A Multicenter Prospective Randomized Controlled Trial Comparing Cxbladder Triage to Cystoscopy in Patients With Microhematuria: The Safe Testing of Risk for Asymptomatic Microhematuria Trial.

PURPOSE: AUA guidelines for patients with microhematuria (≥3 red blood cells [RBC]/high-power field [hpf]) include cystoscopy for most over age 40 due to risk of urothelial cancer (UC). Cxbladder Triage (CxbT) is a urinary genomic test with UC negative predictive value of 99%. In this prospective randomized controlled trial, we compared cystoscopy use in a standard of care (SOC) arm vs a marker-based approach. MATERIALS AND METHODS: All patients with hematuria provided urine for a CxbT. Those categorized as lower risk (LR), defined as 3 to 29 RBC/hpf and minimal smoking history (<10 pack-years) were randomized between the test group provided with the CxbT result vs the SOC control group. Negative CxbT patients were offered omission of cystoscopy with surveillance. "Not lower risk" (NLR) patients (>30 RBC/hpf or >10 pack-year smoking history) had a CxbT but otherwise SOC. Patient decision and outcomes were recorded. RESULTS: Of 390 eligible patients, 255 were NLR and 135 were LR randomized to CxbT informed decision or SOC. The median age was 62 years (range 18-94) and 54% were male. Overall, 63% of CxbT tests were negative. For NLR patients, 82% had cystoscopy. In the LR control group, cystoscopy was performed in 67% of SOC and 27% in the test group (relative risk 0.41 [95% CI 0.27-0.61]). Compared to cystoscopy, CxbT had 90% sensitivity, 56% specificity, and 99% negative predictive value for UC. CONCLUSIONS: In this prospective randomized controlled trial, use of CxbT in patients with LR hematuria resulted in 59% reduction of cystoscopy use. This clinical utility of CxbT can reduce the burden of unnecessary cystoscopies.

Updates to Advanced Prostate Cancer: AUA/SUO Guideline (2023).

PURPOSE: In 2022 the American Urological Association (AUA) requested an Update Literature Review (ULR) to incorporate new evidence generated since the 2020 publication of this guideline. The resulting 2023 Guideline Amendment addresses updated recommendations for patients with advanced prostate cancer. MATERIALS AND METHODS: The ULR addressed 23 of the original 38 guideline statements and included an abstract-level review of eligible studies published since the 2020 systematic review. Sixteen studies were selected for full text review. The current summary presents the updates made to the Guideline as a result of that new literature. RESULTS: The Advanced Prostate Cancer Panel amended evidence- and consensus-based statements based on an updated review to aid clinicians in the management of patients with advanced prostate cancer. These statements are detailed herein. CONCLUSION: This Guideline Amendment provides a framework designed to improve a clinician's ability to treat patients diagnosed with advanced prostate cancer with the most current evidence-based information. Further research and publication of high-quality clinical trials will be essential to continue to improve the quality of care for these patients.

Safety, Tolerability, and Preliminary Efficacy of TAR-200 in Patients With Muscle-invasive Bladder Cancer Who Refused or Were Unfit for Curative-intent Therapy: A Phase 1 Study.

PURPOSE: Half of patients with muscle-invasive bladder cancer worldwide may not receive curative-intent therapy. Elderly or frail patients are most affected by this unmet need. TAR-200 is a novel, intravesical drug delivery system that provides sustained, local release of gemcitabine into the bladder over a 21-day dosing cycle. The phase 1 TAR-200-103 study evaluated the safety, tolerability, and preliminary efficacy of TAR-200 in patients with muscle-invasive bladder cancer who either refused or were unfit for curative-intent therapy. MATERIALS AND METHODS: Eligible patients had cT2-cT3bN0M0 urothelial carcinoma of the bladder. TAR-200 was inserted for 4 consecutive 21-day cycles over 84 days. The primary end points were safety and tolerability at 84 days. Secondary end points included rates of clinical complete response and partial response as determined by cystoscopy, biopsy, and imaging; duration of response; and overall survival. RESULTS: Median age of the 35 enrolled patients was 84 years, and most were male (24/35, 68.6%). Treatment-emergent adverse events related to TAR-200 occurred in 15 patients. Two patients experienced treatment-emergent adverse events leading to removal of TAR-200. At 3 months, complete response and partial response rates were 31.4% (11/35) and 8.6% (3/35), respectively, yielding an overall response rate of 40.0% (14/35; 95% CI 23.9-57.9). Median overall survival and duration of response were 27.3 months (95% CI 10.1-not estimable) and 14 months (95% CI 10.6-22.7), respectively. Progression-free rate at 12 months was 70.5%. CONCLUSIONS: TAR-200 was generally safe, well tolerated, and had beneficial preliminary efficacy in this elderly and frail cohort with limited treatment options.

Postoperative Opiate Use in Urological Patients: A Quality Improvement Study Aimed at Improving Opiate Disposal Practices.

PURPOSE: We aimed to determine trends in postoperative opiate management among urological patients, identify associations with opiate keeping and foster appropriate opiate disposal after surgery via introduction of an educational handout. MATERIALS AND METHODS: We retrospectively analyzed opiate practices in 68 patients who had undergone urological surgery. In a separate consecutive cohort of 59 patients we distributed a handout detailing FDA (Food and Drug Administration) approved disposal methods. Patient opiate obtainment, use and disposal were assessed via telephone interviews with prescription filling data verified using the Tennessee CSMD (Controlled Substances Monitoring Database). Opiate keeping was defined as possessing any opiates more than 3 weeks after surgery or more than 4 times the duration of the postoperative prescription, whichever was longer. RESULTS: Opiate keeping was observed in 41 patients (72%) in our initial cohort. Of these patients 68% left the medication unsecured at home. Major barriers to opiate disposal included concern for return of disease specific pain in 44% of patients and unrelated pain in 29%. As assessed on a short test, opiate keepers were less knowledgeable about safe disposal practices compared to nonkeepers (72% vs 85%, p = 0.005). Among opiate keepers there was an improvement in knowledge scores after the intervention (66% to 77%, p = 0.03). When comparing pre-education to post-education, there was no detectable improvement in the rate of opiate keeping (72% vs 68%, p = 0.66) or proper disposal (9% vs 8%, p = 1.0). CONCLUSIONS: Opiate keeping is common following urological surgery and a major barrier to disposal is concern for the return of disease specific pain. Future interventions aimed at limiting opiate keeping should combine evidence-based prescription practices and targeted patient education.

The Impact of Health Literacy and Clinicodemographic Factors on Use of Discharge Services after Radical Cystectomy.

PURPOSE: There are few data on the relationship between health literacy and discharge disposition. We hypothesized that patient discharge needs after radical cystectomy are affected by health literacy. MATERIALS AND METHODS: We identified 504 patients who underwent radical cystectomy and completed the validated BHLS (Brief Health Literacy Screen) after November 2010. Bivariate and logistic regression analyses were performed to determine whether health literacy is associated with the use of discharge resources after radical cystectomy. RESULTS: Of patients treated with radical cystectomy 50.6% required discharge services and had lower health literacy (BHLS 11.9 vs 12.5, p = 0.016) than patients discharged home without services. On multivariable analysis older age (OR 1.1, 95% CI 1.0-1.1, p = 0.002), female gender (OR 2.3, 95% CI 1.2-4.4, p = 0.019), body mass index (OR 1.1, 95% CI 1.0-1.1, p = 0.034), Charlson comorbidity index score (OR 1.1, 95% CI 1.0-1.2, p = 0.037) and length of stay (OR 1.1, 95% CI 1.0-1.2, p = 0.019) were significantly associated with the use of discharge resources. Patients with continent vs incontinent urinary diversion were less likely to require discharge services (OR 0.4, 95% CI 0.2-0.8, p = 0.013). CONCLUSIONS: Older age, female gender, body mass index, comorbidities, length of stay and incontinent diversion are associated with increased use of discharge resources after radical cystectomy. Low health literacy may affect patient discharge disposition but it was not significant on multivariable analysis. Factors that influence the complex self-care required of patients after cystectomy should be considered during discharge planning.

Current Management of Refractory Germ Cell Tumors and Future Directions.

PURPOSE OF REVIEW: We review current management strategies for patients with relapsed and refractory germ cell tumors (GCTs), defined as relapsed or persistent disease following at least one line of cisplatin-based chemotherapy. Additionally, we discuss future directions in the management of these patients. RECENT FINDINGS: Recent studies involving targeted therapies have been disappointing. Nevertheless, studies of the management of refractory germ cell cancer are ongoing, with a focus on optimal utilization of high-dose chemotherapy and autologous stem cell transplant, as well as the role of immune checkpoint inhibitors in refractory germ cell tumors. Studies aiming to identify those patients who may benefit from more intensive treatment up front to prevent the development of refractory disease are also in progress. Testicular germ cell tumors are among the most curable of all solid tumor malignancies, with cure being possible even in the refractory, metastatic setting. Treatment of refractory disease remains a challenging clinical scenario, but potentially practice changing studies are ongoing.

Natural biology and management of nonmuscle invasive bladder cancer.

PURPOSE OF REVIEW: This article reviews the natural biology of noninvasive bladder cancer and its management strategies while summarizing the most recent advances in the field. RECENT FINDINGS: Nonmuscle invasive bladder cancer (NMIBC) has a tendency to recur and progress. Risk stratification has helped triage patients but improved tools, including biomarkers, are still needed. Enhanced endoscopy with photodynamic imaging, narrow band imaging, optical coherence tomography and confocal laser endomicroscopy show promise for diagnosis, risk stratification and disease monitoring. Attempts at better treatment, especially in refractory high-risk cases, include the addition of intravesical hyperthermia, combination and sequential therapy with existing agents and the use of novel agents such as mycobacterial cell wall extract. New data are emerging regarding the potential role of active surveillance in low-risk patients. SUMMARY: NMIBC represents a variety of disease states and continues to pose management challenges. As our understanding of tumor biology improves and technology advances, achieving better outcomes through individualized care may be possible.

Oncologic Outcomes after Anterior Exenteration for Muscle Invasive Bladder Cancer in Women.

PURPOSE: We investigated oncologic and urinary outcomes after anterior exenteration for urothelial cell carcinoma in females, identifying tumor characteristics associated with female pelvic organ involvement. We hypothesized that a lack of trigonal or bladder floor tumor, intraoperative palpable posterior mass and clinical lymphadenopathy is associated with a lack of female pelvic organ involvement. MATERIALS AND METHODS: We retrospectively reviewed the charts of female patients who underwent radical cystectomy at our institution from 1999 to 2014. Patient and operative characteristics were extracted from the electronic medical record, and performance of hysterectomy was tested for association with disease recurrence. Categorical and continuous variables were analyzed with the chi-square and Student t-test, and Kaplan-Meier analysis was performed to determine recurrence-free survival according to hysterectomy performance. Women who had neobladder creation were additionally evaluated for an association between hysterectomy status, and nighttime wetting and catheter use. RESULTS: Of 322 eligible patients 160 with urothelial cancer did not have a hysterectomy before cystectomy. Mean followup was 2.2 years (SD 2.8). There were 22 patients (13.8%) who had recurrence during followup. No patient or surgical factor other than use of adjuvant chemotherapy or radiation (p <0.01) was associated with recurrence. Of 139 women 32 (23.0%) who underwent exenteration had female pelvic organ involvement. At least 1 of the 3 characteristics of interest were present in 28 of 99 (28.3%) women with any genitourinary organ involvement compared to only 4 of 40 (10.0%) of those who did not (p=0.01). Nighttime continence ranged between 21.9% and 48% but there was no significant association with continence and hysterectomy status. CONCLUSIONS: Lack of trigonal/bladder floor tumor, palpable posterior mass and clinical lymphadenopathy is associated with the absence of pelvic organ involvement. Individualized risk assessment using these factors along with patient preferences should be used to guide surgical planning.

The Impact of Health Literacy on Surgical Outcomes Following Radical Cystectomy.

Health literacy is the ability to obtain, comprehend, and act on medical information and is an independent predictor of health outcomes in patients with chronic health conditions. However, little has been reported regarding the potential association of health literacy and surgical outcomes. We hypothesized that patient complications after radical cystectomy would be associated with health literacy. In a sample of 368 patients, we found that higher health literacy scores (as determined by the Brief Health Literacy Screen) were associated with decreased odds of developing minor complications (odds ratio = 0.90, 95% confidence interval [0.83, 0.97]). Health literacy should be considered when caring for patients undergoing radical cystectomy and should serve as a potential indicator of the need for additional resources to improve postoperative outcomes.

Management of noninvasive bladder cancers.

PURPOSE OF REVIEW: To summarize clinical management of nonmuscle-invasive bladder cancer (NMIBC) and discuss recent advances in the field. RECENT FINDINGS: NMIBC remains a common and expensive clinical entity. Prevention, early detection, and risk-adapted treatment are the mainstays of clinical management, all of which may improve as a result of recent research. Photodynamic diagnosis has demonstrated improved detection of nascent disease, and specific clinical scenarios have been identified in which photodynamic diagnosis may improve clinical outcomes. New intravesical chemotherapeutic and immunotherapeutic agents challenge our current paradigm for intermediate/high-risk NMIBC and may delay need for cystectomy after bacillus Calmette-Guerin failure. Progress in risk stratification increasingly permits individualized management regimens for NMIBC. SUMMARY: NMIBC includes many heterogeneous disease states with a variety of clinical behaviors that may evolve over time. Improved detection and risk stratification promise assignment of the optimal treatment option for an individual patient at a given time.

Towards improved 3D reconstruction of cystoscopies through real-time feedback for frame reacquisition.

Cystoscopic video can be cumbersome to review; however, preservation of data in the form of 3D bladder reconstructions has the potential to improve patient care. Unfortunately, not all cystoscopy videos produce viable reconstructions, because their underlying frames contain artifacts such as motion blur and bladder debris, which consequently make them unusable for 3D reconstructions. Here, we develop a real-time pipeline, termed the Assessment and Feedback Pipeline (AFP), that alerts clinicians when unusable frames are detected and encourages them to recollect the last few seconds of data. We show that the AFP classifies frames as usable or unusable with a balanced accuracy of 81.60% and demonstrate that use of the AFP improves 3D reconstruction coverage. These results suggest that clinical implementation of the AFP would improve 3D reconstruction quality through real-time detection and recollection of unusable frames.

Fiberscopic pattern removal for optimal coverage in 3D bladder reconstructions of fiberscope cystoscopy videos.

Purpose: In the current clinical standard of care, cystoscopic video is not routinely saved because it is cumbersome to review. Instead, clinicians rely on brief procedure notes and still frames to manage bladder pathology. Preserving discarded data via 3D reconstructions, which are convenient to review, has the potential to improve patient care. However, many clinical videos are collected by fiberscopes, which are lower cost but induce a pattern on frames that inhibit 3D reconstruction. The aim of our study is to remove the honeycomb-like pattern present in fiberscope-based cystoscopy videos to improve the quality of 3D bladder reconstructions. Approach: Our study introduces an algorithm that applies a notch filtering mask in the Fourier domain to remove the honeycomb-like pattern from clinical cystoscopy videos collected by fiberscope as a preprocessing step to 3D reconstruction. We produce 3D reconstructions with the video before and after removing the pattern, which we compare with a metric termed the area of reconstruction coverage (ARC), defined as the surface area (in pixels) of the reconstructed bladder. All statistical analyses use paired t-tests. Results: Preprocessing using our method for pattern removal enabled reconstruction for all (n=5) cystoscopy videos included in the study and produced a statistically significant increase in bladder coverage (p=0.018). Conclusions: This algorithm for pattern removal increases bladder coverage in 3D reconstructions and automates mask generation and application, which could aid implementation in time-starved clinical environments. The creation and use of 3D reconstructions can improve documentation of cystoscopic findings for future surgical navigation, thus improving patient treatment and outcomes.

Interruptions in bladder cancer care during the COVID-19 public health emergency.

BACKGROUND: Academic and community urology centers participating in a pragmatic clinical trial in non-muscle-invasive bladder cancer completed monthly surveys assessing restrictions in aspects of bladder cancer care due to the COVID-19 Public Health Emergency. Our objective was to describe pandemic-related restrictions on bladder cancer care. METHODS: We invited 32 sites participating in a multicenter pragmatic bladder cancer trial to complete monthly surveys distributed through REDCap beginning in May 2020. These surveys queried sites on whether they were experiencing restrictions in the use of elective surgery, transurethral resection of bladder tumors (TURBT), radical cystectomy, office cystoscopy, and intravesical bacillus Calmette-Guerin (BCG) availability. Responses were collated with descriptive statistics. RESULTS: Of 32 eligible sites, 21 sites had at least a 50% monthly response rate over the study period and were included in the analysis. Elective surgery was paused at 76% of sites in May 2020, 48% of sites in January 2021, and 52% of sites in January 2022. Over those same periods, coinciding with COVID-19 incidence waves, TURBT was restricted at 10%, 14%, and 14% of sites, respectively, radical cystectomy was restricted at 10%, 14%, and 19% of sites, respectively, and cystoscopy was restricted at 33%, 0%, and 10% of sites, respectively. CONCLUSIONS: Bladder cancer care was minimally restricted compared with more pronounced restrictions seen in general elective surgeries during the COVID-19 pandemic.

The Other Pandemic, Racism, in Urology.

Racism is deeply ingrained in our society with lasting effects within medicine. The COVID-19 pandemic further highlighted racial disparities in the medical field, including in the field of Urology. This has led to investigation regarding the effects of racism on education, patient care, and research within Urology. This article aims to review current literature on the "other pandemic," structural racism, within medicine and specifically urology and provide ways to combat its impact.

Enhancing the image quality of blue light cystoscopy through green-hue correction and fogginess removal.

Blue light cystoscopy (BLC) is a guideline-recommended endoscopic tool to detect bladder cancer with high sensitivity. Having clear, high-quality images during cystoscopy is crucial to the sensitive, efficient detection of bladder tumors; yet, important diagnostic information is often missed or poorly visualized in images containing illumination artifacts or impacted by impurities in the bladder. In this study, we introduce computational methods to remove two common artifacts in images from BLC videos: green hue and fogginess. We also evaluate the effect of artifact removal on the perceptual quality of the BLC images through a survey study and computation of Blind/Referenceless Image Spatial Quality Evaluator scores on the original and enhanced images. We show that corrections and enhancements made to cystoscopy images resulted in a better viewing experience for clinicians during BLC imaging and reliably restored lost tissue features that were important for diagnostics. Incorporating these enhancements during clinical and OR procedures may lead to more comprehensive tumor detection, fewer missed tumors during TURBT procedures, more complete tumor resection and shorter procedure time. When used in off-line review of cystoscopy videos, it may also better guide surgical planning and allow more accurate assessment and diagnosis.