Racial Differences in the Detection Rate of Bladder Cancer Using Blue Light Cystoscopy: Insights from a Multicenter Registry.

The use of blue light cystoscopy (BLC) has been shown to improve bladder tumor detection. However, data demonstrating the efficacy of BLC across different races are limited. Herein, we aim to evaluate heterogeneity in the characteristics of BLC for the detection of malignant lesions among various races. Clinicopathologic information was collected from patients enrolled in the multi-institutional Cysview® registry (2014-2021) who underwent transurethral resection or biopsy of bladder tumors. Outcome variables included sensitivity and negative and positive predictive values of BLC and white light cystoscopy (WLC) for the detection of malignant lesions among various races. Overall, 2379 separate lesions/tumors were identified from 1292 patients, of whom 1095 (85%) were Caucasian, 96 (7%) were African American, 51 (4%) were Asian, and 50 (4%) were Hispanic. The sensitivity of BLC was higher than that of WLC in the total cohort, as well as in the Caucasian and Asian subgroups. The addition of BLC to WLC increased the detection rate by 10% for any malignant lesion in the total cohort, with the greatest increase in Asian patients (18%). Additionally, the positive predictive value of BLC was highest in Asian patients (94%), while Hispanic patients had the highest negative predictive value (86%). Our study showed that regardless of race, BLC increases the detection of bladder cancer when combined with WLC.

Association of household net worth with healthcare costs after radical cystectomy using real-world data.

BACKGROUND: Financial toxicity of bladder cancer care may influence how patients utilize healthcare resources, from emergency department (ED) encounters to office visits. We aim to examine whether greater household net worth (HHNW) confers differential access to healthcare resources after radical cystectomy (RC). METHODS: This population-based cohort study examined the association between HHNW and healthcare utilization costs in the 90 days post-RC in commercially insured patients with bladder cancer. Costs accrued from the index hospitalization to 90 days after including health plan costs (HPC) and out-of-pocket costs (OPC). Multivariable logistic regression models were generated by encounter (acute inpatient, ED, outpatient, and office visit). RESULTS: A total of 141,903 patients were identified with HHNW categories near evenly distributed. Acute inpatient encounters incurred the greatest HPC and OPC. Office visits conferred the lowest HPC while ED visits had the lowest OPC. Black patients harbored increased odds of an acute inpatient encounter (OR 1.22, 95% CI 1.16-1.29) and ED encounter (OR 1.20, 95% CI 1.14-1.27) while Asian (OR 0.76, 95% CI 0.69-0.85) and Hispanic (OR 0.74, 95% CI 0.69-0.78, p < 0.001) patients had lower odds of an outpatient encounter, compared to White counterpart. Increasing HHNW was associated with decreasing odds of acute inpatient or ED encounters and greater odds of office visits. CONCLUSIONS: Lower HHNW conferred greater risk of costly inpatient encounters while greater HHNW had greater odds of less costly office visits, illustrating how financial flexibility fosters differences in healthcare utilization and lower costs. HHNW may serve as a proxy for financial flexibility and risk of financial hardship than income alone.

Evaluation of URO17® to improve non-invasive detection of bladder cancer.

BACKGROUND: The gold standard for detecting bladder cancer is cystoscopy with biopsy or transurethral resection confirming histologic diagnosis. URO17® employs a chromogenically labeled monoclonal antibody to keratin 17 (k17), an intermediate filament cytoskeleton molecule associated with bladder, pancreatic, and cervical cancers. Preliminary studies evaluating k17 demonstrated a high sensitivity and specificity for the detection of bladder cancer, supporting the need for further study. OBJECTIVE: To evaluate the sensitivity and specificity of URO17. METHODS: This is a cross-sectional study of participants undergoing urologic procedures between July 6, 2018 and July 17, 2019 at a single institution. Patients undergoing cystectomy, endoscopic bladder and/or upper tract procedure for probable urothelial carcinoma comprised cases; patients undergoing urologic procedures for other reasons comprised the control group (i.e. prostatectomy, nephrectomy, etc.). Voided urine samples were at the time of procedure; a minority of participants underwent multiple resections in the study period, thus, as many as three urine samples were taken from any given participant. Samples were distributed for blinded testing with URO17. Sensitivity and specificity were calculated. RESULTS: In 152 participants and 167 samples, URO17 demonstrated an overall sensitivity of 90% and 92% and a specificity of 88% and 87%, respectively. In 76 participants and 91 samples from patients with suspected urothelial carcinoma, the sensitivity was 90% and 92%, and the specificity was 50% and 54%, respectively. No controls demonstrated a positive URO17 result, and URO17 superseded urine cytology detection of low-grade and high-grade Ta. False positive results were associated with inflamed tissue or urothelial atypia on histology; the large majority had a history of intravesical therapy. CONCLUSION: Limitations include cross-sectional design and convenience sampling. URO17 may improve sensitivity of urine cytology in the detection of urothelial cancer, though further study is required to refine the application of this biomarker in clinical practice.

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.

Protocol of the Comparison of Intravesical Therapy and Surgery as Treatment Options (CISTO) study: a pragmatic, prospective multicenter observational cohort study of recurrent high-grade non-muscle invasive bladder cancer.

BACKGROUND: Bladder cancer poses a significant public health burden, with high recurrence and progression rates in patients with non-muscle-invasive bladder cancer (NMIBC). Current treatment options include bladder-sparing therapies (BST) and radical cystectomy, both with associated risks and benefits. However, evidence supporting optimal management decisions for patients with recurrent high-grade NMIBC remains limited, leading to uncertainty for patients and clinicians. The CISTO (Comparison of Intravesical Therapy and Surgery as Treatment Options) Study aims to address this critical knowledge gap by comparing outcomes between patients undergoing BST and radical cystectomy. METHODS: The CISTO Study is a pragmatic, prospective observational cohort trial across 36 academic and community urology practices in the US. The study will enroll 572 patients with a diagnosis of recurrent high-grade NMIBC who select management with either BST or radical cystectomy. The primary outcome is health-related quality of life (QOL) at 12 months as measured with the EORTC-QLQ-C30. Secondary outcomes include bladder cancer-specific QOL, progression-free survival, cancer-specific survival, and financial toxicity. The study will also assess patient preferences for treatment outcomes. Statistical analyses will employ targeted maximum likelihood estimation (TMLE) to address treatment selection bias and confounding by indication. DISCUSSION: The CISTO Study is powered to detect clinically important differences in QOL and cancer-specific survival between the two treatment approaches. By including a diverse patient population, the study also aims to assess outcomes across the following patient characteristics: age, gender, race, burden of comorbid health conditions, cancer severity, caregiver status, social determinants of health, and rurality. Treatment outcomes may also vary by patient preferences, health literacy, and baseline QOL. The CISTO Study will fill a crucial evidence gap in the management of recurrent high-grade NMIBC, providing evidence-based guidance for patients and clinicians in choosing between BST and radical cystectomy. The CISTO study will provide an evidence-based approach to identifying the right treatment for the right patient at the right time in the challenging clinical setting of recurrent high-grade NMIBC. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03933826. Registered on May 1, 2019.

Phase 2 Trial of Atezolizumab in Bacillus Calmette-Guérin-unresponsive High-risk Non-muscle-invasive Bladder Cancer: SWOG S1605.

BACKGROUND: Although radical cystectomy (RC) is the standard of care for patients with bacillus Calmette-Guérin (BCG)-unresponsive high-risk non-muscle-invasive bladder cancer (NMIBC), many patients are ineligible for surgery or elect bladder preservation. OBJECTIVE: To evaluate the efficacy and safety of atezolizumab in BCG-unresponsive high-risk NMIBC. DESIGN, SETTING, AND PARTICIPANTS: This was a single-arm phase 2 trial in patients with BCG-unresponsive high-risk NMIBC who were ineligible for or declined RC. INTERVENTION: Intravenous atezolizumab every 3 wk for 1 yr. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was the pathological complete response (CR) rate for patients with carcinoma in situ (CIS) determined via mandatory biopsy at 6 mo. Event-free survival (EFS) at 18 mo for patients with non-CIS tumors and treatment-related adverse events (TRAEs) were key secondary endpoints. RESULTS AND LIMITATIONS: Of 172 patients enrolled in the trial, 166 received at least one dose of atezolizumab (safety analysis) and 129 were eligible (efficacy analysis). Of the 74 patients with CIS, 20 (27%) experienced a CR at 6 mo. The median duration of response was 17 mo, and 56% (95% confidence interval [CI] 34-77%) of the responses were durable to at least 12 mo. The 18-mo actuarial EFS rate among 55 patients with Ta/T1 disease was 49% (90% CI 38-60%). Twelve of 129 eligible patients experienced progression to muscle-invasive or metastatic disease. Grade 3-5 TRAEs occurred in 26 patients (16%), including three treatment-related deaths. The study was limited by the small sample size and a high rate of patient ineligibility. CONCLUSIONS: The efficacy of atezolizumab observed among patients with BCG-unresponsive NMIBC is similar to results from similar trials with other agents, but did not meet the prespecified efficacy threshold. Modest efficacy needs to be balanced with a significant rate of TRAEs and the risk of disease progression when considering systemic immunotherapy in early-stage bladder cancer. PATIENT SUMMARY: We tested intravenous immunotherapy (atezolizumab) in patients with high-risk non-muscle-invasive bladder cancer that recurred after BCG (bacillus Calmette-Guérin) treatment. Although we found similar outcomes to previous trials, the benefit of this therapy is modest and needs to be carefully balanced with the significant risk of side effects. This trial is registered on ClinicalTrials.gov as NCT02844816.

Readmissions trends following radical cystectomy for bladder cancer unchanged in the era of enhanced recovery after surgery (ERAS) protocols.

PURPOSE: To provide nationally representative estimates of contemporary trends in readmission rates, readmission location (index vs. nonindex hospital), and causes of readmission following radical cystectomy (RC) in the era of enhanced recovery after surgery (ERAS) protocol implementation. MATERIALS AND METHODS: Patients with bladder cancer who underwent RC were identified in the Nationwide Readmissions Database (2016-2019). Yearly trends in 30-day and 90-day readmission rates and readmission causes were assessed in the whole cohort and subset of patients who underwent RC at high volume centers (>22 RCs/year). Multivariable logistic regression was used to determine predictors of index readmission, nonindex readmission, death during readmission, and experiencing a second readmission. RESULTS: Among the 20,957 RC patients, the 30-day and 90-day readmission rates were 23.5% (n = 4,931) and 39.1% (n = 7,987), respectively. For 90-day readmissions, 27.6% (n = 2,206) were to nonindex hospitals. During the study period, there was no significant change in the yearly 30-day or 90-day readmission rates and percentage of readmissions to nonindex hospitals (all p > 0.05). This was also true in the subset of patients who underwent RC at high volume centers. The only significant change in causes of readmission during the study period was wound readmissions (2.7% in 2016 vs. 5.1% of readmissions in 2019, p = 0.02). CONCLUSIONS: During the era of ERAS protocol implementation, in this nationally representative study, most causes of readmission and both 30 and 90-day readmission rates were unchanged, even at high volume RC centers. Moving forward, novel interventions are needed which focus on the postdischarge recovery period to help decrease readmission rates following RC.

Cxbladder Monitor testing to reduce cystoscopy frequency in patients with bladder cancer.

PURPOSE: Bladder cancer surveillance is associated with high costs and patient burden. CxMonitor (CxM), a home urine test, allows patients to skip their scheduled surveillance cystoscopy if CxM-negative indicating a low probability of cancer presence. We present outcomes from a prospective multi-institutional study of CxM to reduce surveillance frequency during the coronavirus pandemic. MATERIALS AND METHODS: Eligible patients due for cystoscopy from March-June 2020 were offered CxM and skipped their scheduled cystoscopy if CxM-negative. CxM-positive patients came for immediate cystoscopy. The primary outcome was safety of CxM-based management, assessed by frequency of skipped cystoscopies and detection of cancer at immediate or next cystoscopy. Patients were surveyed on satisfaction and costs. RESULTS: During the study period, 92 patients received CxM and did not differ in demographics nor history of smoking/radiation between sites. 9 of 24 (37.5%) CxM-positive patients had 1 T0, 2 Ta, 2 Tis, 2 T2, and 1 Upper tract urothelial carcinoma (UTUC) on immediate cystoscopy and subsequent evaluation. 66 CxM-negative patients skipped cystoscopy, and none had findings on follow-up cystoscopy requiring biopsy. Six of these patients did not attend follow-up, 4 elected to undergo additional CxM instead of cystoscopy, 2 stopped surveillance, and 2 died of unrelated causes. CxM-negative and positive patients did not differ in demographics, cancer history, initial tumor grade/stage, AUA risk group, or number of prior recurrences. Median satisfaction (5/5, IQR 4-5) and costs (26/33, 78.8% no out-of-pocket costs) were favorable. CONCLUSIONS: CxM safely reduces frequency of surveillance cystoscopy in real-world settings and appears acceptable to patients as an at-home test.

Is a restaging TURBT necessary in high-risk NMIBC if the initial TURBT was performed with blue light?

OBJECTIVES: To evaluate whether a restaging transurethral resection of bladder tumor (TURBT) is necessary in high-risk nonmuscle invasive bladder cancer (NMIBC) if the initial TURBT was performed using blue light (BL) technology. METHODS AND MATERIALS: Using the multi-institutional Cysview registry between 2014 and 2021, all consecutive adult patients with known NMIBC (Ta and T1 disease) who underwent TURBT followed by a restaging TURBT within 8 weeks were reviewed. Patients were stratified according to their initial TURBT, BL vs. white light (WL), and compared to determine rates of residual disease and upstaging. Univariate analysis was performed using Mann-Whitney U and chi-square tests, with P < 0.05 considered significant. RESULTS: Overall, 115 patients had TURBT for NMIBC followed by a restaging TURBT within 8 weeks and were included in the analysis. Patients who underwent BL compared to WL for their initial TURBT had higher rates of benign pathology on restaging TURBT, although this was not statistically significant (47% vs. 30%; P = 0.08). Of patients with residual tumors on restaging TURBT, there were no differences in rates of Ta (22% vs. 26.5%; P = 0.62), T1 (22% vs. 26.5%; P = 0.62), or CIS (5.5% vs. 13%; P = 0.49) when the initial TURBT was done using BL compared to WL. Rates of upstaging to muscle invasive disease were also not different when initial TURBT was performed using BL compared to WL (3% vs. 4%; P = 0.78). CONCLUSIONS: TURBT using BL does not reduce rates of residual disease or risk of upstaging on restaging TURBT in Ta or T1 disease. Thus, a restaging TURBT is still necessary even if initial TURBT was performed using BL.

Applicant perceptions of virtual interviews for society of urologic oncology fellowships during the COVID-19 pandemic.

The COVID-19 public health emergency forced the conversion of in-person SUO fellowship interviews into virtual interviews. We sought to understand applicant perspectives and preferences related to virtual interviews and whether programs should consider virtual interviews in the future. We distributed a survey to 2020 SUO Fellowship interview participants at 4 SUO urologic oncology fellowship programs. Response items were on a Likert scale scored 1-5 with higher scores indicating greater agreement with the survey item construct. Survey responses were collated and thematic mapping used to describe open text responses. Descriptive statistics were used for analysis of survey and open text results. Fifty-eight SUO fellowship applicants completed the survey. Virtual interviews successfully promoted interaction with SUO fellowship program faculty (mean 4.6, SD 0.6), outlined program research opportunities (mean 4.5, SD 0.7), and proffered opportunities to ask questions about the fellowship (mean 4.7, SD 0.5). Applicants exhibited weakly positive orientation to the adequacy of the virtual format (mean 3.5, SD 1.1). 63% of applicants would prefer a virtual format in the future. Qualitative feedback noted the benefits of virtual interviews were lower cost and reduced time away from residency. SUO fellowship applicants exhibited mixed preferences for virtual and in-person interviews. Although virtual fellowship interviews have benefits such as cost savings and time efficiency, notable weaknesses included challenges observing the culture of the programs. Following the pandemic, SUO fellowship programs may consider virtual interviews but should consider incorporating opportunities for informal interactions between faculty, fellows, and fellow applicants.

Wake-Up Call to Address Sleep Health in Non-Muscle Invasive Bladder Cancer: Underappreciated Contributor to Poor Quality of Life.

BACKGROUND: Few studies have specifically examined sleep health in patients with non-muscle invasive bladder cancer (NMIBC). Further study is warranted to inform future strategies in patients with NMIBC. OBJECTIVE: We aim to describe sleep health in a cohort of patients with NMIBC, and its relationship with quality of life (QOL). METHODS: We conducted an observational cross-sectional study in patients undergoing surveillance for NMIBC. The validated Pittsburgh Sleep Quality Index (PSQI) was used to assess sleep health (scores from 0-21) in the overall study population as well as stratified. We assessed QOL among participants with and without poor sleep quality using the SF-12 and QLQ-NMIBC-24. RESULTS: In a cohort of 94 NMIBC patients, median age was 67 years (IQR: 58, 72) and median time since initial diagnosis was 27 months (IQR: 9, 41). The mean PSQI score was 6.3 (SD: 3.8) and 64% percent of participants met or exceeded the PSQI cut-off score of 5, with a score of 5 or more indicating overall poor sleep quality. In those with poor sleep quality, there were statistically significant detriments in multiple QOL domains. CONCLUSIONS: In patients undergoing surveillance for NMIBC, there is a substantial burden of sleep disturbances and resulting decrements in QOL. These data support the need for future interventions to support sleep quality and highlight the importance of addressing sleep health as part of NMIBC survivorship care to improve QOL in patients with NMIBC.

Which Biomarkers are Useful in the Management of Muscle-invasive Bladder Cancer in 2022?

In current clinical practice, the use of biomarkers remains largely experimental for patients with localized disease. However, with continued commitment to prospective trials and collaborative efforts, we are on the horizon of incorporating biomarker use to guide personalized treatment decisions.

Survey Results on Use of a Convex Pouching System in the Postoperative Period.

PURPOSE: The purpose of this study was to validate time frames for postoperative care following stoma surgery and to determine participants' current practice with convex pouching systems during the postoperative period. DESIGN: A Cross-sectional survey. SUBJECTS AND SETTING: The sample comprised 332 ostomy care specialists practicing in the United States. Most (n = 220; 66%) had more than 10 years' experience caring for patients with ostomies, 82% (n = 272) were certified WOC or ostomy care nurses (CWOCN and COCN), and 7% (n = 23) were board-certified colorectal surgeons. METHODS: A 23-item online questionnaire was created for purposes of the study. Items in the questionnaire queried professional background and experience caring for patients with an ostomy. A single item was used to identify postoperative care periods following ostomy surgery. Additional items queried current practice patterns related to use of convex pouching systems and the timing of their use. Data were collected from January 18 to February 8, 2021. RESULTS: Most respondents (n = 270; 90%) agreed with the following postoperative periods after ostomy surgery: immediate postoperative period (days 0-8); postoperative period (days 9-30); and transition phase (days 31-180). Most respondents (n = 274; 95%) indicated they would use a convex pouching system when clinically appropriate during the first 30 days following ostomy surgery and 79% (n = 228) indicated using a convex pouching system regardless of when the surgery was performed. Less than 1% (n = 2) indicated never using convexity within the first 30 days following stoma surgery, and only 3% (n = 8) indicated avoidance of convexity pouching systems in the immediate postoperative period. CONCLUSIONS: Findings indicate that use of convexity during the postoperative period is prevalent to provide a secure seal and predictable wear time.

Origins and Timing of Emerging Lesions in Advanced Renal Cell Carcinoma.

Renal cell carcinoma (RCC) with venous tumor thrombus (VTT) arising from the primary tumor occurs in approximately 10% of cases and is thought to represent more advanced disease. The intravascular nature of VTT suggests that it may serve as a source for hematogenous metastases. RCC with VTT and distant metastasis provides unique opportunities to examine the origins and emergence timing of these distinct tumor lesions, and to identify molecular correlates with disease state. We performed multi-region exome and RNA-sequencing analysis of 16 patients with RCC with VTT, with eight patients also having sequenced metastasis, to identify genomic alterations, biological pathways, and evolutionary processes contributing to VTT and metastasis, and to ask whether metastasis arises directly from or independent of VTT. No specific genomic alterations were associated with VTT. Hallmark copy-number alterations (deletions of 14q, 8p, and 4q) were associated with metastasis and disease recurrence, and secondary driver alterations tended to accumulate in metastatic lineages. Mismatch repair mutational signatures co-occurred across most tumors, suggesting a role for intracellular DNA damage in RCC. Robust phylogenetic timing analysis indicated that metastasis typically emerged before VTT, rather than deriving from it, with the earliest metastases predicted to emerge years before diagnosis. As a result, VTT in metastatic cases frequently derived from a metastatic lineage. Relative to the primary tumor, VTT upregulated immediate-early genes and transcriptional targets of the TNFα/NF-κB pathway, whereas metastases upregulated MTOR and transcriptional targets downstream of mTORC1 activation. IMPLICATIONS: These results suggest that VTT and metastasis formation occur independently, VTT presence alone does not necessarily imply more advanced disease with inevitably poor prognosis.

Holistic Characterization of Tumor Monocyte-to-Macrophage Differentiation Integrates Distinct Immune Phenotypes in Kidney Cancer.

The tumor immune microenvironment (TIME) is commonly infiltrated by diverse collections of myeloid cells. Yet, the complexity of myeloid-cell identity and plasticity has challenged efforts to define bona fide populations and determine their connections to T-cell function and their relationship to patient outcome. Here, we have leveraged single-cell RNA-sequencing analysis of several mouse and human tumors and found that monocyte-macrophage diversity is characterized by a combination of conserved lineage states as well as transcriptional programs accessed along the differentiation trajectory. We also found in mouse models that tumor monocyte-to-macrophage progression was profoundly tied to regulatory T cell (Treg) abundance. In human kidney cancer, heterogeneity in macrophage accumulation and myeloid composition corresponded to variance in, not only Treg density, but also the quality of infiltrating CD8+ T cells. In this way, holistic analysis of monocyte-to-macrophage differentiation creates a framework for critically different immune states.

TROP2 Expression Across Molecular Subtypes of Urothelial Carcinoma and Enfortumab Vedotin-resistant Cells.

Sacituzumab govitecan (SG) is an antibody-drug conjugate (ADC) targeting TROP2, which has recently been approved for treatment-refractory metastatic urothelial cancer (UC). However, the variability of TROP2 expression across different bladder cancer (BC) subtypes, as well as after enfortumab vedotin (EV) exposure, remains unknown. Using gene expression data from four clinical cohorts with >1400 patient samples of muscle-invasive BC and a BC tissue microarray, we found that TROP2 mRNA and protein are highly expressed across basal, luminal, and stroma-rich subtypes, but depleted in the neuroendocrine subtype. In addition, TROP2 mRNA levels are correlated with NECTIN4 mRNA but are more highly expressed than NECTIN4 mRNA in patient cohorts and BC cell lines. Moreover, CRISPR/Cas9-mediated knockdown of TROP2 demonstrates that its expression is one factor governing SG sensitivity. After prolonged EV exposure, cells can downregulate NECTIN4, leading to EV resistance, but retain TROP2 expression and remain sensitive to SG, suggesting nonoverlapping resistance mechanisms to these ADCs. While our findings warrant further validation, they have significant implications for biomarker development, patient selection, and treatment sequencing in the clinic as well as clinical trial design and stratification for metastatic BC patients. PATIENT SUMMARY: In this report, we investigated the expression levels of the drug target TROP2 across different molecular subtypes of bladder cancer in multiple patient cohorts and cell lines. We found high levels of TROP2 in most subtypes except in the neuroendocrine subtype. Overall, TROP2 gene expression is higher than NECTIN4 gene expression, and cells resistant to enfortumab vedotin (EV), a NECTIN4-targeting antibody-drug conjugate, remain sensitive to sacituzumab govitecan (SG). Our findings suggest that SG may be effective across most bladder cancer subtypes, including the bladder cancers previously treated with EV.

Utility of Blue Light Cystoscopy for Post-bacillus Calmette-Guérin Bladder Cancer Recurrence Detection: Implications for Clinical Trial Recruitment and Study Comparisons.

PURPOSE: The utility of blue light cystoscopy (BLC) in patients receiving bacillus Calmette-Guérin (BCG) during post-treatment cystoscopy is not well understood. Our objective was to determine if BLC improves recurrence detection in patients with non-muscle invasive bladder cancer (NMIBC) undergoing BCG. MATERIALS AND METHODS: Using the prospective multi-institutional Cysview® Registry (2014-2019), patients with NMIBC who received BCG within 1 year prior to BLC were identified. Primary outcomes were recurrences and whether lesions were detected on white light cystoscopy (WLC), BLC or both. We calculated the percentage of cystoscopies with recurrences that were missed with WLC alone. The cystoscopy-level BLC false-positive rate was the proportion of cystoscopies with biopsies only due to BLC suspicious lesions without recurrence. RESULTS: Of 1,703 BLCs, 282 cystoscopies were in the analytic cohort. The overall recurrence rate was 45.0% (127). With only WLC, 13% (16/127) of recurrences would have been missed as 5.7% (16/282) of cystoscopies performed had recurrence only identified with BLC. Among 16 patients with recurrence missed with WLC, 88% (14) had carcinoma in situ. The cystoscopy-level BLC false-positive rate was 5% (15). CONCLUSIONS: BLC helped detect recurrences after recent BCG that would have been missed with WLC alone. Providers should consider BLC for high-risk patients undergoing BCG and should discuss the risk of false-positives with these patients. As clinical trials of novel therapies for BCG-unresponsive disease increase and there are no clear guidelines on BLC use for post-treatment cystoscopies, it is important to consider how variable BLC use could affect enrollment in and comparisons of these studies.

Role of blue-light cystoscopy in detecting invasive bladder tumours: data from a multi-institutional registry.

OBJECTIVES: To evaluate the role of blue-light cystoscopy (BLC) in detecting invasive tumours that were not visible on white-light cystoscopy (WLC). PATIENTS AND METHODS: Using the multi-institutional Cysview registry database, patients who had at least one white-light negative (WL-)/blue-light positive (BL+) lesion with invasive pathology (≥T1) as highest stage tumour were identified. All WL-/BL+ lesions and all invasive tumours in the database were used as denominators. Relevant baseline and outcome data were collected. RESULTS: Of the 3514 lesions (1257 unique patients), 818 (23.2%) lesions were WL-/BL+, of those, 55 (7%) lesions were invasive (48 T1, seven T2; 47 unique patients) including 28/55 (51%) de novo invasive lesions (26 unique patients). In all, 21/47 (45%) patients had WL-/BL+ concommitant carcinoma in situ and/or another T1 lesions. Of 22 patients with a WL-/BL+ lesion who underwent radical cystectomy (RC), high-risk pathological features leading to RC was only visible on BLC in 18 (82%) patients. At time of RC, 11/22 (50%) patients had pathological upstaging including four (18%) with node-positive disease. CONCLUSIONS: A considerable proportion of invasive lesions are only detectable by BLC and the rate of pathological upstaging is significant. Our present findings suggest an additional benefit of BLC in the detection of invasive bladder tumours that has implications for treatment approach.

Clinical Utility of Rigid Blue Light Cystoscopy: Results from a Post Procedure User Survey in a Prospective Multicenter Registry.

INTRODUCTION: Despite the effectiveness of blue light cystoscopy (BLC) in the management of bladder cancer, the adoption of BLC since its approval has been limited. We evaluated the perceived clinical utility of BLC and assessed factors associated with higher perceived utility of BLC. METHODS: This study used a prospective multi-institutional registry of patients with known or suspected noninvasive bladder cancer. Following BLC, urologists assessed their perceived clinical utility of BLC on a 4-point Likert scale. The primary outcome was the perceived clinical utility of BLC as assessed by participating urologists. RESULTS: A total of 1,702 rigid cystoscopies performed between 2014 and 2019 were evaluated. Of all lesions biopsied 2,285 were identified with both white light and blue light (60.6%), followed by 867 with blue light only (23.0%) and 423 with white light only (11.2%). Among all post-cystoscopy surveys, urologists perceived BLC to be of some utility (38.1%, 648), moderate assistance (25.4%, 432), essential (19%, 324) and no real utility (17.5%, 298). More urologists perceived BLC to be essential in 2019 (28.3%, 30/106) compared to in 2014 (11.5%, 9/78; p=0.006). On multivariable analysis higher perceived utility was associated with more lesions seen only with blue light (LR 4.88, CI 2.27-8.78), malignant pathology on biopsy (LR 3.31, CI 2.10-5.23), and total number of lesions seen with blue light (LR 1.36, CI 1.19-1.55). CONCLUSIONS: The perceived clinical utility of BLC has been increasing over time, particularly among high-volume urologists. Urologists who identify more lesions with BLC than white light cystoscopy perceive BLC to be most clinically useful.