Overtreatment Of Prostate Cancer Research Articles

Modern biomarkers in prostate cancer diagnosis

IntroductionThe most common malignant neoplasm of the urinary tract is prostate cancer (PCa), which is a heterogeneous disease, ranging from very slowly developing and slightly benign to progressing, aggressive, metastatic and fatal, even when properly treated. Existing, imperfect diagnostic methods often lead to over-diagnosis and over-treatment of PCa. That is why new, better PCa biomarkers are being developed.Material and methodsThis review summarizes the current results of the most promising and clinically used PCa biomarkers, as well as having the potential to create new diagnostic and prognostic tools, based on the Web of Science (www.apps.webofknowledge.com) and Scopus (www.scopus) databases. com).ResultsLimited specificity of the prostate-specific antigen (PSA) test brings a need to develop new and better diagnostic tools. In the last few years, new approaches for providing significantly better biomarkers, an alternative to PSA, have been introduced. Modern biomarkers show improvement in being used as not only a diagnostic procedure, but also for staging, evaluating aggressiveness and managing the therapeutic process. We describe the methods recommended in the diagnosis of PCa and new PCa molecular diagnostics technologies. Individual biomarkers are used in various stages of the PCa diagnostic process, which was presented on the developed diagnostic flowchart describing the role of biomarkers in prostate cancer management.ConclusionsGiven the diverse nature of PCa, one diagnostic test will not answer all questions, so the use of several diagnostic methods will allow physicians to provide patients with better, personalized clinical advice.

PCASTt/SPCG-17—a randomised trial of active surveillance in prostate cancer: rationale and design

IntroductionOvertreatment of localised prostate cancer is substantial despite increased use of active surveillance. No randomised trials help define how to monitor patients or when to initiate treatment with curative intent.Methods...

MP18-12 OPTIMAL BIOPSY STRATEGY FOR PROSTATE CANCER DETECTION BY PERFORMING A BAYESIAN NETWORK META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS

INTRODUCTION AND OBJECTIVES:With the increasing recognition of the over-diagnosis and over-treatment of prostate cancer (PCa), the choice of a better prostate biopsy strategy had confused both the ...

GATA2 exosomal mRNA: A novel urine biomarker for the diagnosis of clinically significant prostate cancer.

18 Background: Prostate specific antigen (PSA) detection in blood is widely used to screen for prostate cancer (PCa). However, PSA has limited utility in discriminating tumors at high risk of progression from indolent-low risk tumors, which leads to PCa overtreatment and highlights the need to identify better biomarkers for the detection of clinically significant PCa (Gleason Score; GS ≥ 7). Here, we introduce a novel mRNA GATA2 exosomal biomarker detected in urine useful to diagnose clinically significant PCa. Exosomes are 50-120 nm sized vesicles shed in body fluids that contain RNA, DNA, and protein that can be used as biomarkers to interrogate the health of the originating cells. GATA2 is a pioneer transcription factor specific to PCa, increased in aggressive tumors. Methods: To evaluate the predictive value of exosomal GATA2 mRNA levels for aggressive PCa, we isolated exosomes using ultracentrifugation in non-DRE urines from 128 males with elevated PSA serum levels (> 4ng/ml) and analyzed them according to their tissue biopsy result. Results: Importantly, prostate origin of GATA2 mRNA detected in urine exosomes was confirmed by observing that exosomal GATA2 mRNA levels significantly dropped after prostatectomy (p < 0.05). Most remarkably, GATA2 exosomal mRNA expression was significantly increased in PCa biopsy positive patients (n=88) when compared to biopsy negative males (n=28, p < 0.001). Furthermore, GATA2 levels in PCa patients were significantly associated with GS, but not with disease stage and PSA levels. Multivariable regression analysis showed that GATA2 exosomal mRNA levels are an independent factor for the diagnosis of aggressive PCa. Urine GATA2 exosome mRNA expression plus SOC (age and PSA) was associated with improved discrimination of GS ≥ 7 versus GS 6 and benign disease: AUC of SOC alone 0.59 (0.49-0.70, p value=0.083) vs SOC plus GATA2 AUC of 0.68 (95% CI, 0.58-0.78, p value=0.0004). Conclusions: The analysis of urine exosomal GATA2 mRNA in individuals with high PSA may help distinguish clinically significant PCa and reduce the number of patients that need biopsy. Future studies are focused on combining this biomarker to others, such as urine exosomal PCA3, already used in the clinic.

Characterization of clinical human prostate cancer lesions using 3.0-T sodium MRI registered to Gleason-graded whole-mount histopathology.

Overtreatment of prostate cancer (PCa) is a healthcare issue. Development of noninvasive imaging tools for improved characterization of prostate lesions might reduce overtreatment. To measure the distribution of tissue sodium concentration (TSC), proton T2 -weighted signal, and apparent diffusion coefficient (ADC) values in human PCa and to test the presence of a correlation between regional differences in imaging metrics and the Gleason grade of lesions determined from histopathology. Cross-sectional. Ten men with biopsy-proven PCa. Sodium, proton T2 -weighted, and diffusion-weighted MRI data were acquired using Broad-Band 3D-Fast-Gradient-Recalled, 3D Cube (Isotropic 3D-Fast-Turbo-Spin-Echo acquisition) and 2D Spin-Echo sequences, respectively, with a 3.0T MR scanner. All imaging data were coregistered to Gleason-graded postprostatectomy histology, as the standard for prostate cancer lesion characterization. Regional TSC and T2 data were assessed using percent changes from healthy tissue of the same patient (denoted ΔTSC, ΔT2 ). Differences in ΔTSC, ADC, and ΔT2 as a function of Gleason score were analyzed for each imaging contrast using a one-way analysis of variance or a nonparametric t-test. Correlations between imaging data measures and Gleason score were assessed using a Spearman's ranked correlation. Evaluation of the correlation of ΔTSC, ADC, and ΔT2 datasets with Gleason scoring revealed that only the correlation between ΔTSC and Gleason score was statistically significant (rs = 0.791, p < 0.01), whereas the correlations of ADC and ΔT2 with Gleason score were not (rs = -0.306, p = 0.079 and r s = -0.069, p = 0.699, respectively). In addition, all individual patients showed monotonically increasing ΔTSC with Gleason score. The results of this preliminary study suggest that changes in TSC, assessed by sodium MRI, has utility as a noninvasive imaging assay to accurately characterize PCa lesions. Sodium MRI may provide useful complementary information on mpMRI, which may assist the decision-making of men choosing either active surveillance or treatment. 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:1409-1419.

Radical prostatectomy then and now: Surgical overtreatment of prostate cancer is declining from 2009 to 2016 at a tertiary referral center

BackgroundIn the era of increasing scrutiny of delivery of quality care, efforts to decrease surgical overtreatment of insignificant prostate cancer (iCaP) continue. ObjectiveTo quantify the incidence of surgical overtreatment over time among a contemporary series of men diagnosed with CaP. MethodsWe retrospectively reviewed the medical records and pathologic specimens for men with CaP who underwent radical prostatectomy between January 2009 and December 2016 at a tertiary referral center. Overtreatment, defined as presence of iCaP in radical prostatectomy specimens, was the primary endpoint. iCaP was defined as a tumor of Gleason score no more than 6 and a tumor diameter ≤10mm (volume <0.5 cc). Independent predictors of iCaP were determined using a multivariable model. ResultsA total of 1,283 men were eligible for analysis. Overtreatment was found in 86 (6.7%) patients. The frequency of overtreatment significantly decreased from 15% (24/165) in 2009 to 3% (4/134) of patients in 2016 (P < 0.001). In the multivariable analysis, prostate-specific antigen density ≥0.15 vs. <0.15 (odds ratio [OR] 0.30, 95% confidence interval [CI] 0.15–0.64, P < 0.01), biopsy Gleason score 3+4 vs. 3+3 (OR 0.15, 95% CI 0.08–0.29, P < 0.01), African American vs. White ethnicity (OR 0.13, 95% CI 0.02–0.96, P = 0.045), and year of surgery (OR 0.88, 95% CI 0.77–0.99, P = 0.03) remained significant predictors of iCaP at surgery. Over the years of study, the odds of overtreatment decreased by 12% annually (OR 0.88, 95 CI 0.77–0.99, P = 0.03). At the same time, the pathological evidence of advanced disease at surgery (≥T3a with/without lymph node involvement) remained unchanged. CommentSurgical overtreatment of CaP has declined to a rate of approximately 3% at this tertiary referral center; further decline is likely. The decline probably has a multifactorial explanation: decreased rate of overdiagnosis, better patient selection for surgery, or change in the referral pattern.

Reducing overtreatment of prostate cancer by radical prostatectomy in Eastern Ontario: a population-based cohort study.

Canadian guidelines recommend against population-based screening for prostate cancer because of the risk of overdiagnosis and overtreatment. We sought to assess whether a higher proportion of patients receiving surgery had clinically significant cancer over time. All hospitals in Eastern Ontario that perform prostatectomy participate in a Prostate Cancer Community of Practice, which prospectively maintains a database for the region. Using these data, we conducted a retrospective cohort study that included all patients who underwent prostatectomy from 2009 to 2015 in the region. We examined trends in biopsy findings, clinical stage, prostate-specific antigen level and Gleason score. We then determined whether the proportion of patients with clinically significant cancer (Gleason score ≥ 7 or stage pT3) increased over time. During the study period, 1897 patients underwent prostatectomy in Eastern Ontario (mean 271 surgeries/yr). The proportion of patients who were determined to have National Comprehensive Cancer Network intermediate or high-risk disease increased from 46.7% in 2009 to 90.2% in 2015. The proportion of men with clinically significant cancer on prostatectomy increased from 59.7% in 2009 to 93.1% in 2015. Adjusted analyses suggested that the proportion of patients with clinically significant cancer increased by 5% per year during the study period. There has been a change in the tumour characteristics of patients who undergo prostatectomy in Eastern Ontario. In recent years, almost all patients have had clinically significant cancer, which suggests that overtreatment of prostate cancer has decreased.

Optimal biopsy strategy for prostate cancer detection by performing a Bayesian network meta-analysis of randomized controlled trials.

Objective: With the increasing recognition of the over-diagnosis and over-treatment of prostate cancer (PCa), the choice of a better prostate biopsy strategy had confused both the patients and clinical surgeons. Hence, this network meta-analysis was conducted to clarify this question.Methods: In the current network meta-analysis, twenty eligible randomized controlled trials (RCTs) with 4,571 participants were comprehensively identified through Pubmed, Embase and Web of Science databases up to July 2017. The pooled odds ratio (OR) with 95% credible interval (CrI) was calculated by Markov chain Monte Carlo methods. A Bayesian network meta-analysis was conducted by using R-3.4.0 software with the help of package “gemtc” version 0.8.2.Results: Six different PCa biopsy strategies and four clinical outcomes were ultimately analyzed in this study. Although, the efficacy of different PCa biopsy strategies by ORs with corresponding 95% CrIs had not yet reached statistical differences, the cumulative rank probability indicated that overall PCa detection rate from best to worst was FUS-GB plus TRUS-GB, FUS-GB, CEUS, MRI-GB, TRUS-GB and TPUS-GB. In terms of clinically significant PCa detection, CEUS, FUS-GB or FUS-GB plus TRUS-GB had a higher, whereas TRUS-GB or TPUS-GB had a relatively lower significant detection rate. Meanwhile, TPUS-GB or TRUS-GB had a higher insignificant PCa detection rate. As for TRUS-guided biopsy, the general trend was that the more biopsy cores, the higher overall PCa detection rate. As for targeted biopsy, it could yield a comparable or even a better effect with fewer cores, compared with traditional random biopsy.Conclusion: Taken together, in a comprehensive consideration of four clinical outcomes, our outcomes shed light on that FUS-GB or FUS-GB plus TRUS-GB showed their superiority, compared with other puncture methods in the detection of PCa. Moreover, TPUS or TRUS-GB was more easily associated with the over-diagnosis and over-treatment of PCa. In addition, targeted biopsy was obviously more effective than traditional random biopsy. The subsequent RCTs with larger sample sizes were required to validate our findings.

Alterations in expressed prostate secretion-urine PSA N-glycosylation discriminate prostate cancer from benign prostate hyperplasia

The prostate specific antigen (PSA) test is widely used for early diagnosis of prostate cancer (PCa). However, its limited sensitivity has led to over-diagnosis and over-treatment of PCa. Glycosylation alteration is a common phenomenon in cancer development. Different PSA glycan subforms have been proposed as diagnostic markers to better differentiate PCa from benign prostate hyperplasia (BPH). In this study, we purified PSA from expressed prostate secretions (EPS)-urine samples from 32 BPH and 30 PCa patients and provided detailed PSA glycan profiles in Chinese population. We found that most of the PSA glycans from EPS-urine were complex type biantennary glycans. We observed two major patterns in PSA glycan profiles. Overall there was no distinct separation of PSA glycan profiles between BPH and PCa patients. However, we detected a significant increase of glycan FA2 and FM5A2G2S1 in PCa when compared with BPH patients. Furthermore, we observed that the composition of FA2 glycan increased significantly in advanced PCa with Gleason score ≥8, which potentially could be translated to clinic as a marker for aggressive PCa.

Autoantibodies against oncogenic ERG protein in prostate cancer: potential use in diagnosis and prognosis in a panel with C-MYC, AMACR and HERV-K Gag.

Overdiagnosis and overtreatment of prostate cancer (CaP) is attributable to widespread reliance on PSA screening in the US. This has prompted us and others to search for improved biomarkers for CaP, to facilitate early detection and disease stratification. In this regard, autoantibodies (AAbs) against tumor antigens could serve as potential candidates for diagnosis and prognosis of CaP. Towards this, our goals were: i) To investigate whether AAbs against ERG oncoprotein (overexpressed in 25-50% of Caucasian American and African American CaP) are present in the sera of CaP patients; ii) To evaluate an AAb panel to enhance CaP detection. The results using an enzyme-linked immunosorbent assay (ELISA) showed that anti-ERG AAbs are present in a significantly higher proportion in the sera of CaP patients compared to healthy controls (p = 0.0001). Furthermore, a panel of AAbs against ERG, AMACR and human endogenous retrovirus-K Gag successfully differentiated CaP patient sera from healthy controls (AUC = 0.791). These results demonstrate for the first time that anti-ERG AAbs are present in the sera of CaP patients. In addition, the data also suggest that AAbs against ERG together with AMACR and HERV-K Gag may be a useful panel of biomarkers for diagnosis and prognosis of CaP.

De klinische relevantie van cribriforme en intraductale prostaatkanker in diagnostische naaldbiopten

Cribriform and intraductal prostate cancer are both associated with an adverse outcome after radical prostatectomy. We included all patients with prostate cancer from the first screening round of the European Randomized Study of Screening for Prostate Cancer (ERSPC). All available slides were revised and scored for presence of cribriform and/or intraductal prostate cancer. Outcome measurements were biochemical recurrence and disease-specific survival. In total, 486 patients had Gleason score (GS) 6 (47%) and 545 GS ≥7 (53%). The disease-specific survival and biochemical-recurrence-free survival of CR/IDC−-GS3+4 patients did not differ significantly from those with GS 6, while patients with CR/IDC+-GS3+4-patients had a significant poorer outcome. Conclusion: The presence of cribriform and intraductal growth in prostate cancer, is a strong clinical prognostic marker with potential. The use of this variable in a clinical setting could contribute to reducing overtreatment of prostate cancer.

Establishment and Application of Prostate Cancer Circulating Tumor Cells in the Era of Precision Medicine.

Prostate cancer (PC) is the second most common cancer in men and is the fifth leading cause of cancer-related deaths worldwide. Additionally, there is concern for overdiagnosis and overtreatment of PC. Thus, selection of an appropriate candidate for active surveillance as well as more accurate and less invasive tools for monitoring advanced PC is required. Circulating tumor cells (CTCs) have emerged as a liquid biopsy tool; there have been several reports on its role, technologies, and applications to various cancers, including PC. Liquid biopsy using CTCs has been gaining attention as a minimal invasive tool for investigation of biomarkers and for prognosis and assessment of response to therapies in patients with PC. Because of the lower invasiveness of liquid biopsy using CTCs, it can be performed more frequently; accordingly, personalized disease status can be successively determined at serial time points. CTC analysis enables detection of genomic alterations, which is drug-targetable, and it is a potential tool for monitoring response to therapeutic agents in patients with PC. This review focuses on the characteristics, technologies for analysis, and advantages and disadvantages of CTCs as a liquid biopsy tool and their application in PC. Finally, we propose future directions of CTCs.

Improving Prostate Cancer Screening and Diagnosis: Health Policy and Biomarkers Beyond PSA.

The initial goal of prostate cancer screening with prostatespecific antigen (PSA) was to identify men with early-stage disease according to the general oncologic principle of secondary prevention that early diagnosis and treatment would prevent disease progressionand improve survival. However, 2 randomized clinical trials evaluating PSA screening and a large body of literature have identified unintended harms of overdiagnosis and overtreatment of potentially indolentprostatecancer.1,2TherevisedUSPreventiveServices Task Force grade D recommendation for PSA screening in 2012, stating that there is a lack of evidence that its benefits outweigh itsharms, further thrustprostate cancer screening into the spotlight of health policy in the United States.3 Recently, one of the intended consequences of the US Preventive ServicesTaskForce recommendationwas realized in that fewer men are being screened for and diagnosed with prostate cancer,withanestimated33000fewer incident cases in 2012 than in 2011.4 Although a uniform recommendation against screeningcan reduceoverdiagnosis andovertreatment of low-riskdisease, it also reduces theopportunity todiagnose higher-riskdisease, inwhich treatmenthas beenproven to reduce deaths from prostate cancer. Amore nuanced approach toPSAscreeningbasedona systematic reviewof the literature was proposed in 2013 by theAmericanUrological Association guideline for the earlydetectionof prostate cancer.5Although the review also investigated other serum and urine biomarkersofprostatecancer, suchasPSAisoforms, theProstateHealth Index, prostate cancer antigen 3 assay, and TMPRSS2-ERG fusion,6 the quality of the reviewed data was insufficient for determining their role in screening. In the current prospective cohort study reported in JAMA Oncology,McKiernanand colleagues7 demonstrate thepotential utility of a urine-based 3-gene exosome expression assay utilizing SAM pointed domain containing ETS transcription factor, ERG, and PCA3 (ExoDx Prostate IntelliScore, Exosome Diagnostics) to discriminate prostate cancer with a Gleason score of 7 ormore from that with a Gleason score of 6 and benign disease at initial biopsy. The population forwhich use of the assaywas intended includedmenolder than50yearswith no prior biopsy and a PSA value between 2 and 10 ng/mL (to convert tomicrograms per liter,multiply by 1.0). Similar estimates of the area under the curve were seen in the training (0.74) and validation (0.71) cohorts for the assay, with statistically significant improvements inmodel areaunder thecurve when the test was added to standard-of-care variables alone. Inapracticalapplication,applyingacutoffvalue fromthetraining cohort to serve as a threshold for biopsy in the validation cohort showed that 27% (138 of 519) of initial biopsies could havebeenavoidedat the cost ofmissing8%(12of 148) of prostate cancers of a Gleason score of 7 or more. A cutoff adjustment avoided 37% (192 of 519) of biopsies at a cost ofmissing 13% (19 of 148) of prostate cancers of a Gleason score of 7 or more (only 4 of the 19 patients had prostate cancer with a Gleason score including dominant pattern 4 disease). McKiernan and colleagues7 suggest that this 3-gene expression signature assay and similar tests could provide a route to reducing thediagnosis of low-riskprostate cancer and decreasing the number of unnecessary prostate biopsies. Instead of uniformly halting efforts to screen for early-stage prostate cancer, the focus shifts to detecting clinically significant disease.Notably, thepopulation included23% (55of 237) of menwith digital rectal examinations that raised the suspicionof prostate cancer and25% (64of 255) ofmenwith a familyhistoryofprostatecancer.These factors, combinedwithPSA values, led to the decision to perform a biopsy of the prostate, which resulted in a diagnosis of prostate cancer in almost half of the men in the study population and the finding that more than one-fourth of the study population had a Gleason score of 7 or more. The performance of the 3-gene expressionassay ina randomsampleofmennot scheduled for biopsy is unknown, making it uncertain whether the assay holds promise as an independent screening modality. Longitudinal assessment of the assay in a screening cohort will provide more data. Therefore, the current role of the 3-gene expression signature assay, if validated in external cohorts, would be as a secondary or reflex test for risk stratification in the setting of exercising stewardship with PSA screening, as suggested in theAmericanUrological Association guidelines, rather than as ameans of completely stopping PSA screening. The introduction of an effective reflex test for risk stratification adds an additional procedure to health policy efforts to combat overdiagnosis and overtreatment of prostate cancer. Health policy considerations in these efforts can be listed in downstream order from population-based screening to individualizedmanagementdecisions. The first step in this process includes guideline statements by the American Urological Association advocating shared decision making for men aged 55 to 69 years and PSA screening intervals of 2 years or more,5 resembling the2009USPreventiveServicesTaskForce recommendation for screeningmammography.A second step is effective risk stratification before conducting a diagnostic biopsy by using a validated gene-expression signature, such Related article page 882 Opinion

Stricter Active Surveillance Criteria for Prostate Cancer do Not Result in Significantly Better Outcomes: A Comparison of Contemporary Protocols

We reviewed various existing active surveillance criteria and determined the competing trade-offs of the stricter vs more inclusive active surveillance criteria. Men enrolled in an active surveillance program at Princess Margaret Cancer Centre between 1998 and 2014 were identified through a prospectively maintained database. All patients were assessed forentry eligibility into the Prostate Cancer Research International: Active Surveillance, Johns Hopkins, University of Miami, University of California SanFrancisco, Memorial Sloan Kettering Cancer Center, University of Toronto-Sunnybrook and Royal Marsden protocols. The 2-sided t-test, ANOVA, Wilcoxon rank sum or chi-square tests were used for comparison as appropriate. Of the 1,365 men identified 1,085 met the Princess Margaret Cancer Centre inclusion criteria. When the Johns Hopkins, Prostate Cancer Research International: Active Surveillance and University of Miami criteria were applied 15.2%, 11.5% and 11.3% of these patients were excluded from active surveillance, respectively. No significant differences were noted between men who met the Princess Margaret Cancer Centre criteria and those who were excluded based on more stringent criteria when grade or volume reclassification was compared. No significant differences in prostate specific antigen velocity or the number of patients who proceeded to seek treatment were noted (p >0.1). Rates of biochemical recurrence among patients who chose to undergo radical prostatectomy after initial active surveillance were not different between men who met the more inclusive vs more exclusive active surveillance protocols. More selective criteria do not significantly improve short-term outcomes when considering the relative risk of grade reclassification or biochemical failure after treatment. In an era of increased awareness regarding the over diagnosis and overtreatment of prostate cancer, we believe that stricter entry criteria should be reconsidered.

Integration of multiparametric MRI into active surveillance of prostate cancer.

Prostate cancer is the most common noncutaneous cancer in men though many men will not die of this disease and may not require definitive treatment. Active surveillance (AS) is an increasingly utilized potential solution to the issue of overtreatment of prostate cancer. Traditionally, prostate cancer patients have been stratified into risk groups based on clinical stage on digital rectal examination, prostate-specific antigen and biopsy Gleason score, though each of these variables has significant limitations. This review will discuss the potential role for prostate multiparametric MRI and targeted biopsy techniques incorporating MRI in the selection of candidates for AS, monitoring patients on AS and as triggers for definitive treatment.

Association of PSA and number of cores positive with likelihood of adverse pathology at radical prostatectomy based on a 17-gene expression assay.

e16570Background: The overtreatment of prostate cancer and underutilization of active surveillance in men with Gleason 6 (GS6) cancer stems from uncertainty with current risk instruments such as vo...

Active surveillance of patients with prostate cancer (Literature review)

Active surveillance (AS) is an important strategy that avoids overtreatment of prostate cancer (PCa). However, the optimal criteria for the possibility of continuing the Academy of Sciences or the factors of disease progression and the need to move to the beginning of the treatment are still contradictory. We have analyzed the primary data on risk factors as predictors of progression of prostate cancer in patients group AN: the patient's age at the Academy of Sciences, race, family history. In practical application can be a combination of some data, such as multivariate clinical algorithm and prediction of long-term results of the Academy of Sciences and to further improve the implementation of these predictors of the future.

Evaluation of MR targeted biopsy for the diagnosis of prostate cancer

Objective To evaluate the efficacy of MR targeted and transrectal ultrasond guided prostate biopsy for the diagnosis of prostate cancer. Methods From July 2014 to March 2015, 35 patients underwent MR guided prostate biopsy and 141 patients underwent TRUS guided biopsy were retrospectively evaluated. The MRI results and pathology were analyzed. Results There were no statistical differences between the two groups in term of age, prostate volume and serum PSA level (P>0.05). The overall positive rate for prostate cancer was 48.3%, with a higher positive rate in MR targeted group (57.1%) compared with TRUS group (46.1%). More patients with high grade prostate cancer were diagnosed by MR targeted biopsy compared with TRUS guided biopsy and statistical significant differences was present in patients with PSA<10 ng/ml. Conclusions The MR targeted biopsy showed a high positive rate for high grade prostate cancer, which is of great value for the prevention of over-diagnosis and overtreatment of prostate cancer. Key words: Prostate cancer; Diagnosis; Biopsy

A preliminary study of the ability of the 4Kscore test, the Prostate Cancer Prevention Trial-Risk Calculator and the European Research Screening Prostate-Risk Calculator for predicting high-grade prostate cancer

IntroductionTo prevent the overdiagnosis and overtreatment of prostate cancer (PCa), therapeutic strategies have been established such as active surveillance and focal therapy, as well as methods for clarifying the diagnosis of high-grade prostate cancer (HGPCa) (defined as a Gleason score ≥7), such as multiparametric magnetic resonance imaging and new markers such as the 4Kscore test (4KsT).By means of a pilot study, we aim to test the ability of the 4KsT to identify HGPCa in prostate biopsies (Bx) and compare the test with other multivariate prognostic models such as the Prostate Cancer Prevention Trial Risk Calculator 2.0 (PCPTRC 2.0) and the European Research Screening Prostate Cancer Risk Calculator 4 (ERSPC-RC 4). Materials and methodsFifty-one patients underwent a prostate Bx according to standard clinical practice, with a minimum of 10 cores. The diagnosis of HGPCa was agreed upon by 4 uropathologists. We compared the predictions from the various models by using the Mann–Whitney U test, area under the ROC curve (AUC) (DeLong test), probability density function (PDF), box plots and clinical utility curves. ResultsForty-three percent of the patients had PC, and 23.5% had HGPCa. The medians of probability for the 4KsT, PCPTRC 2.0 and ERSPC-RC 4 were significantly different between the patients with HGPCa and those without HGPCa (p≤.022) and were more differentiated in the case of 4KsT (51.5% for HGPCa [25–75 percentile: 25–80.5%] vs. 16% [p 25–75: 8–26.5%] for non-HGPCa; p=.002). All models presented AUCs above 0.7, with no significant differences between any of them and 4KsT (p≥.20). The PDF and box plots showed good discriminative ability, especially in the ERSPC-RC 4 and 4KsT models. The utility curves showed how a cutoff of 9% for 4KsT identified all cases of HGPCa and provided a 22% savings in biopsies, which is similar to what occurs with the ERSPC-RC 4 models and a cutoff of 3%. ConclusionsThe assessed predictive models offer good discriminative ability for HGPCas in Bx. The 4KsT is a good classification model as a whole, followed by ERSPC-RC 4 and PCPTRC 2.0. The clinical utility curves help suggest cutoff points for clinical decisions: 9% for 4KsT and 3% for ERSPC-RC 4. This preliminary study should be interpreted with caution due to its limited sample size.

4Kscore Test, Prostate Cancer Prevention Trial-Risk Calculator y European Research Screening Prostate-Risk Calculator en la predicción del cáncer de próstata de alto grado; estudio preliminar

IntroductionTo prevent the overdiagnosis and overtreatment of prostate cancer (PC), therapeutic strategies have been established such as active surveillance and focal therapy, as well as methods for clarifying the diagnosis of high-grade prostate cancer (HGPC) (defined as a Gleason score ≥7), such as multiparametric magnetic resonance imaging and new markers such as the 4Kscore test (4KsT).By means of a pilot study, we aim to test the ability of the 4KsT to identify HGPC in prostate biopsies (Bx) and compare the test with other multivariate prognostic models such as the Prostate Cancer Prevention Trial Risk Calculator 2.0 (PCPTRC 2.0) and the European Research Screening Prostate Cancer Risk Calculator 4 (ERSPC-RC 4). Material and methodsFifty-one patients underwent a prostate Bx according to standard clinical practice, with a minimum of 10 cores. The diagnosis of HGPC was agreed upon by 4 uropathologists. We compared the predictions from the various models by using the Mann-Whitney U test, area under the ROC curve (AUC) (DeLong test), probability density function (PDF), box plots and clinical utility curves. ResultsForty-three percent of the patients had PC, and 23.5% had HGPC. The medians of probability for the 4KsT, PCPTRC 2.0 and ERSPC-RC 4 were significantly different between the patients with HGPC and those without HGPC (p≤.022) and were more differentiated in the case of 4KsT (51.5% for HGPC [25–75 percentile: 25–80.5%] vs. 16% [P 25–75: 8–26.5%] for non-HGPC; p=.002). All models presented AUCs above 0.7, with no significant differences between any of them and 4KsT (p≥.20). The PDF and box plots showed good discriminative ability, especially in the ERSPC-RC 4 and 4KsT models. The utility curves showed how a cutoff of 9% for 4KsT identified all cases of HGPC and provided a 22% savings in biopsies, which is similar to what occurs with the ERSPC-RC 4 models and a cutoff of 3%. ConclusionsThe assessed predictive models offer good discriminative ability for HGPCs in Bx. The 4KsT is a good classification model as a whole, followed by ERSPC-RC 4 and PCPTRC 2.0. The clinical utility curves help suggest cutoff points for clinical decisions: 9% for 4KsT and 3% for ERSPC-RC 4. This preliminary study should be interpreted with caution due to its limited sample size.