 1b evidence, we designed a double-blind randomised controlled trial powered to detect a 20% increase in early UC recovery after robot-assisted RP (RARP). A group of 153 patients with cT1c-3a N0M0 prostate cancer were randomised (73 to control arm and 80 to PRR arm) and 152 completed 12-mo follow-up. For UC defined as no pad use, the recovery hazard ratio at 1-mo follow-up was 2.312 (95% confidence interval [CI] 1.081-4.937; p = 0.030). UC recovery was observed in 33.8% of patients in the PRR arm and 18.1% of patients in the control arm (p = 0.022). At 3-mo follow-up the corresponding rates were 58.8% and 43.1% (p = 0.038). The median time to UC recovery was 106 d (95% CI 73-139) in the control arm and 64 d (95% CI 39-89) in PRR arm (p = 0.897). No differences in pathological outcomes or early and late surgical complications were observed between the arms. We conclude that PRR is safe and increases early UC recovery after RARP. PATIENT SUMMARY: We investigated reconstruction of a muscular ring that controls the flow of urine, called the rhabdosphincter, after removal of the prostate in robot-assisted surgery. The procedure is safe and increases early recovery of urinary continence. This trial is registered at ClinicalTrials.gov as NCT03302169.

Comparative Analysis of PSA Density and an MRI-Based Predictive Model to Improve the Selection of Candidates for Prostate Biopsy.

This study is a head-to-head comparison between mPSAD and MRI-PMbdex. The MRI-PMbdex was created from 2432 men with suspected PCa; this cohort comprised the development and external validation cohorts of the Barcelona MRI predictive model. Pre-biopsy 3-Tesla multiparametric MRI (mpMRI) and 2 to 4-core transrectal ultrasound (TRUS)-guided biopsies for suspicious lesions and/or 12-core TRUS systematic biopsies were scheduled. Clinically significant PCa (csPCa), defined as Gleason-based Grade Group 2 or higher, was detected in 934 men (38.4%). The area under the curve was 0.893 (95% confidence interval [CI]: 0.880−0.906) for MRI-PMbdex and 0.764 (95% CI: 0.774−0.783) for mPSAD, with p < 0.001. MRI-PMbdex showed net benefit over biopsy in all men when the probability of csPCa was greater than 2%, while mPSAD did the same when the probability of csPCa was greater than 18%. Thresholds of 13.5% for MRI-PMbdex and 0.628 ng/mL2 for mPSAD had 95% sensitivity for csPCa and presented 51.1% specificity for MRI-PMbdex and 19.6% specificity for mPSAD, with p < 0.001. MRI-PMbdex exhibited net benefit over mPSAD in men with prostate imaging report and data system (PI-RADS) <4, while neither exhibited any benefit in men with PI-RADS 5. Hence, we can conclude that MRI-PMbdex is more accurate than mPSAD for the proper selection of candidates for prostate biopsy among men with suspected PCa, with the exception of men with a PI-RAD S 5 score, for whom neither tool exhibited clinical guidance to determine the need for biopsy.

Who with suspected prostate cancer can benefit from Proclarix after multiparametric magnetic resonance imaging?

Proclarix is a new blood-based test to assess the likelihood of clinically significant prostate cancer (csPCa) defined as >2 grade group. In this study, we analyzed whether Proclarix and PSA density (PSAD) could improve the selection of candidates for prostate biopsy after multiparametric magnetic resonance imaging (mpMRI). Proclarix and PSAD were assessed in 567 consecutive men with suspected PCa in whom pre-biopsy 3 Tesla mpMRI, scoring with Prostate Imaging-Report and Data System (PI-RADS) v.2, and guided and/or systematic biopsies were performed. Proclarix and PSAD thresholds having csPCa sensitivity over 90% were found at 10% and 0.07 ng/(mL*cm3), respectively. Among 100 men with negative mpMRI (PI-RADS <3), csPCa was detected in 6 cases, which would have been undetected if systematic biopsies were avoided. However, Proclarix suggested performing a biopsy on 70% of men with negative mpMRI. In contrast, PSAD only detected 50% of csPCa and required 71% of prostate biopsies. In 169 men with PI-RADS 3, Proclarix avoided 21.3% of prostate biopsies and detected all 25 cases of csPCa, while PSAD avoided 26.3% of biopsies, but missed 16% of csPCa. In 190 men with PI-RADS 4 and 108 with PI-RADS 5, Proclarix avoided 12.1% and 5.6% of prostate biopsies, but missed 4.8% and 1% of csPCa, respectively. PSAD avoided 18.4% and 9.3% of biopsies, but missed 11.4% and 4.2% csPCa, respectively. We conclude that Proclarix outperformed PSAD in the selection of candidates for prostate biopsy, especially in men with PI-RADS <3.

Improving the Early Detection of Clinically Significant Prostate Cancer in Men in the Challenging Prostate Imaging-Reporting and Data System 3 Category.

BACKGROUND: Prostate Imaging-Reporting and Data System (PI-RADS) category 3 is a challenging scenario for detection of clinically significant prostate cancer (csPCa) and some tools can improve the selection of appropriate candidates for prostate biopsy. OBJECTIVE: To assess the performance of the European Randomized Study of Screening for Prostate Cancer (ERSPC) magnetic resonance imaging (MRI) model, the new Proclarix test, and prostate-specific antigen density (PSAD) in selecting candidates for prostate biopsy among men in the PI-RADS 3 category. DESIGN SETTING AND PARTICIPANTS: We conducted a head-to-head prospective analysis of 567 men suspected of having PCa for whom guided and systematic biopsies were scheduled between January 2018 and March 2020 in a single academic institution. A PI-RADS v.2 category 3 lesion was identified in 169 men (29.8%). OUTCOME MEASUREMENT AND STATISTICAL ANALYSIS: csPCa, insignificant PCa (iPCa), and unnecessary biopsy rates were analysed. csPCa was defined as grade group ≥2. Receiver operating characteristic (ROC) curves, decision curve analysis curves, and clinical utility curves were plotted. RESULTS AND LIMITATIONS: PCa was detected in 53/169 men (31.4%) with a PI-RADS 3 lesion, identified as csPCa in 25 (14.8%) and iPCa in 28 (16.6%). The area under the ROC curve for csPCa detection was 0.703 (95% confidence interval [CI] 0.621-0.768) for Proclarix, 0.657 (95% CI 0.547-0.766) for the ERSPC MRI model, and 0.612 (95% CI 0.497-0.727) for PSAD (p = 0.027). The threshold with the highest sensitivity was 10% for Proclarix, 1.5% for the ERSPC MRI model, and 0.07 ng/ml/cm3 for PSAD, which yielded sensitivity of 100%, 91%, and 84%, respectively. Some 21.3%, 26.2%, and 7.1% of biopsies would be avoided with Proclarix, PSAD, and the ERSPC MRI model, respectively. Proclarix showed a net benefit over PSAD and the ERSPC MRI model. Both Proclarix and PSAD reduced iPCa overdetection from 16.6% to 11.3%, while the ERSPC MRI model reduced iPCa overdetection to 15.4%. CONCLUSIONS: Proclarix was more accurate in selecting appropriate candidates for prostate biopsy among men in the PI-RADS 3 category when compared to PSAD and the ERSPC MRI model. Proclarix detected 100% of csPCa cases and would reduce prostate biopsies by 21.3% and iPCa overdetection by 5.3%. PATIENT SUMMARY: We compared three methods and found that the Proclarix test can optimise the detection of clinically significant prostate cancer in men with a score of 3 on the Prostate Imaging-Reporting and Data System for magnetic resonance imaging scans.

The Efficacy of Proclarix to Select Appropriate Candidates for Magnetic Resonance Imaging and Derived Prostate Biopsies in Men with Suspected Prostate Cancer.

PURPOSE: To analyze how Proclarix is valuable to appropriately select candidates for multiparametric magnetic resonance imaging (mpMRI) and derived biopsies, among men with suspected prostate cancer (PCa). Proclarix is a new marker computing the clinically significant PCa (csPCa) risk, based on serum thosmbospondin-1, cathepsin D, prostate-specific antigen (PSA) and percent free PSA, in addition to age, that has been developed in men with serum PSA 2 to 10 ng/mL, prostate volume ≥35 mL, and normal digital rectal examination (DRE). MATERIALS AND METHODS: Proclarix score (0%-100%) is analyzed in a prospective frozen serum collection of 517 correlative men scheduled for guided and/or systematic biopsies after mpMRI. Outcome variables were csPCa detection (grade group ≥2), insignificant PCa (iPCa) overdetection and avoided mpMRIs. RESULTS: The area under the curve of Proclarix was 0.701 (95% CI 0.637-0.765) among 281 men with serum PSA 2 to 10 ng/mL, prostate volume ≥35 mL, and -normal DRE, and 0.754 (95% CI 0.701-0.807) in the others, p=0.038. Net benefit of Proclarix existed in all men. After selecting 10% threshold, Proclarix was integrated in an algorithm which also used the serum PSA level and DRE. A reduction of 25.4% of mpMRIs request was observed and 17.7% of prostate biopsies. Overdetection of iPCa was reduced in 18.2% and 2.6% of csPCa were misdiagnosed. CONCLUSIONS: Proclarix is valuable in all men with suspected PCa. An algorithm integrating Proclarix score, serum PSA, and DRE can avoid mpMRI requests, unnecessary prostate biopsies and iPCa overdetection, with minimal loss of csPCa detection.

Multiparametric Magnetic Resonance Imaging Grades the Aggressiveness of Prostate Cancer.

We sought to find further evidence showing the increase in PCa aggressiveness as PI-RADS score increases from four surrogates of PCa aggressiveness: i. prostate biopsy GG (≤3 vs. >3), ii. type of pathology in surgical specimens (favourable vs. unfavourable), iii. clinical stage (localised vs. advanced), and risk of recurrence of localised PCa after primary treatment (low-intermediate vs. high). A group of 692 PCa patients were diagnosed after 3-T multiparametric MRI (mpMRI) and guided and/or systematic biopsies, showing csPCa (GG ≥ 2) in 547 patients (79%) and insignificant PCa (iPCa) in 145 (21%). The csPCa rate increased from 32.4% in PI-RADS < 3 to 95.5% in PI-RADS 5 (p < 0.001). GG ≥ 3 was observed in 7.6% of PCa with PI-RADS < 3 and 32.6% in those with PI-RADS > 3 (p < 0.001). Unfavourable pathology was observed in 38.9% of PCa with PI-RAD < 3 and 68.3% in those with PI-RADS > 3 (p = 0.030). Advanced disease was not observed in PCa with PI-RADS ≤ 3, while it existed in 12.7% of those with PI-RADS > 3 (p < 0.001). High-risk recurrence localised PCa was observed in 9.5% of PCa with PI-RADS < 3 and 35% in those with PI-RADS > 3 (p = 0.001). The PI-RADS score was an independent predictor of all surrogates of PCa aggressiveness as PSA density. We confirmed that mpMRI grades PCa aggressiveness.

A Clinically Significant Prostate Cancer Predictive Model Using Digital Rectal Examination Prostate Volume Category to Stratify Initial Prostate Cancer Suspicion and Reduce Magnetic Resonance Imaging Demand.

A predictive model including age, PCa family history, biopsy status (initial vs repeat), DRE (normal vs abnormal), serum prostate-specific antigen (PSA), and DRE prostate volume ca-tegory was developed to stratify initial PCa suspicion in 1486 men with PSA > 3 ng/mL and/or abnormal DRE, in whom mpMRI followed; 2- to 4-core TRUS-guided biopsies where Prostate Imaging Report and Data System (PI-RADS) > 3 lesions and/or 12-core TRUS systematic biopsies were performed in one academic institution between 1 January 2016−31 December 2019. The csPCa detection rate, defined as International Society of Uro-Pathology grade group 2 or higher, was 36.9%. An external validation of designed BCN-RC 1 was carried out on 946 men from two other institutions in the same metropolitan area, using the same criteria of PCa suspicion and diagnostic approach, yielded a csPCa detection rate of 40.8%. The areas under the receiver operating characteristic curves of BCN-RC 1 were 0.823 (95% CI: 0.800−0.846) in the development cohort and 0.837 (95% CI: 0.811−0.863) in the validation cohort (p = 0.447). In both cohorts, BCN-RC 1 exhibited net benefit over performing mpMRI in all men from 8 and 12% risk thresholds, respectively. At 0.95 sensitivity of csPCa, the specificities of BCN-RC 1 were 0.24 (95% CI: 0.22−0.26) in the development cohort and 0.34 (95% CI: 0.31−0.37) in the validation cohort (p < 0.001). The percentages of avoided mpMRI scans were 17.2% in the development cohort and 22.3% in the validation cohort, missing between 1.8% and 2% of csPCa among men at risk of PCa. In summary, BCN-RC 1 can stratify initial PCa suspicion, reducing the demand of mpMRI, with an acceptable loss of csPCa.

The Barcelona Predictive Model of Clinically Significant Prostate Cancer.

A new and externally validated MRI-PM for csPCa was developed in the metropolitan area of Barcelona, and a web-RC designed with the new option of selecting the csPCa probability threshold. The development cohort comprised 1486 men scheduled to undergo a 3-tesla multiparametric MRI (mpMRI) and guided and/or systematic biopsies in one academic institution of Barcelona. The external validation cohort comprised 946 men in whom the same diagnostic approach was carried out as in the development cohort, in two other academic institutions of the same metropolitan area. CsPCa was detected in 36.9% of men in the development cohort and 40.8% in the external validation cohort (p = 0.054). The area under the curve of mpMRI increased from 0.842 to 0.897 in the developed MRI-PM (p < 0.001), and from 0.743 to 0.858 in the external validation cohort (p < 0.001). A selected 15% threshold avoided 40.1% of prostate biopsies and missed 5.4% of the 36.9% csPCa detected in the development cohort. In men with PI-RADS <3, 4.3% would be biopsied and 32.3% of all existing 4.2% of csPCa would be detected. In men with PI-RADS 3, 62% of prostate biopsies would be avoided and 28% of all existing 12.4% of csPCa would be undetected. In men with PI-RADS 4, 4% of prostate biopsies would be avoided and 0.6% of all existing 43.1% of csPCa would be undetected. In men with PI-RADS 5, 0.6% of prostate biopsies would be avoided and none of the existing 42.0% of csPCa would be undetected. The Barcelona MRI-PM presented good performance on the overall population; however, its clinical usefulness varied regarding the PI-RADS category. The selection of csPCa probability thresholds in the designed RC may facilitate external validation and outperformance of MRI-PMs in specific PI-RADS categories.

Prediction of clinically significant prostate cancer after negative prostate biopsy: The current value of microscopic findings.

OBJECTIVE: To assess the current ability of atypical small acinar proliferation (ASAP), multifocal high-grade prostatic intraepithelial neoplasia (mHGPIN), HGPIN with atypia (PINATYP) and other non-malignant lesions to predict clinically significant prostate cancer (csPCa) in repeat prostate biopsies. METHODS: This retrospective study analyzed 377 repeat prostate biopsies, carried out between 2.014 and 2.017, and excluding those with previous PCa or 5-alpha reductase inhibitors treatment. ASAP, mHGPIN, PINATYP, prostatic atrophy, prostatic hyperplastic atrophy, proliferative inflammatory atrophy (PIA), chronic prostatitis, acute prostatitis, or granulomatous prostatitis, were prospectively reported after 12-core transrectal ultrasound (TRUS) systematic negative previous biopsies. 3T-multiparametric magnetic resonance imaging (mpMRI) was performed previous repeat biopsies. At least 2-core TRUS targeted biopsies of Prostate Imaging-Reporting and Data Systemv2 lesions ≥3, and/or 12-core TRUS systematic biopsy were performed in repeat prostate biopsies. The main outcome measurements were csPCa detection, which was defined when the International Society of Uro-Pathology group grade >1 and avoided biopsies. After logistic regression analysis the most efficient model was selected, nomogram was designed with internal validation, and clinical utility was analyzed. RESULTS: Normal benign tissue alone was present in less than 2% of previous negative biopsies. mHGPIN (39.7%), ASAP (4.3%) and PINATYP (3.7%) failed to predict csPCa risk in repeat biopsies. The finding of PIA (38.2%) associated with a decreased the risk of csPCa with an Odd ratio of 0.54 (95% confidence interval: 0.31-0.95), P= 0.031. The area under the curve, to predict csPCa, of mpMRI was 0.736, increasing up to 0.860 (95% confidence internal:0.82-0.90) when PSA density, age, digital rectal examination, and differential PSA between biopsies and PIA finding were integrated in a predictive model. At 6% threshold, more than 20% of repeat prostate biopsies were saved without missing csPCa. CONCLUSION: Currently, mHGPIN in negative prostate biopsy seems not able to predict the risk of future csPCa. The low incidence of ASAP and PINATYP, in our series, did not allow us to draw conclusions. PIA finding associated with a reduced risk of csPCa, and it could be integrated in a useful based-mpMRI predictive nomogram.

Prostatic-specific antigen density behavior according to multiparametric magnetic resonance imaging result.

OBJECTIVE: To analyze prostatic-specific antigen density (PSAD) according to the Prostate Imaging Reporting and Data System (PIRADSv.2) score, in order to determine how it should be used. METHODS: This correlative series considered 952 men with prostatic-specific antigen >3 ng/ml and/or abnormal digital rectal examination who were subjected to prostatic biopsy (PB) between 2016 and 2017. Of these men, 768 had no previous 5-α-reductase inhibitor use or history of prostate cancer (CaP) and had previously undergone 3-T multiparametric magnetic resonance imaging (mpMRI). In this sample, 549 men were biopsy-naïve and 219 had at least 1 previous negative PB. A 12-core transrectal ultrasound-guided PB was performed in all participants, as well as at least 2-core targeted biopsies of every detected lesion with a PIRADSv.2 score ≥3. Significant CaP (sCaP) was defined as an International Society of Uropathologist grade >1 or tumor length >4 mm. RESULTS: The overall CaP detection was 41.7%, with sCaP detected in 37.4%. sCaP was detected in 4.3% of PIRADSv.2 <3, 21.5% of PIRADSv.2 =3, 56.6% of PIRADSv.2 =4, and 78.5% of PIRADSv.2 =5, (P < 0.001). Insignificant CaP detection ranged from 6.5% to 1.5% respectively (P = 0.099). PSAD was an independent predictor of sCaP (odds ratios 1.971, 95% confidence interval [1.633, 2.378], P <0.001) and mpMRI (OR 3.179, 95%CI [2.593, 4.950], P < 0.001). Age (P = 0.013), family history of CaP (P = 0.021), and the type of PB (initial vs. repeated, P < 0.001) were also independent predictors of sCaP. PSAD was determined by PIRADSv.2 (P = 0.013) and the presence of sCaP (P < 0.001). PSAD increased with PIRADSv.2 score, even in men with CaP (P < 0.001) and slightly in men without CaP (P = 0.019). The area under the curve for mpMRI increased from 0.830 to 0.869 when PSAD was associated, (P < 0.001). The area under the curve of PSAD decreased from 0.727 in men with a PIRADSv.2 score <3 to 0.706 in those with a score of 5. CONCLUSIONS: The efficacy of PSAD to detect sCaP decreases with PIRADSv.2. Predictors other than mpMRI and PSAD exist. Considering these conditions, independent predictors should be integrated in a nomogram and risk-calculator to personalize PB recommendation.

Who Benefits from Multiparametric Magnetic Resonance Imaging After Suspicion of Prostate Cancer?

BACKGROUND: Prostate cancer (PC) suspicion is based on prostate-specific antigen (PSA) and digital rectal examination (DRE). Multiparametric magnetic resonance imaging (mpMRI) increases prostate biopsy (PBx) specificity and sensitivity for detection of aggressive PC. OBJECTIVE: To identify who benefits from mpMRI according to biopsy scenario (initial biopsy [IBx] vs repeated biopsy [RBx]) and the risk of aggressive PC according to PSA-DRE groups (G1, PSA <10ng/ml and -DRE; G2, PSA <10ng/ml and +DRE; G3, PSA ≥10ng/ml and -DRE; G4, PSA ≥10ng/ml and +DRE). DESIGN, SETTING, AND PARTICIPANTS: We carried out a retrospective analysis for 768 consecutive men with PC suspicion and scheduled for PBx in a referral institution in 2016 and 2017. INTERVENTION: Pelvic 3-T mpMRI scanning, targeted biopsy (TBx) for suspicious lesions (Prostate Imaging-Reporting and Data System [PI-RADS] score >1), and 12-core systematic biopsy (SBx). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We measured the rate of PBx procedures that could be avoided and the rate of high-grade PC (HGPC) that would be missed among men with negative mpMRI, and the increase in HGPC detection due to TBx. Univariate and multivariate analyses were performed. RESULTS AND LIMITATIONS: The rate of avoidable biopsies (PI-RADS <3) was 24.2% overall, with 25.7% for IBx and 20.5% for RBx (p=0.057). The IBx and RBx rates were 31.2% and 19.8% in G1, 13.5% and 30.4% in G2, 23.7% and 21.9% in G3, and 2.5% and 0% in G4, respectively. The overall rate of missed HGPC was 1.0% for IBx and 6.5% for RBx (p=0.170), while the IBx and RBx rates were 1.1% and 5.2% for G1, 2.0% and 11.1% for G2, 0% and 7.7% for G3, and 0% and 0% for G4, respectively (p<0.001). The rate of HGPC (PI-RADS 3-5) diagnosed following TBx increased to 23.9% for IBx and to 32.6% for RBx overall (p<0.001), while the IBx and RBx rates were 29.0% and 45.5% for G1, 20.0% and 33.3% for G2, 40.0% and 38.9% for G3, and 0% and 0% for G4, respectively (p<0.001). Limitations are the single-institution design, the lack of randomisation, and small samples for subgroup analyses. CONCLUSIONS: mpMRI was of no benefit for men with PSA ≥10ng/ml and +DRE. Among the other men, mpMRI was of benefit in IBx and RBx as would reduce the biopsy rate by up to 25.7% and increase the net HGPC detection rate by up to 28.4%. PATIENT SUMMARY: All men with suspected prostate cancer could benefit from multiparametric prostate cancer and targeted biopsy except for those with prostate-specific antigen ≥10ng/ml and positive digital rectal examination. The benefits include avoiding unnecessary prostate biopsy procedures and increasing the detection of aggressive cancer.