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The study aimed to examine the impact of diabetes mellitus type 2 (DMII) on the oncological outcomes of non-muscle invasive bladder cancer (NMIBC) treated with Bacillus Calmette-Guérin (BCG) using comprehensive real-world data. We performed an analysis of data on NMIBC patients treated with BCG from the United States (US) National Phase II BCG/Interferon (IFN) trial database (125 centers) and pooled databases from three tertiary care institutions: France (FR), Lebanon (LB) (2000–2021), and the US (University of Iowa) (2011–2021). There were 867 patients from the Phase II trial, 1232 from the FR/LB cohort, and 233 from the US (Iowa) cohort (n = 2332). DM II was reported in 13% of the Phase II trial cohort, 14.4% of the FR/LB cohort, and 33.5% of the US (Iowa) cohort. The median follow-up was 24 months in the Phase II trial cohort, 25 months in the FR/LB cohort, and 48 months in the US (Iowa) cohort. In multivariable Cox regression analyses, DMII was not significantly associated with recurrence or progression of the tumor in any of the cohorts included in this study. DMII may not be a clinical prognostic factor for NMIBC patients treated with BCG. Prospective evaluation is needed. [ABSTRACT FROM AUTHOR]

Nogapendekin alfa inbakicept (ANKTIVA®; nogapendekin alfa inbakicept-pmln) is a recombinant interleukin-15 (IL-15) superagonist protein complex being developed by Altor BioScience, LLC, an indirect wholly owned subsidiary of ImmunityBio, Inc., for the treatment of solid and haematological cancers and HIV infection. In April 2024, nogapendekin alfa inbakicept was approved for use with Bacillus Calmette-Guérin (BCG) for the treatment of adult patients with BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumours in the USA. This article summarizes the milestones in the development of nogapendekin alfa inbakicept leading to this first approval for the treatment of cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: The mainstay of treatment for non-muscle invasive bladder cancer is transurethral resection of the tumor followed by intravesical treatment for intermediate- or high-risk disease. Duration and type of intravesical treatment depend on specific characteristics of the tumor and the patient's disease course. Patients with non-muscle invasive bladder cancer are closely monitored with frequent surveillance cystoscopies following treatment. This type of cancer has a low progression rate; however, it has a high rate of recurrence with the current recommended treatments. Therefore, patients often find themselves having to undergo multiple resections and rounds of intravesical treatment throughout their lifetime. This is not only burdensome for patients but also costly for the healthcare system. Given the high recurrence with the standard treatment options, it is important to continue investigating novel therapies. The goal of this review article is to outline the most recent therapies available or in clinical trials for the treatment of non-muscle invasive bladder cancer. The landscape of treatment for non-muscle invasive bladder cancer is rapidly changing. A complete and careful transurethral resection is the mainstay of initial treatment and is followed by intravesical therapy in intermediate or high-risk cases. The standard of care is intravesical BCG. Many alternative or additive approaches to this are being explored. We divided this review into three relevant spaces to consider these novel treatment approaches: (1) low-risk disease, for which intravesical therapy is not usually considered, (2) BCG-naïve disease (i.e., considering alternatives to the standard therapy), and (3) BCG-unresponsive disease. We performed a review of published literature and summarized ongoing trials in the United States. Novel approaches that we explored include surgical techniques for resection, alterations in dwell time for intravesical therapy, delivery method and schedule of intravesical therapies, new intravesical therapy agents, and systemic therapies (especially immunotherapy). These are thoroughly outlined throughout this review article, and the numerous modalities being studied demonstrate significant promise for the future treatment of the expanding space of NMIBC. [ABSTRACT FROM AUTHOR]

Background: Bladder cancer is the sixth most common malignancy in the United States (US). Despite its high prevalence and the significant potential benefits of early detection, no reliable, cost-effective screening algorithm exists for asymptomatic patients at risk. Nonetheless, reports of incidentally identified early bladder cancer on CT/MRI scans performed for other indications are emerging in the literature. This represents a new opportunity for early detection, with over 80 million CT scans performed in the US yearly, 40% of which are abdominopelvic CTs. This investigation aims to define the imaging features of early bladder cancer, with the mission of facilitating early diagnosis. Methods: Following IRB approval with a waiver of informed consent, a retrospective review was performed, identifying 624 patients with non-muscle-invasive bladder cancer diagnosed at Johns Hopkins Hospital between 2000 and 2019. Of these patients, 99 patients underwent pelvic CT within the 5 years preceding pathologic diagnosis. These imaging studies were reviewed retrospectively to evaluate for the presence and features of any focal bladder wall abnormality. Results: Median age at the time of pathologic diagnosis was 70 years (range: 51–88 years), and 82% (81/99) of patients were male. A total of 226 CT studies were reviewed. The number of studies per patient ranged from 1 to 33. Median time interval between all available imaging and pathologic diagnosis was 14 months. A total of 62% (141/226) of the scans reviewed were performed for indications other than suspected urinary tract cancer (UTC). A bladder wall mass was visualized in 67% (66/99) of patients and on 35% (78/226) of scans performed before diagnosis. The majority (84%, 67/80) of masses were intraluminal. Mean transverse long- and short-axis measurements were 24 mm and 17 mm, respectively, with long dimension measurements ranging between 5 and 59 mm. Conclusions: Early bladder cancer was visualized on CT preceding pathologic diagnosis in more than 2/3 of patients, and the majority of scans were performed for indications other than suspected urinary tract cancer/UTC symptoms. These results suggest that cross-sectional imaging performed for other indications can serve as a resource for opportunistic bladder cancer screening, particularly in high-risk patients. [ABSTRACT FROM AUTHOR]

Background: One of the milestones in bacterial-mediated therapy for cancer, Bacillus Calmette-Guerin (BCG) has been used to treat bladder cancer (BC) for more than 30 years. BCG immunotherapy is now the standard of care for high-grade nonmuscle invasive bladder cancer (NMIBC) following transurethral resection. Methods: We searched the Web of Science core collection (WoSCC) database and used bibliometric methods through CiteSpace (version 5.1.R6), VOSviewer (version 1.6.18) and R-Bibliometrix (version R 4.2.1) to analyze and discuss the current status and trends of BCG therapy of BC from 2012 to 2021 in terms of cooccurrence, co-polymerization and visualization. Results: A total of 2476 publications were found, with the majority coming from the United States and China. Over the last decade, overall yearly outputs have increased fivefold, from 117 papers in 2012 to 534 records in 2021. Most publications were produced by the University of Texas System. The authors, Ashish M. Kamat of the University of Texas-MD Anderson Cancer Center in the United States, and Shahrokh F. Shariat of Weill Cornell Medical College, were pioneers in this field with the most publications. The journals, Urologic Oncology Seminars and Original Investigations, Cancers and Frontiers in Oncology, have published a dramatic increase in the number of articles, and tumor and urology nephrology research directions have received the most attention from journals. Furthermore, recent research has concentrated on muscle-invasive bladder cancer (MIBC). BCG therapy mechanism, BCG dose and strains, targeted therapy and immune checkpoint inhibitors (ICIs) for BC were attractive research contents, with ICIs (PD-1, PD-L1) being the most popular study point in recent years. With more research on tumor immunology, screening for more reliable biomarkers for precision treatment, and the development of combination regimens of ICIs, targeted treatment of BC stem cells, and personalized BC therapies may be promising areas of immunotherapy research in the coming years. Conclusion: The results of this bibliometric study can provide the current status and research trends of BCG therapy for BC in the last decade, and also further complements the research content of bacterial-mediated cancer therapy. [ABSTRACT FROM AUTHOR]

Bladder cancer (BC) is the sixth most common cancer in the US and ∼75% of incident cases are non-muscle invasive BC (NMIBC). Current treatments differ by risk evaluation following the first transurethral resection of the bladder tumor. These include cystectomy and bladder preservation therapies (e.g., intravesical bacillus Calmette-Guérin [BCG]). While the burden of cystectomy is significant1, the burden of intravesical treatments is less well understood. This study aimed to describe the life impacts of intravesical therapies for NMIBC from the perspective of the patient. A cross-sectional online survey design was used. Study participants recruited from US patient communities were eligible if they: (1) had a self-reported diagnosis of NMIBC, (2) had intravesical treatment for NMIBC (i.e., BCG, gemcitabine, mitomycin, docetaxel, paclitaxel, epirubicin, doxorubicin) within the past year, and (3) were aged ≥18 years. Individuals were excluded if they were participating in a clinical trial, had other cancers (including muscle invasive or metastatic BC), or had been treated with erdafitinib. Prior to data collection, survey questions were evaluated for comprehension and salience to the NMIBC patient experience in one-on-one interviews. Participants' treatment experiences were evaluated using custom statements with 11-point numerical rating scales. Additionally, validated patient-reported outcome measures were used under license to capture work productivity (Work Productivity and Activity Impairment-Special Health Problem) and impacts of disease-specific symptoms (NCCN/FACT Bladder Symptom Index [FBlSI-18]). The study was approved by the WIRB-Copernicus Group Independent Review Board. Overall, 171 respondents completed the survey (average time=20 minutes; completion rate=36%). The majority were male (64%), ≥55 years old (70%), and attended college (87%). Participants frequently reported receiving BCG (83%), gemcitabine (27%), gemcitabine+docetaxel (13%), mitomycin c(12%), and docetaxel (12%) intravesically during the past year. Participants reported high levels of agreement to having intention to complete their full treatment course and willingness to try a different therapy if needed. Figure 1 shows additional details. Among participants employed for pay (n=77), notable work time missed (absenteeism=17%), impairment while at work (presenteeism=51%), overall work productivity loss (59%), and impairment in daily activities (40%) was reported for the past 7 days due to NMIBC.The FBlSI-18 scale found BC symptoms burden related to impacts on emotional (e.g., worry about their condition worsening) and functional well-being (e.g., low contentment with their HRQoL), physical symptoms (e.g., poor sleep), and bothersome treatment side effects. This study filled an important gap by describing the real-world intravesical treatment experience and its impact on the HRQoL of patients with NMIBC. Participants generally felt adequately informed about treatment, felt expectation of the treatment matched actual experience, and intended to complete their full treatment course. Participants reported high work impairment due to having NMIBC and disease symptom burden negatively impacting their well-being despite receiving intravesical treatment. Overall, these results point to an unmet need in the treatment of NMIBC and participants' willingness to try a different treatment if recommended. [ABSTRACT FROM AUTHOR]

Objective: Among patients diagnosed with non-muscle invasive bladder cancer (NMIBC), those with high risk disease have the greatest risk of recurrence and disease progression. The underutilization of intravesical immunotherapy with Bacillus Calmette-Guérin (BCG) has been a longstanding concern in clinical practice. This study aimed to determine the disparities present in receipt of adjuvant intravesical chemotherapy and immunotherapy in treatment of patients with high grade NMIBC following initial transurethral resection of a bladder tumor (TURBT)., Methods: The California Cancer Registry data was used to identify 19,237 patients diagnosed with high grade NMIBC who underwent TURBT. Treatment variables include re-TURBT, re-TURBT and intravesical chemotherapy (IVC) and/or BCG. Independent variables include age, sex, race/ethnicity, neighborhood socioeconomic status (nSES), primary insurance payer and marital status at diagnosis. Multiple logistic regression and multinomial regression models were used to examine variation in the treatments received following TURBT., Results: The proportion of patients receiving TURBT followed by BCG was similar across all racial and ethnic groups (28%-32%). BCG therapy was higher in patients belonging to the highest nSES quintile (37% for highest vs. 23%-26% for the 2 lowest quintiles). In multiple variable analyses, receipt of any intravesical therapy (IVT) was influenced by nSES, age, marital status, race/ethnicity, and insurance type. Patients in the lowest nSES quintile had a 45% less likelihood of receiving IVT compared to the highest nSES group (OR [95%CI]: 0.55[0.49, 0.61]). Race/ethnicity differences in receipt of any adjuvant therapy were noted in the middle to lowest nSES quintile for Hispanic and Asian/Pacific Islander patients when compared to non-Hispanic White patients. When comparing variation in treatment by insurance type at diagnosis, those with Medicare or other insurance were 24% and 30% less likely to receive BCG after TURBT compared to those with private insurance, (OR [95%CI]: 0.76 [0.70, 0.82] and 0.70[0.62, 0.79]) respectively., Conclusion: In patients with a diagnosis of high risk NMIBC, disparities in utilization of BCG are seen based on SES, age, and insurance type., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Although the role of lifestyle in health-related quality of life (HRQoL) outcomes has been increasingly recognized for various types of cancer, evidence in patients with non-muscle invasive bladder cancer (NMIBC) is very limited. We aimed to evaluate the longitudinal association between adherence to the 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) lifestyle recommendations and HRQoL in patients with NMIBC. This study included 1029 patients with NMIBC recruited between May 2014 and April 2017 from the Dutch multi-centre prospective cohort study UroLife. Lifestyle and HRQoL data were collected at 6 weeks (baseline), 3 months and 15 months after diagnosis. Information on body mass index (BMI), physical activity, diet and alcohol was used to compute the standardized WCRF/AICR adherence score (0-7). HRQoL outcomes were evaluated by the EORTC QLQ-C30. Linear mixed models were used to assess longitudinal confounder-adjusted associations between the WCRF/AICR adherence score and HRQoL outcomes. Adherence to each additional WCRF/AICR recommendation was associated with better global quality of life, physical, role and social functioning, and less fatigue. We found stronger inter-individual than intra-individual associations, suggesting that associations were mainly driven by between-subject differences. Higher adherence to the BMI, physical activity and dietary recommendations was associated with better scores for most HRQoL outcomes, while adherence to the alcohol recommendation (ie, non-consumption) was associated with worse HRQoL. Following the WCRF/AICR lifestyle recommendations may improve HRQoL in patients with NMIBC. Intervention studies are needed to establish whether the association between lifestyle and HRQoL is causal., (© 2023 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Background: Patients with non-muscle invasive bladder cancer (NMIBC) are at a high risk of tumor recurrence. It has not been previously investigated if adherence to cancer prevention recommendations lowers the risk of recurrence., Objectives: We examined whether the standardized lifestyle score measuring adherence to the 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) cancer prevention recommendations was associated with the risk of recurrence and progression among patients with NMIBC., Methods: The study population included patients diagnosed with primary NMIBC between 2014 and 2017 from the prospective cohort UroLife. Lifestyle was assessed at baseline (n = 979; reflecting the prediagnosis period) and 3-mo postdiagnosis (n = 885). The standardized 2018 WCRF/AICR score was constructed based on recommendations for body weight, physical activity, diet, and alcohol intake. We computed multivariable-adjusted HRs and 95% CIs using Cox proportional hazard regression models., Results: During a median follow-up time of 3.7 y, 320 patients developed ≥1 recurrence(s) and 49 experienced progression. Patients in the highest compared with the lowest tertile of postdiagnosis WCRF/AICR scores had a lower risk of first bladder cancer recurrence (HR: 0.74; 95% CI: 0.56, 0.98). No associations were observed for multiple recurrences (HR: 0.90; 95% CI: 0.70, 1.15) or for the baseline score with either first (HR: 1.07; 95% CI: 0.82, 1.40) or multiple recurrences (HR: 1.04; 95% CI: 0.82, 1.31). Improving lifestyle after diagnosis (per 1-point increase) was not significantly associated with the risk of first or multiple recurrence(s) (HR: 0.87; 95% CI: 0.74, 1.02; HR: 0.93; 95% CI: 0.80, 1.08, respectively). No associations were observed for bladder cancer progression, but the power was limited., Conclusions: Better adherence to the WCRF/AICR cancer prevention recommendations 3 mo after NMIBC diagnosis, but not before diagnosis, is associated with a decreased risk of first bladder cancer recurrence. More studies evaluating postdiagnosis lifestyles are needed to provide solid support for lifestyle recommendations for cancer survivors., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Intravesical bacillus Calmette-Guérin (BCG) fails in a considerable proportion of non-muscle invasive bladder cancer (NMIBC) patients despite treatment per recommended protocol. This real-world study aimed to understand the current patterns of treatment and disease management for the broad BCG-unresponsive NMIBC patient population, alongside collecting sufficient data on patients who do not undergo cystectomy., Methods: This was a multicenter, retrospective survey of physicians treating BCG-unresponsive NMIBC patients. Data were collected in eight countries - France, Germany, Spain, Italy, United Kingdom, United States, China, and Japan - between January and May 2019. The study consisted of a short online physician survey and a retrospective chart review of eligible BCG-unresponsive NMIBC patients. Physicians abstracted chart data for the last 10 (five patients in Japan) eligible BCG-unresponsive NMIBC patients meeting the inclusion criteria, and the data were analysed for all countries combined using descriptive statistics. Country-specific analyses were also carried out, as appropriate., Results: Overall, 508 physicians participated in the study. Almost one-quarter (22.9%) of physicians' current NMIBC patient caseload was BCG-unresponsive, whereby BCG therapy was no longer considered an option. Half of physicians (49.4%) did not regularly use biomarker tests in their practice, with particularly few physicians undertaking biomarker testing in Spain and Japan. Biomarker testing varied considerably, with the proportions of physicians selecting 'none' ranging from 11.4% in China to 70.3% in Japan. Physicians reported transurethral resection of the bladder tumor (TURBT) and BCG as the most common current treatments received by their patients. Chemotherapy and anti-PD-L1 treatment options were considered impactful new therapies by 94.7% and 90.0% of physicians surveyed in this study, respectively., Conclusions: The most common treatments received by patients in this study were TURBT and BCG. Emerging new treatments are driven by exploring biomarkers, but in real-world clinical practice only half of physicians or fewer regularly tested their NMIBC patients for biomarkers; PD-1/PD-L1 was the most common biomarker test used. Most physicians reported that, in addition to chemotherapy, anti-PD-L1 was an impactful new therapy., (© 2022. The Author(s).)

Introduction: We evaluated the real-world healthcare resource utilization (HRU) and costs among patients with high-grade non-muscle invasive bladder cancer (HG-NMIBC) following Bacillus Calmette-Guérin (BCG) therapy., Methods: Patients aged ≥ 65 years diagnosed with HG-NMIBC between 2008 and 2015 who received adequate BCG induction and were identified in the SEER-Medicare database. Those who received intravesical chemotherapy or radical cystectomy within 12 months of the last BCG induction dose, and had ≥ 6 months of data availability after treatment (index date), were included. Annualized HRU and mean medical costs (2020 United States dollars) were estimated and compared between patients with versus without progression. Inverse probability of treatment weighting was used to adjust for differences in baseline characteristics., Results: Of 986 patients diagnosed with HG-NMIBC who met the inclusion criteria, 257 (26.1%) progressed; the mean ages were similar between patients who did and did not progress (77.6 vs. 77.0 years). The overall population had a mean of 0.96 [standard deviation (SD): 1.18] inpatient admissions, 6.47 (11.40) hospitalization days, 1.38 (2.19) emergency department (ED) visits, and 48.03 (44.97) outpatient visits per patient-year during the study period; total annualized costs per patient post-BCG were $39,102 ($44,244). Patients experiencing progression had significantly higher mean numbers of inpatient admissions [1.61 (SD 1.40) vs. 0.72 (0.99)], hospitalization days [11.77 (14.96) vs. 4.59 (9.29)], ED visits [2.34 (2.92) vs. 1.03 (1.76)], and outpatient visits [65.97 (44.72) vs. 41.63 (43.09)] per patient-year compared with patients without progression (all p < 0.05). Total mean annualized costs per patient after BCG among those who progressed [$65,668 (SD $53,943)] were more than double compared with patients who did not [$29,780 ($36,425)]., Conclusions: Existing treatments for HG-NMIBC after BCG therapy are associated with substantial HRU and medical costs, particularly after progression. Novel treatments and earlier detection are needed to reduce progression rates and associated costs in this difficult-to-treat population.