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Background: The recommendation to perform biopsy of PIRADS 3 lesions has not been adopted with strength as compared to higher scored lesions on multiparametric MRI. This represents a challenging scenario and an unmet need for clinicians to apply a risk adapted approach in these cases. In the present study, we examined clinical and radiologic characteristics in men with PI-RADS 3 index lesions that can predict csPCa on mpMRI-target biopsy., Methods: Revision of a prospective database with patients who underwent targeted and systematic biopsies from 2015 to 2023 for PI-RADS 3 lesions identified on mpMRI. Baseline variables were collected, such as PSA density (PSAd), 4Kscore, prostate size, and the apparent diffusion coefficient (ADC) value of the lesion on mpMRI. Logistic regression, receiver operating characteristic (ROC) and decision curve analyses (DCA) assessing the association between clinic-radiologic factors and csPCa were performed., Results: Overall, 230 patients were included in the study and the median age was 65 years. The median prostate size and PSA were 50 g and 6.26 ng/mL, respectively. 17.4% of patients had csPCa, while 27.5% had Gleason group 1. In univariable logistic analyses, we found that age, BMI, prostate size, PSAd, ADC, and 4Kscore were significant csPCa predictors (P < 0.05). PSAd showed the best prediction performance in terms of AUC (= 0.679). On multivariable analysis, PSAd and 4Kscore were associated with csPCa. The net benefit of PSAd combined with clinical features was superior to those of other parameters. Within patients with PSAd < 0.15, 4Kscore was a statistically significant predictor of csPCa (OR = 3.25, P = 0.032)., Conclusion: PSAd and 4Kscore are better predictors of csPCa in patients with PIRADS 3 lesions compared to ADC. The predictive role of 4Kscore is higher in patients with low PSAd. These results can assist practitioners in the risk stratification of patients with equivocal lesions to determine the need of biopsy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To assess the efficacy and safety of combined High-Intensity Focused Ultrasound (HIFU) and Holmium Laser Enucleation of the Prostate (HoLEP) in treating patients with both localized prostate cancer (PCa) and prostate > 60 g., Methods: All patients who underwent HIFU for treatment of localized PCa were prospectively enrolled in our study. We reviewed records of patients undergoing procedures from January 2016 to January 2023. For patients with prostate sizes > 60 g, HoLEP was offered before HIFU to prevent worsened urinary symptoms post-treatment. Oncological outcomes-prostatic-specific (PSA) kinetics, recurrence rates, treatment failure - and functional results-Sexual Health Inventory for Men (SHIM), International Prostate Symptoms Score (IPSS), and urinary complications were compared between patients undergoing combined HoLEP and HIFU with those underwent HIFU-monotherapy., Results: Among 100 patients, 74 underwent HIFU-monotherapy and 26 underwent the combined HoLEP and HIFU. The majority had intermediate-risk PCa (67%). Pathologic assessment of HoLEP specimens showed no tumor evidence in 57% of cases. In comparison to the HIFU-only group, the combined group exhibited significantly lower PSA metrics across various intervals, however, no differences were found regarding overall and infield recurrences and treatment failure rates. While the combined treatment initially resulted in higher incontinence rates and shorter catheterization durations (P < 0.001), no significant difference in IPSS was observed during subsequent follow-ups., Conclusion: HoLEP and HIFU can be safely combined for the treatment of PCa in patients with >60 g prostate volume without compromising early oncological outcomes thereby expanding the therapeutic scope of HIFU in treating patients with localized PCa and large adenomas., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: To identify whether there was a disparity in the utilization of immunotherapy in the treatment of black patients with metastatic castration resistant prostate cancer (mCRPC)., Methods: Using the National Cancer Database, we identified patients between 2010- 2015 with likely minimally/asymptomatic mCRPC. We analyzed annual trends for chemotherapy and immunotherapy use and compared utilization by demographic and clinical features. Multivariable analysis was performed to determine predictors of receiving immunotherapy vs chemotherapy., Results: We identified 1301 patients with likely mCRPC. The majority were non Hispanic White (NHW - 63 %) and 23 % were non-Hispanic Black (NHB). Overall, there was increased utilization of immunotherapy in mCRPC from 2010 onwards, with the peak occurring in 2014 (4.6 %). Chemotherapy use increased significantly, peaking in 2014 to 26.1 %. However, the increased utilization of immunotherapy in the mCRPC was mainly seen in White patients: from 50 % to 74.2 % of the cohort. Conversely, there was a decrease in utilization of immunotherapy among Black mCPRC patients: from 50 % to 25.8 %. On multivariable analysis, there was no statistically significant difference between treatment types by race., Conclusion: FDA approval of Sipuleucel-T for mCRPC led to increased utilization of immunotherapy shortly thereafter, but this was mainly noted in white patients. Black patients comparatively did not exhibit increased utilization of this novel agent after 2010. Further studies are necessary to help understand barriers to access to new treatment in mCRPC and eliminate the burden of disease in minority populations.", Competing Interests: Declaration of Competing Interest The authors have no competing interests to declare that are relevant to the content of this article., (Copyright © 2023 National Medical Association. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate clinical risk factors associated with postoperative deep incisional or organ/space surgical site infections (SSI) following radical cystectomy (RC) in a well characterized and large contemporary cohort., Methods: We used the American College of Surgeons National Surgical Quality Improvement Program database to identify adult patients who underwent RC for bladder cancer between 2015 and 2020 (n = 13,081). We conducted multivariable-adjusted logistic regression and Cox adjusted proportional hazards regression analysis to identify clinical predictors of deep incisional or organ/space SSI in the 30-day postoperative-period following RC., Results: Deep incisional or organ/space SSI risk increased with continent urinary diversion (HR = 1.61, 95% CI: 1.38-1.88; P < 0.001), obesity (HR = 1.60, 95% CI: 1.35-1.90; P < 0.001), diabetes mellitus (HR = 1.30, 95% CI: 1.13-1.51; P < 0.001), and being functionally dependent before surgery (HR = 2.09, 95% CI: 1.44-3.03; P < 0.001)., Conclusions: Postoperative deep incisional or organ/space SSIs following RC occur more frequently in patients who were obese, diabetic, functionally dependent before surgery, and those who underwent continent urinary diversion. These findings may assist urologists in preoperative counseling, medical optimization, and choice of urinary diversion approach, as well as improved patient monitoring and identification of candidates for intervention postoperatively., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objectives: To identify patient risk factors that predict nonhome discharge after surgery for urologic malignancies as well as determine whether discharge status had an impact on readmission rates in patients undergoing surgery for urologic malignancies., Methods: We identified patients who had undergone surgery for urologic malignancies including prostate, bladder, kidney, or upper tract urothelial cancer from 2011 to 2019 in the American College of Surgeon National Surgical Quality Improvement Program (ACS-NSQIP) database. Multivariable logistic regression analyses were performed to identify patient characteristics that were associated with nonhome discharges and 30-day postoperative readmission., Results: Nonhome discharge occurred in 2.8% of our study population. Women were less likely to be discharged to home (OR 0.60 p < 0.0001). Nonhome discharge was more common in patients who underwent cystectomy when compared to nephrectomy (OR 1.41 p < 0.0001) or prostatectomy (OR 4.16 p < 0.0001). Those with elevated BMI were less likely to experience non-home discharge (OR 0.86 p=0.0095) while patients who were identified as underweight and those with unexpected weight loss prior to surgery were more likely to have nonhome discharges (OR 1.76 p = 0.0002, OR 1.67, p < 0.0001). Comorbidities and presence of postoperative complications were also found to be significant independent predictors of nonhome discharges. Thirty-day postoperative readmission occurred in 6.9% of our study population. Of the patients who were readmitted 93.1% were initially discharged home, and 6.9% had nonhome discharges. Higher risk of readmission was seen in elderly patients and those with significant comorbidities. When controlling for predictors of readmission, on multivariate analysis, non-home discharge was associated with a decreased likelihood of readmission (OR 0.79, p = 0.0004)., Conclusions: Patient factors including age, gender, weight, comorbidities, postoperative complications, and site of procedure were found to be independent predictors of non-home discharge following surgery for urologic malignancies. Patients with these risk factors should be counseled preoperatively on the likelihood of requiring a non-home discharge to help manage expectations and create a standardized transition of care pathway following surgery., Competing Interests: Declaration of Competing Interest I, nor any of the authors of this paper have any competing interest or anything to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: We investigated the relationship between timing of adjuvant chemotherapy on overall survival following radical cystectomy., Methods: We retrospectively reviewed the National Cancer Data Base for patients with newly diagnosed pT2-T4, N0, M0 urothelial cell carcinoma who received no treatment prior to radical cystectomy. Patients who received no adjuvant chemotherapy or who received adjuvant chemotherapy more than 45 days after radical cystectomy were propensity matched to patients receiving adjuvant chemotherapy within 45 days of radical cystectomy. Selection bias was assessed by comparing the length of stay, readmission rate, and surgical approach between groups. Median survival was calculated using Kaplan-Meier analysis. Adjusted hazard ratios and 95% confidence intervals were calculated from a multivariable Cox regression model to examine factors affecting overall survival., Results: From 2004 to 2014, 284 patients with muscle-invasive bladder cancer met inclusion criteria. Patients receiving chemotherapy within 45 days had the best 5-year overall survival (47.0%, 95%CI: 40.6%-53.2%) compared to those receiving chemotherapy after 45 days (37.5%, 95%CI: 31.4%-43.7%). Chemotherapy after 45 days and no adjuvant chemotherapy were significant predictors of worse overall survival compared to chemotherapy within 45 days (1.27, 1.02-1.59, P = 0.033 and 1.41, 1.12-1.78, P = 0.003). Receiving no adjuvant chemotherapy was not significantly different than chemotherapy after 45 days (1.11, 0.89-1.38, P = 0.348). Significant predictors of poorer overall survival were female sex (1.37, 1.04-1.81, P = 0.028), Medicare (1.37, 1.06-1.76, P = 0.016), pT3 stage (1.79, 1.35-2.38, P < 0.001), and pT4 stage (3.00, 2.20-4.01, P < 0.001). Significantly more patients with length of stay ≤7 days following RC received chemotherapy within 45 days (53.2%) compared to those who received adjuvant chemotherapy after 45 days after RC (44.0%) or no adjuvant chemotherapy (43.0%; P = 0.0369)., Conclusions: Initiation of adjuvant chemotherapy within 45 days of radical cystectomy for patients with pT2-4 bladder cancer was associated with an overall survival benefit compared to patients who received adjuvant chemotherapy after 45 days or no adjuvant chemotherapy., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Contemporary randomized controlled trials exploring adjuvant chemotherapy (AC) for bladder cancer (BCa) have yielded inconsistent results due to premature termination and/or poor patient accrual., Objective: To compare efficacy of AC vs. observation after radical cystectomy stratified by disease stage in a propensity-matched cohort., Design, Setting, and Participants: We performed a retrospective study that included patients who underwent radical cystectomy for any pT, N0-1, M0 BCa from the National Cancer Data Base (2004-2014). Patients who underwent AC were 1:1 propensity matched with patients who received observation only., Outcome Measurements and Statistical Analysis: Overall survival was assessed with multivariable Cox regression models where adjusted hazard ratios (aHR) and 95% confidence intervals (95% CI) were calculated., Results and Limitations: After coarsened exact 1:1 propensity matching, 3,066 patients (AC 1,533; observation 1,533) were included in the analysis. There were no significant differences in patient-, facility-, or tumor-level characteristics among cohorts. Compared with patients who underwent observation, recipients of AC had improved overall survival (aHR 0.67; 95% CI 0.61-0.74). Patients with pT2-4, pN1 disease significantly benefited from AC. Among the pN0 cohort, improved survival from AC was observed only in stages pT3 (aHR 0.67; 95% CI 0.55-0.83) and pT4 (aHR 0.70; 95% CI 0.50-0.98)., Conclusions: AC was associated with improved survival in locally advanced (pT3-4, pN0) and regionally advanced (pT2-4, pN1) chemotherapy-naive BCa., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: We assessed the impact of open or minimally-invasive partial cystectomy on surgical margin status in a nationwide hospital-based cohort., Materials and Methods: Patients who underwent partial cystectomy from 2010 to 2014 were identified in the National Cancer Data Base. The primary outcome was surgical margin status. A multivariable logistic regression model was fitted to identify patient, hospital, and surgical factors associated with positive surgical margins (PSMs)., Results: Partial cystectomy was performed in 1,118 patients via open (n = 715, 64%), laparoscopic (n = 209, 19%), and robotic (n = 194, 17%) approaches. Overall, 220 (19.7%) patients had PSMs. The PSM rate by surgical approach was 19.6% for open, 18.2% for laparoscopic, and 21.6% for robotic (P = 0.678). Compared to open partial cystectomy, the laparoscopic (aOR 1.06, 95%CI 0.70-1.60, P = 0.782), and robotic (aOR 1.28, 95%CI 0.85-1.91, P = 0.235) approaches were not significantly different in terms of PSM rate. There were higher odds of PSMs in non-Hispanic blacks (aOR 1.93, 95%CI 1.09-3.39, P = 0.023) compared to non-Hispanic whites, and in patients with muscle invasive bladder cancer (aOR 3.28, 95%CI 2.00-5.37, P < 0.001) or tumor size ≥ 3 cm (aOR 1.67, 95%CI 1.21-2.30, P = 0.002). Tumors in a dome/urachal location had lower odds of a PSM compared to tumors in a nondome/urachal location (aOR 0.67, 95%CI 0.47-0.94, P = 0.022)., Conclusions: Our results suggest that partial cystectomy using a laparoscopic or robotic-assisted approach is not associated with an increased risk of PSMs compared to open partial cystectomy., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: To determine whether a specific lymph node yield (LNY) affects overall survival (OS) in patients with penile cancer., Materials and Methods: Using the National Cancer Database, we identified 364 men diagnosed with pSCC who underwent ILND between 2004 and 2013. Men diagnosed on autopsy or at the time of death, patients with preoperative chemotherapy or radiotherapy, M+ and N3 disease, or with less than 3-month of follow-up were excluded. Kaplan-Meier analysis was used to compare Overall Survival (OS). A multivariable Cox regression model was developed to assess predictors of OS., Results: The median number of LN retrieved was 16 (IQR: 9-23). There was no significant difference in race, stage, grade for men with LNY ≤15 vs. >15. However, men with LNY ≤15 were significantly older than those with LNY >15 (65 vs. 59 years, p<0.001). On multivariable analysis, radical surgery, age, N+ disease, and LNY ≤15 were independent predictors of worse OS. Patients with LNY ≤15 showed significantly worse 5-year OS versus those with LNY >15 (49% vs. 67%, p=0.008). Nodal density (ND) ≥12.5% was also associated with decreased 5-year OS versus ND <12.5% (31% vs. 70%, p<0.0001)., Conclusions: LNY following ILND for pSCC appears to be an independent predictor of OS. A total LNY of >15 following ILND may have a beneficial impact on OS and serve as the threshold for defining an adequate ILND., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Radical cystectomy is the surgical standard for invasive bladder cancer. Robot-assisted cystectomy has been proposed to provide similar oncological outcomes with lower morbidity. We aimed to compare progression-free survival in patients with bladder cancer treated with open cystectomy and robot-assisted cystectomy., Methods: The RAZOR study is a randomised, open-label, non-inferiority, phase 3 trial done in 15 medical centres in the USA. Eligible participants (aged ≥18 years) had biopsy-proven clinical stage T1-T4, N0-N1, M0 bladder cancer or refractory carcinoma in situ. Individuals who had previously had open abdominal or pelvic surgery, or who had any pre-existing health conditions that would preclude safe initiation or maintenance of pneumoperitoneum were excluded. Patients were centrally assigned (1:1) via a web-based system, with block randomisation by institution, stratified by type of urinary diversion, clinical T stage, and Eastern Cooperative Oncology Group performance status, to receive robot-assisted radical cystectomy or open radical cystectomy with extracorporeal urinary diversion. Treatment allocation was only masked from pathologists. The primary endpoint was 2-year progression-free survival, with non-inferiority established if the lower bound of the one-sided 97·5% CI for the treatment difference (robotic cystectomy minus open cystectomy) was greater than -15 percentage points. The primary analysis was done in the per-protocol population. Safety was assessed in the same population. This trial is registered with ClinicalTrials.gov, number NCT01157676., Findings: Between July 1, 2011, and Nov 18, 2014, 350 participants were randomly assigned to treatment. The intended treatment was robotic cystectomy in 176 patients and open cystectomy in 174 patients. 17 (10%) of 176 patients in the robotic cystectomy group did not have surgery and nine (5%) patients had a different surgery to that they were assigned. 21 (12%) of 174 patients in the open cystectomy group did not have surgery and one (1%) patient had robotic cystectomy instead of open cystectomy. Thus, 302 patients (150 in the robotic cystectomy group and 152 in the open cystectomy group) were included in the per-protocol analysis set. 2-year progression-free survival was 72·3% (95% CI 64·3 to 78·8) in the robotic cystectomy group and 71·6% (95% CI 63·6 to 78·2) in the open cystectomy group (difference 0·7%, 95% CI -9·6% to 10·9%; p non-inferiority =0·001), indicating non-inferiority of robotic cystectomy. Adverse events occurred in 101 (67%) of 150 patients in the robotic cystectomy group and 105 (69%) of 152 patients in the open cystectomy group. The most common adverse events were urinary tract infection (53 [35%] in the robotic cystectomy group vs 39 [26%] in the open cystectomy group) and postoperative ileus (33 [22%] in the robotic cystectomy group vs 31 [20%] in the open cystectomy group)., Interpretation: In patients with bladder cancer, robotic cystectomy was non-inferior to open cystectomy for 2-year progression-free survival. Increased adoption of robotic surgery in clinical practice should lead to future randomised trials to assess the true value of this surgical approach in patients with other cancer types., Funding: National Institutes of Health National Cancer Institute., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objective: To analyze the performance of different radical prostatectomy-based prognostic tools in predicting the biopsy progression in our active surveillance cohort., Materials and Methods: We analyzed 326 patients with biopsy Gleason grade≤6,≤2 positive biopsy cores,≤20% tumor present in any core, prostate-specific antigen<15ng/dl, and clinical stages T1-T2a all of whom had at least single surveillance biopsy. Probabilities of pathologically relatively aggressive disease were estimated using Partin and Dinh risk tables and Kattan, Truong, and Kulkarni nomograms for each individual patient. Using these predictions, performance of these tools was quantified regarding discrimination, stratification at different cut-points, calibration, and the clinical net benefit., Results: Predictions of Partin and Dinh tables were not associated with the biopsy progression. The predictive value of Kattan and Truong nomograms was higher when compared with the other tools, although it was significant only on the first and second surveillance biopsies. Both nomograms were able to identify low- and high-risk subgroups within the cohort. Kattan nomogram demonstrated better correlation with the observed rate of progression over the first 3 biopsies and higher clinical net benefit., Conclusion: Kattan and Truong nomograms demonstrated the best performance in predicting biopsy progression, although their value was largely limited to the first 2 surveillance biopsies. Both tools were able to stratify patients into subgroups with different risks of progression. These nomograms have important differences, which suggest that a more effective predictive model combining the strong sides of both tools and possibly some other variables could be developed., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Mutations in the von Hippel-Lindau (VHL) gene give rise to renal cell carcinoma. Reactive oxygen species, generated by Nox oxidases, are involved in tumorigenesis. We have previously demonstrated that in VHL-deficient cells, p22(phox)-dependent Nox1 and Nox4 oxidases maintain hypoxia inducible factor-2alpha (HIF-2alpha) protein expression through an Akt-dependent translational pathway. Phosphorylation of tuberin, by Akt, results in its inactivation. Here we show that diphenyleneiodonium chloride, an inhibitor of Nox oxidases, and small-interfering RNA-mediated down-regulation of p22(phox) inhibit Akt-dependent phosphorylation of tuberin and stabilizes tuberin protein levels in VHL-deficient renal carcinoma cells. p22(phox)-mediated inactivation of tuberin is associated with an increase in ribosomal protein S6 kinase 1 and eukaryotic initiation factor 4E-binding protein-1 (4E-BP1) phosphorylation as well as HIF-2alpha stabilization. Importantly, we find that marked up-regulation of p22(phox) in human renal cell carcinoma correlates with increased tuberin phosphorylation, decreased tuberin protein levels, and increased phosphorylation of 4E-BP1. Our data provide the first evidence that p22(phox)-based Nox oxidases maintain HIF-2alpha protein expression through inactivation of tuberin and downstream activation of ribosomal protein S6 kinase 1/4E-BP1 pathway.