NCCN Guidelines® Insights: Bladder Cancer, Version 3.2024.

Bladder cancer, the sixth most common cancer in the United States, is most commonly of the urothelial carcinoma histologic subtype. The clinical spectrum of bladder cancer is divided into 3 categories that differ in prognosis, management, and therapeutic aims: (1) non-muscle-invasive bladder cancer (NMIBC); (2) muscle invasive, nonmetastatic disease; and (3) metastatic bladder cancer. These NCCN Guidelines Insights detail recent updates to the NCCN Guidelines for Bladder Cancer, including changes in the fifth edition of the WHO Classification of Tumours: Urinary and Male Genital Tumours and how the NCCN Guidelines aligned with these updates; new and emerging treatment options for bacillus Calmette-Guérin (BCG)-unresponsive NMIBC; and updates to systemic therapy recommendations for advanced or metastatic disease.

Intravascular Ultrasound for the Evaluation and Management of Retroperitoneal, Genitourinary Malignancies.

PURPOSE OF REVIEW: Herein we provide a review of intravascular ultrasound (IVUS) and its ability to assist in the evaluation and surgical management of advanced retroperitoneal, genitourinary tumors. RECENT FINDINGS: Advanced retroperitoneal tumors such as advanced renal cell carcinoma, bulky retroperitoneal lymphadenopathy associated with advanced testicular carcinoma, large adrenal tumors, and retroperitoneal sarcomas can invade, compress, or distort vascular anatomy making surgical resection challenging and high risk. Intravascular ultrasonography is commonly used by vascular and cardiothoracic surgery to provide a real time assessment of vascular invasion, compression, and aberrant anatomy to assist with pre-operative and/or intraoperative decision-making. However, the application of this technology to assist with cancer surgery has been limited. The use of intravascular ultrasound prior to radical, extirpative, retroperitoneal surgery involving large vessels can aid in the planning and execution of such challenging operations.

Pathological and Survival Outcomes Associated with Variant Histology Bladder Cancers Managed by Cystectomy with or without Neoadjuvant Chemotherapy.

PURPOSE: Although neoadjuvant chemotherapy is associated with a survival advantage in pure urothelial, muscle invasive bladder cancer, the role of neoadjuvant chemotherapy is less clear in variant histology or urothelial carcinoma with divergent differentiation. We compared chemotherapy response and survival outcomes of patients with nonpure urothelial carcinoma histology who were managed with neoadjuvant chemotherapy followed by cystectomy vs cystectomy alone. MATERIALS AND METHODS: We analyzed 768 patients with clinical muscle invasive bladder cancer (cT2-4N0M0) who were treated with cystectomy at a tertiary care center from 2007 to 2017. Patients were stratified by histology and treatment strategy. Adjusted logistic and Cox regression models were used to evaluate pathological downstaging, cancer specific survival and overall survival. RESULTS: The cohort consisted of 410 patients (53%) with pure urothelial carcinoma, 185 (24%) with urothelial carcinoma with divergent differentiation and 173 (23%) with variant histology. Overall, 314 patients (41%) received neoadjuvant chemotherapy prior to cystectomy. There were similar rates of complete (18% to 30%) and partial (37% to 46%) pathological downstaging with neoadjuvant chemotherapy across all histological subgroups (p=0.30 and p=0.40, respectively). However, while patients with pure urothelial carcinoma experienced an overall survival benefit (HR 0.71, 95% CI 0.51-0.98, p=0.0013) and those with variant histology experienced a cancer specific survival benefit (HR 0.55, 95% CI 0.30-0.99, p=0.0495) with neoadjuvant chemotherapy, patients with urothelial carcinoma with divergent differentiation did not experience overall or cancer specific survival benefits with the use of neoadjuvant chemotherapy prior to cystectomy. CONCLUSIONS: Among patients with muscle invasive bladder cancer those with nonpure urothelial carcinoma histology with variant histology achieved nearly equivalent response rates and survival benefits with the use of neoadjuvant chemotherapy as those with pure urothelial carcinoma, while patients with urothelial carcinoma with divergent differentiation experienced significantly worse survival outcomes regardless of the use of neoadjuvant chemotherapy prior to cystectomy.

Retroperitoneal Lymph Node Dissection Versus Surveillance for Adult Early Stage Pure Testicular Teratoma: A Nationwide Analysis.

PURPOSE: Following radical orchiectomy, surveillance and primary retroperitoneal lymph node dissection (RPLND) are acceptable options for the management of early stage pure testicular teratoma in adult patients; however, there is no uniform consensus. The aim of this study was to investigate survival outcomes of adults with early stage pure testicular teratoma based on management strategy. METHODS: Data was extracted from the National Cancer Database (NCDB) from testicular cancer patients diagnosed with clinical stage (CS) I pure teratoma (pT1-4N0M0S0) between 2004 and 2014. Kaplan-Meier and Cox regression analyses were used to assess clinical outcomes based on management strategy. RESULTS: Of the 61,167 patients diagnosed with testicular cancer, 692 (1.1%) had pure teratoma. Only individuals with CS I disease were considered (n = 237). The median age was 28 (23-35) years. Overall, 43 (18%) patients underwent RPLND and 194 (82%) patients were managed with surveillance. There was an increase in surveillance for CS I teratoma during the study period. Increasing distance from residence to treatment facility was an unadjusted predictor for undergoing primary RPLND (p < 0.001). Median follow-up was 54 months and there was no significant difference in overall survival between CS I teratoma patients managed with RPLND and those managed with surveillance (p = 0.13). CONCLUSIONS: There has been a trend toward increasing adoption of surveillance for the management of early stage pure testicular teratoma in adults. Our findings suggest that surveillance provides comparable survival outcomes to primary retroperitoneal lymph node dissection in this setting.

Systematic Review and Meta-Analysis-Is there a Benefit in Using Neoadjuvant Systemic Chemotherapy for Locally Advanced Penile Squamous Cell Carcinoma?

PURPOSE: Neoadjuvant chemotherapy is a recommended treatment for patients with penile cancer with bulky inguinal lymphadenopathy or unresectable primary tumors, although there is no evidence of its benefit from randomized trials. MATERIALS AND METHODS: We conducted a systematic search in Embase® and MEDLINE® for studies reporting on patients who received preoperative neoadjuvant chemotherapy for locally advanced penile squamous cell carcinoma. Objective response rate, pathological complete response, grade 3 or greater toxicity and overall mortality were evaluated in terms of neoadjuvant chemotherapy type, which was dichotomized as nontaxane-platinum and taxane-platinum regimens. RESULTS: Overall 10 studies met the inclusion criteria, enrolling a total of 182 patients, with 66 (36.3%) and 116 (63.7%) treated with nontaxane-platinum and taxane-platinum regimens, respectively. The pooled results demonstrated an objective response rate of 53% (95% CI 42-64), pathological complete response rate of 16%, grade 3 or greater toxicity rate of 40% (95% CI 19-64) and overall mortality of 55% (95% CI 40-70) in patients treated with neoadjuvant chemotherapy. Stratified subanalysis revealed an objective response rate of 55% and 49%, a pathological complete response of 9% and 20%, a toxicity rate of 26% and 49%, and an overall mortality of 54% and 58% for nontaxane-platinum vs taxane-platinum regimens, respectively. CONCLUSIONS: The pooled findings in this study suggest that approximately 50% of the patients with bulky regional lymph node metastases from penile cancer respond to platinum based neoadjuvant chemotherapy and approximately 16% of patients achieve a pathological complete response. Nontaxane based regimens appear to be better tolerated than taxane regimens based on reported grade 3 or greater adverse events (26% vs 49%). Ultimately the robustness of these observations should be interpreted with an awareness of the inherent limitations of deriving data from a collection of small, heterogeneous series.

Urinary leak following partial nephrectomy: a contemporary review of 975 cases.

INTRODUCTION: To describe the incidence, contemporary management, risk factors and outcomes of urinary leak following open and robotic partial nephrectomy at a tertiary care, comprehensive cancer center. MATERIALS AND METHODS: We reviewed 975 patients who underwent partial nephrectomy at Moffitt Cancer Center from January 2009 to May 2017. Patient demographic, perioperative and follow up data was recorded and compared stratified for postoperative urine leak. Fisher's exact and Wilcoxon sum-rank testing were performed for categorical and continuous variables as indicated. RESULTS: Twenty-three of 975 (2.3%) patients experienced a urine leak after partial nephrectomy. Median nephrometry score for urine leak patients was 8 (SD +/- 1.3). Median postoperative days to detection was 3.5 and most leaks were discovered due to high drain output. Operative factors associated with urinary leak included open surgery, estimated blood loss, and not using a sliding-clip renorrhaphy (p < 0.05). Ten (44%) were managed conservatively, 9 (39%) patients required ureteral stent placement, 3 (13%) needed a percutaneous nephrostomy tube, one patient (4%) required percutaneous drainage for urinoma (4%). One patient ultimately failed conservative management and required nephrectomy 45 days after the original surgery. Mean time to stent and drain removal was 40 +/- 17 and 24 +/- 7 days, respectively. Five patients with symptomatic leaks were readmitted with a mean length of stay of 3.2 +/- 1.8 days. CONCLUSIONS: The overall incidence of urinary leak after partial nephrectomy remains low regardless of surgical approach. Perioperative characteristics such as tumor complexity and high blood loss, in addition to open surgery and not using a sliding-clip bolstered renorrhaphy are associated with urine leak.

Estimating Minimally Important Differences for the Bladder Cancer Index Using Distribution and Anchor Based Approaches.

PURPOSE: The BCI (Bladder Cancer Index) is a validated, condition specific health questionnaire assessing urinary, bowel and sexual function and quality of life among patients with bladder cancer. We aimed to establish minimally important difference score thresholds that signal clinical importance. MATERIALS AND METHODS: For 1 year after surgery we followed a prospective cohort of 150 patients who underwent radical cystectomy between 2013 and 2016. Usable data on 138 patients were analyzed. The BCI and the Medical Outcomes Study SF-36 (36-Item Short Form Health Survey) questionnaires were completed prior to cystectomy, and 3, 6 and 12 months postoperatively. Distribution based, minimally important differences were estimated at ⅓ and ½ SD for each index domain across time points. Changes in index domain scores anchored to changes in a SF-36 overall health assessment question were used to estimate anchor based, minimally important differences. Pooled averages are reported between time points and methods. RESULTS: The distribution based, minimally important difference of ⅓ SDs for urinary, bowel and sexual domains ranged between 5.3 and 7.3, 4.6 and 5.6, and 6.0 and 8.9 points, respectively. Ranges of ½ SDs were 8.8 and 10.9, 6.8 and 8.4, and 8.9 and 13.5 points, respectively. The anchor based approach resulted in minimally important difference estimates of 6.2, 7.3 and 6.8 points, respectively. Aggregated results across the 2 approaches resulted in minimally important differences of 6 to 9, 5 to 8 and 7 to 11 points for urinary, bowel and sexual domains, respectively. CONCLUSIONS: Using 2 independent approaches to our knowledge we established the first minimally important difference estimates for the BCI. Defining patient reported outcome thresholds is important to interpret changes or differences in BCI scores.

Identifying and Codifying Complications after Radical Cystectomy: Comparison of Administrative Diagnostic and Procedure Codes, and Clinical Chart Review.

PURPOSE: To our knowledge the reliability of administrative claims codes to report postoperative radical cystectomy complications has not been examined. We compared complications identified by claims data to those abstracted from clinical chart review following radical cystectomy. METHODS: We manually reviewed the charts of 268 patients treated with radical cystectomy between 2014 and 2016 for 30-day complications and queried administrative complication coding using 805 ICD-9/10 codes. Complications were categorized. Using Cohen κ statistics we assessed agreement between the 2 methods of complication reporting for 1 or more postoperative complications overall, categorical complications and complications stratified by the top quartile length of hospital stay and patients who were readmitted. RESULTS: At least 1 or more complications were recorded in 122 patients (45.5%) through manual chart review and 80 (29.9%) were recorded via claim coding data with a concordance rate of κ=0.16, indicating weak agreement. Concordance was generally weak for categorical complication rates (range 0.05 to 0.36). However, when examining only the top length of stay quartile, 1 or more complications were reported in 32 patients (65%) by the manual chart review and in 12 (25%) via coding data with a concordance rate of κ=-0.2. Agreement was weak, similar to the total cohort. CONCLUSIONS: Manual chart review and claim code identification of complications are not highly concordant even when stratified by patients with an extended length of stay, who are known to have more frequent complications. Researchers and administrators should be aware of these differences and exercise caution when interpreting complication reports.

Updates on the use of intravesical therapies for non-muscle invasive bladder cancer: how, when and what.

INTRODUCTION: Intravesical therapy has been an important aspect of the management of non-muscle invasive bladder cancer (NMIBC) for 40 years. Bacillus Calmette-Guerin (BCG) is considered standard of care for intermediate and high-grade non-invasive disease, yet understanding the nuances of subsequent intravesical therapy is important for any provider managing bladder cancer. Herein, we review the literature and describe optimal use of intravesical therapies for NMIBC. METHODS: A comprehensive search of the medical literature was performed and highlighted in this review of intravesical therapy for NMIBC. RESULTS: Post-resection intravesical Mitomycin C therapy for low-risk disease remains an important component of care, and gemcitabine now has level-one evidence demonstrating efficacy in this setting but is not yet a guideline recommendation. BCG intravesical therapy remains the most effective therapy preventing recurrence and progression of intermediate and high-risk NMIBC. Adequately characterizing BCG-failure is critical in determining the next step in management which includes radical cystectomy, additional intravesical immunotherapy, chemotherapy with intravesical gemcitabine ± docetaxel and clinical trials. CONCLUSIONS: Intravesical therapy remains the mainstay of treatment for NMIBC and bladder preservation. Intravesical induction BCG followed by maintenance therapy remains standard of care for intermediate and high-risk patients. Detailing the timing and characteristics of recurrence after intravesical therapy is crucial in determining subsequent treatment recommendations. Current clinical trials focus on systemic immunotherapy and enhancing the intravesical immune response by augmenting the delivery mechanism.

Optimal Management of Upper Tract Urothelial Carcinoma: an Unmet Need.

OPINION STATEMENT: Upper tract urothelial carcinoma (UTUC) is a rare genitourinary entity of the renal pelvis and the ureter characterized by a more aggressive disease phenotype when compared with urothelial carcinoma of the bladder (UCB) with more than half of UTUC cases presenting with invasive disease at diagnosis compared to 20% for bladder tumors. There is growing evidence suggesting that its distinct natural history from that of bladder cancer can be related to several genetic and epigenetic differences. Treatment of low-risk disease consists of kidney-sparing surgeries such as ureteroscopic and percutaneous treatments, segmental ureterectomy, and adjuvant topical and intracavitary chemo-immunotherapies. The standard of care for high-risk non-metastatic disease remains radical nephroureterectomy and bladder cuff excision with increasing utilization rates of minimally invasive approaches leading to reduced morbidity without compromising outcomes while the role of lymphadenectomy is still being investigated. The prognosis of UTUC has been stagnant over the past decade highlighting the need for further studies on the role of multimodal therapy (neoadjuvant/adjuvant chemotherapy, immunotherapy, targeted therapy) to optimize management and improve outcomes.

Primitive neuroectodermal tumor arising from an untreated congenital undescended testicle.

A 26-year-old male with a personal history of schizophrenia initially presented with a 13 cm pelvic mass corresponding to a cryptorchidic testis. The patient was treated with primary and second-line chemotherapy for metastatic germ-cell tumor followed by surgical consolidation. Final pathology revealed a primitive neuroectodermal tumor (PNET) mixed with mature teratoma. Despite multidisciplinary management, significant patient non-compliance led to inadequate follow up and treatment delays ultimately resulting in death. To our knowledge, this is the only reported case of teratoma with malignant transformation arising from an untreated congenital undescended testicle.

Erectile Dysfunction is Predictive of Endothelial Dysfunction in a Well Visit Population.

PURPOSE: The relationship between erectile dysfunction and endothelial dysfunction has been described and is associated with adverse cardiac events. Endothelial dysfunction is believed to precede erectile dysfunction. Our objective was to characterize the prevalence of subjective erectile dysfunction, endothelial dysfunction and commonly related comorbidities in a population of men undergoing wellness screening. MATERIALS AND METHODS: A total of 205 men presented for wellness screening. They underwent testing for endothelial dysfunction via peripheral arterial tonometry and completed a health screening questionnaire. Reactive hyperemia index scores were generated by peripheral arterial tonometry testing. A reactive hyperemia index score of 1.67 or less defined endothelial dysfunction. The Student t-test and Fisher exact test were performed for continuous and categorical variables, respectively. The association of endothelial dysfunction, erectile dysfunction and various comorbidities was calculated using univariate and multivariable analyses. RESULTS: Of 205 men 47 reported subjective erectile dysfunction. Median age was 44 years old. The mean reactive hyperemia index in patients with erectile dysfunction was significantly lower than in patients without erectile dysfunction (1.63 vs 1.87, p = 0.001). Endothelial dysfunction was more common in men with than without erectile dysfunction (55% vs 36%, p = 0.027). Multivariable analysis revealed that men with erectile dysfunction and obesity were twofold more likely to have concomitant endothelial dysfunction (OR 2.45, 95% CI 1.13-4.24, p = 0.02 and OR 2.08, 95% CI 1.16-3.75, p = 0.01, respectively). CONCLUSIONS: Among middle-aged men presenting for wellness screening erectile dysfunction and obesity independently predicted endothelial dysfunction, a known risk factor for long-term adverse cardiac events.

A randomized double blinded placebo controlled trial of sildenafil for renoprotection prior to hilar clamping in patients undergoing robotic assisted laparoscopic partial nephrectomy.

OBJECTIVE: To perform a randomized control trial (RCT) assessing the effect of phosphodiesterase 5 inhibitor (PDE5i) used prior to hilar clamping during robot assisted partial nephrectomy (RAPN) for renoprotection. MATERIALS AND METHODS: We performed an institutional review board approved, placebo controlled, double blinded RCT evaluating a single 100 mg oral dose of sildenafil immediately prior to RAPN. Primary end point was accrual, participation and retention of patients with secondary endpoints assessing post-operative renal functional outcomes and safety. Exclusion criteria included history of coronary artery disease, solitary kidney, suspected benign pathology, PDE5i intolerance or pregnant females. RESULTS: Of 40 eligible consecutive patients undergoing RPN between 9/2013 and 12/2014, 30 (75%) were randomized to treatment and there was 100% participation and retention. The groups were well matched for all measured comorbidities. Intraoperative outcomes including warm ischemia time (median 15 vs. 16.5 min, P = 0.29) were similar. Change in eGFR demonstrated similar decrease between sildenafil versus placebo at 1 day (-8% vs. -10%, P = 0.53), 2 days (-9% vs. -9%, P = 0.77), and 1 month (-4% vs. -6%, P = 0.31) following RAPN. Intermediate follow up (median 183 days) demonstrated similar results (-8% vs. -1%, P = 0.16) between the two cohorts. Safety profiles were similar between the two cohorts without any adverse reactions to the sildenafil. CONCLUSIONS: Successful retention of patients was achieved in this RCT. The secondary outcome of renoprotection was not identified. J. Surg. Oncol. 2016;114:785-788. © 2016 2016 Wiley Periodicals, Inc.

The management of prostatic obstruction with urethral stents.

INTRODUCTION: Elderly men with multiple comorbidities may be unfit to undergo surgical management of benign prostatic obstruction (BPO). Permanent and temporary prostatic stents have been developed as an alternative to chronic indwelling catheters in men unfit for surgery. MATERIALS AND METHODS: Herein we review the past and present literature on the role and effectiveness of prostatic stents in the treatment of BPO. RESULTS: Permanent prostatic stents have largely been abandoned in North America due to unfavorable outcomes and improved technologies to allow for treatment of BPO. Currently, the temporary Spanner stent is the only available stent on the market, but its effectiveness has mostly been documented for temporary relief of tissue edema following minimal invasive ablative treatments for BPO. CONCLUSIONS: The advent of well-tolerated surgical treatments for BPO (KTP laser vaporization, bipolar TURP, urethral lift devices) has diminished the need for permanent prostatic stents. The temporary Spanner stent is an alternative to urethral catheter, but requires adequate detrusor function and can cause irritative symptoms.

Pathology of bladder cancer among diabetic patients undergoing radical cystectomy with a history of pioglitazone (Actos) use.

BACKGROUND: Prospective studies suggested an association between pioglitazone (Actos) use and the development of bladder cancer. Cancer pathology among pioglitazone users has not been characterized. We chose to compare the surgical pathology among diabetic users and non-users, as well as non-diabetic patients who underwent radical cystectomy for bladder cancer. METHODS: Our single-center, prospectively-maintained bladder cancer database was reviewed. Patient demographics, surgical pathology, and outcomes were evaluated. Information regarding diabetic history and use of pioglitazone was determined from chart analysis and patient interview. RESULTS: From April 2005 to October 2011, 204 patients undergoing radical cystectomy were identified. Of these, 33 (16.2%) were diabetic and 171 (83.8%) had no history of diabetes. Among diabetic patients, 9 (27.3%) had a history of pioglitazone use. Median duration of therapy was 14 (6-120) months. Pathology in non-diabetic patients was T1 in 17 (9.9%), T2 in 38 (22.2%), T3 in 44 (25.7%), and T4 in 31 (18.1%). Pathology among diabetic non-users was T1 in 1 (4.2%), T2 in 7 (29.2%), T3 in 7 (29.2%), and T4 in 4 (16.7%). Pathologic stage among diabetic users was T1 in 1 (11.1%), T2 in 3 (33.3%), T3 in 3 (33.3%), and T4 in 1 (11.1%). Lymph node involvement in non-diabetics, diabetic non-users, and diabetic users was 25.7%, 33.3%, and 33.3%, respectively. Cancer-specific death was seen in 60.3% of non-diabetics, 58.3% of diabetic non-users, and 75% of diabetic users. CONCLUSIONS: Diabetics have similar stage distribution regardless of pioglitazone use. Lymph node metastases rates and cancer specific death were similar across all groups. Additional studies will serve to better characterize this relationship.

Postoperative Outcomes and Analgesic Requirements of Single-Port vs Multiport Robotic-Assisted Radical Cystectomy.

Objective: To compare outcomes in patients undergoing robotic-assisted radical cystectomy (RARC) with urinary diversion for bladder cancer with either the single-port (SP) or multiport (MP) robotic platform. Methods: All patients who underwent SP and MP RARC at our institution between January 2018 and January 2023 were retrospectively reviewed. Postoperative analgesia was administered by a departmentwide narcotic stewardship protocol, and inpatient and outpatient narcotic use was tracked. The available preoperative clinical, operative, and postoperative outcomes were analyzed using t-test, chi-square, and Fischer exact statistical measures. Kaplan-Meier analysis with log-rank testing was used to determine the freedom from high-grade (Clavien-Dindo grade ≥3) postoperative complications stratified by SP or MP robotic use. Results: Overall, 96 patients underwent RARC with urinary diversion at our institution, with 49 MP and 47 SP procedures performed. Preoperative clinical parameters including age, body mass index, prior abdominal surgery, and use of neoadjuvant chemotherapy were similar between the two groups. Patients undergoing SP RARC had a shorter operative time (386.0 ± 90.9 minutes vs 453.6 ± 94.8 minutes, p < 0.01) and faster return of bowel function (3.4 ± 1.4 days vs 4.5 ± 2.2 days, p < 0.01). However, both cohorts had similar length of hospitalization, postoperative narcotic use, pathologic staging, and rate of positive surgical margin. Within 3 months postoperatively, both cohorts had a similar high-grade complication, hospital readmission, and cancer recurrence rate. Conclusions: The SP robot allows a safe alternative surgical approach for RARC and offers similar postoperative outcomes compared to the MP robot.

Prophylactic effect of tadalafil on bladder function in a rat model of chronic bladder ischemia.

PURPOSE: We investigated the effect of tadalafil on chronic ischemia related bladder dysfunction. MATERIALS AND METHODS: Adult male Sprague-Dawley® rats were divided into control, arterial endothelial injury and arterial endothelial injury with tadalafil treatment groups. The arterial injury and arterial injury-tadalafil groups underwent endothelial injury of the iliac arteries and received a 2% cholesterol diet after injury. Arterial injury-tadalafil rats received tadalafil (2 mg/kg per day) orally for 8 weeks after injury. The control group received a regular diet. At 8 weeks urodynamic investigation was performed. Bladder tissue was harvested for pharmacological studies, and histological examination of the iliac arteries and bladders was performed. RESULTS: Iliac arteries from arterial injury and arterial injury-tadalafil rats showed neointimal formation and luminal occlusion. In the arterial injury group the micturition interval was significantly shorter (mean ± SEM 5.4 ± 0.5 vs 11.1 ± 1.1 minutes), and bladder capacity and voided volume were less than in controls. Contractile responses of bladder strips to KCl, electrical field stimulation and carbachol were significantly less after arterial injury than in controls. The arterial injury group showed a significantly increased percent of collagen compared with controls (mean 37.4% ± 1.8% vs 21.5% ± 1.8%). In the arterial injury-tadalafil group intimal formation and luminal occlusion were not prevented. However, there were significant improvements in all functional and morphological parameters compared with the arterial injury group. CONCLUSIONS: Arterial occlusive disease may lead to chronic bladder ischemia and bladder hyperactivity. Chronic treatment with tadalafil protects bladder function and morphology, resulting in decreased bladder hyperactivity. If valid for humans, the data support phosphodiesterase 5 inhibition as treatment for chronic ischemia related bladder dysfunction.