Comparison of Rotterdam and Barcelona Magnetic Resonance Imaging Risk Calculators for Predicting Clinically Significant Prostate Cancer.

Background: Magnetic resonance imaging (MRI)-based risk calculators (MRI-RCs) individualise the likelihood of clinically significant prostate cancer (csPCa) and improve candidate selection for prostate biopsy beyond the Prostate Imaging Reporting and Data System (PI-RADS). Objective: To compare the Barcelona (BCN) and Rotterdam (ROT) MRI-RCs in an entire population and according to the PI-RADS categories. Design setting and participants: A prospective comparison of BCN- and ROT-RC in 946 men with suspected prostate cancer in whom systematic biopsy was performed, as well as target biopsies of PI-RADS ≥3 lesions. Outcome measurements and statistical analysis: Saved biopsies and undetected csPCa (grade group ≥2) were determined. Results and limitations: The csPCa detection was 40.8%. The median risks of csPCa from BCN- and ROT-RC were, respectively, 67.1% and 25% in men with csPCa, whereas 10.5% and 3% in those without csPCa (p < 0.001). The areas under the curve were 0.856 and 0.844, respectively (p = 0.116). BCN-RC showed a higher net benefit and clinical utility over ROT-RC. Using appropriate thresholds, respectively, 75% and 80% of biopsies were needed to identify 50% of csPCa detected in men with PI-RADS <3, whereas 35% and 21% of biopsies were saved, missing 10% of csPCa detected in men with PI-RADS 3. BCN-RC saved 15% of biopsies, missing 2% of csPCa in men with PI-RADS 4, whereas ROT-RC saved 10%, missing 6%. No RC saved biopsies without missing csPCa in men with PI-RADS 5. Conclusions: ROT-RC provided a lower and narrower range of csPCa probabilities than BCN-RC. BCN-RC showed a net benefit over ROT-RC in the entire population. However, BCN-RC was useful in men with PI-RADS 3 and 4, whereas ROT-RC was useful only in those with PI-RADS 3. No RC seemed to be helpful in men with negative MRI and PI-RADS 5. Patient summary: Barcelona risk calculator was more helpful than Rotterdam risk calculator to select candidates for prostate biopsy.

Methods for Evaluating the Efficacy of Medical Castration: A Systematic Review.

Measuring serum testosterone determination during medical castration is recommended by prostate cancer (PCa) guidelines to assess its efficacy and define castration resistance. It has been suggested that other biochemical compounds, such as free testosterone or luteinising hormone (LH), could also assess castration efficacy. We aimed to analyse the current evidence for serum biochemical compounds that could be appropriate candidates for evaluating medical castration efficacy. A systematic review was conducted after two investigators independently searched the literature in the PubMed, Cochrane Library, and EMBASE databases published between January 1980 and February 2023. Their searches used the medical subject headings 'prostatic neoplasms', 'testosterone and androgen antagonists', 'gonadotropin-releasing hormone/analogues and derivatives', 'free testosterone', and 'luteinising hormone'. Studies were selected according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria, and their eligibility was based on the Participants, Intervention, Comparator, and Outcome strategy. The search was limited to original articles published in English. Among the 6599 initially identified titles, 15 original studies analysing the clinical impact of serum testosterone levels in PCa patients undergoing androgen deprivation therapy (ADT) were selected for evidence acquisition. The risk of bias in individual studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. All selected studies used immunoassays to measure serum testosterone, although only methods based on liquid or gas chromatography and mass spectrometry are recommended to measure low testosterone concentrations. The reported series were not uniform in clinical stage, ADT types, and the time or number of serum testosterone measurements. Only some studies found low serum testosterone levels (<20 or <32 ng/dL) associated with greater survival free of biochemical progression and castration resistance. We conclude that little current evidence justifies the measurement of serum testosterone during ADT using no appropriate methods. No reported longitudinal studies have examined the clinical impact of serum testosterone measured using liquid chromatography with tandem mass spectrometry (LC-MSMS), free testosterone, or LH in PCa patients undergoing medical castration. We conclude that well-designed longitudinal studies examining the clinical impact of serum testosterone measured with LC-MSMS, serum-free testosterone, and LH on biochemical progression and castration resistance in PCa patients undergoing neo-adjuvant castration in radiation therapy or continuous castration are needed.

Relationship between Proclarix and the Aggressiveness of Prostate Cancer.

INTRODUCTION: Proclarix is a CE-marked test that provides the risk of clinically significant prostate cancer (csPCa), ranging from 0% to 100%, based on the serum measurement of Thrombospondin-1, cathepsin D, prostate-specific antigen (PSA), and percentage of free PSA in addition to age. We hypothesize that Proclarix could be correlated with PCa aggressiveness. We analyzed the association of this new biomarker with four surrogates of aggressiveness: grade group (GG) in the biopsy, clinical stage, risk of biochemical recurrence after primary treatment of localized PCa, and pathology in the surgical specimen. MATERIAL AND METHODS: This is a retrospective study from 606 men with suspicion of PCa [PSA of ≥ 3.0 ng/mL and/or abnormal digital rectal examination (DRE)], in whom Proclarix was assessed (0-100%). The GG was defined by the International Society of Urological Pathology categories. The TNM was used for clinical staging (cT based on DRE, whereas cN and cM were established with computed tomography and 99-technetium bone scintigraphy). The risk of biochemical recurrence of localized PCa after primary treatment was defined by combining PSA, GG, and cT. Finally, an unfavorable pathology in a surgical specimen was defined as GG > 2 or pT ≥ 3. RESULTS: The median age of the cohort was 67 years old, with a median PSA of 7 ng/mL and a rate of abnormal DRE of 23.3%. CsPCa was detected in 254 men (41.9%), with a median Proclarix of 60.1% compared with 37.3% obtained in patients with insignificant PCa and 20.7% in men without PCa. Among patients with GG > 3, Proclarix was significantly higher (58.2%) than in those with GG of 3 or lower (33.1%, p < 0.001). Men with localized tumors exhibited a Proclarix median of 37.3% compared with those with advanced disease (60.1%, p < 0.001). Proclarix levels among 197 patients with low and intermediate risk of biochemical recurrence were 24.9% and 35.0%, respectively, significantly lower compared with patients with high-risk disease (58.7%, p < 0.001). Unfavorable pathology was observed in 35 patients out of the 79 who underwent radical prostatectomy, with a Proclarix median of 35.7% compared with 23.7% obtained in patients with favorable pathology (p = 0.013). Proclarix and magnetic resonance imaging were independent predictors of the four surrogates of aggressiveness analyzed. CONCLUSION: There is a correlation between Proclarix and the aggressiveness of PCa.

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.

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.

Magnetic Resonance Imaging-Based Predictive Models for Clinically Significant Prostate Cancer: A Systematic Review.

MRI can identify suspicious lesions, providing the semi-quantitative risk of csPCa through the Prostate Imaging-Report and Data System (PI-RADS). Predictive models of clinical variables that individualise the risk of csPCa have been developed by adding PI-RADS score (MRI-PMs). Our objective is to analyse the current developed MRI-PMs and define their clinical usefulness. A systematic review was performed after a literature search performed by two independent investigators in PubMed, Cochrane, and Web of Science databases, with the Medical Subjects Headings (MESH): predictive model, nomogram, risk model, magnetic resonance imaging, PI-RADS, prostate cancer, and prostate biopsy. This review was made following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) criteria and studied eligibility based on the Participants, Intervention, Comparator, and Outcomes (PICO) strategy. Among 723 initial identified registers, 18 studies were finally selected. Warp analysis of selected studies was performed with the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Clinical predictors in addition to the PI-RADS score in developed MRI-PMs were age, PCa family history, digital rectal examination, biopsy status (initial vs. repeat), ethnicity, serum PSA, prostate volume measured by MRI, or calculated PSA density. All MRI-PMs improved the prediction of csPCa made by clinical predictors or imaging alone and achieved most areas under the curve between 0.78 and 0.92. Among 18 developed MRI-PMs, 7 had any external validation, and two RCs were available. The updated PI-RADS version 2 was exclusively used in 11 MRI-PMs. The performance of MRI-PMs according to PI-RADS was only analysed in a single study. We conclude that MRI-PMs improve the selection of candidates for prostate biopsy beyond the PI-RADS category. However, few developed MRI-PMs meet the appropriate requirements in routine clinical practice.

Multiparametric MRI for Staging of Prostate Cancer: A Multicentric Analysis of Predictive Factors to Improve Identification of Extracapsular Extension before Radical Prostatectomy.

The correct identification of extracapsular extension (ECE) of prostate cancer (PCa) on multiparametric magnetic resonance imaging (mpMRI) is crucial for surgeons in order to plan the nerve-sparing approach in radical prostatectomy. Nerve-sparing strategies allow for better outcomes in preserving erectile function and urinary continence, notwithstanding this can be penalized with worse oncologic results. The aim of this study was to assess the ability of preoperative mpMRI to predict ECE in the final prostatic specimen (PS) and identify other possible preoperative predictive factors of ECE as a secondary end-point. We investigated a database of two high-volume hospitals to identify men who underwent a prostate biopsy with a pre-biopsy mpMRI and a subsequent RP. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of mpMRI in predicting ECE were calculated. A univariate analysis was performed to find the association between image staging and pathological staging. A multivariate logistic regression was performed to investigate other preoperative predictive factors. A total of 1147 patients were selected, and 203 out of the 1147 (17.7%) patients were classified as ECE according to the mpMRI. ECE was reported by pathologists in 279 out of the 1147 PS (24.3%). The PPV was 0.58, the NPV was 0.72, the sensitivity was 0.32, and the specificity was 0.88. The multivariate analysis found that PSA (OR 1.057, C.I. 95%, 1.016-1.100, p = 0.006), digital rectal examination (OR 0.567, C.I. 95%, 0.417-0.770, p = 0.0001), ratio of positive cores (OR 9.687, C.I. 95%, 3.744-25.006, p = 0.0001), and biopsy grade in prostate biopsy (OR 1.394, C.I. 95%, 1.025-1.612, p = 0.0001) were independent factors of ECE. The mpMRI has a great ability to exclude ECE, notwithstanding that low sensitivity is still an important limitation of the technique.

Comparison of Proclarix, PSA Density and MRI-ERSPC Risk Calculator to Select Patients for Prostate Biopsy after mpMRI.

Tools to properly select candidates for prostate biopsy after magnetic resonance imaging (MRI) have usually been analyzed in overall populations with suspected prostate cancer (PCa). However, the performance of these tools can change regarding the Prostate Imaging-Reporting and Data System (PI-RADS) categories due to the different incidence of clinically significant PCa (csPCa). The objective of the study was to analyze PSA density (PSAD), MRI-ERSPC risk calculator (RC), and Proclarix to properly select candidates for prostate biopsy regarding PI-RADS categories. We performed a head-to-head analysis of 567 men with suspected PCa, PSA > 3 ng/mL and/or abnormal rectal examination, in whom two to four core transrectal ultrasound (TRUS) guided biopsies to PI-RADS ≥ three lesions and/or 12-core TRUS systematic biopsies were performed after 3-tesla mpMRI between January 2018 and March 2020 in one academic institution. The overall detection of csPCa was 40.9% (6% in PI-RADS < 3, 14.8% in PI-RADS 3, 55.3% in PI-RADS 4, and 88.9% in PI-RADS 5). MRI-ERSPC model exhibited a net benefit over PSAD and Proclarix in the overall population. Proclarix outperformed PSAD and MRI-ERSPC RC in PI-RADS ≤ 3. PSAD outperformed MRI-ESRPC RC and Proclarix in PI-RADS > 3, although none of them exhibited 100% sensitivity for csPCa in this setting. Therefore, tools to properly select candidates for prostate biopsy after MRI must be analyzed regarding the PI-RADS categories. While MRI-ERSPC RC outperformed PSAD and Proclarix in the overall population, Proclarix outperformed in PI-RADS ≤ 3, and no tool guaranteed 100% detection of csPCa in PI-RADS 4 and 5.

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.

Application of One-Step Nucleic Acid Amplification (OSNA) in different cancer entities and usefulness in prostate cancer: a systematic review.

BACKGROUND: Lymph node (LN) status is a key prognostic factor in the decision-making process of different cancer entities, including prostate cancer (PCa). Sectioning and haematoxylin and eosin (H&E) staining technique remain the gold standard for the evaluation of LN metastases despite some limitations, especially low sensitivity in detecting an accurate tumour burden within the LN, as well as a subjective and time-consuming result. One-step nucleic acid amplification (OSNA) quantifies mRNA copies of cytokeratin 19 (CK19) in a fast, objective, automated, and reproducible way, raising a general interest to explore its utility for lymphatic metastasis identification in different malignancies. METHODS: To present the latest evidence related to the detection of LN metastases in several tumours by using OSNA compared with the conventional H&E method, a systematic review of articles published since March 2021 was conducted using PubMed, Cochrane Library, and Web of Science databases. References from primary papers and review articles were checked to obtain further potential studies. Our procedure for evaluating records identified during the literature search followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses criteria. With the aim to design and justify future clinical routine use of OSNA in PCa, novel PCa evidence has been included in this review for the first time. RESULTS: Twenty five studies were included. LN from six different groups of tumours: breast, gastrointestinal, gynecological, lung, head and neck and prostate cancers has been assessed. OSNA was compared with post-operative formalin-fixed paraffin-embedded tissue sections with H&E staining as the reference standard. Contingency tables were created, and concordance rate, sensitivity, specificity and predictive values were reported. Seventeen studies analysed the discordant cases using different techniques. CONCLUSION: OSNA method has a high diagnostic accuracy for the detection of LN metastases in several CK19 expressing tumours. Available evidence might encourage future investigations about its usage in PCa patients to improve LN staging and prognosis.

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.

Proclarix, A New Biomarker for the Diagnosis of Clinically Significant Prostate Cancer: A Systematic Review.

INTRODUCTION: Multiparametric magnetic resonance imaging (mpMRI) has improved the early detection of clinically significant prostate cancer (csPCa). However, an appropriate selection of men for mpMRI or prostate biopsy is still challenging, which is why new biomarkers or predictive models are recommended to determine those patients who will benefit from prostate biopsy. Proclarix is a new test that provides the risk of csPCa based on thrombospondin-1 (THBS1), cathepsin D (CTSD), prostate-specific antigen (PSA), and percentage of free PSA (%fPSA), as well as age. This systematic review analyzes the current clinical status of Proclarix and future development. EVIDENCE ACQUISITION: A systematic review of the literature was carried out by two independent reviewers. The Medical Subject Heading (MeSH) terms 'prostate', 'thrombospondin-1', 'cathepsin-D' and 'Proclarix' were used. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and the Population, Intervention, Comparison and Outcomes (PICO) selection criteria were followed. Finally, four articles analyzed the clinical usefulness of Proclarix. EVIDENCE SYNTHESIS: Proclarix has been developed in men with PSA levels between 2 and 10 ng/mL, normal digital rectal examination (DRE), and prostate volume (PV)​ ≥ 35 cm3. Proclarix is associated with the PCa grade group and is more effective than %fPSA in detecting csPCa. Two studies analyzed the efficacy of Proclarix in men undergoing guided and systematic biopsies, obtaining similar results to PSA density. CONCLUSION: Initial studies have shown the potential benefit of Proclarix in patients with specific characteristics. Future studies are needed to verify the clinical usefulness of Proclarix in men with suspected PCa before and after mpMRI.

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.

Definition of Castrate Resistant Prostate Cancer: New Insights.

The term castrate resistant prostate cancer (CRPC) was initially proposed by the Prostate Cancer Working Group 2 in 2008 to define the state of clinical and/or biochemical progression of prostate cancer (PCa) in an environment with very low serum testosterone concentration. Clinical progression is based on the radiological imaging proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) adapted to PCa. Biochemical progression is defined as an over 25% increase in serum prostate-specific antigen within two consecutive measurements separated by at least one week, and an absolute value above 2.0 ng/mL. Finally, the castrate environment is usually defined as a serum testosterone concentration maintained below 50 ng/dL or 1.7 nmol/dL. This definition does not incorporate the new and more accurate imaging modalities to assess clinical progression and the capability of the new biochemical measurements to assess the true castration environment. Ga-68-PSMA-11 PET CT/MRI and whole-body MRI are the new imaging modalities that should replace the classic thoracic CT scan, abdomino-pelvic CT scan, and technetium 99-m bone scintigraphy. In addition, Ga-68-PSMA-11 PET is the current basis for the new therapies targeting metastatic sites. Moreover, the current methods for measuring the very low serum testosterone concentrations in clinical laboratories are the widespread chemiluminescent assays, which are inappropriate, while LC-MSMS is the only method recommended to assess the castrate environment. In addition, recent research shows that serum luteinising hormone concentration associates better than serum testosterone with the castration environment, even when it is measured with LC-MSMS. In summary, the current definition of CRPC seems outdated. An extensive update to diagnose true CRPC is also needed to differentiate CRPC men with M0 (non-metastatic) from those with M1 (metastatic) CRPC. WC: 277.

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.

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.

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.