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.

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.

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.

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.

Use of high-resolution micro-ultrasound to predict extraprostatic extension of prostate cancer prior to surgery: a prospective single-institutional study.

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.

The Microbiome of Catheter Collected Urine in Males with Bladder Cancer According to Disease Stage.

PURPOSE: The dogma that urine is sterile has been overturned and dysbiosis of the urinary microbiome has been linked to many urological disorders. We tested the hypothesis that the urinary microbial composition may be different between men with or without bladder cancer in catheter collected urines, bladder washouts and midstream voided urines, and may be dependent on tumor staging. MATERIALS AND METHODS: Liquid samples were collected from male patients with bladder cancer, and sex and age matched nonneoplastic controls. Total DNA was extracted and processed for 16S rRNA gene sequencing. Bioinformatic analysis for microbial classification was performed to assess diversity and variations. RESULTS: The urinary microbiome associated with catheter collected urine samples of patients with bladder cancer was characterized by a significantly increased abundance of Veillonella (p=0.04) and Corynebacterium (p=0.03), and decreased Ruminococcus (p=0.03) compared to controls, with differences exacerbating with disease progression. Compared to catheterized urines, bladder cancer washouts showed the specific increase of some taxa, like Burkholderiaceae (p=0.014), whereas midstream urines were enriched in Streptococcus (p <0.0001), Enterococcus (p <0.0001), Corynebacterium (p=0.038) and Fusobacterium (p <0.0001). CONCLUSIONS: The bladder is colonized by endogenous bacteria and microbial modifications characterize the microbiome of patients with bladder cancer. Different microbial compositions can be characterized by changing sampling strategy. These results pave the way for exploring new diagnostic and therapeutic options based on the manipulation of the bacterial community.

The Clinical Significance of Multiple Negative Surveillance Prostate Biopsies for Men on Active Surveillance-Does Cancer Vanish or Simply Hide?

PURPOSE: Men with low risk prostate cancer on active surveillance undergo multiple biopsies over time. The long-term clinical significance of consecutively negative biopsies is not known. MATERIALS AND METHODS: Men with low risk prostate cancer prospectively enrolled in an active surveillance database with at least 4 biopsies were included in the study. Exposure variables were 0, 1 or 2 consecutively negative biopsies after diagnosis. Other variables included age, prostate specific antigen, prostate specific antigen density, Gleason grade group, percent positive cores and magnetic resonance imaging findings. Outcome variables were the detection of any cancer at fourth biopsy and active treatment. RESULTS: A total of 514 men were included, with 112 (22%) men having 1 negative biopsy and 78 (15%) with 2 consecutively negative biopsies. Median prostate specific antigen density was lower for men with 1 negative biopsy (0.11) and consecutively negative biopsies (0.10) compared to men who never had a negative biopsy (0.13, p <0.01). On univariable logistic regression higher prostate specific antigen density (OR 1.68, 95% CI 1.16-2.45) and suspicious magnetic resonance imaging lesions (OR 2.00, 95% CI 1.16-3.42) were associated with a higher likelihood of detecting cancer on fourth biopsy. On multivariable logistic regression 1 negative biopsy (OR 0.22, 95% CI 0.12-0.41) and consecutively negative biopsies (OR 0.12, 95% CI 0.06-0.24) were associated with a lower likelihood of detecting cancer at outcome biopsy. Unadjusted 10-year treatment-free survival was highest for patients with consecutively negative biopsies (84%) and 1 negative biopsy (74%) than those who had none (66%) (log rank p=0.02). CONCLUSIONS: Consecutively negative surveillance biopsies are correlated with favorable clinical risk factors and independently associated with subsequent negative biopsy and lower risk of active treatment.

Clinical Utility of 4Kscore®, ExosomeDx™ and Magnetic Resonance Imaging for the Early Detection of High Grade Prostate Cancer.

PURPOSE: We aimed to evaluate 4Kscore® and ExosomeDx™ with multiparametric magnetic resonance imaging in the detection of high grade prostate cancer and number of biopsies avoided. MATERIAL AND METHODS: Patients had 1 liquid biomarker test with or without multiparametric magnetic resonance imaging. High grade prostate cancer was defined as Gleason grade group 2 or greater. The overall number of avoided biopsies (with Gleason grade 1 or less), and number of missed Gleason grade 2 or greater cancer among the biopsied patients, were determined. RESULTS: Of the 783 patients in the overall cohort 419 (53.5%) underwent biopsy. 4Kscore and ExosomeDx scores higher than the manufacturers' cut point were associated with PI-RADS™ scores 3 to 5 and Gleason grade 2 or greater prostate cancer. Limiting biopsy to the men with liquid biomarker scores above the manufacturers' cut point would have resulted avoiding 29.5% to 39.9% unnecessary biopsies overall, while missing 4.0% to 4.8% Gleason grade 2 or greater prostate cancer in the biopsy group. Screening algorithms with up-front liquid biomarker testing followed by multiparametric magnetic resonance imaging if the biomarker is above the manufacturers' cut point, then followed by biopsy if the multiparametric magnetic resonance imaging is positive or if 4Kscore 20 or greater or ExosomeDx 19 or greater would have missed 4.8% to 5.6% of Gleason grade 2 or greater prostate cancer in the biopsy group while avoiding 39.4% to 43.0% biopsies and 29.5% to 39.9% multiparametric magnetic resonance imaging overall. Similar algorithms with up-front multiparametric magnetic resonance imaging followed by liquid biomarker testing for negative multiparametric magnetic resonance imaging would have missed 2.4% of Gleason grade 2 or greater prostate cancer in the biopsy group but only avoided 17.2% 19.3% biopsies overall. CONCLUSIONS: Screening algorithms with up-front liquid biomarker testing followed by multiparametric magnetic resonance imaging and biopsy at certain biomarker thresholds could reduce unnecessary biopsies, multiparametric magnetic resonance imaging and overdetection of Gleason grade 1 prostate cancer.

The Long-Term Risks of Metastases in Men on Active Surveillance for Early Stage Prostate Cancer.

PURPOSE: We assessd the long-term outcomes from a large prospective cohort of men diagnosed with prostate cancer managed with active surveillance and determined the clinical prognostic factors that may predict the risk of metastases. MATERIALS AND METHODS: We retrospectively reviewed data of men enrolled on active surveillance at our institution between 1990 and 2018 with low or intermediate risk disease (stage cT1-2, prostate specific antigen less than 20 ng/ml, and biopsy Grade Group [GG]1-2). Patients were classified into 3 groups by diagnostic GG and prostate specific antigen density. Primary outcome was metastatic prostate cancer detected on imaging or at prostatectomy. In addition, upgrade at surveillance biopsy, active treatment, and overall and prostate cancer specific survival outcomes were assessed. Cox proportional hazards regression models were used. RESULTS: A total of 1,450 men met the inclusion criteria. Median followup was 77 months (IQR 49-114). The 7-year metastasis-free survival rate was 99%. Metastases developed in 15 men at a median of 62 months (IQR 29-104), of which 69% were confined to lymph nodes. Men with GG2 had a lower metastasis-free survival rate compared to those with GG1 disease. GG2, prostate specific antigen velocity and PI-RADS® 4-5 lesions on multiparametric magnetic resonance imaging were associated with a higher risk of metastases. The 7-year prostate cancer specific survival was greater than 99%. CONCLUSIONS: Active surveillance seems to preserve favorable long-term prognosis, as metastases and prostate cancer specific death are rare. However, the higher risk of metastases associated with higher Gleason grade, prostate specific antigen velocity, and characteristics on multiparametric magnetic resonance imaging should be considered when selecting and counseling patients for active surveillance.

Clinical performance of Xpert Bladder Cancer (BC) Monitor, a mRNA-based urine test, in active surveillance (AS) patients with recurrent non-muscle-invasive bladder cancer (NMIBC): results from the Bladder Cancer Italian Active Surveillance (BIAS) project.

PURPOSE: To investigate the clinical performance of a new mRNA-based urine test, aiming to avoid unnecessary follow-up cystoscopy in patients under active surveillance (AS) for recurrent NMIBC. METHODS: This is a prospective cohort study enrolling patients with history of low-grade (LG) NMIBC, who developed a recurrence during the follow-up and underwent AS. Their urinary samples were analyzed by Xpert BC Monitor (Cepheid, Sunnyvale, CA, USA). The primary endpoint was to investigate if Xpert BC Monitor could avoid unnecessary cystoscopy during the follow-up period. Its sensitivity, specificity, PPVs and NPVs were calculated. A cutoff of 0.4 "linear discriminant analysis" (LDA) was optimized for the AS setting. RESULTS: The cohort consisted of 106 patients with a mean age of 72 ± 9.52 and a median follow-up from AS start of 8.8 (range 0-56.5) months. No statistically significant difference was found for the mean age, smoker status, lesion size, and number of lesions with a cutoff of 0.4. Of 106 patients, 22 (20.8%) were deemed to require treatment because of cystoscopic changes in size and/or number of lesions during the follow-up period. Using a cutoff value of < 0.4, 34 (33.7%) cystoscopies could be avoided due to low LDA value, missing 2/22 (9%) failures, none with high-grade (HG) NMIBC. Further research on larger population remains mandatory before its clinical use. CONCLUSION: Xpert BC Monitor seems to be a reliable assay, which might avoid unnecessary cystoscopies without missing HG NMIBC when its cutoff is optimized for the AS setting.

Gender-specific risk factors for renal cell carcinoma: a systematic review.

PURPOSE OF REVIEW: The relationship between gender and kidney cancer incidence/outcomes has been largely evaluated and may significantly impact the management of patients diagnosed with these tumors. We reviewed and summarized the most relevant recent publications reporting about this clinically meaningful relationship. RECENT FINDINGS: The incidence of kidney cancer is higher in men than in women. Male gender is clearly associated with more aggressive histological characteristics both in terms of tumor stage and grade. Similarly, male gender has been found to be associated with worse perioperative and oncological outcomes. Several genetic and molecular markers that may partly explain these observed differences have been evaluated. However, the impact of these markers on clinical practice has not been clearly demonstrated. SUMMARY: Gender is significantly associated with kidney cancer incidence, characteristics and outcomes. Future efforts are still needed to explore the biological and molecular basis underlying of this relationship.

Enhancing Prostate Cancer Detection Accuracy in Magnetic Resonance Imaging-targeted Prostate Biopsy: Optimizing the Number of Cores Taken.

Background and objective: The shift toward targeted biopsy (TBx) aims at enhancing prostate cancer (PCa) detection while reducing overdiagnosis of clinically insignificant disease. Despite the improved ability of TBx in identifying clinically significant PCa (csPCa), the optimal number and location of targeted cores remain unclear. This review aims to assess the optimal number of prostate biopsy magnetic resonance imaging (MRI)-targeted cores to detect csPCa. Methods: A narrative literature search was conducted using PubMed, focusing on studies published between January 2014 and January 2024, addressing factors influencing targeted core numbers during prostate biopsy. The search included both retrospective and prospective studies, prioritizing those with substantial sample sizes and employing terms such as "prostate biopsy", "mpMRI", "core number", and "cancer detection". Key findings and limitations: Two biopsy cores identified csPCa in 55-65% of cases. This detection rate improved to approximately 90% when the number of cores was ≥5. The inclusion of perilesional and systematic biopsies could maximize the detection of csPCa (from 10% to 45%), especially in patients under active surveillance or with prior negative biopsy results, although there is an increase in the overdiagnosis of indolent tumors (from 4% to 20%). Transperineal software-assisted target prostate biopsy may enhance cancer detection, particularly for tumors located at the apex/anterior part of the prostate. Increasing the number of TBx cores may incrementally raise the risk of complications (by 2-14% with each added core) and result in severe pain and significant discomfort for up to 17% and 25% of TBx patients, respectively. However, the overall rate and severity of these complications remain within acceptable limits. Conclusions and clinical implications: The optimal number of cores for targeted prostate biopsies should balance minimizing sampling errors with effective cancer detection and should be tailored to each patient's unique prostate characteristics. Up to five cores per MRI target may be considered to enhance the detection of csPCa, with adjustments based on factors such as prostate and lesion volume, Prostate Imaging Reporting and Data System, biopsy techniques, complications, patient discomfort, and anxiety. Patient summary: In this report, we found that increasing the number of biopsy cores up to ≥5 improves the detection rates of significant prostate cancer significantly to around 90%. Although inclusion of nearby and systematic biopsies enhances detection, increasing the biopsy count may lead to higher risks of complications and indolent tumors. A customized biopsy approach based on multiple variables could be helpful in determining the appropriate number of targeted biopsies on a case-by-case basis.

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.

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 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.

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.