Preoperative optimization of the radical cystectomy patient: Current state and future directions.

Radical cystectomy (RC) is associated with high rates of morbidity and mortality despite adoption of robotics and implementation of enhanced recovery after surgery protocols. There have been increased efforts to investigate preoperative optimization through comprehensive nutritional evaluation, preoperative supplementation, and prehabilitation outside of previously described enhanced recovery after surgery protocols to reduce mortality and morbidity from RC. In this review, we summarize and evaluate the current literature on preoperative assessment and optimization in RC.

Percutaneous Nephrolithotomy Access: A Meta-Analysis Comparing Access by Urologist vs Radiologist.

Introduction: Percutaneous nephrolithotomy is a minimally invasive procedure indicated for the management of staghorn calculi or renal calculi >2.0 cm. Percutaneous renal access is a critical step in this procedure and can be performed by either urologists or interventional radiologists. The purpose of this study is to perform a meta-analysis to compare outcomes between urologist and interventional radiologist-mediated access. Methods: An electronic literature search was conducted to identify studies comparing urologist- and interventional radiologist-acquired access. Studies must have included both urologist- and intervention radiologist-acquired access data but were excluded if (1) not in English; (2) abstract without full text; (3) unable to determine who acquired access; and (4) only included either urologist or interventional radiologist data. Meta-analysis comparison was generated with the Review Manager 5.4 software. Results: After screening the abstracts and title, 55 relevant studies were identified. Nine articles were utilized in the meta-analysis. Urologist-acquired access was associated with a greater stone-free rate (risk ratio [RR] = 1.10; 95% confidence interval [CI], 1.01-1.20), a reduction in major complications (RR = 0.69; 95% CI, 0.53-0.92), and a shorter hospital stay (mean difference -0.40; 95% CI, -0.64 to -0.16) in comparison with radiologist-acquired access. Urologist-acquired access was associated with greater blood loss (mean difference 0.46; 95% CI, 0.32-0.60) when compared with interventional radiology-acquired access. No significant differences were found with regard to unusable access, multiple tracts, supracostal access, ancillary procedure requirement, operative time, minor complications, and transfusions. Conclusions: Urologist-acquired access may be associated with a higher stone-free rate and a reduction in major complications, whereas interventional radiologist-mediated access may be associated with a reduction in blood loss, despite similar transfusion rates.

Single Dilation in Primary Inflatable Penile Prosthesis Placement Is Associated With Fewer Corporal Complications Than Sequential Dilation.

OBJECTIVE: To assess the difference in outcomes between single dilation (SingD) and sequential dilation (SeqD) in primary penile implantation, hypothesizing that patients who undergo SeqD had higher rates of noninfectious complications. METHODS: We performed a multicenter, retrospective study of men undergoing primary inflatable penile prosthesis placement. Intraoperative complications and postoperative noninfectious outcomes were assessed between the two groups. Multivariable analysis was performed to identify predictors of complications. RESULTS: A total of 3293 patients met inclusion criteria. After matching, there were 379 patients who underwent SingD and 379 patients who underwent SeqD. There was no significant difference in intraoperative complications between patients who underwent SingD vs SeqD, nor was there any difference in cylinder length (20 cm with interquartile range [IQR] 18-21 cm vs 20 cm with IQR 18-20 cm respectively, P = .4). On multivariable analysis, SeqD (OR 5.23 with IQR 2.74-10, P < .001) and older age (OR 1.04 with IQR 1.01-1.06, P = .007) were predictive of postoperative noninfectious complications. There was no significant difference in intraoperative complications between patients who underwent SingD vs SeqD, nor was there any difference in cylinder length. SeqD and older age were predictive of postoperative noninfectious complications. CONCLUSION: During inflatable penile prosthesis placement in the uncomplicated patient without fibrosis, SingD is a safe technique to utilize during implantation that will minimize postoperative adverse events, and promote device longevity without loss of cylinder length.

Factors associated with postoperative urinary retention in patients undergoing penile prosthesis implantation.

Placement of penile prosthesis had been well described in the outpatient setting, however, one barrier to same-day discharge is postoperative urinary retention (POUR). POUR remains a condition encountered during ambulatory surgical procedures and has yet to be characterized in patients undergoing penile prosthesis. We characterized POUR in a cohort of penile prosthesis recipients along with risk factors and management. Patients undergoing penile prosthesis implantation from 2014 through 2020 without pre-existing retention were included. All patients underwent a void trial immediately following penile prosthesis in the post-anesthesia care unit. POUR was strictly defined as (1) any patient requiring catheter replacement after prosthesis, (2) a rising post-void residual, or (3) inability to void after 6 h regardless of whether a catheter was placed. Independent procedures, demographic, intraoperative, and postoperative risk factors for POUR were assessed. 317 men were included of whom 27.1% experienced POUR. Men experiencing POUR and those not in retention were essentially indistinguishable with respect to previously described risk factors for POUR. Only use of both α-blockers and 5-α-reductase inhibitors was significantly associated with a greater risk of POUR, a finding maintained on adjusted analysis (adjusted odds ratio 10.1, 95% confidence interval 2.1 to 49.8). POUR resolved without intervention in 3.5%, a single episode of clean intermittent catheterization (CIC) in 7.0% of patients, and repeated CIC or indwelling catheter placement with a successful delayed void trial in 88.4% of patients. Rate of prosthesis infection in patients who experienced POUR did not significantly differ from those who did not experience POUR (4.7% vs. 2.2% p = 0.26). Our findings suggest that POUR is experienced in as many as 1 in 4 men undergoing penile prosthesis placement, most of whom must be managed with indwelling catheterization or repeated CIC. Those with indicators of symptomatic prostate enlargement are at significantly greater risk of urinary retention.

Utility of PSA density in patients with PI-RADS 3 lesions across a large multi-institutional collaborative.

INTRODUCTION: Prostate MRI detecting PI-RADs = 3 lesions has low diagnostic utility for prostate malignancy. Use of PSA density has been suggested to further risk-stratify these men, to potentially avoid biopsies in favor of monitoring. We evaluate the ability of PSA density (PSAd) to risk-stratify PIRADs 3 lesions across patients who underwent a prostate biopsy in a large multi-institutional collaborative. MATERIALS AND METHODS: Pennsylvania Urology Regional Collaborative (PURC) is a voluntary quality improvement collaborative of 11 academic and community urology practices in Pennsylvania and New Jersey. A retrospective analysis was performed on all patients in the PURC database that had a prostate MRI with PI-RADs 3 lesions only. PSA just before the MRI and prostate size reported on MRI were used to calculate the PSA. Clinicopathologic data were evaluated. Univariable analysis using Chi-Square and Kruskal Wallis tests and multivariable logistic regression were used to identify predictors of any PCa, and clinically significant prostate cancer (csPCa) was defined as ≥ Grade Group 2 (GG2.) RESULTS: Between May 2015 and March 2021, 349 patients with PIRADs 3 lesions only were identified and comprised the cohort of interest. Median PSA was 5.0 with a prostate volume of 58cc and a median PSA density of 0.11, 10.6% of the cohort was African American with 81.4% being Caucasian. Significant prostate cancer was detected in 70/349 (20.0%) men. Smaller prostate volume, abnormal DRE, and higher PSAd were significantly associated with clinically significant prostate cancer on univariable analysis. In men with PSAd <0.15, 31/228 (13.6%) harbored csPCa. Multivariable analysis confirmed that men with PSAd >0.15 were more likely to harbor clinically significant prostate cancer (P < 0.001). CONCLUSION: Across a large regional collaborative, patients with PIRADs 3 lesions on mpMRI were noted to have clinically significant cancer in 20% of biopsies. Using a PSA density cut-off of 0.15 may result in missing clinically significant prostate cancer in 13.6%. This information is useful for prebiopsy risk stratification and counseling.

Intracorporeal Versus Extracorporeal Neobladder After Robot-assisted Radical Cystectomy: Results From the International Robotic Cystectomy Consortium.

OBJECTIVE: To compare perioperative and oncologic outcomes of intracorporeal (ICNB) and extracorporeal neobladder (ECNB) following robot assisted radical cystectomy (RARC) from a multi-institutional, prospectively maintained database, the International Robotic Cystectomy Consortium (IRCC). METHODS: A retrospective review of IRCC database between 2003 and 2020 (3742 patients from 33 institutions across 14 countries) was performed (I-79606). The Cochran-Armitage trend test was used to assess utilization of ICNB over time. Multivariate logistic regression models were fit to evaluate variables associated with receiving ICNB, overall complications, high-grade complications, and readmissions after RARC. Kaplan Meier curves were used to depict recurrence-free, disease-specific, and overall survival. RESULTS: Four hundred eleven patients received neobladder, 64% underwent ICNB. ICNB utilization increased significantly over time (P <.01). Patients who received ICNB were readmitted and received neoadjuvant chemotherapy more frequently (36% vs 24%, P = .03, 35% vs 8%, P <.01, respectively). ICNB was associated with older age (OR 1.04, 95% CI 1.01-1.07, P = .001), receipt of neoadjuvant chemotherapy (OR 4.63, 95% CI 2.34-9.18, P <.01), and more recent RARC era (2016-2020) (OR 12.6, 95% CI 5.6-28.4, P <.01). On multivariate analysis, ICNB (OR 5.43, 95% CI 2.34-12.58, P <.01), positive surgical margin (OR 4.88, 95% CI 1.29-18.42, P = .019), longer operative times (OR 1.26, 95% CI 1.00-1.58, P = .048), and institutional annual RARC volume (OR 1.09, 95% CI 1.05-1.12, P <.01) were associated with readmissions. CONCLUSION: Utilization of ICNB increased significantly over time. Patients who underwent RARC and ICNB had shorter hospital stays and fewer 30-d reoperations but were readmitted more frequently compared to those who underwent ECNB.

Neuraxial vs General Anesthesia: 30-Day Mortality Outcomes Following Transurethral Resection of Prostate.

OBJECTIVE: To examine the occurrence of 30-day mortality, and other procedure related morbidities in cohorts of patient receiving neuraxial anesthesia (NAX) or general anesthesia (GA) in the setting of transurethral resection of the prostate (TURP). Historically, NAX has been recommended for patients undergoing TURP permitting monitoring of consciousness and early diagnosis of absorption-related hyponatremia. We aim to analyze a broader comparison of mortality and other associated morbidities regarding the form of anesthesia utilized. METHODS: The National Surgical Quality Improvement Program (NSQIP) database was accessed and queried from January 2010 to December 2016 for TURP. 28,486 TURP cases were identified and further stratified by the type anesthesia administration, NAX 7,261 and GA 21,225. Chi-square analyses and Kaplan-Meier tests were performed for univariate comparisons. Using propensity score, data were optimally (1:1) matched to account for potential confounding variables. Outcomes were then compared for NAX vs. GA with a primary endpoint of 30-day mortality, followed by secondary endpoint of adverse outcomes reported per NSQIP. RESULTS: Prior to matching, 30-day mortality was found to be 0.4% in the NAX cohort and 0.7% GA. 12,180 patients equally matched between the 2 groups. NAX was found to be superior to GA in terms of 30-day survival benefit (OR 0.55, 95% CI 0.33 -0.92, P <0.05), sepsis (OR 0.60, 95% CI 0.50 -0.73, P <0.001), and return to operating room (OR 0.76, 95% CI 0.60 -0.98, P <0.05) when comparing matched cohorts. NAX was associated with lower incidence of overall adverse clinical outcomes 12.4% vs 13.7% (P = 0.036). CONCLUSION: NAX was found to have statistically relevant advantage for 30-day postoperative outcomes when compared to GA for TURP based on NSQIP database reporting.

Evidence that EZH2 Deregulation is an Actionable Therapeutic Target for Prevention of Prostate Cancer.

Chemoprevention trials for prostate cancer by androgen receptor or androgen synthesis inhibition have proven ineffective. Recently, it has been demonstrated that the histone methlytransferase, EZH2 is deregulated in mouse and human high-grade prostatic intraepithelial neoplasia (HG-PIN). Using preclinical mouse and human models of prostate cancer, we demonstrate that genetic and chemical disruption of EZH2 expression and catalytic activity reversed the HG-PIN phenotype. Furthermore, inhibition of EZH2 function was associated with loss of cellular proliferation and induction of Tp53-dependent senescence. Together, these data provide provocative evidence for EZH2 as an actionable therapeutic target toward prevention of prostate cancer.

Connexin 43 expression is associated with increased malignancy in prostate cancer cell lines and functions to promote migration.

Impaired expression of connexins, the gap junction subunits that facilitate direct cell-cell communication, have been implicated in prostate cancer growth. To elucidate the crucial role of connexins in prostate cancer progression, we performed a systematic quantitative RT-PCR screening of connexin expression in four representative prostate cancer cell lines across the spectrum of malignancy. Transcripts of several connexin subunits were detected in all four cell lines, and connexin 43 (Cx43) showed marked elevation at both RNA and protein levels in cells with increased metastatic potential. Analysis of gap-junction-mediated intercellular communication revealed homocellular coupling in PC-3 cells, which had the highest C x 43 expression, with minimal coupling in LNCaP cells where C x 43 expression was very low. Treatment with the gap junction inhibitor carbenoxolone or connexin mimetic peptide ACT-1 did not impair cell growth, suggesting that growth is independent of functional gap junctions. PC-3 cells with C x 43 expression reduced by shRNA showed decreased migration in monolayer wound healing assay, as well as decreased transwell invasion capacities when compared to control cells expressing non-targeting shRNA. These results, together with the correlation between C x 43 expression levels and the metastatic capacity of the cell lines, suggest a role of C x 43 in prostate cancer invasion and metastasis.

Top2a identifies and provides epigenetic rationale for novel combination therapeutic strategies for aggressive prostate cancer.

Progression of aggressive prostate cancers (PCa) with androgen receptor splice variants or neuroendrocrine features is currently untreatable in the clinic. Therefore novel therapies are urgently required. We conducted RNA-seq using tumors from a unique murine transplant mouse model which spontaneously progresses to metastatic disease. Differential gene expression analysis revealed a significant increase of topoisomerase IIα, Top2a (Top2a) in metastatic tumors. Interrogation of human data revealed that increased Top2a expression in primary tumors selected patients with more aggressive disease. Further, significant positive correlation was observed between Top2a and the histone methyltransferase, Ezh2. Combination of the Top2 poison etoposide with the Ezh2 inhibitor GSK126 or DZNep significantly increased cell death in vitro in murine and human prostate cancer cell lines. Additionally, combination therapy extended time to progression and increased therapeutic efficacy in vivo. Overall, our studies demonstrate that patients screened for Top2a and Ezh2 expression would exhibit significant response to a combinational treatment involving low dose etoposide combined with Ezh2 inhibition. In addition, our data suggests that this combination therapeutic strategy is beneficial against aggressive PCa, and provides strong rationale for continued clinical development.