Preoperative Age and Its Impact on Long-Term Renal Functional Decline after Robotic-Assisted Partial Nephrectomy: Insights from a Tertiary Referral Center.

Background and Objectives: to investigate the impact of age on renal function deterioration after robotic-assisted partial nephrectomy (RAPN) focusing on a decline to moderate and severe forms of chronic kidney disease (CKD). Materials and Methods: This is a single center prospective analysis of patients who underwent RAPN. The outcomes include the development of de novo CKD-S 3a [estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2)] and de novo CKD-S 3b (eGFR < 45 mL/min/1.73/m2). Multivariable analysis (MVA) via Cox regression identified predictors for CKD-S 3a/b. Kaplan -Meier Analyses (KMA) were fitted for survival assessment. Multivariable linear regression was utilized to identify the predictors of last-eGFR. Results: Overall, 258 patients were analyzed [low age (<50) n = 40 (15.5%); intermediate age (50-70) n = 164 (63.5%); high age (>70) n = 54 (20.9%)] with a median follow-up of 31 (IQR 20-42) months. MVA revealed an increasing RENAL score [Hazard Ratio (HR) 1.32, p = 0.009], age 50-70 (HR 6.21, p = 0.01), age ≥ 70 (HR 10.81, p = 0.001), increasing BMI (HR 1.11, p < 0.001) and preoperative CKD 2 (HR 2.43, p = 0.014) are independent risk factors associated with an increased risk of CKD-S 3a; conversely, post-surgical acute kidney injury was not (p = 0.83). MVA for CKD-S 3b revealed an increasing RENAL score (HR 1.51, p = 0.013) and age ≥ 70 (HR 2.73, p = 0.046) are associated with an increased risk of CKD-S 3b. Linear regression analysis revealed increasing age (Coeff. -0.76, p < 0.001), increasing tumor size (Coeff. -0.31, p = 0.03), and increasing BMI (Coeff. -0.64, p = 0.004) are associated with decreasing eGFR at last follow-up. We compare the survival distribution of our cohort stratified by age elderly patients experienced worsened CKD-S 3a/b disease-free survival (p < 0.001; p < 0.001, respectively). Conclusions: Age is independently associated with a greater risk of significant and ongoing decline in kidney function following RAPN. Recognizing the impact of aging on renal function post-surgery can guide better management practices. Further investigations are required.

A Comparative Evaluation of Multiparametric Magnetic Resonance Imaging and Micro-Ultrasound for the Detection of Clinically Significant Prostate Cancer in Patients with Prior Negative Biopsies.

BACKGROUND: The diagnostic process for prostate cancer after a negative biopsy is challenging. This study compares the diagnostic accuracy of micro-ultrasound (mUS) with multiparametric magnetic resonance imaging (mpMRI) for such cases. METHODS: A retrospective cohort study was performed, targeting men with previous negative biopsies and using mUS and mpMRI to detect prostate cancer and clinically significant prostate cancer (csPCa). RESULTS: In our cohort of 1397 men, 304 had a history of negative biopsies. mUS was more sensitive than mpMRI, with better predictive value for negative results. Importantly, mUS was significantly associated with csPCa detection (adjusted odds ratio [aOR]: 6.58; 95% confidence interval [CI]: 1.15-37.8; p = 0.035). CONCLUSIONS: mUS may be preferable for diagnosing prostate cancer in previously biopsy-negative patients. However, the retrospective design of this study at a single institution suggests that further research across multiple centers is warranted.

Development of a microultrasound-based nomogram to predict extra-prostatic extension in patients with prostate cancer undergoing robot-assisted radical prostatectomy.

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.

Is multiparametric MRI always needed in biopsy-naïve patients with abnormal digital rectal examination? A single-institutional experience combining clinical and micro-ultrasonography-based factors to optimize prostate cancer detection.

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.

Male awareness of prostate cancer risk remains poor in relatives of women with germline variants in DNA-repair genes.

Abstract. Objective: The aim of this study is to evaluate male awareness of developing prostate cancer (PCa) in families with germline DNA-repair genes (DRG) variants. Materials and methods: Data were collected from a prospective, monocentric cohort study. The study was conducted in a university hospital with a multidisciplinary approach to the patient (collaboration of the Departments of Oncology, Urology, Pathology, Radiology, and Medical Genetics Laboratory). We recruited healthy males, relatives of families of women with breast or ovarian cancer who tested positive for pathogenic variants (PVs) or likely pathogenic variants (LPVs) in DRGs. A dedicated PCa screening was designed and offered to men aged 35 to 69 years, based on early visits with digital rectal examination (DRE), prostate health index (PHI) measurement, multiparametric magnetic resonance imaging (mpMRI) and, if necessary, targeted/systematic prostate biopsies. The primary endpoint was to evaluate the willingness of healthy men from families with a DRG variants detected in female relatives affected with breast and/or ovarian cancer to be tested for the presence of familial PVs. The secondary endpoints were the acceptance to participate if resulted positive and compliance with the screening programme. Results: Over 1256 families, of which 139 resulted positive for PVs in DRGs, we identified 378 'healthy' men aged between 35 and 69 years old. Two hundred sixty-one (69.0%) refused to be tested for DRG variants, 66 (17.5%) declared to have been previously tested, and 51 (13.5%) males were interested to be tested. Between those previously tested and those who accepted to be tested, 62 (53.0%) were positive for a DRG variant, and all of them accepted to participate in the subsequent surveillance steps. The main limitation is that is a single-centre study and a short follow-up. Conclusions: All men tested positive for a DRG variants agreed to go under the surveillance scheme. However, only 31% of 'men at risk' (i.e., relative of a DRG variant carrier) expressed their willingness to be tested for the familial DRG variant. This observation strongly supports the urgent need to implement awareness of genetic risk for PCa within the male population.

The diagnostic accuracy of micro-ultrasound for prostate cancer diagnosis: a review.

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.

Diagnostic accuracy of multiparametric MRI- and microultrasound-targeted biopsy in biopsy-naïve patients with a PI-RADS 5 lesion: a single-institutional study.

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.

Evaluation of Semen Self-Sampling Yield Predictors and CTC Isolation by Multi-Color Flow Cytometry for Liquid Biopsy of Localized Prostate Cancer.

Liquid biopsy (LB) for prostate cancer (PCa) detection could represent an alternative to biopsy. Seminal fluid (SF) is a source of PCa-specific biomarkers, as 40% of ejaculate derives from the prostate. We tested the feasibility of an SF-based LB by evaluating the yield of semen self-sampling in a cohort of >750 patients with clinically localized PCa. The overall SF collection yield was 18.2% (39% when considering only compliant patients), with about a half of the patients (53.15%) not consenting to SF donation. Independent favorable predictors for SF collection were younger age and lower prostate volume. We implemented a protocol to enrich prostate-derived cells by multi-color flow cytometry and applied it on SF and urine samples from 100 patients. The number of prostate-enriched cells (SYTO-16+ PSMA+ CD45-) was variable, with higher numbers of cells isolated from SF than urine (p value < 0.001). Putative cancer cells (EpCAMhigh) were 2% of isolated cells in both specimens. The fraction of EpCAMhigh cells over prostate-enriched cells (PSMA+) significantly correlated with patient age in both semen and urine, but not with other clinical parameters, such as Gleason Score, ISUP, or TNM stage. Hence, enumeration of prostate-derived cells is not sufficient to guide PCa diagnosis; additional molecular analyses to detect patient-specific cancer lesions will be needed.

Clinical and pathological predictors of persistent T1 HG at second resection.

BACKGROUND: T1 high-grade (HG) non-muscle invasive bladder cancer (NMIBC) has a significant risk of recurrence and progression, and the European Association of Urology recommends a second transurethral resection of the bladder (ReTUR). Stage at ReTUR has been shown to be a reliable predictor of survival, therefore, we sought to assess clinical and pathological predictors associated with the persistence of T1 at ReTUR in our retrospective multicentric cohort. METHODS: This is a retrospective multicentric study of T1 HG patients at transurethral resection of the bladder (TURB) who underwent subsequent ReTUR. All histological samples were sub-classified according to Rete Oncologica Lombarda (ROL) T1 sub-staging system. RESULTS: One hundred and sixty-six patients were enrolled. Forty-four (26.5%) had T1 HG tumor at ReTUR while 93 (56%) had residual tumor of any stage. Lesion size was significantly greater in T1 HG patients at ReTUR, as well as the prevalence of multifocality. The multivariable logistic regression model showed lesion dimension and multifocality as predictors of T1 HG at ReTUR, after adjusting for significant covariables (CIS and detrusor muscle presence). ROL sub-staging system was not a significant predictor, but ROL2 prevalence was higher in the T1 HG at ReTUR group. CONCLUSIONS: Lesion size and multifocality were independent predictors of T1 HG persistence at ReTUR, and patients at risk should be promptly identified and treated accordingly. Our results could help physicians make patient-tailored decisions by identifying those most likely to benefit from a second resection.

Diagnostic performance of microUltrasound at MRI-guided confirmatory biopsy in patients under active surveillance for low-risk prostate cancer.

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.

Evaluating the Protective Effect of Intravesical Bacillus Calmette-Guerin against SARS-CoV-2 in Non-Muscle Invasive Bladder Cancer Patients: A Multicenter Observational Trial.

We aim to evaluate the potential protective role of intravesical Bacillus Calmette-Guerin (BCG) against SARS-CoV-2 in patients with non-muscle invasive bladder cancer (NMIBC). Patients treated with intravesical adjuvant therapy for NMIBC between January 2018 and December 2019 at two Italian referral centers were divided into two groups based on the received intravesical treatment regimen (BCG vs. chemotherapy). The study's primary endpoint was evaluating SARS-CoV-2 disease incidence and severity among patients treated with intravesical BCG compared to the control group. The study's secondary endpoint was the evaluation of SARS-CoV-2 infection (estimated with serology testing) in the study groups. Overall, 340 patients treated with BCG and 166 treated with intravesical chemotherapy were included in the study. Among patients treated with BCG, 165 (49%) experienced BCG-related adverse events, and serious adverse events occurred in 33 (10%) patients. Receiving BCG or experiencing systemic BCG-related adverse events were not associated with symptomatic proven SARS-CoV-2 infection (p = 0.9) nor with a positive serology test (p = 0.5). The main limitations are related to the retrospective nature of the study. In this multicenter observational trial, a protective role of intravesical BCG against SARS-CoV-2 could not be demonstrated. These results may be used for decision-making regarding ongoing and future trials.

Prospective Validation of the ROL System in Substaging pT1 High-Grade Urothelial Carcinoma: Results from a Mono-Institutional Confirmatory Analysis in BCG Treated Patients.

Patients with pT1 high-grade (HG) urothelial carcinoma (UC) and a very high risk of progression might benefit from immediate radical cystectomy (RC), but this option remains controversial. Validation of a standardized method to evaluate the extent of lamina propria (LP) invasion (with recognized prognostic value) in transurethral resection (TURBT) specimens is still needed. The Rete Oncologica Lombarda (ROL) system showed a high predictive value for progression after TURBT in recent retrospective studies. The ROL system was supposed to be validated on a large prospective series of primary urothelial carcinomas from a single institution. From 2016 to 2020, we adopted ROL for all patients with pT1 HG UC on TURBT. We employed a 1.0-mm threshold to stratify tumors in ROL1 and ROL2. A total of 222 pT1 HG UC were analyzed. The median age was 74 years, with a predominance of men (73.8%). ROL was feasible in all cases: 91 cases were ROL1 (41%), and 131 were ROL2 (59%). At a median follow-up of 26.9 months (IQR 13.8-40.6), we registered 81 recurrences and 40 progressions. ROL was a significant predictor of tumor progression in both univariable (HR 3.53; CI 95% 1.56-7.99; p < 0.01) and multivariable (HR 2.88; CI 95% 1.24-6.66; p = 0.01) Cox regression analyses. At Kaplan-Meier estimates, ROL showed a correlation with both PFS (p = 0.0012) and RFS (p = 0.0167). Our results confirmed the strong predictive value of ROL for progression in a large prospective series. We encourage the application of ROL for reporting the extent of LP invasion, substaging T1 HG UC, and improving risk tables for urological decision-making.

Assessing the Role of High-resolution Microultrasound Among Naïve Patients with Negative Multiparametric Magnetic Resonance Imaging and a Persistently High Suspicion of Prostate Cancer.

Background: Multiparametric magnetic resonance imaging (mpMRI) is an invaluable diagnostic tool in the decision-making for prostate biopsies (PBx). However, a non-negligible proportion of patients with negative MRI (nMRI) may still harbour prostate cancer (PCa). Objective: To assess whether microultrasound (micro-US) can help in substratifying the presence of PCa and clinically significant PCa (csPCa; ie, any Gleason score ≥7 PCa) in patients with nMRI despite a persistently high clinical suspicion of PCa. Design setting and participants: A total of 125 biopsy-naïve patients who underwent micro-US-guided PBx with the ExactVu system for a persistently high suspicion of PCa despite nMRI were prospectively enrolled. Intervention: The Prostate Risk Identification using micro-US (PRI-MUS) protocol was used to identify suspicious areas; PBx included targeted sampling of PRI-MUS ≥3 areas and systematic sampling. Outcome measurements and statistical analysis: The primary endpoint was the assessment of micro-US diagnostic accuracy in detecting csPCa. Secondary endpoints included determining the proportion of patients with nMRI who may avoid PBx after micro-US or transrectal US, presence of cribriform and intraductal patterns on biopsy core examination, predictors of csPCa in patients presenting with nMRI, and comparing micro-US-targeted and systematic PBx in identifying csPCa. Results and limitations: Considering csPCa detection rate, micro-US showed optimal sensitivity and negative predictive value (respectively, 97.1% and 96.4%), while specificity and positive predictive value were 29.7% and 34.0%, respectively. Twenty-eight (22.4%) patients with a negative micro-US examination could have avoided PBx with one (2.9%) missed csPCa. Cribriform and intraductal patterns were found in 14 (41.2%) and four (11.8%) of csPCa patients, respectively. In multivariable logistic regression models, positive micro-US, age, digital rectal examination, and prostate-specific antigen density ≥0.15 emerged as independent predictors of PCa. Targeted and systematic sampling identified 33 (97.1%) and 26 (76.5%) csPCa cases, respectively. The main limitation of the current study is represented by its retrospective single-centre nature on an operator-dependent technology. Conclusions: Micro-US represents a valuable tool to rule out the presence of csPCa among patients with a persistent clinical suspicion despite nMRI. Patient summary: According to our results, microultrasound (micro-US) may represent an effective tool for the diagnosis of clinically significant prostate cancer in patients with negative magnetic resonance imaging (nMRI), providing high sensitivity and negative predictive value. Further randomised studies are needed to confirm the potential role of micro-US in the diagnostic pathway of patients with a persistent suspicion of prostate cancer despite nMRI.

Prospective evaluation of the role of imaging techniques and TMPRSS2:ERG mutation for the diagnosis of clinically significant prostate cancer.

Objectives: To test the hypothesis of a relationship between a specific genetic lesion (T2:ERG) and imaging scores, such as PI-RADS and PRI-MUS, and to test the effectiveness of these parameters for the diagnosis of prostate cancer (PCa) and clinically significant PCa (csPCa). Materials and methods: This is a prospective study of men with suspected PCa enrolled between 2016 and 2019 at a high-volume tertiary hospital. Patients underwent systematic US-guided biopsy, plus targeted biopsy if they were presenting with >=1 suspicious lesion (PI-RADS>2) at mpMRI or PR-IMUS >2 at micro-ultrasound assessment. For each patient, one core from the highest PI-RADS or PRI-MUS lesion was collected for T2:ERG analysis. Multivariable logistic regression models (LRMs) were fitted for csPCa with a clinical model (age, total PSA, previous biopsy, family history for PCa), a clinical plus PI-RADS, clinical plus T2:ERG, clinical plus PI-RADS plus T2:ERG, and T2:ERG plus PI-RADS alone. Results: The cohort consists of 158 patients: 83.5% and 66.2% had respectively a diagnosis of PCa and csPCa after biopsy. A T2:ERG fusion was found in 37 men and 97.3% of these patients harbored PCa, while 81.1% were diagnosed with csPCa. SE of T2:ERG assay for csPCa was 28.8%, SP 87.0%, NPV 38.8%, and PPV 81.1%. Of 105 patients who performed mpMRI 93.% had PIRADS ≥3. SE of mpMRI for csPCa was 98.5%, SP was 12.8%, NPV was 83.3%, and PPV was 65.7%. Among 67 patients who were subjected to micro-US, 90% had a PRI-MUS ≥3. SE of micro-US for csPCa was 89.1%, SP was 9.52%, NPV was 28.6%, and PPV was 68.3%. At univariable LRM T2:ERG was confirmed as independent of mpMRI and micro-US result (OR 1.49, p=0.133 and OR 1.82, p=0.592, respectively). At multivariable LRM the clinical model alone had an AUC for csPCa of 0.74 while the clinical model including PI-RADS and T2:ERG achieved an AUC of 0.83. Conclusions: T2:ERG translocation and imaging results are independent of each other, but both are related csPCa. To evaluate the best diagnostic work-up for PCa and csPCa detection, all available tools (T2:ERG detection and imaging techniques) should be employed together as they appear to have a complementary role.

External Validation and Comparison of Two Nomograms Predicting the Probability of Lymph Node Involvement in Patients subjected to Robot-Assisted Radical Prostatectomy and Concomitant Lymph Node Dissection: A Single Tertiary Center Experience in the MRI-Era.

Introduction: To externally validate and directly compare the performance of the Briganti 2012 and Briganti 2019 nomograms as predictors of lymph node invasion (LNI) in a cohort of patients treated with robot-assisted radical prostatectomy (RARP) and extended pelvic lymph node dissection (ePLND). Materials and Methods: After the exclusion of patients with incomplete biopsy, imaging, or clinical data, 752 patients who underwent RARP and ePLND between December 2014 to August 2021 at our center, were included. Among these patients, 327 (43.5%) had undergone multi-parametric MRI (mpMRI) and mpMRI-targeted biopsy. The preoperative risk of LNI was calculated for all patients using the Briganti 2012 nomogram, while the Briganti 2019 nomogram was used only in patients who had performed mpMRI with the combination of targeted and systematic biopsy. The performances of Briganti 2012 and 2019 models were evaluated using the area under the receiver-operating characteristics curve analysis, calibrations plot, and decision curve analysis. Results: A median of 13 (IQR 9-18) nodes per patient was removed, and 78 (10.4%) patients had LNI at final pathology. The area under the curves (AUCs) for Briganti 2012 and 2019 were 0.84 and 0.82, respectively. The calibration plots showed a good correlation between the predicted probabilities and the observed proportion of LNI for both models, with a slight tendency to underestimation. The decision curve analysis (DCA) of the two models was similar, with a slightly higher net benefit for Briganti 2012 nomogram. In patients receiving both systematic- and targeted-biopsy, the Briganti 2012 accuracy was 0.85, and no significant difference was found between the AUCs of 2012 and 2019 nomograms (p = 0.296). In the sub-cohort of 518 (68.9%) intermediate-risk PCa patients, the Briganti 2012 nomogram outperforms the 2019 model in terms of accuracy (0.82 vs. 0.77), calibration curve, and net benefit at DCA. Conclusion: The direct comparison of the two nomograms showed that the most updated nomogram, which included MRI and MRI-targeted biopsy data, was not significantly more accurate than the 2012 model in the prediction of LNI, suggesting a negligible role of mpMRI in the current population.

Xpert Bladder Cancer Monitor May Avoid Cystoscopies in Patients Under "Active Surveillance" for Recurrent Bladder Cancer (BIAS Project): Longitudinal Cohort Study.

OBJECTIVES: To test the hypothesis that patients under active surveillance (AS) for Non-muscle Invasive Bladder Cancer (NMIBC) who were negative on longitudinal re-testing by the Xpert® Bladder Cancer Monitor (Xpert BC Monitor) assay may avoid unnecessary cystoscopies and urine cytology (UC). SUBJECTS/PATIENTS OR MATERIALS AND METHODS: This is a prospective cohort study of patients enrolled in the AS protocol for recurrent NMIBC (Bladder Cancer Italian Active Surveillance, BIAS project), whose urine samples were analyzed by Xpert BC Monitor upon entry in the study (T0). Patients who had a negative Xpert test and did not fail AS, underwent additional Xpert tests after 4 (T1), 8 (T2), and 12 (T3) months. The clinical utility of Xpert was assessed by determining the number of cystoscopies and UC that could be avoided within 1 year. RESULTS: Overall, 139 patients were tested with Xpert at T0. Median follow-up was 23 (IQR 17-27) months. Sixty-eight (48.9%) patients failed AS, 65 (46.7%) are currently on AS, and 6 (4.3%) were lost at follow-up. At T0 57 (41.0%) patients had a negative test and 36 (63.2%) are still in AS. In patients with 2 consecutives negative Xpert tests, we could have avoided 73.9% of unnecessary cystoscopies, missing 26.4% failure, up to avoid all cystoscopies with 4 negative tests missing only 12% of failure. All the patients with negative Xpert had negative UC. Failure-free-survival at median follow-up (23 month) stratified for having 0, 1, or ≥2 negative tests was 67.0, 55.1. and 84.1, respectively. CONCLUSION: Our findings suggest that Xpert BC Monitor assay, when it is longitudinally repeated, could significantly reduce the number of unnecessary cystoscopies and UC during their follow-up.

The use of 29 MHz transrectal micro-ultrasound to stratify the prostate cancer risk in patients with PI-RADS III lesions at multiparametric MRI: A single institutional analysis.

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.

Feasibility, safety, and efficacy of ultrasound-guided transperineal laser ablation for the treatment of benign prostatic hyperplasia: a single institutional experience.

PURPOSE: To evaluate the feasibility, safety, and efficacy of ultrasound-guided transperineal laser ablation (TPLA) as a new minimally invasive surgical therapy (MIST) for the treatment of lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: Under local anesthesia and conscious sedation up to two laser fibers for each prostatic lobe were inserted under US-guidance by a percutaneous approach. TPLA was performed using a continuous wave diode laser (SoracteLite-EchoLaserX4) able to generate a light-induced thermal heating and subsequent coagulative necrosis of the prostatic tissue. Patients were evaluated at 3, 6, and 12 months after TPLA. RESULTS: Twenty-two consecutive patients were prospectively enrolled (median age 61.9 years). All procedures were well tolerated and no procedural complications were recorded. Median catheterization time was 7 days, while the median hospitalization time was 1 day. Three out of twenty-two patients (13.6%) experienced acute urinary retention and two (9.1%) of them urinary tract infection requiring major antibiotic treatment. At 3, 6, and 12 months, median prostate volume significantly decreased by a - 21.3%, - 29%, and - 41%, respectively. At the same time point, median IPSS was 8 (- 63.6%), 5 (- 74%), and 6 (- 75%), while median QoL score was 1 in all the scheduled timepoints of follow-up. The median postoperative Qmax at 3, 6, and 12 months improved by + 57.8%, + 98%, and + 115.8%, respectively. Ejaculatory function was preserved in 21 out of 22 patients (95.5%). CONCLUSIONS: TPLA of the prostate appears to be a promising MIST for BPH. Long-term results and comparative studies against standard treatments are warranted before implementations of this technique in the urologist's armamentarium.