Bladder Cancer Diagnoses Research Articles

Contemporary Treatment of NMIBC-Is It Time to Move on from BCG?

Non-muscle-invasive bladder cancer (NMIBC) encompasses approximately three-quarters of all bladder cancer (BC) diagnoses. Intravesical Bacillus Calmette-Guerin (BCG) has been the long-standing gold standard treatment for patients following endoscopic resection. However, despite reasonable efficacy, recurrence rates are still suboptimal, and this, combined with treatment tolerability and BCG shortages, has prompted an investigation into alternative treatment modalities. Advances in this landscape have been predominantly for patients with BCG-unresponsive disease, and there are currently four FDA-approved treatments for these patients. More recently, trials have emerged looking for alternatives to BCG for patients who are treatment-naïve. We performed a literature search via PubMed to find recent publications on alternatives to BCG, as well as a search on clinicaltrials.gov and recent conference presentations for ongoing clinical trials. Studies have shown that combination intravesical chemotherapy, combination intravesical therapy with BCG, and combination intravenous therapy with BCG preliminarily have good efficacy and safety profiles in this disease space. Ongoing trials are underway, and we anticipate as these studies mature, there will be a shift in NMIBC treatment regimens.

Targeted Therapy in Non-Muscle Invasive Bladder Cancer-Clinical Updates

Non muscle invasive bladder cancer (NMIBC) comprises almost 75% of all bladder cancer (BC) diagnoses. Longstanding intravesical treatment options include chemotherapy or Bacillus Calmette-Guerin (BCG). However, despite these treatment options, there is a high rate of relapse for NMIBC patients, reaching up to 40-50% for patients with high risk disease. Radical cystectomy is recommended by guideline committees for patients with high risk NMIBC and for patients who fail intravesical treatment options however this is a procedure with high morbidity and many patients are not good candidates or prefer more conservative treatment approaches. Given this and the high failure rates of current therapies, much ongoing research in NMIBC is focused on other bladder sparing treatment modalities. There have been new advances in molecular features of BC with findings of genetic alterations in NMIBC leading way to a rise in precision medicine targeting a patient’s individual gene mutation. While data surrounding these targeted therapies in NMIBC specifically are all preliminary, many trials are currently underway derived from success in targeted treatments for locally advanced or metastatic BC. Preliminary results are promising and the targeted therapies for NMIBC are increasing. We performed a PubMed and Medline (OVID) literature review assessing recently published studies on targeted therapy on NMIBC, and an additional search on clinicaltrials.gov for active clinical trials. We report on preliminary outcomes and ongoing later stage trials for targeted therapies in NMIBC and anticipate upcoming promising changes to the treatment landscape.

Clinical use of nadofaragene firadenovec-vncg.

Non-muscle-invasive bladder cancer (NMIBC), which is restricted to the mucosa (stage Ta, carcinoma in situ (CIS)) or submucosa (stage T1), comprises 75% of bladder cancer diagnoses. Intravesical bacillus Calmette-Guérin (BCG) therapy is the standard-of-care initial treatment for high-risk NMIBC; however, a significant proportion of patients have BCG-unresponsive disease. While radical cystectomy is a definitive treatment in this setting, not all patients are willing or able to undergo this complex procedure associated with morbidity, mortality, and decreased quality of life. Bladder-preserving options for patients with BCG-unresponsive NMIBC represent an unmet need in this patient population. Nadofaragene firadenovec-vncg (Adstiladrin) is a nonreplicating adenoviral vector-based gene therapy indicated for the treatment of adult patients with high-risk BCG-unresponsive NMIBC with CIS with or without papillary tumors. The antitumor efficacy of nadofaragene firadenovec is driven by its local delivery of copies of the gene encoding for interferon alpha-2b (IFNα-2b) to urothelial cells. In the phase III CS-003 study, over half of participants with CIS exhibited a complete response by month 3 after instillation, with minimal serious adverse events. The favorable efficacy and safety profile, clinical utility, novel mechanism of action, and every 3-month dosing schedule give nadofaragene firadenovec a unique role in the treatment of high-risk BCG-unresponsive NMIBC. This review provides a practical approach to the effective clinical use of nadofaragene firadenovec regarding pre-instillation visit arrangements, storage, handling, instillation procedures, and post-instillation procedures. Implementation of these recommendations will ensure efficient real-world use of nadofaragene firadenovec and the development of useful training materials and relevant standard operating procedures to help support a clinic's treatment for patients with BCG-unresponsive NMIBC with CIS. Video Abstract https://vimeo.com/user17898099/review/953723559/e18af7ec43.

Pre-diagnostic prescription patterns in bladder and renal cancer: a longitudinal linked data study.

Understanding pre-diagnostic prescribing activity could reveal windows during which more timely cancer investigation and detection may occur. To examine prescription patterns for common urological clinical features prior to renal and bladder cancer diagnoses. A retrospective cohort study was performed using electronic primary care and cancer registry data on patients with bladder and renal cancer, who received their diagnosis between April 2012 and December 2015 in England. Primary care prescriptions up to 2 years pre- diagnosis were analysed for five groups of clinical features (irritative urological symptoms, obstructive symptoms, urinary tract infections [UTIs], genital infections, and atrophic vaginitis). Poisson regressions estimating the inflection point from which the rate of prescriptions increased from baseline were used to identify the start of diagnostic windows during which cancer could be detected. A total of 48 094 prescriptions for 5322 patients were analysed. Inflection points for an increase in UTI prescriptions were identified 9 months pre- diagnosis for renal (95% confidence interval [CI] = 5.3 to 12.7) and bladder (95% CI = 7.4 to 10.6) cancers. For bladder cancer, the change in UTI antibiotic prescription rates occurred 4 months earlier in females (11 months pre- diagnosis, 95% CI = 9.7 to 12.3) than in males (7 months pre-diagnosis, 95% CI = 5.4 to 8.6). For other clinical features, no inflection points were identified and, as such, no diagnostic windows could be defined. Prescription rates for UTIs increased 9 months before bladder and renal cancer diagnoses, indicating that there is potential to expedite diagnosis of these cancers in patients presenting with features of UTI. The greatest opportunity for more timely diagnosis may be in females with bladder cancer, who experienced the earliest increase in UTI prescription rate.

5-alpha reductase inhibitors (5-ARi) with or without alpha-blockers (α-B) for Benign Prostatic Hyperplasia do NOT lower the risk of incident Bladder Cancer: United States insurance claims data.

Chemoprotective effect of 5-alpha reductase inhibitors (5-ARi) on bladder cancer (BCa) risk in men with Benign Prostatic Hyperplasia (BPH) has been explored with conflicting results. We sought to examine the effect of 5-ARi on new BCa diagnoses in a large US database. Men ≥ 50 y/o with a prescription for 5-ARi after BPH diagnosis were identified in the IBM® Marketscan® Research de-identified Databases between 2007 and 2016 and matched with paired controls. Incident BCa diagnoses were identified after BPH diagnosis and/or pharmacologic treatment. Multivariable regression modeling adjusting for relevant factors was implemented. Sub-group analyses by exposure risk were performed to explore the association between 5-ARi and BCa over time. Administration of alpha-blockers (α-B) w/o 5-ARi was also examined. In total, n = 24,036 men on 5-ARi, n = 107,086 on 5-ARi plus alpha-blockers, and n = 894,275 without medical therapy for BPH were identified. The percentage of men diagnosed with BCa was 0.8% for the 5-ARi, 1.4% for the 5-ARi + α-B, and 0.6% for the untreated BPH group of incident BCa (adjusted hazard ratio [aHR], 0.90, 95% confidence interval [CI] 0.56 - 1.47), and 1.08, 95%CI 0.89 - 1.30, respectively). This was also true at both shorter (≤ 2yr) and longer-term (> 2yr) follow up. In addition, α-B alone had no change in BCa risk (HR 1.06, 0.86-1.30). We did not find any diminished risk of new BCa in men treated with 5-ARi (i.e., chemoprotective effect). The current report suggests that 5-ARi do not change a man's bladder cancer risk.

(389) Highlighting the Necessity of Cancer Survivorship Clinics in Rural America: Urologic Malignancy as an Independent Risk Factor of ED

Abstract Introduction Erectile dysfunction (ED) affects up to 30 million men in the United States and as many as 150 million men worldwide. Although the most common contributing factors such as cardiovascular disease, obesity, and diabetes currently receive the most attention, cancer diagnosis as an independent risk factor deserves further scrutiny. Prior studies have shown increased incidence of ED in cancer patients with both direct and indirect pathways postulated. Despite this, documentation of a history of ED before and after cancer treatment remains understudied. Objective To document the difference in SHIM scores between a group of patients carrying a urologic malignancy diagnosis and a second group of general urologic patients. Secondary endpoints included prevalence of several comorbid conditions and descriptive statistics of ED prevalence and both desire for and treatment of ED. Methods A standardized questionnaire was prospectively administered at a tertiary care academic urology clinic which treats all forms of urologic malignancy in a rural population of about 2 million. The survey included the validated Sexual Health Inventory for Men (SHIM), information regarding oncologic diagnosis, and comorbid medical conditions including BPH, tobacco use disorder, alcohol consumption, diabetes, depression, hypertension, and high cholesterol. Surveys were administered pre- and post-treatment to all consenting patients. The control group consisted of male urologic patients with no present or past diagnosis of urologic malignancy (UM). Mann-Whitney U tests were used to compare means for continuous variables and chi-squared tests for categorical variable comparison. Results A total of 762 patients completed the entire survey, with 214 (28.1%) patients reporting a history of UM. Sixty-one (28.1%) were bladder cancer diagnoses with an additional 83 (38.8%) renal cancer and 125 (58.4%) prostate cancer. Analysis revealed a statistically significant difference in mean SHIM scores between patients with UM and without UM (p <0.05), with SHIM total mean 15.478 +/− 7.823 in UM patients while non-oncologic patients scored 17.598 +/− 7.574. There were no significant differences in the prevalence of 7 of the 8 studied comorbid conditions (HTN p=0.007). Only 2.8% of oncology patients reported receiving treatment for ED while 64% reported interest in receiving treatment for ED. Conclusions Urologic malignancy is significantly associated with lower SHIM scores. More striking however is the large discrepancy between those interested in treatment and those receiving it, especially at a tertiary care academic center. As a result, our institution is working towards a urologic cancer survivorship protocol involving evaluation by a sexual dysfunction specialist within one year of treatment or earlier. The present study emphasizes the need for physician vigilance and both physician and patient education to improve outcomes in a distressed population. Disclosure No

Why has sexuality research in women with bladder cancer undergoing radical cystectomy been ignored for so long?

The impact of invasive bladder cancer treatment in women has historically been an overlooked area of focus. By the end of 2022, there were an estimated 19, 480 new bladder cancer diagnoses among women.1 The impact of bladder cancer treatment on quality of life cannot be understated, in particular the effect of radical cystectomy (RC) on a woman’s sexuality, as this procedure traditionally involves removal of the anterior vaginal wall, urethra, uterus, bilateral fallopian tubes and ovaries. However, despite the obvious consequences such radical surgery for bladder cancer may have on sexual function, this topic of inquiry has been investigated in only a limited number of studies. In fact, from 1992 to 2002, only approximately 13 reports of results were available on the MEDLINE database, with each proceeding decade producing twice as many articles as the decade prior. Here, we aim to provide an outline for such disparities that covers differences in epidemiology, research in surgical techniques, prioritization of oncologic over sexual function outcomes, lack of appropriate counseling, and failure to properly characterize sexual dysfunction in women.

MP22-02 THE IMPACT OF RURAL RESIDENCY ON THE TREATMENT AND OUTCOMES OF LOCALLY INVASIVE/ADVANCED BLADDER CANCER IN LOUISIANA

You have accessJournal of UrologyCME1 Apr 2023MP22-02 THE IMPACT OF RURAL RESIDENCY ON THE TREATMENT AND OUTCOMES OF LOCALLY INVASIVE/ADVANCED BLADDER CANCER IN LOUISIANA Megan Escott, Tingting Li, Mei-Chin Hsieh, Scott Delacroix, Jessie Gills, Xiao-Cheng Wu, and Mary Westerman Megan EscottMegan Escott More articles by this author , Tingting LiTingting Li More articles by this author , Mei-Chin HsiehMei-Chin Hsieh More articles by this author , Scott DelacroixScott Delacroix More articles by this author , Jessie GillsJessie Gills More articles by this author , Xiao-Cheng WuXiao-Cheng Wu More articles by this author , and Mary WestermanMary Westerman More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003247.02AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: A later stage at diagnosis, gender, and race are independent predictors of bladder cancer-specific survival. There remains a need, however, to investigate additional contributors. We investigated the effect of urban and rural residency on a patient’s likelihood to receive standard of care in Louisiana and its impact on cancer-specific and overall survival. METHODS: Using the Louisiana Tumor Registry, we identified microscopically confirmed AJCC stage II – III bladder cancer diagnoses between 2014 and 2018. Multivariable logistic regression, Kaplan-Meier method, and Multivariate Cox proportional hazard analysis was performed. RESULTS: We identified 704 patients, with 75% having AJCC stage two disease. 598 (85%) patients lived in urban settings and 106 (15%) patients lived in rural settings. After controlling for race, socioeconomic status, and insurance coverage, there was no significant difference in the probability of urban and rural residents receiving the standard of care for definitive management. However, rural residency was independently associated with an increased risk of cancer-specific mortality (Figure 1). The median overall survival for residents of urban areas was 27 months (95% CI [23, 33]) compared to 13 months (95% CI [10, 20]) for residents of rural areas (Figure 2). CONCLUSIONS: A recent study using national census data called for further epidemiologic investigations after finding that patients with bladder cancer who lived in rural areas had significantly higher overall mortality and marginally increased cancer-specific mortality. Despite all Louisiana residents receiving the standard of care for definitive management of locally invasive bladder cancer, rural patients still had increased risks of cancer-specific and overall mortality after controlling for several demographic factors, only highlighting the need for continued investigation into disparities in bladder cancer outcomes. Source of Funding: NCI’s Surveillance, Epidemiology, End Result (SEER): HHSN261201800007I/HHSN26100002. CDC’s National Program Cancer Registries (NPCR): NU58DP006332 © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e295 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Megan Escott More articles by this author Tingting Li More articles by this author Mei-Chin Hsieh More articles by this author Scott Delacroix More articles by this author Jessie Gills More articles by this author Xiao-Cheng Wu More articles by this author Mary Westerman More articles by this author Expand All Advertisement PDF downloadLoading ...

Utility of ctDNA in predicting outcome and pathological complete response in patients with bladder cancer as a guide for selective bladder preservation strategies.

563 Background: Muscle-invasive bladder cancer (MIBC) accounts for ~25–30% of all bladder cancer diagnoses. With neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) as standard-of-care, the 5-year survival rate ranges from 40%–60%. Bladder-sparing protocols (BSP) have emerged as a feasible alternative to RC for MIBC treatment, however better tools are needed. In this study, we evaluated the prognostic value of circulating tumor DNA (ctDNA) in predicting recurrence in patients who achieved pathological complete response (pCR). Methods: We analyzed a previously described cohort of 68 patients (656 plasma samples; Christensen et al., JCO 2019) with MIBC who received NAC prior to cystectomy. Patients had an updated median follow-up of 58.94 months (range: 7.19-81.77) post-cystectomy. ctDNA was analyzed at baseline (before NAC; N=64), and prior to cystectomy (N=65) using a commercially available assay (Signatera, Natera, Inc.). Additionally, exploratory RNA-Seq was performed on tumors from 59 patients (samples with >5M total counts were utilized). Pathway analysis was used to compare ctDNA-positive and ctDNA-negative patients who failed to achieve pCR. Results: Of the 64 patients with ctDNA results available at baseline, 59.4% (38/64) tested ctDNA-negative, and of these 84.2% (32/38) achieved pCR. Furthermore, 40.6% (26/64) tested ctDNA-positive, and only 34.6% (9/26) achieved pCR. Likewise, prior to cystectomy, 83.9% (52/62) of patients were ctDNA-negative, and 80.7% (42/52) achieved pCR, while none of the ctDNA-positive patients achieved pCR (positive predictive value 100%; negative predictive value 80.8%). Based on both ctDNA timepoints, the probability of ctDNA-negative patients to achieve pCR was significantly higher than ctDNA-positive patients ( p<0.0001). Notably, ctDNA-positive patients without pCR demonstrated significantly poorer RFS and OS compared to the ctDNA-negative patients, at both timepoints (Baseline: RFS; HR=8.2, p=0.017, OS; HR=8.4, p=0.015, prior to cystectomy: RFS; HR=5.2, p=0.0078, OS; HR=4.8, p=0.012). Furthermore, ctDNA status at baseline and before cystectomy was a better predictor of RFS compared to pCR (HR=8.5, p<0.0001, HR=14, p<0.0001, respectively). Transcriptomic pathway analysis of patients who did not achieve pCR showed an enrichment of oncogenic pathways, namely EMT and angiogenesis, in tumors from ctDNA positive patients, whereas tumors from ctDNA negative patients showed an enrichment of anti-tumor immune signatures, including IFNα and IFNγ. Conclusions: Absence of ctDNA was significantly associated with pCR both at baseline and prior to cystectomy, identifying patients who may benefit from BSP. Larger cohorts are warranted to test the prognostic value of ctDNA combined with transcriptomic profiling in informing patient selection for avoiding cystectomy.

Bladder and Kidney Cancer Diagnosis and Survival Increase With Medicare Eligibility at Age 65

Medicare eligibility at 65 has been associated with increased diagnosis and survival for certain cancers due to greater health care utilization. We aim to assess for a similar "Medicare effect" for bladder and kidney cancers, which has not been previously established. Patients diagnosed with bladder or kidney cancer from 2000-2018 at ages 60-69 years were identified with the Surveillance, Epidemiology, and End Results database. We used age-over-age percent change calculations to characterize trends in cancer diagnoses focusing on patients aged 65. Multivariable Cox models were used to compare cancer-specific mortality across ages at diagnosis. We identified 63,960 patients diagnosed with bladder cancer and 52,316 diagnosed with kidney cancer. Age-over-age change in diagnosis was highest for patients aged 65 compared to all other ages for both cancers (P < .01 for both). Stratified by stage, patients aged 65 had a higher age-over-age change than those aged 61-64 or 66-69 for in situ (P = .01, P < .01, respectively), localized (P = .03, P = .01), and regional (P = .02, P = .02) bladder cancer and localized (P = .01, P = .01) kidney cancer. Bladder cancer patients aged 65 had lower cancer-specific mortality than patients aged 66 (HR = 1.17, P = .01) and 69 (HR = 1.18, P = .01), while kidney cancer patients aged 65 had lower mortality than patients aged 64 (HR = 1.18, P < .01) and 66-69. The age of 65, marking the onset of Medicare eligibility, is associated with more diagnoses of bladder and kidney cancer. Patients diagnosed at age 65 demonstrate decreased bladder and kidney cancer-specific mortality.

Challenges and opportunities in the management of non-urothelial bladder cancers

Urothelial carcinoma accounts for approximately 90% of all bladder cancer diagnoses. Localized, muscle-invasive disease is often managed with a multidisciplinary approach including either neoadjuvant chemotherapy (NAC) followed by radical cystectomy or concurrent chemoradiation, whereas multiple immunotherapies and novel antibody drug conjugates have recently joined platinum-based chemotherapy as standard of care therapy for metastatic disease. However, the clinical trials leading to these standards often require majority if not complete urothelial histology for eligibility. As many as one quarter of patients diagnosed with bladder cancer will have either divergent differentiation of their urothelial carcinoma or an alternate epithelial tumor such as squamous cell carcinoma, adenocarcinoma, or small cell carcinoma; even more rare are non-epithelial tumors such as sarcoma. The rarity of these diseases and their general exclusion from treatment within prospective clinical trials has created a challenging situation where treatment plans are often derived from case series or extrapolated from other disease types and outcomes are poor compared to pure urothelial carcinoma. In this review, we summarize the existing data on the diagnosis and treatment of epithelial, non-urothelial bladder cancers including adenocarcinoma, squamous cell carcinoma, and small cell carcinoma in their localized and advances stages. We will also review the current clinical trial landscape investigating novel approaches to these diseases.

Bacillus Calmette‐Guérin (BCG) treatment of bladder cancer protects against Alzheimer’s Disease in older adults: The Massachusetts General Brigham cohort

AbstractBackgroundRetraining the immune system offers a potential means of preventing or treating Alzheimer’s disease (AD). Vaccines can confer non‐specific beneficial effects (NSBEs), impacting diseases far afield from the original target. The Bacillus Calmette‐Guérin (BCG) vaccine, used worldwide in the prevention of tuberculosis, causes NSBE on non‐TB respiratory infections, type 1 diabetes, and multiple sclerosis. BCG is the gold‐standard therapy for non–muscle‐invasive bladder cancer. Recently, several retrospective studies have associated intravesicular BCG treatment of bladder cancer with lowered risk of AD (Gofrit et al., 2019, Klinger et al., 2021, Kim et al., 2021). We sought to replicate the retrospective study in a large cohort of patients in the Massachusetts General Brigham (MGB) System.MethodWe retrieved 30y of electronic health records from MGB, consisting of 17,920 subjects with new bladder cancer diagnoses. We limited records to patients aged &gt;50y, without a previous dementia diagnosis, and with at least one year MGB follow‐up after diagnosis. Using natural language processing (NLP), we identified and assigned pathological stages to each patient’s first transurethral resection of bladder tumor (TURBT) surgical pathology report. The study population consisted of non‐muscle‐invasive bladder cancer (NMIBC) patients (n = 6467). The intervention group was patients who had any exposure to intravesical BCG, determined by semiautomated methods using NLP and manual validation. The control group was NMIBC patients without exposure to intravesical BCG.ResultWe found a protective effect of BCG on the risk of dementia. Cox analysis of time to AD: HR 0.84, CI (0.7‐0.99), p = 0.049, age and sex‐adjusted. In a stratified analysis by age, the effect of BCG treatment on patients 70 or older was more pronounced (HR 0.77, CI 0.63‐0.95, p = 0.017), whereas there was no effect on patients younger than 70 (HR 0.98, CI 0.72 ‐ 1.36, p = 0.98).ConclusionFindings from our large retrospective study suggest an overall protective effect of BCG treatment on the subsequent incidence of Alzheimer’s Disease, with the effect largely drawing from patients 70yo or older. Further survival and competing risk analyses will be provided to contextualize the basis for these apparently beneficial effects of BCG.

Smoking Behaviors and Prognosis in Patients With Non–Muscle-Invasive Bladder Cancer in the Be-Well Study

Tobacco smoking is an established risk factor associated with bladder cancer, yet its impact on bladder cancer prognosis is unclear. To examine associations of use of tobacco (cigarettes, pipes, and cigars), e-cigarettes, and marijuana with risk of recurrence and progression of non-muscle-invasive bladder cancer (NMIBC) and to explore use of smoking cessation interventions. The Be-Well Study is a prospective cohort study of patients with NMIBC diagnosed from 2015 to 2019 and followed-up for 26.4 months in the Kaiser Permanente Northern and Southern California integrated health care system. Eligibility criteria were age at least 21 years, first NMIBC diagnosis (stages Ta, Tis, or T1), alive, and not in hospice care. Exclusion criteria were previous diagnosis of bladder cancer or other cancer diagnoses within 1 year prior to or concurrent with NMIBC diagnosis. Data were analyzed from April 1 to October 4, 2022. Use of cigarettes, pipes, cigars, e-cigarettes, and marijuana was reported in the baseline interview. Use of smoking cessation interventions (counseling and medications) was derived from electronic health records. Hazard ratios (HRs) and 95% CIs of recurrence and progression of bladder cancer were estimated by multivariable Cox proportional hazards regression. A total of 1472 patients (mean [SD] age at diagnosis, 70.2 [10.8%] years; 1129 [76.7%] male patients) with NMIBC were enrolled at a mean (SD) of 2.3 (1.3) months after diagnosis, including 874 patients (59.4%) who were former smokers and 111 patients (7.5%) who were current cigarette smokers; 67 patients (13.7%) smoked pipes and/or cigars only, 65 patients (4.4%) used e-cigarettes, 363 patients (24.7%) used marijuana. Longer cigarette smoking duration and more pack-years were associated with higher risk of recurrence in a dose-dependent manner, with the highest risks for patients who had smoked for 40 or more years (HR, 2.36; 95% CI, 1.43-3.91) or 40 or more pack-years (HR, 1.97; 95% CI, 1.32-2.95). There was no association of having ever smoked, being a former or current cigarette smoker, and years since quit smoking with recurrence risk. No associations with pipes, cigars, e-cigarettes, or marijuana were found. Of 102 patients offered a smoking cessation intervention, 57 (53.8%) received an interventions after diagnosis, with female patients more likely than male patients to engage in such interventions (23 of 30 female patients [76.7%] vs 34 of 76 male patients [44.7%]; P = .003). These findings suggest that longer duration and more pack-years of cigarette smoking were associated with higher risk of NMIBC recurrence. Cigarette smoking remains a critical exposure before and after diagnosis in survivors of NMIBC.

Applications of Exosomes in Diagnosing Muscle Invasive Bladder Cancer.

Muscle Invasive Bladder Cancer (MIBC) is a subset of bladder cancer with a significant risk for metastases and death. It accounts for nearly 25% of bladder cancer diagnoses. A diagnostic work-up for MIBC is inclusive of urologic evaluation, radiographic imaging with a CT scan, urinalysis, and cystoscopy. These evaluations, especially cystoscopy, are invasive and carry the risk of secondary health concerns. Non-invasive diagnostics such as urine cytology are an attractive alternative currently being investigated to mitigate the requirement for cystoscopy. A pitfall in urine cytology is the lack of available options with high reliability, specificity, and sensitivity to malignant bladder cells. Exosomes are a novel biomarker source which could resolve some of the concerns with urine cytology, due to the high specificity as the surrogates of tumor cells. This review serves to define muscle invasive bladder cancer, current urine cytology methods, the role of exosomes in MIBC, and exosomes application as a diagnostic tool in MIBC. Urinary exosomes as the specific populations of extracellular vesicles could provide additional biomarkers with specificity and sensitivity to bladder malignancies, which are a consistent source of cellular information to direct clinicians for developing treatment strategies. Given its strong presence and differentiation ability between normal and cancerous cells, exosome-based urine cytology is highly promising in providing a perspective of a patient’s bladder cancer.

The Impact of the COVID-19 Pandemic on Bladder Cancer Care in the Netherlands.

The COVID-19 pandemic has disrupted regular health care with potential consequences for non-COVID diseases like cancer. To ensure continuity of oncological care, guidelines were temporarily adapted. To evaluate the impact of the COVID-19 outbreak on bladder cancer care in the Netherlands. The number of bladder cancer (BC) diagnoses per month during 2020-2021 was compared to 2018-2019 based on preliminary data from the Netherlands Cancer Registry (NCR). Additionally, detailed data were retrieved from the NCR for the cohort diagnosed between March 1st-May 31st 2020 (first COVID wave) and 2018-2019 (reference cohort). BC diagnoses, changes in age and stage at diagnosis, and time to first-line treatment were compared between both periods. Changes in treatment were evaluated using logistic regression. During the first COVID wave (week 9-22), the number of BC diagnoses decreased by 14%, corresponding with approximately 300 diagnoses, but increased again in the second half of 2020. The decline was most pronounced from week 13 onwards in patients≥70 years and patients with non-muscle invasive BC. Patients with muscle-invasive disease were less likely to undergo a radical cystectomy (RC) in week 17-22 (OR = 0.62, 95% CI = 0.40-0.97). Shortly after the start of the outbreak, use of neoadjuvant chemotherapy decreased from 34% to 25% but this (non-significant) effect disappeared at the end of April. During the first wave, 5% more RCs were performed compared to previous years. Time from diagnosis to RC became 6 days shorter. Overall, a 7% reduction in RCs was observed in 2020. The number of BC diagnoses decreased steeply by 14% during the first COVID wave but increased again to pre-COVID levels by the end of 2020 (i.e. 600 diagnoses/month). Treatment-related changes remained limited and followed the adapted guidelines. Surgical volume was not compromised during the first wave. Altogether, the impact of the first COVID-19 outbreak on bladder cancer care in the Netherlands appears to be less pronounced than was reported for other solid tumors, both in the Netherlands and abroad. However, its impact on bladder cancer stage shift and long-term outcomes, as well as later pandemic waves remain so far unexamined.

En bloc resection of bladder tumors: challenges and unmet needs in 2022

Non-muscle invasive bladder cancer accounts for the majority of new bladder cancer diagnoses, and endoscopic transurethral resection of bladder tumor (TURBT) represents the standard-of-care. Although a relatively safe and common procedure, TURBT is often hampered by the questionable quality of resection. The evolution of surgical techniques has brought en bloc resection of bladder tumor (ERBT) to the forefront. ERBT has emerged as an alternative to conventional TURBT, incorporating a more delicate en bloc sculpting and tumor excision, in contrast to 'piecemeal'resection by conventional TURBT. ERBT appears safe, feasible and effective with demonstrably higher rates of detrusor muscle in the pathologic specimen, all while providing better staging and obviating the need for a re-TURBT in selected patients. However, the method's adoption in the field is still limited. This review summarizes the recent evidence relevant to ERBT while further highlighting the technique's limitations and unmet needs.

Emerging treatment options for bacillus Calmette-Guérin-unresponsive non-muscle invasive bladder cancer.

The majority of new bladder cancer diagnoses are non-muscle invasive bladder cancer (NMIBC). For patients with intermediate-risk and high-risk NMIBC, the preferred treatment after transurethral tumor resection is bacillus Calmette-Guérin (BCG) intravesical therapy; however, some patients receiving BCG do not respond and are at risk for recurrence and progression to muscle invasive disease. Currently, there is a lack of bladder-sparing therapies for patients that do not respond to BCG therapy. This review highlights recent advances in bladder-sparing therapies for NMIBC that do not respond to BCG therapy. Several clinical trials have emerged over the past several years using novel agents. Systemic immunotherapy with pembrolizumab has shown promising activity, and recently gained FDA approval for use in BCG-unresponsive NMIBC. Gene therapy using Nadofaragene firadenovec, a replication-deficient adenoviral vector delivering interferon (IFN) alfa, shows durable results and is pending regulatory approval. Several other agents are on the horizon and there will likely be an emergence of therapies over the next several years. Patients with NMIBC that do not respond to BCG therapy are at high risk for progression to muscle invasive disease. Bladder-sparing therapeutic options for these patients are sparse but now include pembrolizumab and several other potential options are emerging. These bladder-sparing therapies will benefit patients unwilling or unable to undergo radical cystectomy.

Bladder cancer biomarker screening based on non-targeted urine metabolomics.

Bladder cancer is one of the most common malignancies of the urinary system, and its screening relies heavily on invasive cystoscopy, which increases the risk of urethral injury and infection. This study aims to use non-targeted metabolomics methods to screen for metabolites that are significantly different between the urine of bladder cancer patients and cancer-free controls. In this study, liquid chromatography-mass spectrometry was used to analyze the urine of bladder cancer patients (n = 57) and the cancer-free controls (n = 38) by non-targeted metabolomic analysis and metabolite identification. The results showed that there were significant differences in the expression of 27 metabolites between bladder cancer patients and the cancer-free controls. In the multivariate statistical analysis of this study, the urinary metabolic profile data of bladder cancer patients were analyzed, and the receiver operating characteristic curve analysis showed that it is possible to perform non-invasive clinical diagnoses of bladder cancer through these candidate biomarkers.

Bladder cancer risk variants and overall and disease-specific survival in two independent cohorts.

Each year 573,000 bladder cancer diagnoses and 212,000 bladder cancer-related deaths occur worldwide [1]. In the United States, five-year survival for bladder cancer ranges from 69% for localized disease to 6% for metastatic disease [2]. Bladder cancer prognosis and response to treatment varies among patients. Currently, clinical decisions regarding treatment and follow up are driven primarily by grade and stage. Unfortunately, despite intensive research few somatic mutations have sufficient prognostic or predictive value such that they change clinical management.

Impact of the COVID-19 Pandemic on Urological Care Delivery in the United States.

We examined changes in urological care delivery due to COVID-19 in the U.S. based on patient, practice, and local/regional demographic and pandemic response features. We analyzed real-world data from the American Urological Association Quality (AQUA) Registry collected from electronic health record systems. Data represented 157 outpatient urological practices and 3,165 providers across 48 U.S. states and territories, including 3,297,721 unique patients, 12,488,831 total outpatient visits and 2,194,456 procedures. The primary outcome measure was the number of outpatient visits and procedures performed (inpatient or outpatient) per practice per week, measured from January 2019 to February 2021. We found large (>50%) declines in outpatient visits from March 2020 to April 2020 across patient demographic groups and states, regardless of timing of state stay-at-home orders. Nonurgent outpatient visits decreased more across various nonurgent procedures (49%-59%) than for procedures performed for potentially urgent diagnoses (38%-52%); surgical procedures for nonurgent conditions also decreased more (43%-79%) than those for potentially urgent conditions (43%-53%). African American patients had similar decreases in outpatient visits compared with Asians and Caucasians, but also slower recoveries back to baseline. Medicare-insured patients had the steepest declines (55%), while those on Medicaid and government insurance had the lowest percentage of recovery to baseline (73% and 69%, respectively). This study provides real-world evidence on the decline in urological care across demographic groups and practice settings, and demonstrates a differential impact on the utilization of urological health services by demographics and procedure type.