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The prognostic value of prostate-specific antigen (PSA) kinetics in primary high-volume metastatic hormone-sensitive prostate cancer (mHSPC) patients treated with novel hormonal therapy agents is still unclear. Here, we retrospectively reviewed the data of 102 patients with primary high-volume mHSPC who received novel hormonal therapy agents. The median follow-up was 32.25 ± 14.51 months and the median nadir PSA (nPSA) was 0.20 (0.06, 11.71) ng/mL after treatment. The mean time to nPSA was 10.82 ± 7.27 months and 55 patients (53.9%) had a PSA-density (PSA-D) ≤ 0.08 at 3-months. Univariate and multivariate Cox regression analyses showed that the absence of visceral metastases, nPSA ≤ 0.2 and PSA-D ≤ 0.08 were independent prognostic factors for better PFS and OS (all P < 0.05). Moreover, patients with nPSA ≤ 0.2 and PSA-D ≤ 0.08 had the best PFS and OS, and the combination of the nPSA and PSA-D had a better predictive accuracy for PFS and OS than nPSA and PSA-D alone. Thus, Visceral metastases, nPSA and PSA-D were independent prognostic factors for primary high-volume mHSPC patients treated with novel hormonal therapy agents. Patients with lower nPSA and PSA-D had a best survival outcome, and the combination of nPSA and PSA-D had a better effect on prognosis predicting. [ABSTRACT FROM AUTHOR]

Prostate cancer (PCa) is one of the most prevalent and deadly cancers among men, particularly affecting men of African descent and contributing significantly to cancer-related morbidity and mortality worldwide. The disease varies widely, from slow-developing forms to highly aggressive or potentially fatal variants. Accurate risk stratification is crucial for making therapeutic decisions and designing adequate clinical trials. This review assesses a broad spectrum of diagnostic and prognostic biomarkers, many of which are incorporated into clinical guidelines, including the Prostate Health Index (PHI), 4Kscore, STHLM3, PCA3, SelectMDx, ExoDx Prostate Intelliscore (EPI), and MiPS. It also highlights emerging biomarkers with preclinical support, such as urinary non-coding RNAs and DNA methylation patterns. Additionally, the review explores the role of tumor-associated microbiota in PCa, offering new insights into its potential contributions to disease understanding. By examining the latest advancements in PCa biomarkers, this review enhances understanding their roles in disease management. [ABSTRACT FROM AUTHOR]

Objective: To investigate the value of adjusted prostate-specific antigen density (PSADadj) in the diagnosis of prostate cancer (PCa). Methods: Data from 410 patients who underwent transrectal ultrasound-guided prostate biopsy were retrospectively analyzed in Beijing Tsinghua Changgung Hospital between November 2014 and March 2024. All patients were divided into PCa and benign prostatic hyperplasia (BPH) groups according to pathological results. Multivariate logistic regression analyses were performed to evaluate the odd ratios (ORs) of predictors for PCa occurrence. Receiver operating characteristic curves were plotted, and the area under the curve (AUC) values were used to assess and compare the diagnostic accuracies of total PSA (tPSA), free-to-total (f/t) PSA, free PSA (fPSA), PSAD, and PSADadj (PSAD×weight). Results: There were 166 patients in the PCa group and 244 in the BPH group. Multivariate analyses demonstrated that PSAD was positively correlated with the presence of PCa, with the highest OR value among all PSA-related parameters (OR = 19.075, p<0.001). tPSA, fPSAD, PSAD, and PSADadj had high accuracy in predicting PCa, with AUC values of 0.633, 0.730, 0.778, and 0.780. Of note, PSADadj had the highest AUC with a sensitivity of 63.3% and specificity of 81.6%. Similarly, in patients with a PSA level in the gray zone, the diagnostic accuracy of PSADadj in predicting PCa (AUC, 0.709; 95% CI, 0.616-0.802) remained better than other PSA-related markers. Conclusion: PSADadj has an advantage over other PSA-related markers in detecting PCa and could be used for making biopsy decisions. [ABSTRACT FROM AUTHOR]

Background: The majority of men referred with a raised PSA for suspected prostate cancer will receive unnecessary tertiary investigations including MRI and biopsy. Here, we compared different types of biomarkers to refine tertiary referrals and when different definitions of clinically significant cancer were used. Methods: Data and samples from 798 men referred for a raised PSA (≥ 3 ng/mL) and investigated through an MRI-guided biopsy pathway were accessed for this study. Bloods were acquired pre-biopsy for liquid biomarkers and germline DNA. Variables explored included PSA + Age (base model), free/total PSA (FTPSA), Prostate Health Index (phi), PSA density (PSAd), polygenic risk score (PRS) and MRI (≥ LIKERT 3). Different diagnostic endpoints for significant cancer (≥ grade group 2 [GG2], ≥ GG3, ≥ Cambridge Prognostic Group 2 [CPG2], ≥ CPG3) were tested. The added value of each biomarker to the base model was evaluated using logistic regression models, AUC and decision curve analysis (DCA) plots. Results: The median age and PSA was 65 years and 7.13 ng/mL respectively. Depending on definition of clinical significance, ≥ grade group 2 (GG2) was detected in 57.0% (455/798), ≥ GG3 in 27.5% (220/798), ≥ CPG2 in 61.6% (492/798) and ≥ CPG3 in 42.6% (340/798). In the pre-MRI context, the PSA + Age (base model) AUC for prediction of ≥ GG2, ≥ GG3, ≥ CPG2 and ≥ CPG3 was 0.66, 0.68, 0.70 and 0.75 respectively. Adding phi and PSAd to base model improved performance across all diagnostic endpoints but was notably better when the composite CPG prognostic score was used: AUC 0.82, 0.82, 0.83, 0.82 and AUC 0.74, 0.73, 0.79, 0.79 respectively. In contrast, neither FTPSA or PRS scores improved performance especially in detection of ≥ GG3 and ≥ CPG3 disease. Combining biomarkers did not alter results. Models using phi and PSAd post-MRI also improved performances but again benefit varied with diagnostic endpoint. In DCA analysis, models which incorporated PSAd and phi in particular were effective at reducing use of MRI and/or biopsies especially for ≥ CPG3 disease. Conclusion: Incorporating phi or PSAd can refine and tier who is referred for tertiary imaging and/or biopsy after a raised PSA test. Incremental value however varied depending on the definition of clinical significance and was particularly useful when composite prognostic endpoints are used. [ABSTRACT FROM AUTHOR]

Objective: We reviewed our institutional experience of radical prostatectomy with and without preoperative multiparametric magnetic resonance imaging (mpMRI) to assess the impact of preoperative prostate mpMRI on surgical outcomes of radical prostatectomy. Methods: We identified patients at our institution who underwent radical prostatectomy for prostate cancer (PCa) between January 2012 and December 2017 ( n = 1044). Using propensity scoring analysis, patients who underwent preoperative mpMRI (n = 285) were matched 1:1 to patients who did not receive preoperative mpMRI (n = 285). Multivariable regression analysis was performed to identify factors predictive of operative time, estimated blood loss (EBL), lymph node yield, rates of complications within 30 days, and positive surgical margin (PSM). Results: There were no significant differences in operative time, EBL, PSM, lymph node yield, or complication rates between the two cohorts. Multivariable analysis demonstrated that preoperative mpMRI was not predictive of the measured perioperative outcomes. Significant comorbidity (Charlson Comorbidity Index ≥3) was the sole predictor of perioperative complications ( P = 0.015). Increasing biopsy Gleason score predicted increased lymph node yield (P < 0.001). The probability of PSM was associated with increasing preoperative prostate-specific antigen (odds ratio 1.036, P = 0.009). Body mass index was a predictor of operative time (P = 0.016) and EBL (P = 0.001). Conclusions: Although preoperative mpMRI has an important role in the diagnosis and staging of PCa, it does not impact perioperative radical prostatectomy outcomes. Our findings do not support the routine use of preoperative mpMRI for surgical planning in patients already diagnosed with clinically localized PCa. [ABSTRACT FROM AUTHOR]

Biochemical recurrence is a process that progresses to castration-resistant prostate cancer (CRPC) and prediction of biochemical recurrence is useful in determining early therapeutic intervention and disease treatment. Prostate cancer is surrounded by adipose tissue, which secretes adipokines, affecting cancer progression. This study aimed to investigate the correlation between blood adipokines and CRPC biochemical recurrence. We retrospectively analyzed the clinical data, including preoperative serum adipokine levels, of 99 patients with pT3a pN0 prostate cancer who underwent proctectomy between 2011 and 2019. The primary outcome was biochemical recurrence (prostate-specific antigen: PSA > 0.2). We identified 65 non-recurrences and 34 biochemical recurrences (one progressed to CRPC). The initial PSA level was significantly higher (p = 0.006), but serum adiponectin (p = 0.328) and leptin (p = 0.647) levels and their ratio (p = 0.323) were not significantly different in the biochemical recurrence group compared with the non-recurrence group. In contrast, significantly more biochemical recurrences were observed in the group with adiponectin < 6 μg/mL and Leptin < 4 ng/mL (p = 0.046), initial PSA > 15 ng/mL, clinical Gleason pattern ≥ 4, and positive resection margin. A significant difference was also observed in the multivariate analysis (hazard ratio: 4.04, 95% confidence interval: 1.21–13.5, p = 0.0232). Thus, low preoperative serum adiponectin and high leptin levels were significantly associated with biochemical recurrence in adipose tissue-invasive prostate cancer, suggesting that they may be useful predictors of biochemical recurrence. Further studies with larger cases are needed to increase the validity of this study. [ABSTRACT FROM AUTHOR]

Prostate cancer screening using prostate-specific antigen (PSA) testing is controversial but remains prevalent in many countries. There is little information in Sweden or elsewhere on the spatial variation in PSA testing. This study aims to describe the spatio-temporal variation in PSA testing prior to a prostate cancer diagnosis in the Stockholm region at the municipality and small area levels. A population-based register study comprised men aged 40 years and over living in the Stockholm region during 2007–2016. For Stockholm in 2016, we reported the proportion of men who had a PSA test for the preceding one, two, five and ten years by ten-year age groups. The age-standardised proportion of men having a PSA test was reported for municipalities by calendar years. We used spatial smoothing for calculating the age-standardised proportion of men having a PSA test in a small area for each calendar year. In 2016, 74.0% and 77.8% of men aged 60–69 and 70–79 years respectively had taken a PSA test in the previous ten years. The municipalities of Danderyd and Ekerö showed high proportions of PSA testing. A marked heterogeneity in such proportions within each municipality was observed. The odds ratio for having a PSA test for those born in Sweden was 2.22 (95% CI 2.00–2.52). Opportunistic PSA testing is widespread with three quarters of men in their sixties and seventies having had a test in the preceding decade. We found evidence for marked geographical heterogeneity, where more affluent and metropolitan areas had higher levels of testing. Variations in PSA testing was associated with socio-economic position and demographic factors including education, income and country of birth. [ABSTRACT FROM AUTHOR]

There is a significant unmet need for clinical reflex tests that increase the specificity of prostate-specific antigen blood testing, the longstanding but imperfect tool for prostate cancer diagnosis. Towards this endpoint, we present the results from a discovery study that identifies new prostate-specific antigen reflex markers in a large-scale patient serum cohort using differentiating technologies for deep proteomic interrogation. We detect known prostate cancer blood markers as well as novel candidates. Through bioinformatic pathway enrichment and network analysis, we reveal associations of differentially abundant proteins with cytoskeletal, metabolic, and ribosomal activities, all of which have been previously associated with prostate cancer progression. Additionally, optimized machine learning classifier analysis reveals proteomic signatures capable of detecting the disease prior to biopsy, performing on par with an accepted clinical risk calculator benchmark. [ABSTRACT FROM AUTHOR]

Background: Prostate cancer (PCa) screening strategies are being developed and evaluated in several countries. However, most of the evidence regarding PCa screening has been generated in study populations aged 50 and older. Aims: This study summarizes findings of a screening trial in younger men and discuss those findings in the context of other screening trials. Methods: Non-systematic review. Results: Screening of 45-year-old men resulted in a low PCa detection rate. Nonetheless, almost 70% of screen-detected PCa at this age was clinically significant. In young men ISUP GG 1 screen-detected cancers warrant rigorous follow-up. A baseline, midlife prostate-specific antigen (PSA) value at age 45 may safely exclude the vast majority of men from further screening investigations for at least 5 years. At age 45, a confirmatory PSA value reduces the number of subsequent tests almost by half. Sequential magnetic resonance imaging (MRI) as a reflex test subsequent to an elevated PSA ≥ 3 ng/mL needs further investigation in young men. Conclusions: Screening in young men needs to be carefully investigated in order to avoid overscreening and overdiagnosis. [ABSTRACT FROM AUTHOR]

Simple Summary: Prostate specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) is a promising and recently approved treatment option for patients with metastatic castration-resistant prostate cancer (mCRPC). The aim of this study was to analyze which laboratory and PET imaging parameters are able to predict biochemical response and overall survival with this treatment. Two quantitative imaging biomarkers were identified that allow prediction of RLT outcome, further improving the pre-therapeutic characterization of mCRPC patients undergoing PSMA-RLT. The aim of this retrospective study was to identify pre-therapeutic predictive laboratory and molecular imaging biomarkers for response and overall survival (OS) in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT). Pre-therapeutic laboratory and [68Ga]Ga-PSMA-11 PET/CT data of n = 102 mCRPC patients receiving [177Lu]Lu-PSMA-617 RLT within a prospective registry (REALITY Study, NCT04833517) were analyzed including laboratory parameters such as alkaline phosphatase (ALP), prostate-specific antigen (PSA), gamma glutamyl transferase (GGT), glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT), neuron specific enolase (NSE), hemoglobin (Hb), and imaging parameters such as maximum standardized uptake value of the tumor lesions (SUVmax), the mean standardized uptake value of all tumor lesions (SUVmean), the whole-body molecular tumor volume (MTV), and the whole-body total lesion PSMA (TLP). Mann–Whitney U test, univariate and multivariable Cox-regression were performed to test for association of the parameters with response and OS. The SUVmean of all lesions was significantly different between responders and non-responders (SUVmean responders 8.95 ± 2.83 vs. non-responders 7.88 ± 4.46, p = 0.003), whereas all other tested biochemical and imaging parameters did not reveal significant differences. Hb and the molecular imaging parameters MTV and TLP showed a significant association with OS (p = 0.013, p = 0.005; p = 0.009) in univariant Cox regression; however, only TLP remained significant in multivariable analysis (Hazard ratio 1.033, p = 0.009). This study demonstrates a statistically significant association between the quantitative PET/CT imaging parameter SUVmean and PSA response, as well as between the baseline TLP and OS of mCRPC patients undergoing RLT. [ABSTRACT FROM AUTHOR]

Simple Summary: We retrospectively evaluated the clinical outcomes and prognostic factors of 127 patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) treated with first-line androgen receptor signaling inhibitors (ARSI) in real-world clinical practice. Overall survival (OS), metastatic-free survival (MFS), and prostate-specific antigen–progression-free survival (PSA–PFS) from the initiation of ARSI were assessed. The median OS and MFS for all patients were 79.0 and 42.0 months, respectively. Median PSA–PFS varied among patients treated with enzalutamide, abiraterone acetate, apalutamide, and darolutamide (27.0, 20.0, 10.0, and 14.0 months, respectively; p = 0.33). Multivariate analysis indicated that a baseline PSA level of ≥3.67 ng/mL (p = 0.002) was significantly associated with poorer OS prognosis. ARSI demonstrated favorable efficacy in nmCRPC patients, with no significant differences in clinical outcomes among different types of ARSI. High baseline PSA of ARSI was found to have a significantly poor prognosis associated with OS. We conducted a retrospective evaluation of the clinical outcomes and prognostic factors in patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) treated with first-line androgen receptor signaling inhibitors (ARSI) in real-world clinical practice in Japan. Between 2012 and 2023, a total of 127 consecutive patients with nmCRPC received ARSI treatment. Overall survival (OS), metastatic-free survival (MFS), and prostate-specific antigen–progression-free survival (PSA–PFS) from ARSI initiation were assessed using the Kaplan–Meier methodology. Clinical factors associated with OS in nmCRPC were analyzed using the Cox proportional hazards model. Among the patients, 72, 26, 12, and 17 received enzalutamide (ENZ), abiraterone (ABI), apalutamide (APA), and darolutamide (DARO) as first-line therapy. The median OS and MFS for all patients were 79.0 and 42.0 months, respectively. Median PSA–PFS was 27.0, 20.0, 10.0, and 14.0 months for patients treated with ENZ, ABI, APA, and DARO, respectively (p = 0.33). Multivariate analysis revealed that a baseline PSA level ≥ 3.67 ng/mL at ARSI initiation was significantly associated with poorer OS (p = 0.002). ARSI demonstrated favorable efficacy in nmCRPC patients. There were no significant differences in clinical outcomes among different types of ARSI therapy for nmCRP. Elevated baseline PSA at ARSI initiation was significantly associated with poorer OS. [ABSTRACT FROM AUTHOR]

Simple Summary: For decades, a blood test showing elevated prostate-specific antigen (PSA) has been the mainstay for detecting prostate cancer. However, the PSA is often elevated in the absence of cancer. Here, we show that the neuroendocrine marker (NEM) outperforms the PSA test, both for sensitivity and for the exclusion of false-positive results. The purpose of this study was to assess the efficacy, specificity, and predictive value of a newly discovered biomarker, Zinc finger-like1 protein (referred to as neuroendocrine marker, NEM) for the detection of prostate cancer (PCa). We retrospectively analyzed banked plasma samples from 508 men, with a median age of 67 years (range 48–97), to compare the performance of NEM and PSA in predicting subsequent histologic PCa. The cohort consisted of four groups of patients visiting a urology clinic: (1) patients not diagnosed with either benign prostatic disease or prostate cancer (PCa) were defined as normal; (2) patients diagnosed with benign hyperplasia (BPH) but not PCa; (3) patients with confirmed PCa; and (4) patients with cancer other than PCa. The normal men displayed a mean NEM plasma level of 0.948 ± 0.051 ng/mL, which increased to 1.813 ± 0.315 ng/mL in men with BPH, 86.49 ± 15.51 ng/mL in men with PCa, and 10.47 ± 1.029 ng/mL in men with other Ca. The corresponding concentrations of prostate-specific antigen (PSA) in these subjects were 1.787 ± 0.135, 5.405 ± 0.699, 35.77 ± 11.48 ng/mL, and 8.036 ± 0.518, respectively. Receiver operating characteristic (ROC) curve analysis was performed to compare NEM and PSA performance, and the Jouden Index for each biomarker was calculated to determine cut-off points for each biomarker. The area under the ROC curve to predict PCa was 0.99 for NEM and 0.81 for PSA (p < 0.0001). The cut-off for NEM was at 1.9 ng/mL, with sensitivity of 98% and specificity of 97%. The corresponding PSA values were 4.4 ng/mL, with sensitivity of 76% and specificity of 95%. The predictive value of each biomarker in a patient was matched with his pathologic data to determine the accuracy of each biomarker. NEM was more accurate than PSA in differentiating cancer from benign conditions, such as BPH or prostatitis. In conclusion, NEM was a better predictor of PCa than PSA in patients visiting urology clinics. NEM tests, either alone or in conjunction with other biomarkers, provide a reliable, non-invasive, and inexpensive test to remarkably reduce false positives and thereby reduce the number of diagnostic biopsies and associated painful procedures and the loss of quality of life. [ABSTRACT FROM AUTHOR]

Background: Many people struggle with the choice in a series of processes, from prostate cancer (PCa) diagnosis to treatment. We investigated the degree of regret after the prostate biopsy (PBx) and relevant factors in patients recommended for biopsy for suspected PCa. Methods: From 06/2020 to 05/2022, 198 people who performed PBx at three institutions were enrolled and analyzed through a questionnaire before and after biopsy. Before the biopsy, a questionnaire was conducted to evaluate the sociodemographic information, anxiety scale, and health literacy, and after PBx, another questionnaire was conducted to evaluate the decision regret scale. For patients diagnosed as PCa after biopsy, a questionnaire was conducted when additional tests were performed at PCa staging work-up. Results: 190 patients answered the questionnaire before and after PBx. The mean age was 66.2 ± 7.8 years. Overall, 5.5% of men regretted biopsy, but there was no significant difference between groups according to the PCa presence. Multivariate analysis, to identify predictors for regret, revealed that the case when physicians did not properly explain what the prostate-specific antigen (PSA) test was like and what PSA elevation means (OR 20.57, [95% CI 2.45–172.70], p = 0.005), low media literacy (OR 10.01, [95% CI 1.09–92.29], p = 0.042), and when nobody to rely on (OR 8.49, [95% CI 1.66–43.34], p = 0.010) were significantly related. Conclusions: Overall regret related to PBx was low. Decision regret was more significantly related to media literacy rather than to educational level. For patients with relatively low media literacy and fewer people to rely on in case of serious diseases, more careful attention and counseling on PBx, including a well-informed explanation on PSA test, is helpful. [ABSTRACT FROM AUTHOR]

Prostate cancer management has undergone radical changes in recent times, due to early diagnosis in localized stage and availability of multiple treatment modalities. But the onus of selecting appropriate treatment rests with the urologist. Radiological investigations are immensely important in these patients. Measurement of prostate-specific antigen and its derivatives is the primary investigation in the diagnosis of prostate carcinoma. Ultrasonogram is of limited utility in prostate carcinoma. Magnetic resonance imaging provides extensive information to the treating physician regarding the approach and the treatment modality to be used in the management of prostate carcinoma. Radiological investigations are the cornerstones for efficient management of prostate carcinoma. [ABSTRACT FROM AUTHOR]

Our aim was to evaluate the predictors of prostate cancer and clinically significant prostate cancer in patients with prostate-specific antigen (PSA) level between 4-10 ng/ml who had pre-biopsy Prostate Imaging–Reporting and Data System (PI-RADS) score of 3. The study analyzed data from 94 patients who underwent transrectal prostate biopsy with the PI-RADS score of 3 between January 2019 and December 2023. The detection rates of prostate cancer and clinically significant prostate cancer were calculated. Simple and multiple logistic regression analysis were conducted to evaluate the predictors of prostate cancer and clinically significant prostate cancer. The receiver operating characteristics curve analysis and area under curve values were used to determine the priority of parameters. In our study, the incidence of PI-RADS 3 lesion was 18.5%. The overall prostate cancer detection rate was 38.2% with the clinically significant prostate cancer detection rate was 22.3%. For prostate carcinoma and clinically significant prostate carcinoma logistic regression analysis revealed that free to total prostate-specific antigen (f/t PSA) ratio and age were the independent predictors. Receiver Operating Characteristic curve analysis and area under curve revealed that f/t PSA ratio had the highest value (0.770) followed by prostate volume (PV) (0,751) for clinically significant prostate cancer. Prostate-specific antigen density (PSAD) had the third highest area under curve value of 0.739. Although current guidelines recommend not performing biopsy for patients with PSAD<0.10 ng/ml/cc in patients with PI-RADS score 3, our clinically significant prostate cancer detection rate was 13% with this level. Therefore, we recommend that each patient should be evaluated individually with PI-RADS score 3. For deciding on biopsy, not only PSAD but also f/t PSA and PV should be considered, especially in PSA gray zone patients. However, further studies with more patients are required to validate this recommendation. [ABSTRACT FROM AUTHOR]

Objectives: To develop a novel biopsy prostate cancer (PCa) prevention calculator (BioPrev-C) using data from a prospective cohort all undergoing mpMRI targeted and transperineal template saturation biopsy. Materials and methods: Data of all men who underwent prostate biopsy in our academic tertiary care center between 11/2016 and 10/2019 was prospectively collected. We developed a clinical prediction model for the detection of high-grade PCa (Gleason score ≥7) based on a multivariable logistic regression model incorporating age, PSA, prostate volume, digital rectal examination, family history, previous negative biopsy, 5-alpha-reductase inhibitor use and MRI PI-RADS score. BioPrev-C performancewas externally validated in another prospective Swiss cohort and compared with two other PCa risk-calculators (SWOP-RC and PBCG-RC). Results: Of 391 men in the development cohort, 157 (40.2%) were diagnosed with high-grade PCa. Validation of the BioPrev C revealed good discrimination with an area under the curve for high-grade PCa of 0.88 (95% Confidence Interval 0.82- 0.93), which was higher compared to the other two risk calculators (0.71 for PBCG and 0.84 for SWOP). The BioPrev-C revealed good calibration in the low-risk range (0 - 0.25) andmoderate overestimation in the intermediate risk range (0.25 - 0.75). The PBCG-RC showed good calibration and the SWOP-RC constant underestimation of high-grade PCa over the whole prediction range. Decision curve analyses revealed a clinical net benefit for the BioPrev-C at a clinical meaningful threshold probability range (≥4%), whereas PBCG and SWOP calculators only showed clinical net benefit above a 30% threshold probability. Conclusion: BiopPrev-C is a novel contemporary risk calculator for the prediction of high-grade PCa. External validation of the BioPrev-C revealed relevant clinical benefit, which was superior compared to other well-known risk calculators. The BioPrev-C has the potential to significantly and safely reduce the number of men who should undergo a prostate biopsy. [ABSTRACT FROM AUTHOR]

Risk-stratified pathways (RSPs) are recommended by the European Association of Uro-logy (EAU) to improve the early detection of clinically significant prostate cancer (csPCa). RSPs can reduce magnetic resonance imaging (MRI) demand, prostate biopsies, and the over-detection of insignificant PCa (iPCa). Our goal is to analyze the efficacy and cost-effectiveness of several RSPs by using sequential stratifications from the serum prostate-specific antigen level and digital rectal examination, the Barcelona risk calculators (BCN-RCs), MRI, and Proclarix™. In a cohort of 567 men with a serum PSA level above 3.0 ng/mL who underwent multiparametric MRI (mpMRI) and targeted and/or systematic biopsies, the risk of csPCa was retrospectively assessed using Proclarix™ and BCN-RCs 1 and 2. Six RSPs were compared with those recommended by the EAU that, stratifying men from MRI, avoided 16.7% of prostate biopsies with a prostate imaging–reporting and data system score of <3, with 2.6% of csPCa cases remaining undetected. The most effective RSP avoided mpMRI exams in men with a serum PSA level of >10 ng/mL and suspicious DRE, following stratifications from BCN-RC 1, mpMRI, and Proclarix™. The demand for mpMRI decreased by 19.9%, prostate biopsies by 19.8%, and over-detection of iPCa by 22.7%, while 2.6% of csPCa remained undetected as in the recommended RSP. Cost-effectiveness remained when the Proclarix™ price was assumed to be below EUR 200. [ABSTRACT FROM AUTHOR]

Objectives: This study was to explore the feasibility of combining contrastenhanced transrectal ultrasound (CE-TRUS) with biparametric MRI (CEUSBpMRI) score for diagnosing prostate cancer (PCa). Methods: A total of 183 patients with suspected PCa who underwent multiparametric MRI (Mp-MRI) and CE-TRUS were included. CEUS-BpMRI score was developed based on the results of Mp-MRI and CE-TRUS. The diagnostic performance was evaluated by the area under the curve (AUC). The diagnostic efficacy of the CEUS-BpMRI score, BpMRI score, and PI-RADS v2.1 score were compared. Total patients were randomly assigned to a training cohort (70%) or validation cohort (30%). A nomogram was constructed based on univariate and multivariate logistic regression. The model was evaluated by AUC and calibration curve. Results: The diagnostic performance of CEUS-BpMRI score (AUC 0.857) was comparable to that of PI-RADS v2.1 (AUC 0.862) (P = 0.499), and both were superior to Bp-MRI score (AUC 0.831, P < 0.05). In peripheral zone lesions with Bp-MRI score of 3, there was no statistically significant difference between PIRADS v2.1 score (AUC 0.728) and CEUS-BpMRI score (AUC 0.668) (P = 0.479). Multivariate analysis showed that age, total prostate specific antigen/free prostate specific antigen (F/T), time to peak (TTP), and CEUS-BpMRI score were independent factors. The AUC of the nomogram was 0.909 in the training cohort and 0.914 in the validation cohort. Conclusions: CEUS-BpMRI score has high diagnostic efficacy for diagnosing PCa. A nomogram model established by combining age, F/T, TTP, and CEUSBpMRI score can achieve the best predictive accuracy for PCa. [ABSTRACT FROM AUTHOR]

Purpose: The primary aim of this study was to evaluate if exposure to 5-alpha-reductase inhibitors (5-ARIs) modifies the effect of MRI for the diagnosis of clinically significant Prostate Cancer (csPCa) (ISUP Gleason grade ≥ 2). Methods: This study is a multicenter cohort study including patients undergoing prostate biopsy and MRI at 24 institutions between 2013 and 2022. Multivariable analysis predicting csPCa with an interaction term between 5-ARIs and PIRADS score was performed. Sensitivity, specificity, and negative (NPV) and positive (PPV) predictive values of MRI were compared in treated and untreated patients. Results: 705 patients (9%) were treated with 5-ARIs [median age 69 years, Interquartile range (IQR): 65, 73; median PSA 6.3 ng/ml, IQR 4.0, 9.0; median prostate volume 53 ml, IQR 40, 72] and 6913 were 5-ARIs naïve (age 66 years, IQR 60, 71; PSA 6.5 ng/ml, IQR 4.8, 9.0; prostate volume 50 ml, IQR 37, 65). MRI showed PIRADS 1–2, 3, 4, and 5 lesions in 141 (20%), 158 (22%), 258 (37%), and 148 (21%) patients treated with 5-ARIs, and 878 (13%), 1764 (25%), 2948 (43%), and 1323 (19%) of untreated patients (p < 0.0001). No difference was found in csPCa detection rates, but diagnosis of high-grade PCa (ISUP GG ≥ 3) was higher in treated patients (23% vs 19%, p = 0.013). We did not find any evidence of interaction between PIRADS score and 5-ARIs exposure in predicting csPCa. Sensitivity, specificity, PPV, and NPV of PIRADS ≥ 3 were 94%, 29%, 46%, and 88% in treated patients and 96%, 18%, 43%, and 88% in untreated patients, respectively. Conclusions: Exposure to 5-ARIs does not affect the association of PIRADS score with csPCa. Higher rates of high-grade PCa were detected in treated patients, but most were clearly visible on MRI as PIRADS 4 and 5 lesions. Trial registration: The present study was registered at ClinicalTrials.gov number: NCT05078359. [ABSTRACT FROM AUTHOR]

Simple Summary: This study demonstrated a correlation between the apparent diffusion coefficient (ADC) of diffusion-weighted images and potentially malignant prostate lesions, with even better correlation when using the ratio of ADC and prostate-specific antigen density (PSAD), or ADC/PSAD, as a biomarker. Threshold values were determined in order to distinguish between histological cancer grades. Retrospectively, 403 patients with a total of 468 prostate lesions were enrolled. All patients had undergone multiparametric magnetic resonance imaging (mpMRI) and a subsequent biopsy of their prostate lesions, whereby their histological cancer grade was determined. Lower ADC values and lower ADC/PSAD ratios correlated with higher histological cancer stages. Therefore, it was possible to distinguish between histological cancer stages, and thus to reduce the number of unnecessary biopsies. The aim of this study was to demonstrate the correlation between ADC values and the ADC/PSAD ratio for potentially malignant prostate lesions classified into ISUP grades and to determine threshold values to differentiate benign lesions (noPCa), clinically insignificant (nsPCa) and clinically significant prostate cancer (csPCa). We enrolled a total of 403 patients with 468 prostate lesions, of which 46 patients with 50 lesions were excluded for different reasons. Therefore, 357 patients with a total of 418 prostate lesions remained for the final evaluation. For all lesions, ADC values were measured; they demonstrated a negative correlation with ISUP grades (p < 0.001), with a significant difference between csPCa and a combined group of nsPCa and noPCa (ns-noPCa, p < 0.001). The same was true for the ADC/PSAD ratio, but only the ADC/PSAD ratio proved to be a significant discriminator between nsPCa and noPCa (p = 0.0051). Using the calculated threshold values, up to 31.6% of biopsies could have been avoided. Furthermore, the ADC/PSAD ratio, with the ability to distinguish between nsPCa and noPCa, offers possible active surveillance without prior biopsy. [ABSTRACT FROM AUTHOR]

Background: The introduction of prostate-specific antigen (PSA) has revolutionized the diagnosis of prostate cancer (PC). However, there is a wide variation in the daily practice of PSA testing with ongoing efforts to increase its sensitivity. This study aims to evaluate the attitude of Sudanese urologists toward the PSA test in their daily practice. Methods: An online questionnaire was formed and sent to the academic group of Sudanese urologists; it was left for two months with weekly reminders. The group contains 135 members. Data were then collected and analyzed. Results: Of the 135 members, 83 (61.5%) responded to the questionnaire, all were males, with 43% of them being consultants, and 37% having an experience between 5 and 10 years. Most participants (85%) use the test according to international guidelines, the majority (60%) counsel patients before the test, with 72% finding the test more than 50% reliable. In addition, >33% face problems when requesting PSA with >29% of them finding it unreliable. Moreover, in >13%, the test is unavailable. Nearly all participants (95%) think that there is a need for national guidelines to regulate the use of PSA test. Conclusion: For the diversity of practice toward the PSA test and the unavailability of adjunct methods that increase its sensitivity, there is a need for national guidelines to regulate the use of the test in the context of other clinical factors. [ABSTRACT FROM AUTHOR]

Background: Prostate cancer screening with prostate-specific antigen (PSA) can result in unnecessary biopsies and overdiagnosis. Alternately, PSA density (PSAD) calculation may help support biopsy decisions; however, evidence of its usefulness is not concrete. Objective: To evaluate the predictive value of PSAD for clinically significant prostate cancer detection by systematic and MRI-targeted biopsies. Methods: This prospective study was conducted at two tertiary hospitals in Riyadh, Saudi Arabia, between December 2018 and November 2021. Patients suspected of prostate cancer were subjected to multi-parametric MRI, and for those with positive findings, systematic and targeted biopsies were performed. Clinically non-significant and significant prostate cancer cases were classified based on histopathology-defined ISUP grade or Gleason score. The PSAD was measured using the prostate volume determined by the MRI and categorized into ≤0.15, 0.16–0.20, and >0.20 ng/ml2 subgroups. Results: Systematic and targeted biopsies were carried out for 284 patients. The discriminant ability of PSAD is higher in MRI-targeted biopsy compared with systematic biopsy (AUC: 0.77 vs. 0.73). The highest sensitivity (97%) and specificity (87%) were detected at 0.07 ng/ml2 in targeted biopsy. More than half of the clinically significant cases were detected in the >0.2 ng/ml2 PSAD category (systematic: 52.4%; targeted: 51.1%). The CHAID methodology found that the probability of having clinically significant cancer (CSC) in patients with PSAD >0.15 ng/ml2 was more than threefold than that in patients with PSAD ≤0.15 ng/ml2 (64% vs. 20.2%). When considered by age, in PSAD ≤0.15 ng/ml2 subgroup, the percentage of CSC detection rate increased from 20.2% to 24.6% in patients aged ≥60 years. Conclusion: PSAD has good discriminant power for predicting clinically significant prostate cancer. A cutoff of 0.07 ng/ml2 should be adopted, but should be interpreted with caution and by considering other parameters such as age. [ABSTRACT FROM AUTHOR]

Simple Summary: Targeted biopsies of suspicious lesions on multiparametric magnetic resonance imaging (mpMRI) improve the sensitivity of systematic biopsies for clinically significant prostate cancer (csPCa) detection. However, systematic biopsies are still recommended, since a small, albeit significant, percentage of csPCa is only detected in them. In a contemporary series, 13.9% of csPCa cases were only detected in systematic biopsies, which represented 6.7% of its overall detection rate. The finding of independent predictive factors for csPCa detection in targeted biopsies allowed the possibility to develop a predictive model for avoiding systematic biopsies with a low risk of missing csPCa. 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. [ABSTRACT FROM AUTHOR]

We attempted to perform risk categories based on the free/total prostate-specific antigen ratio (%fPSA), prostate-specific antigen (PSA) density (PSAD, in ng ml-2), and multiparametric magnetic resonance imaging (mpMRI) step by step, with the goal of determining the best clinical diagnostic strategy to avoid unnecessary tests and prostate biopsy (PBx) in biopsy-naive men with PSA levels ranging from 4 ng ml-1 to 10 ng ml-1. We included 439 patients who had mpMRI and PBx between August 2018 and July 2021 (West China Hospital, Chengdu, China). To detect clinically significant prostate cancer (csPCa) on PBx, receiver-operating characteristic (ROC) curves and their respective area under the curve were calculated. Based on %fPSA, PSAD, and Prostate Imaging-Reporting and Data System (PI-RADS) scores, the negative predictive value (NPV) and positive predictive value (PPV) were calculated sequentially. The optimal %fPSA threshold was determined to be 0.16, and the optimal PSAD threshold was 0.12 for %fPSA ≥0.16 and 0.23 for %fPSA <0.16, respectively. When PSAD <0.12 was combined with patients with %fPSA ≥0.16, the NPV of csPCa increased from 0.832 (95% confidence interval [CI]: 0.766-0.887) to 0.931 (95% CI: 0.833-0.981); the detection rate of csPCa was similar when further stratified by PI-RADS scores (P = 0.552). Combining %fPSA <0.16 with PSAD ≥0.23 ng ml-2 predicted significantly more csPCa patients than those with PSAD <0.23 ng ml-2 (58.4% vs 26.7%, P < 0.001). Using PI-RADS scores 4 and 5, the PPV was 0.739 (95% CI: 0.634-0.827) when further stratified by mpMRI results. In biopsy-naïve patients with PSA level of 4-10 ng ml-1, stratification of %fPSA and PSAD combined with PI-RADS scores may be useful in the decision-making process prior to undergoing PBx. [ABSTRACT FROM AUTHOR]

Background: Multi-step testing might enhance performance of the prostate cancer diagnostic pipeline. Using PSA >1 ng/ml for first-line risk stratification and the Stockholm 3 Model (S3M) blood-test >10% risk of Gleason Score > 7 prostate cancer to inform biopsy decisions has been suggested. We aimed to determine the effects of changing the PSA cutoff to perform reflex testing with S3M and the subsequent S3M cutoff to recommend prostate biopsy while maintaining the sensitivity to detect Gleason Score ≥ 7 prostate cancer.Methods: We used data from the prospective, population-based, paired, diagnostic Stockholm 3 (STHLM3) study with participants invited by date of birth from the Swedish Population Register during 2012-2014. All participants underwent testing with PSA and S3M (a combination of plasma protein biomarkers [PSA, free PSA, intact PSA, hK2, MSMB, MIC1], genetic polymorphisms, and clinical variables [age, family, history, previous prostate biopsy, prostate exam]). Of 47,688 men in the STHLM3 main study, we used data from 3133 men with S3M >10% and prostate biopsy data. Logistic regression models were used to calculate prostate cancer detection rates and proportion saved biopsies.Results: 44.2%, 62.5% and 67.9% of the participants had PSA <1, <1.5 and <1.7 ng/ml, respectively. Increasing the PSA cut-off for additional work-up from 1 ng/ml to 1.5 ng/ml would thus save 18.3% of the performed tests, 4.9% of the biopsies and 1.3% (10/765) of Gleason Grade ≥ 7 cancers would be un-detected. By lowering the S3M cutoff to recommend biopsy, sensitivity to high-grade prostate cancer can be restored, to the cost of increasing the number of performed biopsies modestly.Conclusion: The sensitivity to detect prostate cancer can be maintained when using different PSA cutoffs to perform additional testing. Biomarker cut-offs have implications on number of tests and prostate biopsies performed. A PSA cutoff of 1.5 ng/ml to perform additional testing such as the S3M test might be considered.Trial Registration: ISRCTN84445406 . [ABSTRACT FROM AUTHOR]

Background: Prostate cancer, which is associated with gland biology and also with environmental risks, is a serious clinical problem in the male population worldwide. Important progress has been made in the diagnostic and clinical setups designed for the detection of prostate cancer, with a multiparametric magnetic resonance diagnostic process based on the PIRADS protocol playing a key role. This method relies on image evaluation by an imaging specialist. The medical community has expressed its desire for image analysis techniques that can detect important image features that may indicate cancer risk. Methods: Anonymized scans of 41 patients with laboratory diagnosed PSA levels who were routinely scanned for prostate cancer were used. The peripheral and central zones of the prostate were depicted manually with demarcation of suspected tumor foci under medical supervision. More than 7000 textural features in the marked regions were calculated using MaZda software. Then, these 7000 features were used to perform region parameterization. Statistical analyses were performed to find correlations with PSA-level-based diagnosis that might be used to distinguish suspected (different) lesions. Further multiparametrical analysis using MIL-SVM machine learning was used to obtain greater accuracy. Results: Multiparametric classification using MIL-SVM allowed us to reach 92% accuracy. Conclusions: There is an important correlation between the textural parameters of MRI prostate images made using the PIRADS MR protocol with PSA levels > 4 mg/mL. The correlations found express dependence between image features with high cancer markers and hence the cancer risk. [ABSTRACT FROM AUTHOR]

Purpose: Prostate cancer (PCa) screening, which relies on prostate-specific antigen (PSA) testing, is a contentious topic that received negative attention due to the low sensitivity and specificity of PSA to detect clinically significant PCa. In this context, due to the higher sensitivity and specificity of magnetic resonance imaging (MRI), several trials investigate the feasibility of "MRI-only" screening approaches, and question if PSA testing may be replaced within prostate cancer screening programs. Methods: This narrative review discusses the current literature and the outlook on the potential of MRI-based PCa screening. Results: Several prospective randomized population-based trials are ongoing. Preliminary study results appear to favor the "MRI-only" approach. However, MRI-based PCa screening programs face a variety of obstacles that have yet to be fully addressed. These include the increased cost of MRI, lack of broad availability, differences in MRI acquisition and interpretation protocols, and lack of long-term impact on cancer-specific mortality. Partly, these issues are being addressed by shorter and simpler MRI approaches (5–20 min bi-parametric MRI), novel quality indicators (PI-QUAL) and the implementation of radiomics (deep learning, machine learning). Conclusion: Although promising preliminary results were reported, MRI-based PCa screening still lack long-term data on crucial endpoints such as the impact of MRI screening on mortality. Furthermore, the issues of availability, cost-effectiveness, and differences in MRI acquisition and interpretation still need to be addressed. [ABSTRACT FROM AUTHOR]

Objectives: Prostate volume (PV) in combination with prostate specific antigen (PSA) yields PSA density which is an increasingly important biomarker. Calculating PV from MRI is a time-consuming, radiologist-dependent task. The aim of this study was to assess whether a deep learning algorithm can replace PI-RADS 2.1 based ellipsoid formula (EF) for calculating PV. Methods: Eight different measures of PV were retrospectively collected for each of 124 patients who underwent radical prostatectomy and preoperative MRI of the prostate (multicenter and multi-scanner MRI's 1.5 and 3 T). Agreement between volumes obtained from the deep learning algorithm (PVDL) and ellipsoid formula by two radiologists (PVEF1 and PVEF2) was evaluated against the reference standard PV obtained by manual planimetry by an expert radiologist (PVMPE). A sensitivity analysis was performed using a prostatectomy specimen as the reference standard. Inter-reader agreement was evaluated between the radiologists using the ellipsoid formula and between the expert and inexperienced radiologists performing manual planimetry. Results: PVDL showed better agreement and precision than PVEF1 and PVEF2 using the reference standard PVMPE (mean difference [95% limits of agreement] PVDL: −0.33 [−10.80; 10.14], PVEF1: −3.83 [−19.55; 11.89], PVEF2: −3.05 [−18.55; 12.45]) or the PV determined based on specimen weight (PVDL: −4.22 [−22.52; 14.07], PVEF1: −7.89 [−30.50; 14.73], PVEF2: −6.97 [−30.13; 16.18]). Inter-reader agreement was excellent between the two experienced radiologists using the ellipsoid formula and was good between expert and inexperienced radiologists performing manual planimetry. Conclusion: Deep learning algorithm performs similarly to radiologists in the assessment of prostate volume on MRI. Key Points: • A commercially available deep learning algorithm performs similarly to radiologists in the assessment of prostate volume on MRI. • The deep-learning algorithm was previously untrained on this heterogenous multicenter day-to-day practice MRI data set. [ABSTRACT FROM AUTHOR]

Nowadays, in the case of suspected prostate cancer (PCa), tissue needle biopsy remains the benchmark for diagnosis despite its invasiveness and poor tolerability, as serum prostate-specific antigen (PSA) is limited by low specificity. The aim of this proteomic study was to identify new diagnostic biomarkers in urine, an easily and non-invasively available sample, able to selectively discriminate cancer from benign prostatic hyperplasia (BPH), evaluating whether the presence of inflammation may be a confounding parameter. The analysis was performed by two-dimensional gel electrophoresis (2-DE), mass spectrometry (LC-MS/MS) and Enzyme-Linked Immunosorbent Assay (ELISA) on urine samples from PCa and BPH patients, divided into subgroups based on the presence or absence of inflammation. Significant quantitative and qualitative differences were found in the urinary proteomic profile of PCa and BPH groups. Of the nine differentially expressed proteins, only five can properly be considered potential biomarkers of PCa able to discriminate the two diseases, as they were not affected by the inflammatory process. Therefore, the proteomic research of novel and reliable urinary biomarkers of PCa should be conducted considering the presence of inflammation as a realistic interfering element, as it could hinder the detection of important protein targets. [ABSTRACT FROM AUTHOR]

Thymidine kinase 1 (TK1) is an intracellular enzyme involved in DNA-precursor synthesis. Increased serum TK1 levels are used as a biomarker in various malignancies. We combined serum TK1 with PSA and evaluated its capacity to predict overall survival (OS) in 175 men with prostate cancer (PCa), detected by screening in 1988–1989 (n = 52) and during follow-up (median 22.6 years) (n = 123). TK1 was measured in frozen serum, age was stratified into four groups, and dates of PCa diagnosis and dates of death were obtained from Swedish population-based registries. The median concentration of TK1 and PSA was 0.25 and 3.8 ng/ml. TK1 was an independent variable of OS. In the multivariate analysis, PSA was not statistically significant in combination with age whereas the significance remained for TK1 + PSA. Measured once, TK1 + PSA predicted a difference of up to 10 years (depending on patient subgroup) in OS at a median of 9 years before PCa diagnosis. The TK1 concentration in 193 controls without malignancies did not differ from that of the PCa patients, hence TK1 was likely not released from incidental PCa. Thus, TK1 in the blood circulation may indicate the release of TK1 from sources other than cancers, nonetheless associated with OS. [ABSTRACT FROM AUTHOR]

PROBASE is a population‐based, randomized trial of 46 495 German men recruited at age 45 to compare effects of risk‐adapted prostate cancer (PCa) screening starting either immediately at age 45, or at a deferred age of 50 years. Based on prostate‐specific antigen (PSA) levels, men are classified into risk groups with different screening intervals: low‐risk (<1.5 ng/ml, 5‐yearly screening), intermediate‐risk (1.5‐2.99 ng/ml, 2 yearly), and high risk (>3 ng/ml, recommendation for immediate biopsy). Over the first 6 years of study participation, attendance rates to scheduled screening visits varied from 70.5% to 79.4%, depending on the study arm and risk group allocation, in addition 11.2% to 25.4% of men reported self‐initiated PSA tests outside the PROBASE protocol. 38.5% of participants had a history of digital rectal examination or PSA testing prior to recruitment to PROBASE, frequently associated with family history of PCa. These men showed higher rates (33% to 57%, depending on subgroups) of self‐initiated PSA testing in‐between PROBASE screening rounds. In the high‐risk groups (both arms), the biopsy acceptance rate was 64% overall, but was higher among men with screening PSA ≥4 ng/ml (>71%) and with PIRADS ≥3 findings upon multiparameter magnetic resonance imaging (mpMRI) (>72%), compared with men with PSA ≥3 to 4 ng/ml (57%) or PIRADS score ≤ 2 (59%). Overall, PROBASE shows good acceptance of a risk‐adapted PCa screening strategy in Germany. Implementation of such a strategy should be accompanied by a well‐structured communication, to explain not only the benefits but also the harms of PSA screening. What's new? Screening for prostate‐specific antigen (PSA) reduces deaths from prostate cancer, but routine PSA screening for all participants leads to overdiagnosis and overtreatment. The PROBASE study, initiated in 2014, uses a risk‐adapted PSA screening strategy that adjusts the screening schedule depending on the participant's initial PSA level. Here, the authors report that adherence rates during the first 6 years of the trial were good, with attendance rates in the 70% to 80% range, and the biopsy acceptance rate was 71% among men with PSA of 4 or higher. [ABSTRACT FROM AUTHOR]

The objective of this study was to identify the prognostic factors and to propose a new risk model in metastatic castration-resistant prostate cancer (mCRPC) patients. The clinical data were retrospectively obtained for 102 mCRPC patients who received cancer treatment between 2005 and 2018 at the University of Tokyo Hospital. We investigated clinical and pathological parameters, including prostate-specific antigen (PSA) kinetic profiles under androgen deprivation treatment, and identified predictors of overall survival (OS). The median age and PSA were 73 (Interquartile range [IQR], 68–79) years and 5.00 (IQR, 2.77–13.6) ng/ml. The median follow-up was 34 (IQR, 17–56) months. In univariate analysis, 'lymph node metastasis', 'Hemoglobin (Hb)', 'Time to nadir PSA (TNPSA)', 'PSA doubling time (PSADT)', 'Time to CRPC', and 'presence of pain' were prognostic factors. Multivariate analysis identified 'Hb < 11 g/dL', 'TNPSA < 7 months' and 'PSADT < 5 months' as independent prognostic factors of OS. The high-risk group (patients with two or three factors) demonstrated shorter OS (23 vs. 50 months) with an increased risk of death (HR = 2.997; 95% CI 1.632–5.506; P = 0.0004). The proposed risk stratification model may contribute to the prediction of survival and provide supportive information in treatment decision-making. [ABSTRACT FROM AUTHOR]

Neuroendocrine prostate cancer (NEPC) is an aggressive form of prostate cancer frequently seen after prolonged treatment of castration resistant prostate cancer (CRPC). NEPC has become increasingly prevalent over the last 20 years, with a poor prognosis caused by a late diagnosis and limited treatment options. Recent advances in PET/CT imaging and targeted radioimmunotherapy are promising, but more research into additional treatment options is needed. The aim of this review is to analyze the current imaging and treatment options for NEPC, and to highlight future potential treatment strategies. A Pubmed search for 'Neuroendocrine Prostate Cancer' was performed and relevant articles were reviewed. The recent FDA approval and success of 177 PSMA Lutetium in CRPC is promising, as 177 Lutetium could potentially be paired with a NEPC specific biomarker for targeted therapy. Recent laboratory studies pairing DLL3, which is overexpressed in NEPC, with 177 Lutetium and new PET agents have showed good efficacy in identifying and treating NEPC. The success of future development of NEPC therapies may depend on the availability of 177 Lutetium, as current supplies are limited. Further research into additional imaging and treatment options for NEPC is warranted. Neuroendocrine prostate cancer (NEPC) is a rare form of prostate cancer. People with NEPC have typically had previous treatment for prostate cancer. NEPC is usually found after prostate cancer cells have spread outside of the prostate. NEPC may not produce typical prostate cancer markers such as prostate specific antigen (PSA). This can make detection of NEPC difficult. NEPC is difficult to treat because NEPC does not respond very well to typical prostate cancer medications. Because of this, people with NEPC typically have a shortened survival. Many researchers have been developing new ways to find and treat NEPC. New methods of imaging with PET/CT scans are better at detecting NEPC than standard imaging. Treatments that specifically target NEPC cells are currently being researched, but these treatments have not been used on any patients yet. This article describes these research efforts and recommends that more research should be done to find treatments for NEPC. [ABSTRACT FROM AUTHOR]

Prostate biopsy is recommended in cases of positive magnetic resonance imaging (MRI), defined as Prostate Imaging Reporting and Data System (PIRADS) category ≥ 3. However, most men with positive MRIs will not be diagnosed with clinically significant prostate cancer (csPC). Our goal was to evaluate pre-biopsy characteristics that influence the probability of a csPC diagnosis in these patients. We retrospectively analyzed 740 consecutive men with a positive MRI and no prior PC diagnosis who underwent MRI-ultrasound fusion biopsies of the prostate in three centers. csPC detection rates (CDRs) for each PIRADS category were calculated. Patient, disease, and lesion characteristics were studied for interdependencies with the csPC diagnosis. The CDR in patients with PIRADS categories 3, 4, and 5 was 10.5%, 30.7%, and 54.6%, respectively. On both uni- and multivariable regression models, older age, being biopsy-naïve, prostate specific antigen ≥ 10 ng/mL, smaller prostate volume, PIRADS > 3, a larger maximum lesion size, a lesion in the peripheral zone, and a positive digital rectal examination were associated with csPC. In this large, multicenter study, we provide new data regarding CDRs in particular PIRADS categories. In addition, we present several strong predictors that further alter the risk of csPC in MRI-positive patients. Our results could help in refining individual risk assessment, especially in PIRADS 3 patients, in whom the risk of csPC is substantially low. [ABSTRACT FROM AUTHOR]

Simple Summary: Controversy exists regarding prostate cancer (PC) screening using the prostate-specific antigen (PSA) test. It may reduce PC mortality risk but is associated with false-positive results. We aimed to evaluate the incidence of false-positive and false-negative results in a general clinical setting and the associated variables. We found a high rate of false-positive results (46.6%), resulting in a positive predictive value of 12.7%. Patients also showed a low rate of false-negative results (3.7%) with a negative predictive value of 99.5%. Age, alcohol intake, and having a urinary tract infection were associated with a higher probability of false-positive results; having diabetes mellitus type II was associated with a lower rate of false-positive results. This study showed a higher rate of false-positive results in clinical practice than in previous clinical trials, mainly in patients over 60 years. (1) Background: There are no real-world data evaluating the incidence of false-positive results. We analyzed the clinical and analytical factors associated with the presence of false-positive results in PSA determinations in practice. (2) Methods: A prospective cohort study of patients with a PSA test was performed in clinical practice. We followed the patients by reviewing their medical records for 2 years or until the diagnosis of PCa was reached, whichever came first. (3) Results: False-positive PSA rate was 46.8% (95% CI 44.2–49.2%) and false-negative PSA rate was 2.8% (95% CI 2–3.5%). Patients aged 61–70 years and those over 70 years were more likely to have a false-positive result than those under 45 years (aOR 2.83, 95% CI 1.06–7.55, p = 0.038, and aOR 4.62, 95% CI 1.75–12.22, p = 0.002, respectively). Patients with urinary tract infection were more likely to have a false-positive result (aOR 8.42, 95% CI 2.42–29.34, p = 0.001). Patients with diabetes mellitus were less likely to have a false-positive result (aOR 0.63, 95% CI 0.41–0.98, p = 0.038); (4) Conclusions: This study has generated relevant information that could be very useful for shared decision making in clinical practice. [ABSTRACT FROM AUTHOR]

Purpose: To inform updated recommendations by the Canadian Task Force on Preventive Health Care on screening for prostate cancer in adults aged 18 years and older in primary care. This protocol outlines the planned scope and methods for a series of systematic reviews. Methods: Updates of two systematic reviews and a de novo review will be conducted to synthesize the evidence on the benefits and harms of screening for prostate cancer with a prostate-specific antigen (PSA) and/or digital rectal examination (DRE) (with or without additional information) and patient values and preferences. Outcomes for the benefits of screening include reduced prostate cancer mortality, all-cause mortality, and incidence of metastatic prostate cancer. Outcomes for the harms of screening include false-positive screening tests, overdiagnosis, complications due to biopsy, and complications of treatment including incontinence (urinary or bowel), and erectile dysfunction. The quality of life or functioning (overall and disease-specific) and psychological effects outcomes are considered as a possible benefit or harm. Outcomes for the values and preferences review include quantitative or qualitative information regarding the choice to screen or intention to undergo screening. For the reviews on benefits or harms, we will search for randomized controlled trials, quasi-randomized, and controlled studies in MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials. For the review on values and preferences, we will search for experimental or observational studies in MEDLINE, Embase, and PsycInfo. For all reviews, we will also search websites of relevant organizations, gray literature, and reference lists of included studies. Title and abstract screening, full-text review, data extraction, and risk of bias assessments will be completed independently by pairs of reviewers with any disagreements resolved by consensus or by consulting with a third reviewer. The GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach will be used to assess the certainty of the evidence for each outcome. Discussion: The series of systematic reviews will be used by the Canadian Task Force on Preventive Health Care to update their 2014 guideline on screening for prostate cancer in adults aged 18 years and older. Systematic review registration This review has been registered with PROSPERO (CRD42022314407) and is available on the Open Science Framework (osf.io/dm32k). [ABSTRACT FROM AUTHOR]

Purpose: The diagnostic approach for prostate cancer still depends on PSA and DRE. Objectives: to evaluate the diagnostic validity of PSA-Density and PIRADSv2 as diagnostic tests regarding biopsy results, and to design nomograms that include all diagnostic variables for malignancy, significant tumor (ST) and high-grade tumor. Methods: Cross-sectional study which included men with PSA ≥ 4 ng/ml and/or suspicious DRE, PIRADSv2 ≥ 3 lesions on multiparametric MRI and prostate biopsy. The gold standard test was the maximum ISUP of the targeted biopsy per patient (malignancy: ISUP ≥ 1, ST: ISUP ≥ 2, high-grade tumor: ISUP ≥ 4). Association and logistic regression tests were used and diagnostic validity parameters using PSA-Density and PIRADSv2 classification was analyzed. Nomograms were designed for malignancy, ST, and high-grade tumor using the best model selection procedure from all possible equations. Results: 336 men with median age, PSA and PSA-Density of 67.7 years (IQR:12.6), 6.3 ng/ml (IQR:3.3) and 0.12 ng/ml/cc (IQR:0.10), respectively; 63 index lesions were PIRADS3, 204 PIRADS4, and 69 PIRADS5. 65.8% and 37.8% were malignant and ST, respectively. The significant positive association highlighted between malignancy and ST with age, DRE, PSA-Density and PIRADSv2. PSA-Density and PIRADSv2 ≥ 3 presented the highest sensitivity to detect malignancy, and their combination showed sensitivity nearly 95% (AUC:0.803). Nomograms for malignancy and ST included the variables age, DRE, PSA-Density, and PIRADSv2 with a sensitivity closely 91% (AUC:0.833), and a specificity of almost 85% for ST, exposing risk < 5% for ST when PSA-Density is < 0.15, not suspicious DRE and PIRADS3. Conclusion: PSA-Density and PIRADSv2 classification in risk nomograms can provide highly relevant information to increase the accuracy in the diagnosis of PC and ST. [ABSTRACT FROM AUTHOR]

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Background: Prostate cancer is an epidemic of the modern age, and despite efforts to improve awareness, it remains the case that mortality has hardly altered over the decades, driven largely by late presentation. There is a strong public perception that male urinary symptoms is one of the key indicators of prostate cancer, and this continues to be part of messaging from national guidelines and media health campaigns. This narrative, however, is not based on evidence and may be seriously hampering efforts to encourage early presentation.Discussion: Anatomically, prostate cancer most often arises in the peripheral zone, while urinary symptoms result from compression of the urethra by prostatic enlargement more centrally. Biopsy studies show that mean prostate volume is actually lower in men found to have (early) prostate cancer compared to those with benign biopsies. This inverse relationship between prostate size and the probability of cancer is so strong that PSA density (PSA corrected for prostate volume) is known to be significantly more accurate in predicting a positive biopsy than PSA alone. Thus, this disconnect between scientific evidence and the current perception is very striking. There is also evidence that using symptoms for investigating possible cancer may lead to higher proportions of men presenting with locally advanced or metastatic disease compared to PSA testing or screening programmes. Concerns about overwhelming health care services if men are encouraged to get tested without symptoms may also be overstated, with recent newer approaches to reduce over-investigation and treatment. In this article, we explore the link between urinary symptoms and prostate cancer and propose that public and professional messaging needs to change.Conclusion: If rates of earlier diagnosis are to improve, we call for strong clear messaging that prostate cancer is a silent disease especially in the curable stages and men should come forward for testing regardless of whether or not they have symptoms. This should be done in parallel with other ongoing efforts to raise awareness including targeting men at highest risk due to racial ancestry or family history. While the current resurgence in interest and debate about prostate cancer screening is timely, change of this message by guideline bodies, charities and the media can be a first simple step to improving earlier presentation and hence cures rates. [ABSTRACT FROM AUTHOR]

BACKGROUND: Prostate-specific antigendensity (PSAD) is an important, but under-utilized addition to clinical and laboratory diagnosis of prostate malignancy. It is calculated by dividing the level of prostate-specific antigen (PSA) in serum by the volume of prostate gland. OBJECTIVES: The aim of this study is to determine the sensitivity, specificity and accuracy of PSAD in outcome of prostate biopsies, and to compare PSAD values in patients of prostatic cancer with and without lymphovascular and perineural invasion at histopathology. METHODS: This study included data of seventy-seven patients who underwent transrectal ultrasound-guided (TRUS) biopsy of prostate gland at our centre. Volume of prostate was calculated sonographically using endorectal coil. PSAD was calculated by dividing serum PSA level by prostatic volume. CONCLUSION: Sensitivity of PSAD is high for diagnosis of prostate cancer with fair degree of accuracy and moderate specificity. [ABSTRACT FROM AUTHOR]

Objectives: To predict castration-resistant prostate cancer (CRPC) and prostate cancer (Pca) death by use of clinical variables at Pca diagnosis and PSA levels after start of gonadotropin-releasing hormone agonists (GnRH) in men with non-metastatic castration sensitive prostate cancer (nmCSPC). Materials and Methods: PSA values for 1603 men with nmCSPC in the National Prostate Cancer Register of Sweden who received GnRH as primary treatment were retrieved from Uppsala-Örebro PSA Cohort and Stockholm PSA and Biopsy Register. All men had measured PSA before (pre-GnRH PSA) and 3–6 months after (post-GnRH PSA) date of start of GnRH. Unadjusted and adjusted Cox models were used to predict CRPC by PSA levels. PSA levels and ISUP grade were used to construct a risk score to stratify men by tertiles according to risk of CRPC and Pca death. Results: 788 (49%) men reached CRPC and 456 (28%) died of Pca during follow-up. Post-GnRH PSA predicted CRPC regardless of pre-GnRH PSA. CRPC risk increased with higher post-GnRH PSA, HR 4.7 (95% CI: 3.4–6.7) for PSA > 16 ng/mL vs 0–0.25 ng/mL and with ISUP grade, HR 3.7 (95%: 2.5–5.4) for ISUP 5 vs ISUP 1. Risk of Pca death in men above top vs bellow bottom tertile of post-GnRH PSA and ISUP grade was HR 4.1 (95% CI: 3.0–5.5). Conclusion: A risk score based on post-GnRH PSA and ISUP grade could be used for early identification of a target group for future clinical trials on additional therapy to GnRH. [ABSTRACT FROM AUTHOR]

Background: Almost 50,000 men in the United Kingdom (UK) are diagnosed each year with prostate cancer (PCa). Secondary referrals for investigations rely on serum prostate-specific antigen (PSA) levels and digital rectal examination. However, both tests lack sensitivity and specificity, resulting in unnecessary referrals to secondary care for costly and invasive biopsies. Materials and Methods: Serum samples and clinical information were collected from N = 125 age-matched patients (n = 61 non-PCa and n = 64 PCa) and analyzed using Biochip Array Technology on high-sensitivity cytokine array I (IL-2, IL-4, IL-6, IL-8, IL-10, IL-1α, IL-1β, TNFα, MCP-1, INFγ, EGF, and VEGF), cerebral array II (CRP, D-dimer, neuron-specific enolase, and sTNFR1), and tumor PSA oncology array (fPSA, tPSA, and CEA). Results: The data showed that 11/19 (68.8%) markers were significantly different between the non-PCa and the PCa patients. A combination of EGF, log10 IL-8, log10 MCP-1, and log10 tPSA significantly improved the predictive potential of tPSA alone to identify patients with PCa (DeLong, p < 0.001). This marker combination had an increased area under the receiver operator characteristic (0.860 vs. 0.700), sensitivity (78.7 vs. 68.9%), specificity (76.5 vs. 67.2%), PPV (76.2 vs. 66.7%), and NPV (79.0 vs. 69.4%) compared with tPSA. Conclusions: The novel combination of serum markers identified in this study could be employed to help triage patients into "low-" and "high-risk" categories, allowing general practitioners to improve the management of patients in primary care settings and potentially reducing the number of referrals for unnecessary, invasive, and costly treatments. [ABSTRACT FROM AUTHOR]

Simple Summary: Magnetic resonance imaging (MRI)-associated prostate-specific antigen density (mPSAD) and MRI predictive models have been proposed for improving the selection of candidates for prostate biopsy among men with suspected prostate cancer (PCa). While the calculation of mPSAD only requires a simple division, the individual risk assessment of PCa using the available risk calculators is also a swift process. We aim to compare the clinical usefulness of mPSAD and an MRI predictive model that utilises the same predictors as the recently developed and externally validated Barcelona MRI predictive model (MRI-PMbdex). 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. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the diagnostic performance of combining the Prostate Imaging Reporting and Data System (PI-RADS) scoring system v2.1 with prostate-specific antigen density (PSAD) to detect prostate cancer (PCa). Methods: A total of 266 participants with suspicion of PCa underwent multiparametric magnetic resonance imaging (mpMRI) in our hospital, after at least 4 weeks all patients underwent subsequent systematic transrectal ultrasound (TRUS)-guided biopsy or MRI-TRUS fusion targeted biopsy. All mpMRI images were scored in accordance with the PI-RADS v2.1, and univariate and multivariate logistic regression analyses were performed to determine significant predictors of PCa. Results: A total of 119 patients were diagnosed with PCa in the biopsy, of them 101 patients were diagnosed with clinically significant PCa. The multivariate analysis revealed that PI-RADS v2.1 and PSAD were independent predictors for PCa. For peripheral zone (PZ), the area under the ROC curve (AUC) for the combination of PI-RADS score and PSAD was 0.90 (95% CI 0.83-0.96), which is significantly superior to using PI-RADS score (0.85, 95% CI 0.78-0.93, P=0.031) and PSAD alone (0.83, 95% CI 0.75-0.90, P=0.037). For transition zone (TZ), however, the combination model was not significantly superior to PI-RADS alone, with AUC of 0.94 (95% CI 0.89-0.99) vs. 0.93 (95% CI 0.88-0.97, P=0.186). Conclusion: The combination of PI-RADS v2.1 with PSAD could significantly improve the diagnostic performance of PCa in PZ. Nevertheless, no significant improvement was observed regarding PCa in TZ. [ABSTRACT FROM AUTHOR]

Background: Early screening of clinically significant prostate cancer (csPCa) may offer opportunities in revolutionizing the survival benefits of this lethal disease. We sought to introduce a modified prostate health index density (mPHI) model using imaging indicators and to compare its diagnostic performance for early detection of occult onset csPCa within the prostate-specific antigen (PSA) gray zone with that of PHI and PHID. Methods and Participation: Between August 2020 and January 2022, a training cohort of 278 patients (total PSA 4.0–10.0 ng/ml) who were scheduled for a prostate biopsy were prospectively recruited. PHI and PHID were compared with mPHI ( LD TRD × APD × TPV × PHI) for the diagnosis performance in identifying csPCa. Pathology outcomes from systematic prostate biopsies were considered the gold standard. Results: This model was tested in a training cohort consisting of 73 csPCa, 14 non-clinically significant prostate cancer(non-csPCa), and 191 benign prostatic hyperplasia (BPH) samples. In the univariate analysis for the PSA gray zone cohort, for overall PCa, the AUC of mPHI (0.856) was higher than PHI (0.774) and PHID (0.835). For csPCa, the AUC of mPHI (0.859) also surpassed PHI (0.787) and PHID (0.825). For detection of csPCa, compared with lower specificities from PHI and PHID, mPHI performed the highest specificity (76.5%), by sparing 60.0% of unnecessary biopsies at the cost of missing 11 cases of csPCa. The mPHI outperformed PHI and PHID for overall PCa detection. In terms of csPCa, mPHI exceeds diagnostic performance with a better net benefit in decision curve analysis (DCA) compared with PHI or PHID. Conclusions: We have developed a modified PHI density (mPHI) model that can sensitively distinguish early-stage csPCa patients within the PSA gray zone. Clinical Trial Registration: ClinicalTrials.gov , NCT04251546. [ABSTRACT FROM AUTHOR]

Prostate cancer (PCa) diagnostic and therapeutic work-up has evolved significantly in the last decade, with pre-biopsy multiparametric MRI now widely endorsed within international guidelines. There is potential to move away from the widespread use of systematic biopsy cores and towards an individualised risk-stratified approach. However, the evidence on the optimal biopsy approach remains heterogeneous, and the aim of this review is to highlight the most relevant features following a critical assessment of the literature. The commonest biopsy approaches are via the transperineal (TP) or transrectal (TR) routes. The former is considered more advantageous due to its negligible risk of post-procedural sepsis and reduced need for antimicrobial prophylaxis; the more recent development of local anaesthetic (LA) methods now makes this approach feasible in the clinic. Beyond this, several techniques are available, including cognitive registration, MRI–Ultrasound fusion imaging and direct MRI in-bore guided biopsy. Evidence shows that performing targeted biopsies reduces the number of cores required and can achieve acceptable rates of detection whilst helping to minimise complications and reducing pathologist workloads and costs to health-care facilities. Pre-biopsy MRI has revolutionised the diagnostic pathway for PCa, and optimising the biopsy process is now a focus. Combining MR imaging, TP biopsy and a more widespread use of LA in an outpatient setting seems a reasonable solution to balance health-care costs and benefits, however, local choices are likely to depend on the expertise and experience of clinicians and on the technology available. [ABSTRACT FROM AUTHOR]

Background: Prostate-specific antigen (PSA) is a commonly used test to detect prostate cancer. Attention has mostly focused on the use of PSA in screening asymptomatic patients, but the diagnostic accuracy of PSA for prostate cancer in patients with symptoms is less well understood.Methods: A systematic database search was conducted of Medline, EMBASE, Web of Science, and the Cochrane library. Studies reporting the diagnostic accuracy of PSA for prostate cancer in patients with symptoms were included. Two investigators independently assessed the titles and abstracts of all database search hits and full texts of potentially relevant studies against the inclusion criteria, and data extracted into a proforma. Study quality was assessed using the QUADAS-2 tool by two investigators independently. Summary estimates of diagnostic accuracy were calculated with meta-analysis using bivariate mixed effects regression.Results: Five hundred sixty-three search hits were assessed by title and abstract after de-duplication, with 75 full text papers reviewed. Nineteen studies met the inclusion criteria, 18 of which were conducted in secondary care settings with one from a screening study cohort. All studies used histology obtained by transrectal ultrasound-guided biopsy (TRUS) as a reference test; usually only for patients with elevated PSA or abnormal prostate examination. Pooled data from 14,489 patients found estimated sensitivity of PSA for prostate cancer was 0.93 (95% CI 0.88, 0.96) and specificity was 0.20 (95% CI 0.12, 0.33). The area under the hierarchical summary receiver operator characteristic curve was 0.72 (95% CI 0.68, 0.76). All studies were assessed as having a high risk of bias in at least one QUADAS-2 domain.Conclusions: Currently available evidence suggests PSA is highly sensitive but poorly specific for prostate cancer detection in symptomatic patients. However, significant limitations in study design and reference test reduces the certainty of this estimate. There is very limited evidence for the performance of PSA in primary care, the healthcare setting where most PSA testing is performed. [ABSTRACT FROM AUTHOR]

Although prostate-specific antigen-based prostate cancer screening had a positive impact in reducing prostate cancer mortality, it also led to overdiagnosis, overtreatment and a significant number of unnecessary biopsies. In the post-prostate-specific antigen era, new biomarkers have emerged that can complement the information given by prostate-specific antigen, towards a better cancer diagnostic specificity, and also allowing a better estimate of the aggressiveness of the disease and its clinical outcome. That means those markers have the potential to assist the clinician in the decision-making processes, such as whether or not to perform a biopsy, and to make the best treatment choice among the new therapeutic options available, including active surveillance in lower risk disease. In this article, we will review several of those more recent diagnostic markers (4Kscore®, [-2]proPSA and Prostate Health Index, SelectMDx®, ConfirmMDx®, Progensa® Prostate Cancer Antigen 3, Mi-Prostate Score, ExoDx™ Prostate Test, the Stockholm3 test and ERSPC risk calculators) and prognostic markers (OncotypeDX® Genomic Prostate Score, Prolaris®, Decipher® and ProMark®). We will also address some new liquid biopsy approaches – circulating tumour cells and cell-free DNA – with a potential role in metastatic castration-resistant prostate cancer and will briefly give some future perspectives, mostly outlooking epigenetic markers. [ABSTRACT FROM AUTHOR]

Background: Prostate-specific antigen (PSA) is considered neither sensitive nor specific for prostate cancer (PCa). We aimed to compare total PSA (tPSA), percentage of free PSA (%fPSA), the PSA density (PSAD), Prostate Health Index (PHI), and the PHI density (PHID) to see which one could best predict clinically significant prostate cancer (csPCa): a potentially lethal disease. Methods: A total of 412 men with PSA of 2–20 ng/mL were prospectively included. Serum biomarkers for PCa was collected before transrectal ultrasound guided prostate biopsy. PHI was calculated by the formula: (p2PSA/fPSA) x √tPSA. PHID was calculated as PHI divided by prostate volume measured by transrectal ultrasound. Results: Of the 412 men, 134 (32.5%) and 94(22.8%) were diagnosed with PCa and csPCa, respectively. We used the area under the receiver operating characteristic curve (AUC) and decision curve analyses (DCA) to compare the performance of PSA related parameters, PHI and PHID in diagnosing csPCa. AUC for tPSA, %fPSA, %p2PSA, PSAD, PHI and PHID were 0.56、0.63、0.76、0.74、0.77 and 0.82 respectively for csPCa detection. In the univariate analysis, the prostate volume, tPSA, %fPSA, %p2PSA, PHI, PSAD, and PHID were all significantly associated with csPCa, and PHID was the most important predictor (OR 1.41, 95% CI 1.15–1.72). Besides, The AUC of PHID was significantly larger than PHI in csPCa diagnosis (p =0.004). At 90% sensitivity, PHID had the highest specificity (54.1%) for csPCa and could reduce the most unnecessary biopsies (43.7%) and miss the fewest csPCa (8.5%) when PHID ≥ 0.67. In addition to AUC, DCA re-confirmed the clinical benefit of PHID over all PSA-related parameters and PHI in csPCa diagnosis. The PHID cut-off value was positively correlated with the csPCa ratio in the PHID risk table, which is useful for evaluating csPCa risk in a clinical setting. Conclusion: The PHID is an excellent predictor of csPCa. The PHID risk table may be used in standard clinical practice to pre-select men at the highest risk of harboring csPCa. [ABSTRACT FROM AUTHOR]