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Objectives: To develop a microultrasound-based nomogram including clinicopathological parameters and microultrasound findings to predict the presence of extra-prostatic extension and guide the grade of nerve-sparing., Material and Methods: All patients underwent microultrasound the day before robot-assisted radical prostatectomy. Variables significantly associated with extra-prostatic extension at univariable analysis were used to build the multivariable logistic model, and the regression coefficients were used to develop the nomogram. The model was subjected to 1000 bootstrap resamples for internal validation. The performance of the microultrasound-based model was evaluated using the area under the curve (AUC) of the receiver operating characteristic (ROC) curve, calibration plot, and decision curve analysis (DCA)., Results: Overall, 122/295 (41.4%) patients had a diagnosis of extra-prostatic extension on definitive pathology. Microultrasound correctly identify extra-prostatic extension in 84/122 (68.9%) cases showing a sensitivity and a specificity of 68.9% and 84.4%, with an AUC of 76.6%. After 1000 bootstrap resamples, the predictive accuracy of the microultrasound-based model was 85.9%. The calibration plot showed a satisfactory concordance between predicted probabilities and observed frequencies of extra-prostatic extension. The DCA showed a higher clinical net-benefit compared to the model including only clinical parameters. Considering a 4% cut-off, nerve-sparing was recommended in 173 (58.6%) patients and extra-prostatic extension was detected in 32 (18.5%) of them., Conclusion: We developed a microultrasound-based nomogram for the prediction of extra-prostatic extension that could aid in the decision whether to preserve or not neurovascular bundles. External validation and a direct comparison with mpMRI-based nomogram is crucial to corroborate our results., Competing Interests: Declaration of competing interest The authors declare that they have no competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Purpose: To assess the diagnostic performance of microultrasound-targeted biopsy (microUSTBx) and systematic biopsy (SBx) in detecting clinically significant prostate cancer (csPCa) among men with abnormal digital rectal examination (DRE) and suspicious lesions at multiparametric magnetic resonance imaging (mpMRI), and to compare the diagnostic performance of this approach with a mpMRI-guided targeted biopsy (MTBx) plus SBx-based strategy., Methods: Biopsy-naïve men with suspicious lesions at mpMRI and abnormal DRE were prospectively evaluated between October 2017 and January 2023. csPCa detection rate by microUSTBx plus SBx and MTBx plus SBx was assessed and then compared by McNemar's test. The added value of prostate-specific antigen density (PSAd) was also evaluated., Results: Overall, 182 biopsy naïve men were included. MicroUSTBx plus SBx achieved comparable detection rate to MTBx plus SBx in diagnosis of ciPCa and csPCa (ciPCa: 9.3% [17/182] vs 10% [19/182]; csPCa: 63% [114/182] vs 62% [113/182]). MicroUSTBx outperformed MTBx (ciPCa: 5.5% [10/182] vs 6.0% [11/182]; csPCa: 57% [103/182] vs 54% [99/182]). Using microUSTBx plus SBx would have avoided 68/182 (37%) unnecessary mpMRI, while missing only 2/116 (1.7%) csPCa. The decision curve analysis of suspicious microUS plus PSAd ≥ 0.15 ng/ml showed higher net benefit in the ability to identify true positives and reduce the number of unnecessary prostate biopsy in this subcategory of patients., Conclusions: The combination of microUSTBx and SBx showed equal diagnostic performance to an mpMRI-based approach in biopsy-naïve patients with an abnormal DRE. The combination of this approach with PSAd maximize the diagnostic accuracy while lowering the need for unnecessary biopsies., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Micro-UltraSound (microUS) is a new imaging modality capable of identifying and targeting suspicious areas, which might further increase the diagnostic yield of prostate biopsy (PBx). Aim of this review is to provide insights into the usefulness of microUS for the sub-stratification of prostate cancer (PCa), clinically significant PCa (i.e., any Gleason score ≥ 7 PCa; csPCa) along with non-organ-confined disease in patients undergoing PBx., Methods: A PubMed literature search was performed using keywords: prostate cancer diagnosis, prostate cancer diagnosis surveillance, systematic biopsy, target biopsy, micro-ultrasound, and prostate risk identification using micro-ultrasound., Results: MicroUS could significantly improve multiparametric magnetic resonance imaging (mpMRI) findings by adding valuable anatomical and pathological information provided by real-time examination. Furthermore, microUS target biopsy could replace systematic biopsy in clinical practice by reducing the detection of clinically insignificant (ciPCa) and increasing that of csPCa. Finally, microUS may be useful in predicting the presence of non-organ confined PCa before radical prostatectomy and it could also be an effective add-on tool for patient monitoring within the active surveillance program., Conclusion: MicroUS may represent an attractive step forward for the management of csPCa as a complementary or alternative tool to mpMRI. Nevertheless, further longitudinal studies are warranted, and the strength of the evidence is still suboptimal to provide clear recommendations for daily clinical practice., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: To evaluate the diagnostic accuracy of multiparametric magnetic resonance imaging (MRI)- and microultrasound (microUS)-guided targeted biopsy (TBx) in detecting prostate cancer (PCa) and clinically significant (cs) PCa among men with Prostate Imaging Reporting and Data System (PI-RADS 5) lesions and to compare this combined TBx (CTBx) strategy with CTBx plus systemic biopsy (SBx)., Methods: One hundred and thirty-six biopsy-naïve patients with PI-RADS 5 lesion at multiparametric MRI undergoing CTBx plus SBx were retrospectively evaluated. Analysis of diagnostic performance of microUS-TBx, MRI-TBx, CTBx, SBx and combined CTBx plus SBx was performed. Cost (downgrade, upgrade and biopsy core) to effectiveness (detection rate) was compared., Results: CTBx achieved a comparable detection rate to CTBx plus SBx in diagnosis of PCa and csPCa (PCa: 78.7% [107/136] vs 79.4% [108/136]; csPCa: 67.6% [92/136] vs 67.6% [92/136]; p > 0.05) and outperformed SBx (PCa: 58.8% [80/136]; csPCa: 47.8% [65/136]; p < 0.001). Using CTB would have avoided 41.1% (56/136) unnecessary SBx, without missing any csPCa. The rate of any upgrading or csPCa upgrading was significantly higher by SBx than by CTBx [33/65 (50.8%) vs 17/65 (26.1%) and 20/65 (30.8%) vs 4/65 (6.15%), respectively, p < 0.05]. Considering csPCa detection rate, microUS showed high sensitivity and positive predictive value (94.6%, 87.9%, respectively), with lower specificity and negative predictive value (25.0% and 44.4%, respectively). At multivariable logistic regression models, positive microUS was identified as an independent predictor of csPCa (p = 0.024)., Conclusions: A combined microUS/MRI-TBx approach could be the ideal imaging tool for characterizing primary disease in PI-RADS five patients, allowing SBx to be avoided., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Active surveillance (AS) represents a standard of care of low-risk prostate cancer (PCa). However, the identification and monitoring of AS candidates remains challenging. Microultrasound (microUS) is a novel high-resolution imaging modality for transrectal ultrasonography (TRUS). We explored the impact of microUS TRUS and targeted biopsies in mpMRI-guided confirmatory biopsies., Methods: Between October 2017 and September 2021, we prospectively enrolled 100 patients scheduled for MRI-guided confirmatory biopsy at 1 year from diagnosis of ISUP 1 PCa. TRUS was performed using the ExactVu microUS system; PRI-MUS protocol was applied to identify suspicious lesions (i.e., PRIMUS score ≥ 3). All patients received targeted biopsies of any identified microUS and mpMRI lesions and complementary systematic biopsies. The proportion of patients upgraded to clinically significant PCa (defined as ISUP ≥ 2 cancer; csPCa) at confirmatory biopsies was determined, and the diagnostic performance of microUS and mpMRI were compared., Results: Ninety-two patients had a suspicious MRI lesion classified PI-RADS 3, 4, and 5 in respectively 28, 16, and 18 patients. MicroUS identified 82 patients with suspicious lesions, classified as PRI-MUS 3, 4, and 5 in respectively 20, 50, and 12 patients, while 18 individuals had no lesions. Thirty-four patients were upgraded to ISUP ≥ 2 cancer and excluded from AS. MicroUS and mpMRI showed a sensitivity of 94.1% and 100%, and an NPV of 88.9% and 100%, respectively, in detecting ISUP ≥ 2 patients. A microUS-mandated protocol would have avoided confirmatory biopsies in 18 patients with no PRI-MUS ≥ 3 lesions at the cost of missing four upgraded patients., Conclusions: MicroUS and mpMRI represent valuable imaging modalities showing high sensitivity and NPV in detecting csPCa, thus allowing their use for event-triggered confirmatory biopsies in AS patients. MicroUS offers an alternative imaging modality to mpMRI for the identification and real-time targeting of suspicious lesions in AS patients., (© 2023 Wiley Periodicals LLC.)

Background: This prospective single-arm study is designed to compare in parallel 68Ga-PSMA PET/TRUS (transrectal or transperineal) fusion biopsy ("experimental test") with multiparametric MRI (mpMRI)/TRUS fusion prostate biopsy ("standard test") in men with a high suspicion of prostate cancer (PCa) after at least one negative biopsy. The primary objective was to evaluate the diagnostic performance of 68Ga-PSMA PET/TRUS fusion prostate biopsy in comparison to mpMRI/TRUS fusion prostate biopsy analyzed in parallel. Secondarily, we aimed to determine the relationship between the "experimental test" and the histopathological characteristics of the specimen, along with the clinical utility of the "experimental test" compared to the "standard test.", Summary: To test the superiority of 68Ga-PSMA PET/CT compared to mpMRI, we will enroll a minimum cohort of 128 patients. Inclusion criteria comprise: age >18 years; blood PSA level >4.0 ng/mL; free-to-total PSA ratio <20%; progressive rise of PSA levels in two consecutive blood samples despite antibiotics; serum blood tests suspicious for PCa; at least one previous negative biopsy; ASAP and/or high-grade PIN; negative digital rectal examination. All eligible patients will undergo 68Ga-PSMA PET/CT and mpMRI scans within 1 month's distance from each other, followed by biopsy session to be completed within 1 month's distance. Targeted TRUS fusion needle biopsy will be performed for all lesions detected with PET and mpMRI. The total duration of the study is 36 months., Key Messages: By comparing the "experimental test" and the "standard test" in parallel, we will be able to determine the superior diagnostic performance of 68Ga-PSMA PET/CT over mpMRI in detecting PCa, and in particular clinically significant PCa, in the specific cohort of patients with a high suspicion of PCa who are candidates to re-biopsy. The clinical impact of the "experimental test" will be subsequently analyzed in terms of the number of prostate biopsies that could be spared, time-consuming, patient friendliness, and cost-effectiveness., (© 2023 S. Karger AG, Basel.)

Tumor-associated macrophages (TAMs) are correlated with the progression of prostatic adenocarcinoma (PCa). The mechanistic basis of this correlation and therapeutic strategies to target TAMs in PCa remain poorly defined. Here, single-cell RNA sequencing was used to profile the transcriptional landscape of TAMs in human PCa, leading to identification of a subset of macrophages characterized by dysregulation in transcriptional pathways associated with lipid metabolism. This subset of TAMs correlates positively with PCa progression and shorter disease-free survival and is characterized by an accumulation of lipids that is dependent on Marco. Mechanistically, cancer cell-derived IL-1β enhances Marco expression on macrophages, and reciprocally, cancer cell migration is promoted by CCL6 released by lipid-loaded TAMs. Moreover, administration of a high-fat diet to tumor-bearing mice raises the abundance of lipid-loaded TAMs. Finally, targeting lipid accumulation by Marco blockade hinders tumor growth and invasiveness and improves the efficacy of chemotherapy in models of PCa, pointing to combinatorial strategies that may influence patient outcomes., Competing Interests: Disclosures: R.A. DePinho reported being a Founder and Advisor for Tvardi Therapeutics, Asylia Therapeutics, Nirogy Therapeutics, Stellanova Therapeutics, and Sporos Bioventures. The focus of these companies is not directly related to the content of this manuscript. S. Gordon reported personal fees from Verseau, Myeloid Therapeutics, and Alnylam outside the submitted work. No other disclosures were reported., (© 2021 Masetti et al.)

Background: Active surveillance (AS) is a safe and accepted option for managing men with low-risk prostate cancer. Nevertheless, some patients lack confidence in or access to AS. Focal therapy (FT) is a possible alternative to radical treatment for such patients., Objective: We evaluated dominant tumor (DT) progression across serial biopsies to determine whether men on AS could be reasonable candidates for FT., Design, Setting, and Participants: Men enrolled in AS at University of California, San Francisco between 1996 and 2017 with low/intermediate risk were included., Outcome Measurements and Statistical Analysis: Changes in biopsy grade, volume, and focality of the DT over time were assessed. Focality (good or poor for FT) was defined by the number of cores, laterality, and contiguity of prostate sites containing tumor (based on pathology reports). Candidates (either for targeted/quadrant ablation or for hemigland ablation) were defined based on good focality, grade group (GG) ≤2, and low-volume disease. Patients were classified as favorable (GG ≤ 2 with good focality and concordant multiparametric magnetic resonance imaging [mpMRI]) or unfavorable (poor focality or high-volume disease or discordant mpMRI) for FT at surveillance biopsies., Results and Limitations: A total of 1057 men met the inclusion criteria. The median number of biopsies per patient was three (interquartile range 2-4), and 196 patients (18.5%) underwent five or more biopsies. At confirmatory biopsy, 43% remained candidates for FT (67% for targeted/quadrant ablation and 33% for hemigland ablation) and 20% had a negative biopsy. Of the candidates for FT at initial biopsy, 11% had less favorable characteristics at confirmatory biopsy. Among candidates for FT based on both initial and confirmatory biopsies, 70% remained favorable for hemigland ablation at subsequent biopsies. Limitations include retrospective design and mpMRI information only at surveillance biopsy., Conclusions: Serial biopsy findings in men with early-stage cancer on AS show that tumor location remains relatively stable and significant changes in grade and/or volume occur largely in the DT. Combined diagnostic and confirmatory biopsy findings help better select patients for FT than the use of the diagnostic biopsy alone., Patient Summary: In a large cohort of patients on active surveillance for prostate cancer, we evaluated changes across serial biopsies to identify potential candidates for focal therapy (FT). Our findings showed that the dominant tumor remained stable over time and the majority of men were favorable candidates for FT., (Copyright © 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Purpose: We aim to evaluate the accuracy of micro-ultrasound (microUS) in predicting extraprostatic extension (EPE) of Prostate Cancer (PCa) prior to surgery., Methods: Patients with biopsy-proven PCa scheduled for robot-assisted radical prostatectomy (RARP) were prospectively recruited. The following MRI-derived microUS features were evaluated: capsular bulging, visible breach of the prostate capsule (visible extracapsular extension; ECE), presence of hypoechoic halo, and obliteration of the vesicle-prostatic angle. The ability of each feature to predict EPE was determined., Results: Overall, data from 140 patients were examined. All predictors were associated with non-organ-confined disease (p < 0.001). Final pathology showed that 79 patients (56.4%) had a pT2 disease and 61 (43.3%) ≥ pT3. Rate of non-organ-confined disease increased from 44% in those individuals with only 1 predictor (OR 7.71) to 92.3% in those where 4 predictors (OR 72.00) were simultaneously observed. The multivariate logistic regression model including clinical parameters showed an area under the curve (AUC) of 82.3% as compared to an AUC of 87.6% for the model including both clinical and microUS parameters. Presence of ECE at microUS predicted EPE with a sensitivity of 72.1% and a specificity of 88%, a negative predictive value of 80.5% and positive predictive value of 83.0%, with an AUC of 80.4%., Conclusions: MicroUS can accurately predict EPE at the final pathology report in patients scheduled for RARP., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Magnetic Resonance Imaging (MRI) has emerged as the most accurate diagnostic tool, showing a high sensitivity in the diagnosis of clinically significant prostate cancer (csCaP). However only a minority of patients with a PI-RADS 3 lesion at multiparametric magnetic resonance imaging (MRI) are diagnosed with csCaP. The aim of the current study was to assess whether high resolution micro-ultrasound (microUS) could help in sub-stratifying the risk of csCaP in this specific population., Material and Methods: We retrospectively analyzed the records of 111 consecutive patients scheduled for a prostate biopsy with at least 1 PI-RADS 3 lesions at MRI. We excluded patients with a PIRADS >3 lesion, even if they had a coexisting PIRADS 3 lesions. MicroUS was performed in all patients before prostate biopsy by an operator blind to MRI results. The Prostate Risk Identification using MicroUS (PRI-MUS) protocol was used to assess the risk of CaP and csCaP. All patients received both targeted and systematic biopsies. The primary endpoint was to determine the diagnostic accuracy of microUS in detection of csCaP in patients with a PI-RADS 3 lesion at MRI. Specifically, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of microUS were determined. Multivariable logistic regression models (MLRMs) were fitted to identify predictors of CaP. The diagnostic accuracy was reported as area under the receiver operator characteristic (ROC) curve., Results: Overall, 43 patients (38.7%) harboured CaP and 22 (20%) csCaP. MicroUS showed a high sensitivity and negative predictive value (100%), while its specificity and positive predictive value were 33.7% and 27.2%, respectively. Among patients without lesions at microUS, 25 (83.3%) did not harbour CaP, while 5 (16.7%) patients were diagnosed with a Gleason score 6 CaP, with no patients harbouring csCaP. Using microUS, the csCaP detection would have remained 100%, while reducing the detection of insignificant CaP of a 23.8% extent (n = 5). In MLRMs, lesion identified at microUS and continuously-coded PSAd were independent predictors of CaP. The accuracy of a model including PRI-MUS score, digital rectal examination (DRE), PSA density, age and family history was 0.744 (95% CI: 0.645 - 0.843)., Conclusion: In our single-institutional retrospective study, microUS was potentially capable to stratify the presence of CaP in patients with an equivocal MRI. Further prospective studies on larger populations are needed to validate our results., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Multiparametric magnetic resonance imaging (MRI) represents the gold standard for the diagnosis of clinically significant prostate cancer (csPCa). The search for alternative diagnostic techniques is still ongoing., Objective: To determine the accuracy of microultrasound (microUS) for the diagnosis of csPCa within prospectively collected cohort of patients with a suspicion of prostate cancer (PCa) according to MRI., Design, Setting, and Participants: A total of 320 consecutive patients with at least one Prostate Imaging Reporting and Data System (PIRADS) ≥3 lesion according to MRI were prospectively enrolled., Intervention: All patients received microUS before prostate biopsy using the ExactVu system; the Prostate Risk Identification using microUS (PRI-MUS) protocol was used to identify targets. The urologists were blinded to MRI results until after the microUS targeting was completed. All patients received both targeted (based on either microUS or MRI findings) and randomized biopsies., Outcome Measurements and Statistical Analysis: The sensitivity and specificity of microUS to determine the presence of csPCa (defined as at least one core with a Gleason score ≥7 PCa) were determined. Multivariable logistic regression analysis was fitted to determine the predictors of csPCa., Results and Limitations: Clinically significant PCa was diagnosed in 116 (36.3%) patients. The sensitivity and negative predictive value of microUS for csPCa diagnosis were 89.7% and 81.5%, while specificity and positive predictive value were 26.0% and 40.8%, respectively. A combination of microUS-targeted and randomized biopsies would allow diagnosing the same proportion of csPCa as that diagnosed by an approach combining MRI-targeted and randomized biopsies (n = 113; 97.4%), with only three (2.6%) csPCa cases diagnosed by a microUS-targeted and three (2.6%) by an MRI-targeted approach. In a logistic regression model, an increasing PRI-MUS score was an independent predictor of csPCa (p ≤ 0.005). The main limitation of the current study is represented by the fact that all patients had suspicious MRI., Conclusions: Microultrasound is a promising imaging modality for targeted prostate biopsies. Our results suggest that a microUS-based biopsy strategy may be capable of diagnosing the great majority of cancers, while missing only few patients with csPCa., Patient Summary: According to our results, microultrasound (microUS) may represent an effective diagnostic alternative to magnetic resonance imaging for the diagnosis of clinically significant prostate cancer, providing high sensitivity and a high negative predictive value. Further randomized studies are needed to confirm the potential role of microUS in the diagnostic pathway of patients with a suspicion of prostate cancer., (Copyright © 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objective: Many individuals with bladder cancer have undergone a surgical urostomy and often complain of being self-conscious of the unpleasant smell of their own urine. The focus of this study was to test the efficacy of a pouch cover made of a carbon and zeolite containing polyester material to inhibit the smell of urine by comparing two trained dogs' response time in detecting volatile organic compounds (VOCs) in urine, with and without the fabric covering the samples., Methods: This study used a randomized, blinded experimental design to evaluate the efficacy of a fabric to interfere with two highly trained dogs' ability to detect specific VOCs present in the urine of prostate cancer patient. Ninety urine samples were analyzed in this study., Results: Prior to the experiment, both dogs accurately detected VOCs in the uncovered test urine samples of men with prostate cancer with a sensitivity and specificity of nearly 100%. Both dogs recognized the "uncovered" urine samples of men with prostate cancer within two seconds. When the test sample was covered with the study fabric, the test urine samples were detected within 30-40 seconds and in some instances the dogs were not able to identify the covered samples, whatsoever., Conclusion: The findings of this study demonstrate that the carbon and zeolite containing polyester fabric did significantly interfere with the ability of the dogs to detect VOCs in urine of men with prostate cancer. The fabric may show promise as a pouch cover in controlling offensive urine odor which many ostomates experience.

Background: Positron emission tomography (PET)/computed tomography (CT) with 68 Ga-labeled prostate-specific membrane antigen ligand ( 68 Ga-PSMA) may represent the most promising alternative to multiparametric magnetic resonance imaging (mpMRI) for prostate cancer (PCa) diagnosis., Objective: To test the diagnostic performance of 68 Ga-PSMA PET/CT in this clinical context., Design, Setting, and Participants: From January 2017 to December 2018 we prospectively enrolled 97 patients with persistently elevated prostate-specific antigen and/or Prostate Health Index score, negative digital rectal examination, and previous negative biopsy. We also included patients with either negative mpMRI or contraindications to or positive mpMRI but previous negative biopsy., Intervention: Patients underwent 68Ga-PSMA PET/CT with additional pelvic reconstruction., Outcome Measurements and Statistical Analysis: The primary endpoint of the study was the diagnostic performance of 68 Ga-PSMA PET/CT in detecting malignant lesions and clinically significant PCa (Gleason score [GS] ≥7)., Results and Limitations: 68 Ga-PSMA PET/transrectal ultrasound fusion biopsy was performed in 64 of 97 patients (66%) for 114 regions of interest (ROIs). Forty patients (41%) had already undergone mpMRI with either a negative result for PCa (n = 15; 22 ROIs) or a positive mpMRI result but a previous negative biopsy. According to pathology, 23 patients (36%) had evidence of PCa: eight (16 ROIs) with GS 6, 13 (21 ROIs) with GS 7 (3 + 4 or 4 + 3), one (2 ROIs) with GS 8, and one (2 ROIs) with GS 10. Clinically significant PCa was identified in four patients with previous negative mpMRI (25%). PET/CT demonstrated PCa in seven patients (14 ROIs) with previous positive mpMRI and negative biopsy. The median maximum standardized uptake value (SUVmax) and median SUV ratio were significantly higher for PCa lesions than for benign lesions (p <  0.001). Optimal cutoff points obtained for SUVmax (>5.4) and SUV ratio (>2.2) could identify clinically significant PCa with accuracy of 81% and 90%, respectively., Conclusions: In our cohort of patients with high suspicion of cancer, 68 Ga-PSMA PET/CT was capable of detecting malignancy and accurately identifying clinically relevant PCa., Patient Summary: Positron emission tomography/computed tomography with a 68 Ga-labeled ligand for prostate-specific membrane antigen is capable of detecting prostate cancer in patients with a high suspicion of cancer and a previous negative biopsy., (Copyright © 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background and Purpose: Urinary continence (UC) represents the main non-oncological goal in patients undergoing robotic-assisted radical prostatectomy (RARP). To evaluate the efficacy in early UC achievement, we described a new sling technique using the retrotrigonal muscular layer (TZ sling) combined with total anatomical reconstruction (TAR)., Patients and Methods: We prospectively enrolled 407 consecutive prostate cancer (PC) patients undergoing RARP between May 2017 and January 2020. The first 250 patients underwent only TAR, while the following 157 patients TAR + TZ sling, by isolating and anchoring the retrotrigonal muscular layer to the pubic bone with 2 bilateral sutures. We defined UC as ≤ 1 pad/die, which was assessed after catheter removal at 1, 4 and 12wk using the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) score. Sling-related operative time and post-operative complications were analyzed., Results: In the TAR group, the UC rates at the 1, 4 and 12wk were 58%, 66% and 86%; in the TAR + TZ sling group 72%, 76% and 88%, respectively. A statistically significant difference was observed in the two groups at 1wk (p = 0.0049) and 4wk (p = 0.035) favoring the TZ sling surgical strategy. This difference in UC rates was lost at 12wk (p ≥ 0.05). No statistically significant differences in operative time, acute urinary retentions and other complication rates were observed between the two groups (p = NS)., Conclusions: We have described a new, safe, feasible modification of RARP using a sling with the retrotrigonal muscular layer associated with TAR. We have demonstrated a statistically significant improvement in early UC rate in patients who are undergoing TAR and TZ sling compared to undergoing only TAR., (© 2020. Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: To compare the diagnostic performance of 68 Ga-PSMA PET/TC with PRI-MUS (prostate risk identification using micro-ultrasound) in the primary diagnosis of prostate cancer (PCa)., Methods: From September till December 2018, we prospectively enrolled 25 candidates to 68 Ga-PSMA PET/TRUS (transrectal ultrasound) fusion biopsy and compared them with PRI-MUS. This included patients with persistently elevated PSA and/or PHI (prostate health index) suspicious for PCa, negative digital rectal examination, with either negative or contraindication to mpMRI, and at least one negative biopsy. The diagnostic performance of the two modalities was calculated based on pathology results., Results: Overall, 20 patients were addressed to 68 Ga-PSMA PET/TRUS fusion biopsy. Mean SUVmax and SUVratio for PCa lesions resulted significantly higher than in benign lesions (p = 0.041 and 0.011, respectively). Using optimal cut-off points, 68 Ga-PSMA PET/CT demonstrated an overall accuracy of 83% for SUVmax ≥ 5.4 and 94% for SUVratio ≥ 2.2 in the detection of clinically significant PCa (GS ≥ 7). On counterpart, PRI-MUS results were: score 3 in nine patients (45%), score 4 in ten patients (50%), and one patient with score 5. PRI-MUS score 4 and 5 demonstrated an overall accuracy of 61% in detecting clinically significant PCa., Conclusion: In this highly-selected patient population, in comparison to PRI-MUS, 68 Ga-PSMA PET/CT shows a higher diagnostic performance.

Background: The adoption of robotic technology in the treatment of prostate cancer (PCa) could lead to improvement in outcomes., Objective: To evaluate feasibility, to compare functional outcomes, and to assess the economic benefits of removing catheter on the postoperative day (POD) 3 versus POD 5 after robot-assisted radical prostatectomy (RARP)., Design, Setting, and Participants: From September 2016 to May 2017, patients selected to undergo RARP for clinically localized PCa at a high-volume center were prospectively randomized into group 1 (POD 3; n=72) versus group 2 (POD 5, n=74)., Intervention: All patients underwent RARP with anatomical posterior and anterior reconstruction., Outcome Measurements and Statistical Analysis: The primary endpoint was to compare acute urinary retention (AUR) and urinary leakage rate in the two groups. The secondary endpoints were early and mid-term postoperative functional outcomes assessed through questionnaires (ICIQ-MLUTS, IPSS), early continence rate, and postoperative pain/discomfort (visual analog scale score). The economic impact of early catheter removal was also assessed., Results and Limitations: AUR was reported in two (1.4%) cases, one for each study group (p=0.9). One case of vesicourethral leakage was reported (0.7%) in group 1. Urethral discomfort and pain at discharge was significantly higher in group 2 (p=0.03). In our clinical practice, POD 3 catheter removal approach would determine a saving of approximately €80 000 and 405 d of hospitalization yearly. The main limitation is the small sample size., Conclusions: Early catheter removal after RARP does not lead to an increase in perioperative complications. No negative effect on early and mid-term functional outcomes was observed. A significant impact on saving economic resources was reported., Patient Summary: We demonstrated that early catheter removal has no negative effect on spontaneous voiding, complications, or urinary continence recovery after robot-assisted radical prostatectomy., (Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: There is an unmet clinical need for more biochemical specific tests that may detect clinically significant recurrent PCa at an early stage after radical prostatectomy (RP). Our purpose is to test the hypothesis that p2PSA (Index test) detects prostate cancer relapse (BCR) earlier than the current Reference Standard Test (total prostate-specific antigen [tPSA]) in patients who underwent RP for localized PCa., Methods: This is an observational, prospective, cohort, follow-up study in patients subjected to RALP (robotic assisted laparoscopic radical prostatectomy) for clinically localized PCa from January 2013 to July 2013 at a high-volume Institution (450 average RP/year). A blood sample, for tPSA and p2PSA, was prospectively drawn after 3, 6, and 12 months and then every 6 months during the following two years. The primary outcome is to determine whether or not kinetics in rising of p2PSA significantly anticipates the tPSA kinetics. Exploratory data analysis was used to identify relationship between different variables., Results: Over 134 patients 20 BCRs were detected according to tPSA cut-off. Five patients showed a contemporary increase of tPSA and p2PSA, 11 presented a p2PSA increase earlier than tPSA increase (13.9 months ±9.7). In four patients, the increase of PSA was not associated with a p2PSA>0.8 pg/mL. The correlation between tPSA and p2PSA according to Sperman's rho coefficient was statistically significant at 3, 6, 18 and 30 months: 0.416 (P<0.01), 0.255 (P<0.01), 0.359 (P<0.01) and 0.413 (P<0.01) respectively. When subjects were stratified according to stage/grade and margins (positive vs. negative), patients with higher stage and positive surgical margins could be considered the target categories. The low rate of observed BCR and high rate of p2PSA false positive are the main limitations., Conclusions: The current findings showed that p2PSA might be more sensitive than tPSA in detecting earlier BCR within 3-year follow-up. Further studies with a longer follow-up and larger population remain mandatory before considering p2PSA for clinical decision-making.

Multiparametric magnetic resonance imaging (mpMRI) and MRI/ultrasound (US) fusion targeted biopsies are an increasingly popular alternative to randomized biopsies, but adoption of this technique has been limited owing to its additional costs and complexity. High-resolution micro-ultrasound (micro-US) is a real-time US-based imaging modality that allows real-time targeted prostate biopsies using the Prostate Risk Identification Using Micro-Ultrasound risk identification protocol. We compared the diagnostic accuracy of micro-US targeted biopsies (index test) and MRI/US fusion targeted biopsies (reference standard test) in detecting clinically significant prostate cancer (csPC), defined as Gleason ≥7 disease, in a prospectively collected cohort of 104 patients with suspected PC defined according to prostate-specific antigen, digital rectal examination, and the presence of at least one Prostate Imaging-Reporting and Data System ≥3 lesion at mpMRI. PC was diagnosed in 56 patients (54%) and csPC in 35 (34%). Micro-US sensitivity for csPC detection was 94%, with 33/35 csPC cases correctly identified. The negative predictive value was 90%, while the positive predictive value was 40% and the specificity was 28%. Of the 61 targeted zones concordant between micro-US and mpMRI, 24 were csPC. Discordant targeted lesions led to csPC discovery by micro-US in three cases and mpMRI in four cases. Both techniques missed one case for which csPC was diagnosed by systematic biopsies only. PATIENT SUMMARY: According to the results of our preliminary trial, micro-ultrasound may provide additional information regarding the presence or absence of clinically significant prostate cancer (PC) in patients with suspected PC. Further studies are warranted to investigate how this new imaging modality can best be leveraged within the PC diagnostic pathway., (Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Asians have a lower incidence of prostate cancer (PC). We compared the performance of the Prostate Health Index (PHI) for 2488 men in different ethnic groups (1688 Asian and 800 European men from 9 sites) with PSA 2-20ng/ml and PHI test and transrectal ultrasound-guided biopsy results available. Of these, 1652 men had PSA 2-10ng/ml and a normal digital rectal examination and underwent initial biopsy. The proportions of PC (Gleason ≥6) and higher-grade PC (HGPC, Gleason ≥7) across different PHI ranges were compared. The performance of PSA and PHI was compared using the area under the receiver operating characteristic curve (AUC) and decision curve analyses (DCA). Among Asian men, HGPC would be diagnosed in 1.0%, 1.9%, 13%, and 30% of men using PHI thresholds of <25, 25-35, 35-55, and >55, respectively. At 90% sensitivity for HGPC (PHI >30), 56% of biopsies and 33% of Gleason 6 PC diagnoses could have been avoided. Among European men, HGPC would be diagnosed in 4.1%, 4.3%, 30%, and 34% of men using PHI thresholds of <25, 25-35, 35-55, and >55, respectively. At 90% sensitivity for HGPC (PHI >40), 40% of biopsies and 31% of Gleason 6 PC diagnoses could have been avoided. AUC and DCA confirmed the benefit of PHI over PSA. The benefit of PHI was also seen at repeat biopsy (n=397) and for PSA 10-20ng/ml (n=439). PHI is effective in cancer risk stratification for both European and Asian men. However, population-specific PHI reference ranges should be used. PATIENT SUMMARY: The Prostate Health Index (PHI) blood test helps to identify individuals at higher risk of prostate cancer among Asian and European men, and could significantly reduce unnecessary biopsies and overdiagnosis of prostate cancer. Different PHI reference ranges should be used for different ethnic groups., (Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Purpose: 68 Ga labeled prostate specific membrane antigen positron emission tomography/computerized tomography may represent the most promising imaging modality to identify and risk stratify prostate cancer in patients with contraindications to or negative multiparametric magnetic resonance imaging., Materials and Methods: In this prospective observational study we analyzed 68 Ga labeled prostate specific membrane antigen positron emission tomography/computerized tomography in a select group of patients with persistently elevated prostate specific antigen and/or Prostate Health Index suspicious for prostate cancer, negative digital rectal examination and at least 1 negative biopsy. The cohort comprised men with equivocal multiparametric magnetic resonance imaging (Prostate Imaging-Reporting and Data System, version 2 score of 2 or less), or an absolute or relative contraindication to multiparametric magnetic resonance imaging. Sensitivity, specificity and CIs were calculated compared to histopathology findings. ROC analysis was applied to determine the optimal cutoff values of 68 Ga labeled prostate specific membrane antigen uptake to identify clinically significant prostate cancer (Gleason score 7 or greater)., Results: A total of 45 patients with a median age of 64 years were referred for 68 Ga labeled prostate specific membrane antigen positron emission tomography/computerized tomography between January and August 2017. The 25 patients (55.5%) considered to have positive positron emission tomography results underwent software assisted fusion biopsy. We determined the uptake values of regions of interest, including a median maximum standardized uptake value of 5.34 (range 2.25 to 30.41) and a maximum-to-background standardized uptake value ratio of 1.99 (range 1.06 to 14.42). Mean and median uptake values on 68 Ga labeled prostate specific membrane antigen positron emission tomography/computerized tomography (ie the maximum standardized uptake value or the maximum-to-background standardized uptake value ratio) were significantly higher for Gleason score 7 lesions than for Gleason score 6 or benign lesions (p <0.001). On ROC analysis a maximum standardized uptake value of 5.4 and a maximum-to-background standardized uptake value ratio of 2 discriminated clinically relevant prostate cancer with 100% overall sensitivity in each case, and 76% and 88% specificity, respectively., Conclusions: Our findings support the use of 68 Ga labeled prostate specific membrane antigen positron emission tomography/computerized tomography for primary detection of prostate cancer in a specific subset of men., (Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Evidence regarding the diagnostic accuracy of a [-2]proPSA derivative, namely, the prostate health index (PHI), to predict the presence of prostate cancer (PCa) in individuals with high total prostate-specific antigen (tPSA) levels is lacking. We tested the hypothesis that these markers could assist clinicians in the biopsy decision path of patients with tPSA>10ng/ml., Methods: The primary endpoint was to evaluate the sensitivity, specificity, and diagnostic accuracy of PHI in determining the presence of PCa at biopsy in comparison to tPSA, free PSA, and % of free to total PSA. We calculated the number of prostate biopsies that could have been spared by using this marker to decide whether or not to perform a biopsy. A secondary endpoint was to determine the relationship between PHI and PCa characteristics., Results: The PCa was diagnosed in 136 of 262 patients (51.9%). Total PSA and PHI values were significantly higher (P<0.005) and % of free to total PSA values significantly lower (P<0.0001) in patients with PCa relative to those with a negative biopsy. In multivariable logistic regression models, PHI achieved the independent predictor status and significantly increased the accuracy of the base multivariable model by an extent of 8.2% (P = 0.0005). The inclusion of PHI in the biopsy decision path would decrease the number of unnecessary biopsies by an extent of 50.0%, while missing only few cases with clinically significant PCa. Finally, Gleason score was significantly related to PHI levels., Conclusions: The results of our study support the diagnostic effectiveness of PHI even in patients with tPSA >10ng/ml. Further validation studies with larger sample size are needed to corroborate our findings., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: To investigate prostate cancer (PC) detection rate, employing endorectal multiparametric 3-tesla magnetic resonance imaging (MRI) driving subsequent cognitive systematic prostatic biopsy (CSPB) versus a homogenous group of patients who did not undergo endorectal MRI., Materials and Methods: A series of patients with a first negative biopsy were enrolled in the study. Patients were randomized into two groups: Group A: patients underwent MRI and subsequent CSPB; Group B: patients that did not undergo MRI. Each patient underwent a 13-core sampling. Patients from Group A had four cores more for each MRI suspected lesion. The cancer detection rate was calculated for each group with regard to possible matches or mismatches between MRI evidence and pathological reports., Results: Two hundred consecutive patients were investigated. Fifty out of 200 (25 %) patients had a diagnosis of PC, 24 in Group A and 26 in Group B. In Group A, 67 patients (67 %) were positive for suspected lesions at the MRI. The mismatch between MRI findings and the CSPB outcome was 61 % with an MRI-driven detection rate of 15 %. Group B detection rate was 26 % with no significant differences versus Group A (P = NS). Patient discomfort was higher in Group A (82 %). The accuracy of CSPB was 41 % with a positive predictive value of 22.3 %. This rate is lower in high-grade cancers (11.9 %). The cost-effectiveness was higher in Group A., Conclusions: Prostate cancer detection rate does not improve by CSPB. The accuracy of CSPB was lower in high-grade PC, and a higher cost was found with CSPB.

Context: The process of care for patients with prostate cancer is subject to different degrees of uncertainty. Patients and clinicians could, therefore, greatly benefit from improved prognostic instruments. One emerging tool is the cell cycle progression (CCP) score., Objective: This systematic review assesses evidence on the value of the CCP instrument in prostate cancer treatment by reviewing current publications and integrating the results via a meta-analysis., Evidence Acquisition: We performed a review of Medline and Embase in April 2014, according to Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA). Unpublished studies were retrieved from the 2013-2014 proceedings of major conferences in the field. Sixteen publications were selected for inclusion., Evidence Synthesis: The results show that use of the CCP score is better than existing assessments at elucidating the aggressive potential of prostate cancer in an individual. The pooled hazard ratio for biochemical recurrence per 1-unit increase in the CCP score was 1.88 in a univariate model and 1.63 in a multivariate model. Four studies showed that CCP testing can impact the decisions of physicians regarding treatment, and potentially lead to a decrease in surgical interventions for low-risk patients., Conclusions: This review offers a comprehensive overview of existing evidence on CCP testing, and provides clinicians, patients, and policy makers with a strong summary measure of its prognostic validity and clinical utility. It will be important to develop economic studies to measure the impact of such technology on health care systems., Patient Summary: In this paper, we review current evidence related to the cell cycle progression (CCP) score for patients with prostate cancer. We found good evidence suggesting that use of the CCP score improves prognosis, and can be a valuable tool for clinicians in treating patients. The economic benefits are yet to be studied., (Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: The aim of this study was to test the hypothesis that preoperative prostate health index (PHI) levels could help to predict early biochemical recurrence (BCR) in a contemporary population of patients with prostate cancer treated with robot-assisted radical prostatectomy (RARP)., Methods: The study population consisted of 313 patients treated with RARP for clinically localized prostate cancer at a single institution between 2010 and 2011. Patients subjected to neoadjuvant or adjuvant therapies and patients with a follow-up of<2 years were excluded. BCR was defined as a postoperative level of total prostate-specific antigen ≥0.2 ng/ml and elevating after RARP. The minimum P-value method was used to determine the most significant PHI cutoff value to discriminate between patients with and without BCR. The Kaplan-Meier method was used to determine BCR-free survival rates. Finally, Cox regression models were fitted to determine the predictors of BCR, and the predictive accuracy (area under the curve) of each predictor was determined with the Harrell concordance index., Results: Mean total prostate-specific antigen and mean PHI levels were 5.76 ng/ml (interquartile range: 4.2-8.7) and 46.0 (35-62), respectively. Biopsy Gleason score was 6 in 173 (55.3%), 7 in 121 (38.7%), and ≥8 in 19 (6.1%) patients. At final pathology, extracapsular extension was observed in 59 (18.8%), seminal vesicle invasion in 24 (7.7%), and lymph node invasion in 11 (3.5%) patients, whereas 228 (72.8%) patients had organ-confined disease. The 2-year BCR-free survival rate was 92.5% in the overall population and was 96.7% in patients with organ-confined disease. The most significant PHI cutoff value to discriminate between patients with and without BCR was 82. Specifically, the 2-year BCR-free survival rate was 97.7% in patients with a preoperative PHI level<82 relative to 69.7% in patients with a PHI level ≥82 (log-rank test: P<0.001). Finally, in multivariable Cox regression analyses, PHI level emerged as an independent predictor of BCR in both the preoperative and the postoperative settings and was more accurate than several established BCR predictors were., Conclusions: Preoperative PHI levels may discriminate between patients who are at a high risk vs. low risk of BCR after RARP. External validation of our findings within a larger population with a longer follow-up time is needed., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Currently available predictive models fail to assist clinical decision making in prostate cancer (PCa) patients who are potential candidates for radical prostatectomy (RP). New biomarkers would be welcome., Objective: To test the hypothesis that prostate-specific antigen (PSA) isoform p2PSA and its derivatives, percentage of p2PSA to free PSA (%p2PSA) and the Prostate Health Index (PHI), predict PCa characteristics at final pathology., Design, Setting, and Participants: An observational prospective multicentre European study was performed in 489 consecutive PCa patients treated with RP. Total PSA (tPSA), free PSA (fPSA), and p2PSA levels were determined. The %fPSA [(fPSA / tPSA) × 100], %p2PSA [(p2PSA pg/ml) / (fPSA ng/ml × 1000) × 100], and PHI [(p2PSA / fPSA) × √tPSA] were calculated., Intervention: Open or robot-assisted RP., Outcome Measurements and Statistical Analysis: Logistic regression models were fitted to test the predictors of pT3 stage and/or pathologic Gleason score (GS) ≥7 and to determine their predictive accuracy. The base multivariable model included tPSA, digital rectal examination, biopsy GS, and percentage of positive biopsy cores. Decision curve analysis provided an estimate of the net benefit obtained using p2PSA, %p2PSA, or PHI., Results and Limitations: Overall, 344 patients (70%) were affected by pT3 disease or pathologic GS ≥7; pT3 disease and pathologic GS ≥7 were present in 126 patients (26%). At univariable analysis, p2PSA, %p2PSA, and PHI were significant predictors of pT3 disease and/or pathologic GS ≥7 (all p ≤ 0.001). The inclusion of PHI significantly increased the accuracy of the base multivariable model by 2.3% (p=0.003) and 2.4% (p=0.01) for the prediction of pT3 disease and/or pathologic GS ≥7, respectively. However, at decision curve analysis, models including PHI did not show evidence of a greater clinical net benefit., Conclusions: Both %p2PSA and PHI are significant predictors of unfavourable PCa characteristics at final pathology; however, %p2PSA and PHI did not provide a greater net benefit for clinical decision making., Patient Summary: Prostate-specific antigen (PSA) isoform p2PSA and its derivatives, percentage of p2PSA to free PSA and the Prostate Health Index, are associated with adverse characteristics of prostate cancer; however, these biomarkers provided only a slight net benefit for clinical decision making., (Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objectives: To test the hypothesis that [-2]proPSA (p2PSA) and its derivatives are more accurate than total prostate-specific antigen (tPSA), free prostate-specific antigen (fPSA) and fPSA as percentage of tPSA (%fPSA) in detecting prostate cancer (PCa) in men aged <60 years., Patients and Methods: The analysis consisted of a nested case-control study from the PRO- PSA Multicentric European Study (PROMEtheuS) project. The primary outcomes were measures of sensibility, specificity and accuracy of serum p2PSA, p2PSA as percentage of fPSA (%p2PSA) and Beckman Coulter prostate health index (PHI) in men aged <60 years who had undergone a prostate biopsy. The potential reduction in the number of unnecessary biopsies and the characteristics of the potentially missed PCa cases were reported as secondary outcomes. Multivariate logistic regression models were complemented by predictive accuracy and decision-curve analyses., Results: Of the 1036 patients enrolled in the PROMEtheus project, 238 (22.9%) were aged < 60 years. PCa was found in 67 subjects (28.1%); p2PSA, %p2PSA and PHI values were significantly higher (P < 0.001) among these subjects, while no differences were found in tPSA, fPSA and %fPSA values. On univariate analysis, %p2PSA (area under the curve [AUC]: 0.704) and PHI (AUC: 0.7) were the most accurate predictors, and these significantly outperformed tPSA (AUC: 0.549), fPSA (AUC: 0.511) and %fPSA (AUC: 0.557) in the prediction of PCa at biopsy (P ≤ 0.001). In multivariate logistic regression models, %p2PSA and PHI achieved independent predictor status and significantly increased the accuracy of multivariate models by 6.3 and 7.6%, respectively (P ≤ 0.05)., Conclusion: PHI and %p2PSA are more accurate than the reference standard tests in predicting PCa in young men., (© 2014 The Authors. BJU International © 2014 BJU International.)

Objectives: To test serum prostate-specific antigen (PSA) isoform [-2]proPSA (p2PSA), p2PSA/free PSA (%p2PSA) and Prostate Health Index (PHI) accuracy in predicting prostate cancer in obese men and to test whether PHI is more accurate than PSA in predicting prostate cancer in obese patients., Patients and Methods: The analysis consisted of a nested case-control study from the pro-PSA Multicentric European Study (PROMEtheuS) project. The study is registered at http://www.controlled-trials.com/ISRCTN04707454. The primary outcome was to test sensitivity, specificity and accuracy (clinical validity) of serum p2PSA, %p2PSA and PHI, in determining prostate cancer at prostate biopsy in obese men [body mass index (BMI) ≥30 kg/m(2) ], compared with total PSA (tPSA), free PSA (fPSA) and fPSA/tPSA ratio (%fPSA). The number of avoidable prostate biopsies (clinical utility) was also assessed. Multivariable logistic regression models were complemented by predictive accuracy analysis and decision-curve analysis., Results: Of the 965 patients, 383 (39.7%) were normal weight (BMI <25 kg/m(2) ), 440 (45.6%) were overweight (BMI 25-29.9 kg/m(2) ) and 142 (14.7%) were obese (BMI ≥30 kg/m(2) ). Among obese patients, prostate cancer was found in 65 patients (45.8%), with a higher percentage of Gleason score ≥7 diseases (67.7%). PSA, p2PSA, %p2PSA and PHI were significantly higher, and %fPSA significantly lower in patients with prostate cancer (P < 0.001). In multivariable logistic regression models, PHI significantly increased accuracy of the base multivariable model by 8.8% (P = 0.007). At a PHI threshold of 35.7, 46 (32.4%) biopsies could have been avoided., Conclusion: In obese patients, PHI is significantly more accurate than current tests in predicting prostate cancer., (© 2014 The Authors. BJU International © 2014 BJU International.)

Background: External validation of a prediction tool is mandatory to assess the tool's accuracy and generalizability within different patient cohorts., Objective: To externally validate a previously developed Prostate Health Index (PHI)-based nomogram for predicting the presence of prostate cancer (PCa) at biopsy., Design, Setting, and Participants: The study population consisted of 883 patients who were scheduled for a prostate biopsy at one of five European tertiary care centers. Total prostate-specific antigen (tPSA), free prostate-specific antigen (fPSA), and [-2]pro-prostate-specific antigen (p2PSA) levels were determined. The fPSA-to-tPSA ratio (%fPSA), p2PSA, and PHI ([p2PSA / fPSA] × √tPSA) were calculated., Intervention: Extended initial and repeat prostate biopsy., Outcome Measurements and Statistical Analysis: Logistic regression models were fitted to test the predictors of PCa and to determine their predictive accuracy. A calibration plot was used to evaluate the extent of overestimation or underestimation between nomogram predictions and observed PCa rate. Decision curve analysis (DCA) provided an estimate of the net benefit obtained by using the PHI-based nomogram., Results and Limitations: Of 833 patients, 365 (41.3%) were diagnosed with PCa at extended prostate biopsy. In accuracy analyses, PHI was the most informative predictor of PCa (0.68), outperforming tPSA (0.51) and %fPSA (0.64). The predictive accuracy of the previously developed nomogram was 75.2% (95% confidence interval, 71.4-78.1). Calibration of the nomogram was good in patients at a low to intermediate predicted probability of PCa, while calibration was suboptimal, with a tendency to overestimate the presence of PCa, in high-risk patients. Finally, DCA demonstrated that the use of the PHI-based nomogram resulted in the highest net benefit. The main limitation of the study is the fact that only Caucasian patients were included., Conclusions: At external validation, the previously developed PHI-based nomogram confirmed its ability to determine the presence of PCa at biopsy. These findings provide further evidence supporting the potential role of the nomogram in the biopsy decision pathway for European men with suspected PCa., Patient Summary: In the current study, we externally validated a Prostate Health Index-based nomogram to predict the presence of prostate cancer (PCa) at biopsy. This tool may help clinicians determine the need for a prostate biopsy in European patients with suspected PCa., (Copyright © 2013 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Context: The incidence of localised prostate cancer is increasing worldwide. In light of recent evidence, current, radical, whole-gland treatments for organ-confined disease have being questioned with respect to their side effects, cancer control, and cost. Focal therapy may be an effective alternative strategy., Objective: To systematically review the existing literature on baseline characteristics of the target population; preoperative evaluation to localise disease; and perioperative, functional, and disease control outcomes following focal therapy., Evidence Acquisition: Medline (through PubMed), Embase, Web of Science, and Cochrane Review databases were searched from inception to 31 October 2012. In addition, registered but not yet published trials were retrieved. Studies evaluating tissue-preserving therapies in men with biopsy-proven prostate cancer in the primary or salvage setting were included., Evidence Synthesis: A total of 2350 cases were treated to date across 30 studies. Most studies were retrospective with variable standards of reporting, although there was an increasing number of prospective registered trials. Focal therapy was mainly delivered to men with low and intermediate disease, although some high-risk cases were treated that had known, unilateral, significant cancer. In most of the cases, biopsy findings were correlated to specific preoperative imaging, such as multiparametric magnetic resonance imaging or Doppler ultrasound to determine eligibility. Follow-up varied between 0 and 11.1 yr. In treatment-naïve prostates, pad-free continence ranged from 95% to 100%, erectile function ranged from 54% to 100%, and absence of clinically significant cancer ranged from 83% to 100%. In focal salvage cases for radiotherapy failure, the same outcomes were achieved in 87.2-100%, 29-40%, and 92% of cases, respectively. Biochemical disease-free survival was reported using a number of definitions that were not validated in the focal-therapy setting., Conclusions: Our systematic review highlights that, when focal therapy is delivered with intention to treat, the perioperative, functional, and disease control outcomes are encouraging within a short- to medium-term follow-up. Focal therapy is a strategy by which the overtreatment burden of the current prostate cancer pathway could be reduced, but robust comparative effectiveness studies are now required., (Copyright © 2013 European Association of Urology. All rights reserved.)

Prostate-specific antigen (PSA) is recognized as an organ-specific marker with low specificity and sensitivity in discriminating prostate cancer (PCa) from other benign conditions, such as prostatic hyperplasia or chronic prostatitis. Thus, in the case of clinical suspicion, a PCa diagnosis cannot be made without a prostate biopsy. [-2]proPSA (p2PSA), a precursor of PSA, has been investigated as a new marker to accurately detect PCa. The aim of this systematic review was to discuss the available literature regarding the clinical validity and utility of p2PSA and its derivatives, p2PSA/fPSA (%p2PSA) and the Prostate Health Index (PHI). A systematic search of the PubMed and Scopus electronic databases was performed in accordance with the PRISMA statement (http://www.prisma-statement.org), considering the time period from January 1990 to January 2014 and using the following search terms: proprostate specific antigen, proenzyme PSA, proPSA, [-2]proPSA, p2PSA, Prostate Health Index, and PHI. To date, 115 studies have been published, but only 35 were considered for the qualitative analysis. These studies suggested that p2PSA is the most cancer-specific form of PSA, being preferentially expressed in PCa tissue and being significantly elevated in the serum of men with PCa. It is now evident that p2PSA, %p2PSA, and PHI measurements improve the specificity of the available tests (PSA and derivatives) in detecting PCa. Moreover, increasing PHI values seem to correlate with more aggressive disease. Some studies have compared p2PSA and its derivatives with other new biomarkers and found p2PSA to be significantly more accurate. Indeed, the implementation of these tests in clinical practice has the potential to significantly increase the physician's ability to detect PCa and avoid unnecessary biopsies, while also having an effective impact on costs. Further studies in large, multicenter, prospective trials are required to confirm these encouraging results on the clinical utility of these new biomarkers.

Objective: To investigate the relationship between serum [-2]proPSA (p2PSA) and derivatives with chronic histologic prostatic inflammation (CHPI) in men undergoing prostate biopsy for suspected prostate cancer (PCa)., Methods: This nested case-control study resulted from an observational prospective trial for the definition of sensibility, specificity, and accuracy of p2PSA, %p2PSA, and Beckman Coulter Prostate Health Index (PHI), in men undergoing prostate biopsy, with a total prostate-specific antigen (PSA) of 4-10 ng/mL and normal digital rectal examination. CHPI was the outcome of interest and defined as the presence of moderate to large infiltration of lymphomononuclear cells with interstitial and/or glandular disruption in absence of PCa. p2PSA, %p2PSA, and PHI were considered the index tests and compared with the established biomarker reference standard tests: tPSA, fPSA, %fPSA., Results: Of 267 patients subjected to prostate biopsy, 73 (27.3%) patients were diagnosed with CHPI. Comparing CHPI with PCa patients, %p2PSA and PHI were found to be significantly lower, whereas fPSA and %fPSA were significantly higher. %p2PSA and PHI were the most accurate predictors of CHPI at biopsy, significantly outperforming tPSA, fPSA, and %fPSA. On the contrary, no significant differences were found in PSA, p2PSA, and derivatives between CHPI and benign prostatic hyperplasia (BPH) patients., Conclusion: Our findings showed that p2PSA, %p2PSA, and PHI values might discriminate PCa from CHPI or BPH, but not CHPI from BPH, in men with a total PSA 4-10 ng/mL and normal digital rectal examination. p2PSA isoform and its derivatives could be useful in clinical decision making to avoid unnecessary biopsies in patients with CHPI and elevated tPSA value., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: To confirm the accuracy of serum proPSA (p2PSA) and its derivatives, percentage of p2PSA to free PSA (%p2PSA) and Prostate Health Index (PHI) and to test the value of prostate dimension-adjusted related index p2PSA density (p2PSAD), %p2PSA density (%p2PSAD) and PHI density (PHID) in discriminating between patients with and without prostate cancer (PCa)., Patients and Methods: This is a prospective cohort study of 275 patients with a total PSA (tPSA) of 2-10 ng/ml who underwent initial prostate biopsy. Multivariate logistic regression models were complemented by predictive accuracy analysis., Results: PCa was diagnosed in 31.2% of subjects. Median tPSA did not differ between groups, while PSA density (PSAD), percent free PSA (%fPSA), p2PSA, %p2PSA, PHI, p2PSAD, %p2PSAD and PHID (all p < 0.05) were different between men with and without PCa. Univariate accuracy analysis showed p2PSAD (area under the receiver-operating characteristic curve [AUC]: 0.71), %p2PSAD (AUC: 0.76) and PHID (AUC: 0.77) to be the most accurate predictors of PCa at biopsy, significantly outperforming tPSA (AUC: 0.54), PSAD (AUC: 0.68) and %fPSA (AUC: 0.59) (p ≤ 0.001). At multivariate logistic regression models, p2PSAD and PHID significantly increased the accuracy of the basal multivariate model (all p < 0.01). At 90% specificity, sensitivity for p2PSAD, %p2PSAD and PHID were 33.7, 43 and 40.7%, respectively. Spearman's rho coefficient analysis demonstrated a significant relationship between Gleason score, %p2PSA (r = 0.216, p = 0.046), PHI (r = 0.223, p = 0.039) and %p2PSAD (r = 0.205, p = 0.05)., Conclusions: Considering patients suited for initial prostate biopsy by a tPSA range of 2-10 ng/ml, PSA isoforms were confirmed to be strong predictors of PCa. The prostate dimension-adjusted PSA isoforms have been shown to differentiate between patients with or without PCa, with an AUC of 0.71-0.77, p2PSAD offering a gain in accuracy with respect to tPSA, %fPSA and PSAD., (2014 S. Karger AG, Basel.)

The International Task Force on Prostate Cancer defines focal therapy (FT) for prostate cancer (PCa) as the therapy that "selectively ablates known disease and preserves existing functions, with the overall objective of minimizing lifetime morbidity without compromising life expectancy". FT for the treatment of PCa has been called the "male lumpectomy", an analogue to women's breast lumpectomy for the treatment of breast cancer. Radical prostatectomy continues to be the most frequently performed treatment for localized PCa, as anatomic knowledge and several technical advances, i.e. the introduction of robotic assisted surgery, have led to successful oncological outcome and lower rates of post-treatment morbidity. However, a proportion of patients still experiences a no negligible sexual, urinary, and bowel morbidity. Although the rationale of active surveillance for low-risk PCa (PSA <10 ng/mL, Gleason grade 6 or less, and clinical stage T1c-T2a) is sound, only few of newly diagnosed patients elect this approach. Thus, in the recent years the concept of a "subtotal therapy" gained the interest of some urological schools. The aim of this paper is to review the existing literature in order to provide the status of art on FT for PCa. The manuscript will focus on the characteristics of the target population, on the pre-operative evaluation to localise disease, as well as on perioperative, functional, and disease-control following focal therapy.

Objectives: To test the sensitivity, specificity and accuracy of serum prostate-specific antigen isoform [-2]proPSA (p2PSA), %p2PSA and the prostate health index (PHI), in men with a family history of prostate cancer (PCa) undergoing prostate biopsy for suspected PCa. To evaluate the potential reduction in unnecessary biopsies and the characteristics of potentially missed cases of PCa that would result from using serum p2PSA, %p2PSA and PHI., Patients and Methods: The analysis consisted of a nested case-control study from the PRO-PSA Multicentric European Study, the PROMEtheuS project. All patients had a first-degree relative (father, brother, son) with PCa. Multivariable logistic regression models were complemented by predictive accuracy analysis and decision-curve analysis., Results: Of the 1026 patients included in the PROMEtheuS cohort, 158 (15.4%) had a first-degree relative with PCa. p2PSA, %p2PSA and PHI values were significantly higher (P < 0.001), and free/total PSA (%fPSA) values significantly lower (P < 0.001) in the 71 patients with PCa (44.9%) than in patients without PCa. Univariable accuracy analysis showed %p2PSA (area under the receiver-operating characteristic curve [AUC]: 0.733) and PHI (AUC: 0.733) to be the most accurate predictors of PCa at biopsy, significantly outperforming total PSA ([tPSA] AUC: 0.549), free PSA ([fPSA] AUC: 0.489) and %fPSA (AUC: 0.600) (P ≤ 0.001). For %p2PSA a threshold of 1.66 was found to have the best balance between sensitivity and specificity (70.4 and 70.1%; 95% confidence interval [CI]: 58.4-80.7 and 59.4-79.5 respectively). A PHI threshold of 40 was found to have the best balance between sensitivity and specificity (64.8 and 71.3%, respectively; 95% CI 52.5-75.8 and 60.6-80.5). At 90% sensitivity, the thresholds for %p2PSA and PHI were 1.20 and 25.5, with a specificity of 37.9 and 25.5%, respectively. At a %p2PSA threshold of 1.20, a total of 39 (24.8%) biopsies could have been avoided, but two cancers with a Gleason score (GS) of 7 would have been missed. At a PHI threshold of 25.5 a total of 27 (17.2%) biopsies could have been avoided and two (3.8%) cancers with a GS of 7 would have been missed. In multivariable logistic regression models, %p2PSA and PHI achieved independent predictor status and significantly increased the accuracy of multivariable models including PSA and prostate volume by 8.7 and 10%, respectively (P ≤ 0.001). p2PSA, %p2PSA and PHI were directly correlated with Gleason score (ρ: 0.247, P = 0.038; ρ: 0.366, P = 0.002; ρ: 0.464, P < 0.001, respectively)., Conclusions: %p2PSA and PHI are more accurate than tPSA, fPSA and %fPSA in predicting PCa in men with a family history of PCa. Consideration of %p2PSA and PHI results in the avoidance of several unnecessary biopsies. p2PSA, %p2PSA and PHI correlate with cancer aggressiveness., (© 2013 BJU International.)