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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., (Copyright © 2021. Published by Elsevier Inc.)

Purpose: To conduct a rigorous assessment of in-hospital morbidity after urethroplasty according with the European Association of Urology (EAU) guidelines for complication reporting., Methods: We retrospectively (2015-2019) identified 469 consecutive patients receiving urethroplasty (e.g. bulbar urethroplasty with grafts, penile urethroplasty with/without grafts/flaps, Johanson, de novo or revision perineostomy, end-to-end anastomosis, meatoplasty and/or meatotomy) at our tertiary care institution. Complications were graded with Clavien-Dindo score and Comprehensive Complication Index (CCI). Complications were classified in: bleeding no gastrointestinal, cardiac, gastrointestinal, genitourinary, infectious, neurological, oral, wound, miscellaneous, and pulmonary. Logistic regression tested for predictors of in-hospital complications and prolonged hospitalization (> 75th percentile). Kaplan-Meier and Cox regression investigated the effect of complications on failure after urethroplasty., Results: Overall, 161 (34.3%) patients experienced at least one complication. Of those, 47 (10%) experienced two or more complications and 59 (12.6%) experienced at least one Clavien-Dindo ≥ II complication. Only two patients had Clavien-Dindo III complications. Infectious was the most frequent complication, and de novo or revision perineostomy was associated with the highest rate of complications. The occurrence of any complications, as well as complication with Clavien-Dindo ≥ II were associated with prolonged hospitalizations, but not with higher rates of post-urethroplasty failure., Conclusions: Complications after urethroplasty were common events, but rarely with severe sequelae. Infectious were the most common complications and perineostomy was the type of urethroplasty with the highest rate of complications. The application of the EAU recommendations allowed the identifications of a higher number of complications after urethroplasty if compared with previous reports based on unsupervised chart review., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

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

Objective: To explore the margin, ischemia, and complications (MIC) system achievement rate within a population of patients who were treated with robotic partial nephrectomy (RAPN), at 3 different tertiary care centers, and to determine the factors predicting MIC achievement., Methods: The study population consisted of 339 patients who underwent RAPN for cT1 renal tumors at 3 centers. Cancer control was defined as the absence of positive surgical margin. Ideal threshold of warm ischemia time (WIT) was considered ≤20 minutes. Safety was defined as the absence of major complications. The achievement of MIC was considered as the fulfillment of all these 3 outcomes. The primary endpoint was to determine the MIC rate in our study population; the secondary endpoint was to detect factors affecting its achievement., Results: The overall MIC rate was 67%. Median WIT was 17 minutes (range, 7-51 minutes). In 88 cases (26%), WIT was >20 minutes. Positive surgical margins were found in 22 patients (6.5%). Overall postoperative and major complication rates were 14.5% (n = 49) and 3.8% (n = 13). In multivariate logistic regression analysis, continuously coded and categorically coded preoperative aspects and dimensions used for an anatomical scores were an independent predictor of MIC achievement (odds ratio, 0.636; confidence interval, 0.436-0.928; P = .019 and odds ratio, 0.098; confidence interval, 0.030-0.326; P <.001)., Conclusion: The MIC binary system may represent a useful tool to summarize the achievement of optimal perioperative outcomes of RAPN. In the current population, tumor complexity was significantly associated with MIC achievement., (Copyright © 2015 Elsevier Inc. All rights reserved.)

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