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.

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.

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 Performance and Clinical Impact of PSMA PET/CT versus mpMRI in Patients with a High Suspicion of Prostate Cancer and Previously Negative Biopsy: A Prospective Trial (PROSPET-BX).

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.

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.

Intratumoral Switch of Molecular Phenotype and Overall Survival in Muscle Invasive Bladder Cancer.

In recent years, immunohistochemical protein expression was studied as a surrogate to the molecular classification of bladder cancer, although no tissue biomarkers are available for clinical use to predict survival or the response to neoadjuvant chemotherapy (CT) in UC, as the literature produced conflicting results. This retrospective study included TURB specimens harboring foci of HG pT2 muscle-invasive bladder carcinoma (MIBC) from 251 patients who subsequently underwent radical cystectomy. We performed immunohistochemical analysis on tumor samples, for relevant gene-expression-based markers for basal type (CD44, CK5/6) and luminal type (CK20 and pPARγ). Piescore, investigated in both non-muscle-invasive (NMI) and muscle-invasive (MI) components of the tumor, divided basal and luminal UC-types when at least three of the four markers were consistent with a specific phenotype, mixed types if one/two luminal and basal markers were present simultaneously, and neu-like types when all four markers investigated were negative. Eighteen selected cases were also investigated with RT-PCR to validate, and to increase the specificity of, the immunohistochemical results. We observe an immunophenotypical difference in the NMI and MI components in 96/251 UC patients (38.25%): half of tumors (44/96 cases) have a transition to basal, 36.46% (35/96 cases) to neu-like, 12.5% (12/96 cases) to mixed, and 5.2% (5/96 cases) to luminal phenotypes. Mixed tumors in the NMI component are more likely to change phenotype than other groups, particularly compared with basal tumors, which demonstrate greater stability (only 8/96 cases, p < 0.00001). The transition of luminal tumors to basal display a better OS compared with the transition toward neu-like tumors (p = 0.027). Overall, the phenotypical switch does not affect lymphovascular invasion, pT, DFS, or OS compared with non-switched cases. In the MI component, the presence of CD44 expression, irrespective of score-related phenotype, shows a protective effect in papillary-type UC (OS p = 0.008, HR 0.453, PFS p = 0.07, HR 0.599), and in UC naïve for CT (p = 0.0479). Piescore immunophenotyping reveals an intratumoral phenotypical transition between the NMI and MI components of the same tumor. The molecular change is a common event in the mixed and luminal categories, but not in basal tumors, which show better phenotypical stability. This phenomenon could partially explain the sensitivity of a subset of luminal UC to chemotherapy: good responders could be "non-real" luminal UC, which acquire nasal markers, such as CD44.

Could We Safely Avoid a Second Resection in Selected Patients With T1 Non-Muscle-Invasive Bladder Cancer? Preliminary Results of Cost-Effectiveness Study From HUmanitas New Indications for ReTUR (HuNIRe) Multicenter Prospective Trial.

Objectives: The aim of this study is to assess whether restaging transurethral resection (ReTUR) could be safely replaced with urine cytology (UC) and in-office fiexible cystoscopy in selected T1 non-muscle-invasive bladder cancer (NMIBC). Materials and Methods: This is an ongoing prospective multicenter trial enrolling patients diagnosed with T1 BC from 5 Italian centers. Patients with a macroscopically incomplete initial resection or absence of detrusor muscle were subjected to ReTUR according to European Association of Urology (EAU) guidelines. Conversely, those with a complete tumor resection at initial TUR underwent UC at 3-4 weeks and in-office fiexible white-light and narrow-band cystoscopy at 4-6 weeks. In case of positive UC, or evidence of recurrence at cystoscopy, ReTUR was performed within 2 weeks. Otherwise, patients started Bacillus Calmette-Guérin (BCG) induction course without ReTUR. The primary endpoint was to determine the feasibility and the clinical utility of not performing ReTUR in selected T1 NMIBC patients. The secondary endpoint was to perform a cost-benefit analysis of this alternative approach. Results: Since May 2020, among 87 patients presenting with T1, 76 patients were enrolled. Nineteen (25%) patients underwent standard ReTUR after initial resection, 10 (13.2%) due to the absence of the detrusor muscle and 9 (11.8%) due to a macroscopically incomplete initial TUR. Overall, 57 (75%) patients initially avoided immediate ReTUR and underwent UC plus in-office flexible cystoscopy. Among them, 38 (66.7%) had no evidence of residual disease and immediately started the BCG induction course. Nineteen patients (33.3%) underwent "salvage" ReTUR due to either positive UC (7; 12.3%) or suspicious cystoscopy (12; 21%). Considering only the patients who initially avoided the ReTUR, disease recurrence was observed in 10/57. The saving of resource for each safely avoided ReTUR was estimated to be 1,759 €. Considering the entire sample, we estimated a saving of 855 € per patient if compared with the EAU guideline approach. Conclusion: The preliminary results of our trial suggested that ReTUR might be safely avoided in highly selected T1 BC patients with a complete resection at first TUR. Longer follow-up and larger sample size are needed to investigate the long-term oncological outcomes of this alternative approach.

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.

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.

Oncofid-P-B: a novel treatment for BCG unresponsive carcinoma in situ (CIS) of the bladder: Results of a prospective European Multicentre study at 15 months from treatment start.

PURPOSE: This study reports the safety and efficacy of Oncofid-P-B, a novel compound under development by Fidia Farmaceutici S.p.A. with specific binding to CD44 receptor, in patients with CIS unresponsive or intolerant to BCG. MATERIALS AND METHODS: This is a phase 1 open-label, single arm, multicenter European study to assess safety, tolerability and efficacy of Oncofid-P-B administered in 20 patients with CIS ± Ta-T1, unresponsive or intolerant to BCG, unwilling or unfit for cystectomy. Oncofid-P-B was administered by intravesical instillation for 12 consecutive weeks (intensive phase) followed, in CR patients, by 12 monthly instillations (maintenance phase). The primary objective was the overall safety profile. Secondary objectives included: i) any evidence of antitumor activity, ii) patient's compliance, iii) systemic absorption. The CR was defined as a negative cystoscopy, negative biopsy of the urothelium and negative cytology. RESULTS: At the end of the intensive phase, 15 of the 20 enrolled patients (75%), achieved the CR. Patients still in CR after 3, 6, 9 and 12 months of maintenance phase were 13 (65%), 12 (60%), 9 (45%) and 8 (40%), respectively. Only seven (5 mild and 2 moderate) drug-related AEs were reported in three patients. No drug related serious AEs and no drug related withdrawals have been reported. In all plasma samples, the drug concentratiosn was below the LLOQ (1ng/ml). CONCLUSIONS: Oncofid-P-B is very safe, well tolerated and highly effective (75% CR) when administered weekly for up to 12 consecutive weeks (75% CR), with 40% CR still after 15 months from treatment start.

Combination of AST to ALT and neutrophils to lymphocytes ratios as predictors of locally advanced disease in patients with bladder cancer subjected to radical cystectomy: Results from a single-institutional series.

BACKGROUND: Bladder cancer (BC) staging is challenging. There is an important need for available and affordable predictors to assess, in combination with imaging, the presence of locally-advanced disease. OBJECTIVE: To determine the role of the De Ritis ratio (DRR) and neutrophils to lymphocytes ratio (NLR) in the prediction of locally-advanced disease defined as the presence of extravescical extension (pT ⩾ 3) and/or lymph node metastases (LNM) in patients with BC treated with radical cystectomy (RC). METHODS: We retrospectively analyzed clinical and pathological data of 139 consecutive patients who underwent RC at our institution. Logistic regression models (LRMs) were fitted to test the above-mentioned outcomes. RESULTS: A total of 139 consecutive patients underwent RC at our institution. Eighty-six (61.9%) patients had a locally-advanced disease. NLR (2.53 and 3.07; p = 0.005) and DRR (1 and 1.17; p = 0.01) were significantly higher in patients with locally-advanced disease as compared to organ-confined disease. In multivariable LRMs, an increasing DRR was an independent predictor of locally-advanced disease (OR = 3.91; 95% CI: 1.282-11.916; p = 0.017). Similarly, an increasing NLR was independently related to presence of locally-advanced disease (OR = 1.28; 95% CI: 1.027-1.591; p = 0.028). In univariate LRMs, patients with DRR > 1.21 had a higher risk of locally advanced disease (OR = 2.83; 95% CI: 1.312-6.128; p = 0.008). Similarly, in patients with NLR > 3.47 there was an increased risk of locally advanced disease (OR = 3.02; 95% CI: 1.374-6.651; p = 0.006). In multivariable LRMs, a DRR > 1.21 was an independent predictor of locally advanced disease (OR = 2.66; 95% CI: 1.12-6.35; p = 0.027). Similarly, an NLR > 3.47 was independently related to presence of locally advanced disease (OR = 2.24; 95% CI: 0.95-5.25; p = 0.065). No other covariates such as gender, BMI, neoadjuvant chemotherapy or diabetes reached statistical significance. The AUC of the multivariate LRM to assess the risk of locally advanced disease was 0.707 (95% CI: 0.623-0.795). Limitations include the retrospective nature of the study and the relatively small sample size.

Long-term Follow-up and Factors Associated with Active Surveillance Failure for Patients with Non-muscle-invasive Bladder Cancer: The Bladder Cancer Italian Active Surveillance (BIAS) Experience.

Active surveillance (AS) has been proposed as an alternative to transurethral resection (TUR) in selected patients with recurrent low-risk non-muscle-invasive bladder cancer (NMIBC). Here we report long-term results for patients on AS and investigate features associated with AS failure. Cases with recurrence after diagnosis of low-grade (LG) pTa/pT1a NMIBC were enrolled in the Bladder Italian Active Surveillance (BIAS) project. Over 251 AS events, we observed 130 failures (51.8%). In these patients, final pathology showed 25 benign lesions (19.2%) and 92 LG Ta (70.7%), 12 high-grade Ta/T1 (9.2%), and one T2 (0.7%) tumor. The treatment-free probability at 12, 18, 24, and 36 mo was 59.7%, 54.5%, 46.3%, and 40.4%, respectively. We identified 95 patients (37.8%) who remained on AS for >18 mo. A multivariable Cox regression model confirmed that patients with a history of multiple TURs (hazard ratio [HR] 1.59, 95% confidence interval [CI] 1.01-2.51) and those with more than one lesion at AS entry (HR 1.63, 95% CI 1.05-2.54) were significantly more likely to experience AS failure. Our results confirm that well-selected patients with NMIBC can safely remain on AS for a long period of time. Multiple TURs and multiple lesions at AS enrollment are associated with a higher risk of AS failure. PATIENT SUMMARY: Active surveillance has been proposed as an alternative to surgery for patients with recurrent low-risk superficial bladder cancer. Our report confirms that well-selected patients can safely avoid or postpone surgery.

Hope for Ostomates: A Carbon and Zeolite Impregnated Polyester Fabric Inhibits Urine Odor in Cancer Patients: A Randomized Experimental Study.

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.

Long-term Follow-up After En Bloc Transurethral Resection of Non-muscle-invasive Bladder Cancer: Results from a Single-center Experience.

BACKGROUND: En bloc resection (ERBT) is a valid alternative to piecemeal resection for non-muscle-invasive bladder cancer (NMIBC), guaranteeing pathological outcomes. However, very few studies investigated long-term oncological outcomes of ERBT. OBJECTIVE: To report long-term oncological outcome of ERBT. DESIGN SETTING AND PARTICIPANTS: This is a retrospective analysis of prospectively collected data. We included patients who underwent ERBT from June 2010 to February 2014, and were diagnosed with NMIBC at pathology evaluation. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary study endpoint was recurrence-free survival at 5 yr. Secondary outcomes were presence of detrusor muscle, recurrence rate at the first follow-up cystoscopy, progression to muscle-invasive bladder cancer (MIBC) at 5 yr, and factors associated with long-term oncological outcomes. Kaplan-Meier curves were used to describe recurrence-free survival time. A univariate analysis was used to investigate factors associated with recurrence. RESULTS AND LIMITATIONS: Overall, 74 patients were included in this study. The median age was 71 (66-76) yr. Most of the patients presented with only one bladder tumor, and the median tumor diameter was 2 (interquartile range [IQR] 1-2.5) cm. After histopathological examination, eight, 35, and 31 patients were diagnosed with low-, intermediate-, and high-risk disease, respectively. All the en bloc resected tumors showed the presence of detrusor muscle. The median follow-up was 72 (IQR 66-90) mo. The recurrence rate at the first follow-up cystoscopy was 5.4% (four out of 74 patients). Overall, 57 (77%) patients were free of recurrence at 5 yr. No progression to MIBC was observed: progression-free survival was 100%. Limitations include retrospective design and small size. CONCLUSIONS: Our findings showed that ERBT for NMIBC presents an optimal long-term oncological outcome. Further studies with larger cohorts are necessary for confirming our preliminary results and for a direct comparison with the traditional piecemeal resection. PATIENT SUMMARY: In case of superficial bladder tumors, transurethral resection of the entire tumor and its base in one piece seems to provide good long-term results in terms of recurrence and progression rates.

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.