Management Of Bladder Cancer Research Articles

Diagnostic Protocol, Outcomes and Future Perspectives of the Vesical Imaging-Reporting and Data Systems (VI-RADS), a Narrative Review

Bladder cancer (BC) is common worldwide, and has aggressive features and high rates of relapse despite treatments. Approximately 30% of patients present with muscle invasive disease, and therefore, high risk of metastasis. This review provides an overview of the state of the art for the ‘Vesical Imaging Reporting and Data System’ (VI-RADS). This scoring system presents a tool for the local staging of BC and has been validated across several institutions. We discuss the current application and the potential future clinical implications of VI-RADS in BC diagnosis, management and follow-up.

Immune Checkpoint Inhibitors as a Treatment Option for Bladder Cancer: Current Evidence.

Bladder cancer is a prevalent disease, and treatment options for advanced bladder cancer remain limited. However, immune checkpoint inhibitors (ICIs) targeting cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) and programmed cell death-1 (PD-1) have shown promise in treating bladder cancer. These drugs work by blocking receptors and ligands, disrupting signaling, and allowing T cells to recognize and attack cancer cells. ICIs have been found to be effective in treating bladder cancer, especially in cases of metastatic urothelial carcinoma (UC) that have progressed after chemotherapy. Furthermore, combination therapy with ICIs and chemotherapy or radiation therapy has shown promise in treating bladder cancer. While there are challenges associated with ICIs, including adverse effects, immune-related adverse events, and lack of efficacy in some patients, they remain a promising option for bladder cancer treatment, especially in cases where other treatment options have failed. This review paper focuses on the current role, challenges, and future trends of immunotherapy in the management of bladder cancer.

CarePoint assay in the management of bladder cancer: A pilot study.

e16593 Background: Bladder cancer afflicts over 700,000 patients in the US and is one of the most expensive cancers to treat. Given a recurrence rate of up to 70%, regular often prolonged surveillance is required. In addition to urine based tests, current standard evaluation includes cystoscopy which is burdensome for patients and physicians; there has long been a need for a reliable non-invasive alternative diagnostic tool. While there is a wealth of literature on urinary biomarkers, no single biomarker has demonstrated consistent high sensitivity and specificity. Methods: The CarePoint Assay, a point-of-care (POC) tool, can perform multiple biomarker tests simultaneously. In this study, urine was collected from patients undergoing urologic evaluation for hematuria from three separate institutions. The urine was sent for central evaluation and the CarePoint Assay was used to detect the bladder cancer biomarker BTA. POC results were then compared to results from a highly sensitive 6-hour ELISA. The accuracy of distinguishing high-grade tumors, low-grade tumors and no tumor present were compared between the two methods. Results: The CarePoint Assay demonstrated excellent correlation with the ELISA in detecting biomarker levels and distinguishing high-grade tumors as well as a superior specificity (88% versus 77%) for ELISA, sensitivity (52% vs. 72%) for ELISA and a limit of detection of 2.55 ng/mL (16 picomolar). Conclusions: With this high performance, the CarePoint Assay has the ability to detect and multiplex multiple other bladder cancer biomarkers with higher sensitivity and specificity. Additional biomarker analysis using the CarePoint Assay may yield the medically desired higher levels of sensitivity and specificity for a non-invasive point-of-care bladder cancer test, ultimately limiting the patient burden of bladder cancer surveillance.

Identifying care fragmentation in the management of non-metastatic muscle-invasive bladder cancer.

e13527 Background: Measuring care fragmentation facilitates exploration of breakdowns in cancer care delivery that may impact quality of care and patient outcomes. Bladder cancer often requires a multimodal approach of surgery, chemotherapy and radiation, increasing the risk of fragmented care. This study assesses the extent of care fragmentation across different inpatient facilities and examines patient characteristics associated with inpatient care fragmentation. Methods: We adapt the modified Herfindahl-Hirschman market concentration index to construct a Fragmentation Index (FI) capturing the distribution of a patient’s care across inpatient facilities. We calculate FI for the 15 months following diagnosis for non-metastatic muscle-invasive bladder cancer (MIBC) patients who underwent radical cystectomy from 2010-2016 and had at least 2 admissions during the study period. We use Pennsylvania Cancer Registry data linked to statewide facility discharge records to estimate patient-level multivariable regression models of the relationship between FI and patient demographics, disease features, rurality, area deprivation index (ADI), payer, and Commission on Cancer hospital (CoC-H) accreditation status. Results: Of 965 patients, 87.3% (n = 842) lived in urban areas, 8.9% in large towns and 3.8% rural. Approximately 8% had Medicaid and 5.7% had uninsured or unknown payer status. A majority (64%; n = 614) were age 60-79; 76% were men and 92% non-Hispanic White; 19.5% (n = 188) had T4 disease and 25% (n = 239) received neoadjuvant chemotherapy. Almost half of patients (45.3%; n = 437) had an FI of 0, indicating all admissions were at the same hospital. The mean FI was 0.254 for the total cohort and 0.464 for patients with FI > 0. Residency in a large town or rural area was associated with 0.59 (CI 0.003—0.114) and 0.14 (CI 0.060—0.220) higher FI relative to urban areas. T4 disease was associated with 0.063 higher FI (CI 0.019—0.107) relative to <T2 disease. Factors associated with lower FI included Non-White race (-0.092, CI -0.151 – -0.033) and no admissions to CoC-H (-0.138, CI -0.182 – -0.095) relative to patients admitted to at least 1 CoC-H. Patients never admitted to a CoC-H (n = 134) mostly lived in urban areas (88%) and 49% had Medicare insurance: they were disproportionately from the most disadvantaged ADI quartile in the cohort (37.3%). Conclusions: Our findings highlight that many MIBC patients receive inpatient care across at least two different hospitals. Advanced disease and patient residence in non-urban areas are associated with greater fragmentation of inpatient care. Patients who never received care at a CoC hospital experienced less fragmentation but were more likely to be relatively economically disadvantaged. Future research will investigate relationships between fragmentation and clinical outcomes to inform policy and clinical strategies aimed at optimizing patterns of care.

Accuracy of genome-wide mutational analysis for tumor-informed ctDNA-guided MRD monitoring in bladder cancer.

4589 Background: Neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) is the standard management of localized muscle-invasive bladder cancer (MIBC). However, about 45% of patients develop metastases within 2 years after RC. Biomarkers for treatment efficacy evaluation and early detection of minimal residual disease (MRD) are needed for earlier treatment initiation and monitoring of treatment response. Tumor-informed detection of mutations in cell-free DNA (cfDNA) has shown promising results to monitor MRD. However, the low tumor fraction after surgery and limited input material obtained from a typical plasma sample limits the probability of detecting low metastatic burden scenarios. Here we implemented and applied a whole-genome sequencing (WGS) approach to monitor circulating tumor DNA (ctDNA) for sensitive ctDNA detection. Methods: 110 MIBC patients undergoing NAC and RC were enrolled. cfDNA was extracted from ~1mL plasma (n=978) and procured from longitudinal plasma sampling during NAC and pre-RC and post-RC. WGS of tumor/germline pairs (30x/20x) and plasma cfDNA (>20x) was performed, facilitating detection of genome-wide genomic alterations and quantification of ctDNA using the C2inform method. Results: For each patient we developed a tumor-informed WGS model by integrating genome-wide mutation and copy number variation data coupled with advanced signal processing and AI-based error suppression. Patient-specific somatic variant patterns were used for detection and measuring ctDNA levels in low-input blood samples by WGS. Post-RC ctDNA analysis identified patients with recurrence with 78% sensitivity and 95% specificity and with a median lead time over radiographic imaging of 118 days (full follow-up included). When restricting follow-up time to 12 months following the latest ctDNA test, a sensitivity of 86% and specificity of 94% was achieved. ctDNA status was associated with recurrence-free (p<0.0001) and overall survival (p<0.0001). Furthermore, ctDNA clearance during NAC was also associated with recurrence-free survival (p=0.0051). The APOBEC associated signatures SBS2 and SBS13 were identified as the primary contributors to the mutational landscape of the primary tumors and TP53, KMT2D, PIK3CA, RB1 and KDM6A were the main affected driver genes. Half of the tumors displayed whole genome doubling. Moreover, our analysis of plasma samples after treatment showed the presence of chemotherapy-induced mutational signatures not present in the primary tumor, along with increases in copy numbers on chromosomes 19q and 20, and a focal amplification of the FGFR3 gene on chromosome 4. Conclusions: Our results highlight the clinical potential of personalized genome-wide mutation integration as an ultra-sensitive, non-invasive method for MRD detection and treatment response monitoring.

Medicarpin induces G1 arrest and mitochondria-mediated intrinsic apoptotic pathway in bladder cancer cells.

Bladder cancer (BC) is the tenth most commonly diagnosed cancer. High recurrence, chemoresistance, and low response rate hinder the effective treatment of BC. Hence, a novel therapeutic strategy in the clinical management of BC is urgently needed. Medicarpin (MED), an isoflavone from Dalbergia odorifera, can promote bone mass gain and kill tumor cells, but its anti-BC effect remains obscure. This study reve aled that MED effectively inhibited the proliferation and arrested the cell cycle at the G1 phase of BC cell lines T24 and EJ-1 in vitro. In addition, MED could significantly suppress the tumor growth of BC cells in vivo. Mechanically, MED induced cell apoptosis by upregulating pro-apoptotic proteins BAK1, Bcl2-L-11, and caspase-3. Our data suggest that MED suppresses BC cell growth in vitro and in vivo via regulating mitochondria-mediated intrinsic apoptotic pathways, which can serve as a promising candidate for BC therapy.

NK Cell-Targeted Immunotherapies in Bladder Cancer: Beyond Checkpoint Inhibitors.

For decades, immunotherapies have been integral for the treatment and management of bladder cancer, with immune checkpoint inhibitors (ICIs) transforming patient care in recent years. However, response rates are poor to T cell-targeted ICIs such as programmed cell death protein 1 (PD-1) and programmed cell death-ligand 1 (PD-L1) blocking antibodies, framing a critical need for complementary immunotherapies. Promising strategies involve harnessing the activation potential of natural killer (NK) cells. They quickly exert their antitumor activity via signaling through germline-encoded activating receptors and are rapidly sensitized to new tissue microenvironments via their regulation by polymorphic HLA class I, KIR and NKG2A receptors. In this review, we examined the roles of currently available NK-targeted antitumor treatment strategies such as engineered viral vectors, small-molecule IMiDs, NK agonist antibodies, interleukins, and chimeric antigen receptor (CAR) NK cells, and their potential for improving the efficacy of immunotherapy in the treatment of bladder cancer. Through review of current literature, we summarized our knowledge of NK cells in solid tumors and hematologic malignancies as their roles pertain to novel immunotherapies already being applied to the treatment of bladder cancer or that offer rationale for considering as potential novel immunotherapeutic strategies. NK cells play a critical role in shaping the tumor microenvironment (TME) that can be exploited to improve T cell-targeted immunotherapies. Emerging evidence suggests that NK cells are a prime target for improving antitumor functions in immunotherapies for the treatment of bladder cancer. Further research into profiling NK cells in settings of immunotherapies for bladder cancer could help identify patients who might maximally benefit from NK cell-targeted immunotherapies and the various approaches for exploiting their antitumor properties.

Real-life benchmarking bladder cancer care: A population-based study.

Radical cystectomy (RC) is a complex oncological surgical procedure and population studies of routine surgical care have suggested suboptimal results compared to high-volume centers of excellence. A previous Canadian bladder cancer quality-of-care consensus led to adoption of multiple key quality-of-care indicators, with associated benchmarks created using available evidence and expert opinion to inform and measure future performance. Herein, we report real-life benchmark performance for the management of muscle-invasive bladder cancer (MIBC) relative to expert opinion guidance. This is a population-based, retrospective, cohort study that used the Ontario Cancer Registry (OCR) to identify all incident patients who underwent RC from 2009-2013. Electronic records of treatment from 1573 patients were linked to OCR; pathology records were obtained for all cases and reviewed by a team of trained data abstractors. The primary objective was to describe benchmarks for identified indicators, first as median values obtained across hospitals or providers, as well as a "pared-mean" approach to identify a benchmark population of "top performance," as defined as the best outcome accomplished for at least 10% of the population. Overall, performance in Ontario across all indicators fell short of expert opinion-determined benchmarks. Annual surgical volume by each surgeon performing a RC (benchmark >6, percent of institutions meeting benchmark=20%), percent of patients with MIBC referred preoperatively to medical oncology (MO; benchmark>90%, percent of institutions meeting benchmark=2%) and radiation oncology (RO; benchmark>50%, percent of institutions meeting benchmark=0%), time to cystectomy within six weeks of transurethral resection of bladder tumor (TURBT) in patients without neoadjuvant chemotherapy (benchmark <6 weeks, percent of institutions meeting benchmark=0%), percent of patients with adequate lymph node dissection (defined as >14 nodes, benchmark>85%, percent of institutions meeting benchmark=0%), percent of patients with positive margins post-RC (benchmark <10%, percent of institutions meeting benchmark=46%), and 90-day mortality (benchmark<5%, percent of institutions meeting benchmark=37%) fell considerably short. Simply evaluating benchmarks across the province as median performance significantly underestimated benchmarks that were possible by top-performing hospitals. Performance through most bladder cancer quality-of-care indicators fall short of benchmarks proposed by expert opinion. Different methodologies, such as a paredmean approach of top performers, may provide more realistic benchmarking.

Disparities in the prevalence and management of high-risk non-muscle invasive bladder cancer.

To evaluate the associations of socioeconomic characteristics with the management of non-muscle invasive bladder cancer (NMIBC). We identified adult patients aged 18 to 89 years with Ta, T1, or Tis NMIBC in the NCDB. We then examined the associations of patient and socioeconomic characteristics with the guidelines-based management of high-risk NMIBC using multivariable logistic regression. 163,949 patients were included in the study cohort, including 64% with Ta, 32% with T1, and 4% with Tis disease. Among those diagnosed with bladder cancer, male (OR 1.24, 95%CI 1.21-1.27), uninsured (OR 1.10, 95%CI 1.01-1.19 vs. private), and non-White (OR 1.34, 95%CI 1.28-1.41 for Black; OR 1.10; 95%CI 1.03-1.18 for Other vs. White) patients were more likely to be diagnosed with high-risk disease, as well as patients from lower education level areas. Among those with high-risk NMIBC, patients who were older, non-White, Hispanic, uninsured or insured with Medicaid were less likely to receive guideline recommended intravesical BCG, while those residing in rural and higher education level areas were more likely to receive BCG. When examining non-guidelines based use of radiotherapy for HGT1 disease, older age (OR 1.06; 95% CI 1.04-1.07) and VA/Military insurance (OR 2.73; 95%CI 1.07, 6.98 vs. private) were associated with radiotherapy use. There are strong disparities in the prevalence and management of high-risk NMIBC. These observations highlight important targets for future strategies to reduce such healthcare disparities and provide more equitable bladder cancer treatment to patients.

Nano theranostics involved in bladder cancer treatment

Bladder cancer (BC) is a complex disease with multiple clinical manifestations and treatment challenges, and current standard-of-care therapies remain limited and unfavorable. Theranostics, the integration of diagnostic and therapeutic technologies, has emerged as a promising strategy to address these challenges. The rapid development of nanomedicine has been a source of hope for the improvement of BC therapies and diagnostics by reducing side effects, enhancing tumor suppression, and overcoming drug resistance. Metal nanoparticles (NPs), inorganic NPs, polymer NPs, etc. have their respective advantages and show encouraging potential in the therapy of BC. In this review, we provide an overview on the state of the art in nanotechnology-based theranostics for BC, offering insights into the design and discovery of novel NPs for future BC management.

Cost-Effectiveness and Economic Impact of Bladder Cancer Management: An Updated Review of the Literature

Bladder cancer remains one of the costliest malignancies to manage. We provide a narrative review of literature assessing the economic burden and cost-effectiveness of bladder cancer treatment and surveillance. This is an update to a previous review and focuses on data published within the past 10 years. We queried PubMed and MEDLINE for all bladder cancer cost-related literature between 2013 and 2023. After initial screening, 117 abstracts were identified, 50 of which were selected for inclusion in our review. Management of disease recurrence and treatment complications contributes significantly to the high cost of care. High-value interventions are therefore treatments that improve recurrence-free and overall survival at minimal additional toxicity. De-escalation of surveillance and diagnostic interventions may help to reduce costs in this space without compromising oncologic control. The persistently rising cost of novel cancer drugs undermines their value when only modest gains in efficacy are observed. Multiple cost-effectiveness analyses have been published and are useful for contextualizing the cost, efficacy, and impact on quality of life that interventions have in this population. Further cost-effectiveness work is needed to better characterize the impact that treatment costs have on patients' financial well-being and quality of life.

Novel Delivery Mechanisms for Existing Systemic Agents and Emerging Therapies in Bladder Cancer.

Systemic agents including immune checkpoint inhibitors, antibody-drug conjugates, and targeted therapies play a critical role in the management of bladder cancer. Novel localized delivery mechanisms for existing systemic agents explore solutions to improve treatment response without compromising safety. Herein, we review the contemporary innovations in modern intravesical agents, hyperthermic drug delivery, reverse-thermal gels, nanocarriers, gene therapy, and subcutaneous therapies.

PET Imaging in Bladder Cancer: An Update and Future Direction.

Molecular imaging with positron emission tomography is a powerful tool in bladder cancer management. In this review, we aim to address the current place of the PET imaging in bladder cancer care and offer perspectives on potential future radiopharmaceutical and technological advancements. A special focus is given to the following: the role of [18F] 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography in the clinical management of bladder cancer patients, especially for staging and follow-up; treatment guided by [18F]FDG PET/CT; the role of [18F]FDG PET/MRI, the other PET radiopharmaceuticals beyond [18F]FDG, such as [68Ga]- or [18F]-labeled fibroblast activation protein inhibitor; and the application of artificial intelligence.

Altered Glycosylation in Progression and Management of Bladder Cancer.

Bladder cancer (BC) is the 10th most common malignancy worldwide, with an estimated 573,000 new cases and 213,000 deaths in 2020. Available therapeutic approaches are still unable to reduce the incidence of BC metastasis and the high mortality rates of BC patients. Therefore, there is a need to deepen our understanding of the molecular mechanisms underlying BC progression to develop new diagnostic and therapeutic tools. One such mechanism is protein glycosylation. Numerous studies reported changes in glycan biosynthesis during neoplastic transformation, resulting in the appearance of the so-called tumor-associated carbohydrate antigens (TACAs) on the cell surface. TACAs affect a wide range of key biological processes, including tumor cell survival and proliferation, invasion and metastasis, induction of chronic inflammation, angiogenesis, immune evasion, and insensitivity to apoptosis. The purpose of this review is to summarize the current information on how altered glycosylation of bladder cancer cells promotes disease progression and to present the potential use of glycans for diagnostic and therapeutic purposes.

Cost of Bladder Cancer Care: A Single Centre Comparison of Radical Cystectomy and Trimodal Therapy.

Radical cystectomy (RC) and trimodal therapy (TMT) are both accepted options in the management of muscle invasive bladder cancer (MIBC). As such, we sought to evaluate the micro-level costs associated with both modalities. All patients undergoing TMT or RC for primary treatment of urothelial MIBC at a single academic centre between 2008 and 2012 were included. Direct costs associated with each phase of a patient's clinical course were collected from the hospital's financial department and physician costs were calculated based on the provincial fee schedule. Costs of radiation treatments were derived from previously published literature. A total of 137 patients were included. The mean patient age was 69 (+/-12). Overall, 89 (65%) patients underwent RC and 48 (35%) were treated with TMT. The RC group had higher rates of cT3/T4 compared to those in the TMT group (51% vs 26%, P < .001). The median cost in the treatment phase for RC was $30,577 (IQR: $23,908-$38,837) versus $18,979 (IQR: $17,271-$23,519) for TMT (P < .001). There was no significant difference between treatment groups with respect to cost of diagnosis or work up. However, the cost of follow up care was numerically higher for patients undergoing TMT compared to RC ($3,096/year vs $1,974/year, P = .09). In appropriately selected patients with MIBC where TMT costs are not prohibitive and are lower than in RC. With increasing follow up time after primary treatment, the cost difference between modalities may be mitigated by the need for bladder surveillance and salvage therapy in the TMT cohort.

Abstract 1802: Personalization of oncolytic virus therapy: Heterogenous anti-tumor responses in preclinical prostate and bladder cancer models

Abstract Clinical studies revealed that single-agent immunotherapies yield limited efficacy in the management of prostate and bladder cancer (PCa, BCa). PCa and BCa often induce immunosuppressive and immune evasion mechanisms that restrict anti-tumor responses. Oncolytic viruses (OVs) offer promising and safe therapeutic options in the treatment of cancer as OVs target and or preferentially replicate in tumor cells, potentially evoking systemic anti-tumor immune responses. Combination of immunotherapy with OVs may, therefore, unleash the full potential of immunotherapy for these cancers. To achieve beneficial anti-tumor responses a more personalized OV therapy approach seems crucial. Strikingly, only few studies describe head-to-head comparison of the effects of different OVs. Together with our partners in the oncolytic viro-immunotherapy (OVIT) consortium we are developing and evaluating multiple OVs for their abilities to induce oncolysis and subsequent immunomodulation. Furthermore, we are developing tools to predict oncolytic virus effectiveness and design strategies to personalize oncolytic virus therapy. The OVs that were generated by our consortium encompass the spontaneous Orthoreovirus mutant (jin-3), a non-human primate Adenovirus (AdV-lumc007dRbD), and a Newcastle Disease Virus variant (NDV-F0).In this study we determined the anti-tumor and immunomodulatory effects of selected OVs in multiple ‘near-patient and patient-derived human PCa and BCa models; 1) tumor cell line cultures, 2) cocultures of tumor cell lines and monocyte-derived dendritic cells (mo-DCs), and 3) ex-vivo cultured tumor tissue slices and explants from patient material or patient-derived xenograft (PDX) models. The selected OVs infected a panel of PCa and BCa cell lines and displayed heterogenous effects on tumor cell viability and expression of immunogenic cell death markers (HSP90, Calreticulin, and HMGB1). For instance, the jin-3 virus showed enhanced tumor tropism in most PCa cells, while AdV-lumc007dRbD was more efficient in BCa cells. Virus infection of tumor cells resulted in maturation and activation of moDCs. Furthermore, OVs were able to infect and replicate in ex-vivo cultured tumor tissue slices and viability of ex-vivo tumor tissue explants was reduced following viral inoculation. Transcriptomic analysis of infected patient tissues revealed heterogenous responses to the tested OVs.Taken together, we established and compared the oncolytic properties of various OVs in multiple preclinical models of PCa and BCa. The data indicate heterogeneity of response for the tested OVs in urological cancers. In order for OV therapy to reach robust clinical efficacy, better appreciation of underlying molecular and cellular mechanisms is crucial for the personalization of oncolytic viro-immunotherapy. Citation Format: Thijs J. Janssen, Geertje van der Horst, Arjanneke F. van der Merbel, Maaike van der Mark, Martine L. Lamfers, Bernadette G. van den Hoogen, Sjoerd S. van der Burg, Dana A. Mustafa, Niven Mehra, Tilly Aalders, Nadine van Montfoort, Jack Schalken, Rob C. Hoeben, Gabri van der Pluijm. Personalization of oncolytic virus therapy: Heterogenous anti-tumor responses in preclinical prostate and bladder cancer models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1802.

MP22-20 CONTEMPORARY TRENDS IN THE MANAGEMENT OF T1 BLADDER CANCER

You have accessJournal of UrologyCME1 Apr 2023MP22-20 CONTEMPORARY TRENDS IN THE MANAGEMENT OF T1 BLADDER CANCER Michael Hung, Adithya Balasubramanian, and Douglas Scherr Michael HungMichael Hung More articles by this author , Adithya BalasubramanianAdithya Balasubramanian More articles by this author , and Douglas ScherrDouglas Scherr More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003247.20AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The current treatment strategy for T1 non muscle invasive bladder cancer is centered around bladder preservation with an emphasis on complete tumor resection and BCG therapy. However, the insidious nature of T1 bladder cancer lead many to offer early radical cystectomy with or without additional systemic therapy. We sought to examine the contemporary treatment patterns in the management of T1 bladder cancer in a nationwide cohort. METHODS: The National Cancer Database (NCDB) was queried to identify all cases of cT1 bladder cancer from 2004 to 2017. Demographic and clinical characteristics were compared and trended over the study period. We identified subsequent surgical therapy after initial diagnosis and stratified patients who underwent radical cystectomy and those who underwent bladder preserving surgery alone. Kaplan Meier curves were used to estimate survival in these cohorts, stratified by the treatment facility. RESULTS: The total of 128,400 patients were identified in the study period. The rate of radical cystectomy in patients with T1 bladder cancer increased from 4.6% in 2004 to 7.5% in 2017 (Figure 1a). In patients who underwent radical cystectomy, the overall rate of neoadjuvant and adjuvant chemotherapy was 11% and 17%, respectively. There was no significant difference in median OS among patients who received neoadjuvant chemotherapy compared to no systemic therapy (8.6 yrs vs 7.5 yrs, p=0.15), and no difference in rates of pathologic upgrade to T2-4 at cystectomy (36.7% vs 34.6%, p=0.42). Patients who underwent cystectomy had significantly longer median OS compared to those who had bladder preserving surgery alone (7.5 yrs vs 7 yrs, p=0.01). A majority (58%) of all radical cystectomies were performed at academic facilities and median OS was significantly higher at academic facilities versus community hospitals (8.1 yrs vs 6.1 yrs, p<0.01) (Figure 1b). CONCLUSIONS: Rates of radical cystectomy for the management of T1 bladder cancer have increased over time, congruent with evidence suggesting improved survival compared to local therapy alone. However, increased rates of neoadjuvant chemotherapy were observed despite the lack of clear guidelines or benefits for use. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e305 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Michael Hung More articles by this author Adithya Balasubramanian More articles by this author Douglas Scherr More articles by this author Expand All Advertisement PDF downloadLoading ...

MP12-08 EVALUATING THE IMPACT OF EXCLUDING THE RACE FACTOR FROM THE eGFR EQUATION ON BLADDER CANCER TREATMENT OPTIONS

You have accessJournal of UrologyCME1 Apr 2023MP12-08 EVALUATING THE IMPACT OF EXCLUDING THE RACE FACTOR FROM THE eGFR EQUATION ON BLADDER CANCER TREATMENT OPTIONS Amir Khan, Shu Wang, Rehan Choudhary, Michael Phelan, Eberechukwu Onukwugha, and M. Minhaj Siddiqui Amir KhanAmir Khan More articles by this author , Shu WangShu Wang More articles by this author , Rehan ChoudharyRehan Choudhary More articles by this author , Michael PhelanMichael Phelan More articles by this author , Eberechukwu OnukwughaEberechukwu Onukwugha More articles by this author , and M. Minhaj SiddiquiM. Minhaj Siddiqui More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003227.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The estimated glomerular filtration rate (eGFR) equation is based on several factors among which the race factor has been broadly criticized. In September 2021, the National Kidney Foundation and American Society of Nephrology Task Force announced a new race-free calculation for eGFR. Aspects of treatment decisions for muscle-invasive bladder cancer (MIBC) are dependent on eGFR, specifically neoadjuvant cisplatin eligibility and choice of diversion with cystectomy. Herein, we evaluate the impact of removal of race-based eGFR calculation on the management of patients with MIBC. METHODS: Using the National Surgical Quality Improvement Program database, adult patients diagnosed with MIBC and who received radical cystectomy from 2015 to 2020 were included in this study. eGFR was calculated using the Modification of Diet in Renal Disease (MDRD) equation. We calculated the proportion of African American patients who were candidates for neobladder urinary diversions and cisplatin-based chemotherapy using >30 and >60 ml/min/1.73m2 as the cutoff for eGFR, respectively, as calculated with and without the race factor. RESULTS: African Americans constituted 4.5% (579) of the total sample population (12,192) among which 39.7% (230) were female and 60.3% (349) were male. There was no association of eGFR with gender. Using the MDRD equation, the mean eGFR decreased from 70.0 to 57.8 ml/min/1.73m2 after removing the race factor. With the adjusted eGFR without race, 4.1% fewer patients (94.6% vs 90.5%) were eligible for neobladder urinary diversion with a >30 ml/min/1.73m2 eGFR cutoff. Furthermore, among patients who were previously eligible to receive cisplatin chemotherapy, 18.0% fewer patients (63.0% vs 45.0%) would remain eligible with a >60 ml/min/1.73m2 eGFR. (Figure 1) CONCLUSIONS: Excluding race from the eGFR equation will preclude some previously eligible African American patients for certain treatment in bladder cancer management. Further studies are needed to understand the relative risks and benefits of decisions that are based on the adjusted eGFR. Source of Funding: No source of funding © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e136 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Amir Khan More articles by this author Shu Wang More articles by this author Rehan Choudhary More articles by this author Michael Phelan More articles by this author Eberechukwu Onukwugha More articles by this author M. Minhaj Siddiqui More articles by this author Expand All Advertisement PDF downloadLoading ...

PD29-02 BENCHMARKING BLADDER CANCER CARE: A REAL-LIFE POPULATION-BASED STUDY

You have accessJournal of UrologyCME1 Apr 2023PD29-02 BENCHMARKING BLADDER CANCER CARE: A REAL-LIFE POPULATION-BASED STUDY Nicolas Vanin-Moreno, Marlo Whitehead, and Robert Siemens Nicolas Vanin-MorenoNicolas Vanin-Moreno More articles by this author , Marlo WhiteheadMarlo Whitehead More articles by this author , and Robert SiemensRobert Siemens More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003315.02AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Radical cystectomy (RC) is a complex oncological surgical procedure and population studies of routine surgical care have suggested suboptimal results compared to high-volume centers of excellence. A previous Canadian bladder cancer quality-of-care consensus led to adoption of multiple key quality-of-care indicators with associated benchmarks created utilizing available evidence and expert opinion to inform and measure future performance. Herein we report real-life benchmark performance for the management of muscle invasive bladder cancer (MIBC) relative to expert opinion guidance. METHODS: This is a population-based, retrospective, cohort study that used the Ontario Cancer Registry (OCR) to identify all incident patients who underwent RC from 2009 and 2013. Electronic records of treatment from 1,573 patients were linked to OCR; pathology records were obtained for all cases and reviewed by a team of trained data abstractors. The primary objective was to describe benchmarks for identified indicators first as median values obtained across hospitals or providers as well as a “pared-mean” approach to identify a benchmark population of "top performance" as defined as the best outcome accomplished for at least 10 percent of the population. RESULTS: Overall, performance in Ontario across all indicators fell short of expert-opinion determined benchmarks. Annual surgical volume by each surgeon performing a RC (benchmark>6, percent of institutions meeting benchmark =20%), percent of patients with MIBC referred pre-operatively to Medical Oncology (MO; benchmark >90%, percent of institutions meeting benchmark =2%) and Radiation Oncology (RO; benchmark >50%, percent of institutions meeting benchmark =0%), time to cystectomy within 6 weeks of TURBT in patients without neoadjuvant chemotherapy (benchmark <6 weeks, percent of institutions meeting benchmark =0%), percent of patients with adequate lymph node dissection (defined as >14 nodes, benchmark >85%, percent of institutions meeting benchmark =0%), percent of patients with positive margins post RC (benchmark <10%, percent of institutions meeting benchmark =46%), and 90 day mortality (benchmark <5%, percent of institutions meeting benchmark =37%) fell considerably short. Simply evaluating benchmarks across the province as median performance significantly under-estimated benchmarks that were possible by top-performing hospitals. CONCLUSIONS: Performance through the majority of BC quality of care indicators fall short of benchmarks proposed by expert-opinion. Different methodologies such as a pared-mean approach of top performers may provide more realistic benchmarking. Source of Funding: This study was supported by the Institute for Clinical Evaluative Sciences (ICES), which is funded by an annual grant from the Ontario Ministry of Health and Long-Term Care (MOHLTC). Parts of this material are based on data and information compiled and provided by CIHI. © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e824 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Nicolas Vanin-Moreno More articles by this author Marlo Whitehead More articles by this author Robert Siemens More articles by this author Expand All Advertisement PDF downloadLoading ...

Comprehensive analysis of scRNA-Seq and bulk RNA-Seq reveals dynamic changes in the tumor immune microenvironment of bladder cancer and establishes a prognostic model

BackgroundThe prognostic management of bladder cancer (BLCA) remains a great challenge for clinicians. Recently, bulk RNA-seq sequencing data have been used as a prognostic marker for many cancers but do not accurately detect core cellular and molecular functions in tumor cells. In the current study, bulk RNA-seq and single-cell RNA sequencing (scRNA-seq) data were combined to construct a prognostic model of BLCA.MethodsBLCA scRNA-seq data were downloaded from Gene Expression Omnibus (GEO) database. Bulk RNA-seq data were obtained from the UCSC Xena. The R package "Seurat" was used for scRNA-seq data processing, and the uniform manifold approximation and projection (UMAP) were utilized for downscaling and cluster identification. The FindAllMarkers function was used to identify marker genes for each cluster. The limma package was used to obtain differentially expressed genes (DEGs) affecting overall survival (OS) in BLCA patients. Weighted gene correlation network analysis (WGCNA) was used to identify BLCA key modules. The intersection of marker genes of core cells and genes of BLCA key modules and DEGs was used to construct a prognostic model by univariate Cox and Least Absolute Shrinkage and Selection Operator (LASSO) analyses. Differences in clinicopathological characteristics, immune microenvironment, immune checkpoints, and chemotherapeutic drug sensitivity between the high and low-risk groups were also investigated.ResultsscRNA-seq data were analyzed to identify 19 cell subpopulations and 7 core cell types. The ssGSEA showed that all 7 core cell types were significantly downregulated in tumor samples of BLCA. We identified 474 marker genes from the scRNA-seq dataset, 1556 DEGs from the Bulk RNA-seq dataset, and 2334 genes associated with a key module identified by WGCNA. After performing intersection, univariate Cox, and LASSO analysis, we obtained a prognostic model based on the expression levels of 3 signature genes, namely MAP1B, PCOLCE2, and ELN. The feasibility of the model was validated by an internal training set and two external validation sets. Moreover, patients with high-risk scores are predisposed to experience poor OS, a larger prevalence of stage III-IV, a greater TMB, a higher infiltration of immune cells, and a lesser likelihood of responding favorably to immunotherapy.ConclusionBy integrating scRNA-seq and bulk RNA-seq data, we constructed a novel prognostic model to predict the survival of BLCA patients. The risk score is a promising independent prognostic factor that is closely correlated with the immune microenvironment and clinicopathological characteristics.