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Abstract Background Intravesical Bacillus Calmette–Guérin (BCG) is used as a standard adjuvant therapy for non-muscle invasive urothelial cancer. Most patients tolerate the treatment well, with mild side effects. Systemic complications are extremely rare, occur due to BCG dissemination and are associated with immunocompromised state and urothelial breach. Case presentation We present a case of a 78-year-old male, a former smoker, with history of non-muscle invasive urothelial carcinoma status post partial resection followed by intravesical BCG therapy. An autopsy was performed due to the sudden nature of his death. Autopsy showed multiple necrotizing granulomas in the brain, atrium, ventricles, lungs, kidneys, and urinary bladder. Stains for acid-fast bacilli and fungi were negative. In addition, bilateral lungs showed evidence of bronchopneumonia secondary to cytomegalovirus. Conclusion Granulomatous myocarditis arising from BCG therapy is extremely rare. Our patient with urothelial cancer treated with BCG developed multiorgan granulomas, most likely due to a hypersensitivity reaction to intravesical BCG. Arrhythmia induced by granulomatous myocarditis was the cause of his death. Although there have been few cases of systemic BCG-osis causing fatal sepsis leading to death, a cardiac cause of death is unique.

Failure, intolerance, or shortage of bacillus Calmette-Guerin (BCG) treatment for patients with high-risk (HR) non-muscle invasive bladder cancer (NMIBC) leave many facing the prospect of radical cystectomy (RC). However, despite the lack of large-scale randomized controlled studies with single-agent intravesical gemcitabine (Gem), it has emerged as a popular salvage agent after BCG failure or even a treatment alternative to BCG. 1. Characterization of treatment regimen details pertaining to single-agent intravesical adjuvant Gem use among disease states of NMIBC characterized by risk and BCG exposure. 2. Comparison of safety and efficacy of Gem according to risk category, type of tumor (papillary vs. carcinoma in situ (CIS)), and tumor grades. Two randomized studies in early BCG failure disease demonstrate that single-agent Gem has superior efficacy versus repeated BCG therapy or mitomycin C. Studies enrolling patients with predominantly papillary disease without CIS, intermediate-risk (IR) disease, and less BCG exposure appear to derive the highest benefits from adjuvant Gem in terms of recurrence and progression. However, studies with cohorts enriched for a predominance of CIS, HR disease and/or more extensive BCG failure have poorer 2-year recurrence free survival and a somewhat higher risk of progression and RC. [ABSTRACT FROM AUTHOR]

Background: Photodynamic therapy (PDT) is a promising treatment for nonmuscle-invasive bladder cancer (NMIBC), we conducted this systematic review to comprehensively assess its efficacy and safety. Methods: A comprehensive literature research was conducted using PubMed, Web of Science, and Scopus, and studies reporting the safety and efficacy of PDT in NMIBC were included. Complete response (CR) rates, recurrence-free survival (RFS) at different time points, and complication incidences were extracted and synthesized. Pooled results were presented as rates with a 95% confidence interval (95% CI). Results: Overall, 28 single arm studies were included in the meta-analysis. For unresectable NMIBC, therapeutic PDT achieved CR in 68% (95% CI: 59%-77%) of patients. Among these CR cases, 71% (95% CI: 56%-85%) and 38% (95% CI: 12%- 64%) have a RFS longer than 12 and 24 months, respectively. For Tis patients, the CR rate was 68% (95% CI: 56%-80%), and 84% (95% CI: 48%-100%) and 13% (95% CI: 1%-32%) have a RFS longer than 12 and 24 months. For patients with resectable tumors, post-resection adjuvant PDT could provide a 12 and 24 months RFS in 81% (95% CI:76%-87%) and 56% (95% CI:41%-71%) of them. Especially, for NMIBC patients who failed BCG therapy, adjuvant PDT could still achieve a 1-year and 2-year RFS in 68% (95% CI:51%-86%) and 56% (95% CI:32%- 81%) patients. The complications were mostly mild and transient, including lower urinary tract symptoms and photosensitivity. Conclusion: Both therapeutic and adjuvant PDT present satisfying safety and efficacy for NMIBC, including these cases that are resistant to the standard of care. As a promising option for NMIBC, PDT deserves further exploration by future high-quality research. [ABSTRACT FROM AUTHOR]

Introduction. Transurethral resection of bladder tumor (TURBT) is the gold standard treatment for patients with non-muscle invasive bladder cancer (NMIBC). However, the high recurrence rate after TURBT makes necessary not only regular following to reveal recurrence disease timely, but it also talks about a necessity of adjuvant antitumor therapy in some cases, that allows to prevent disease recurrence and progression. In this regard, patients belonging to high- and sometimes intermediate- risk progression groups are shown to undergo postoperative adjuvant intravesical Bacillus Calmette–Guérin (BCG) therapy. Despite the long experience of using BCG therapy for NMIBC treatment the question of the existence of possible prognostic markers and response predictors to intravesical BCG therapy remains open.Objective. To review cutting-edge data on different markers that can be used as predictive response markers to ongoing intravesical BCG therapy in NMIBC-patients.Materials and methods. A literature search was conducted using PubMed/ Medline and Google Scholar databases. We used terms 'bladder cancer', 'non-muscle-invasive bladder cancer' in conjunction with 'recurrence', 'progression', 'BCG', 'intravesical therapy', 'immune response', 'molecular markers' to choose relevant articles published between 2000 and 2022.Results. Clinical and pathological characteristics of the tumor and the patient himself remain leading in predicting the response to intravesical BCG therapy in NMIBC-patients. However, to improve the effectiveness of assessing the risk of developing adverse BC outcomes and choosing the most appropriate strategy for monitoring and treatment in each case, it is necessary to introduce additional assessment parameters. Molecular and genetic markers could be considered as such parameters, make it possible to reveal differences between tumors at a deeper level.Conclusion. Currently, there are no markers that have high-evidence in predicting response to intravesical BCG therapy in NMIBC-patients compared with the cliniсal and pathological characteristics of the tumor and the patient himself. The clearer awareness of molecular genetic pathways of BC pathogenesis, the mechanism of BCG antitumor effect will make it possible to competently select markers that have the highest specificity for BC, which will increase the predictive ability of currently existing tools to assess the risks of BC recurrence and progression.

Bladder cancer is the 10th most common cancer worldwide. Approximately 75% of patients with bladder cancer will present with non-muscle invasive disease. Patients are usually treated with transurethral resection of bladder tumor (TURBT), in addition to adjuvant intravesical therapy (chemotherapy or anti-cancer immunotherapy with Bacillus Calmette Guerin- BCG) for those at intermediate-risk and high-risk of recurrence and progression. For many years, urine has been thought to be "sterile"; however, advanced microbiological and molecular techniques, including 16S ribosomal RNA (16S rRNA) sequencing, have negated that previous paradigm and confirmed the presence of a urinary microbiome. The urinary microbiome has been associated with several urological diseases, including interstitial cystitis, urgency urinary incontinence, neurogenic bladder dysfunction, and others. More recently, many reports are emerging about the role of the urinary microbiome in urothelial carcinogenesis, including gender disparity in bladder cancer and responses to treatments. The urinary microbiome may serve as a biomarker that can help with risk stratification as well as prediction of the response to intravesical therapies. However, the microbiome literature has been hampered by the lack of a unified standardized methodology for sample collection, type, preservation, processing, as well as bioinformatics analysis. Herein we describe and critique the literature on the association between urinary microbiome and bladder cancer and highlight some of the future directions. [ABSTRACT FROM AUTHOR]

Background/aim: Intravesical BCG treatment fails inexplicably in 30%-45% of patients for high-grade nonmuscle-invasive bladder cancer (NMIBC). We aimed to investigate the role of PD-1/PD-L1 interaction on BCG failure of high-grade NMIBC and to identify biomarkers for predicting BCG responsive cases. Materials and methods: Thirty BCG responsive and 29 nonresponsive NMIBCs were included in the study. Expressions of PDL1(SP-263), MSH2, MSH6, PMS2, and MLH1 were evaluated on pre- and post-BCG transurethral resection (TUR-B) specimens by immunohistochemistry. PD-L1(SP-263) expression was categorised as negative/low, high. DNA mismatch repair protein (MMR) expressions were classified as "reduced" if ≤30% of nuclei stained, "preserved" if >30% of nuclei stained. Microsatellite instability (MSI) testing was performed by PCR using five mononucleotide markers. Results: Reduced DNA MMR protein expression was found to be significantly higher in the pretreatment biopsies of BCG-responsive group than the BCG nonresponsive tumour group (p = 0.022). PD-L1 expression did not show any significant difference between the pre- and posttreatment TUR-B specimens of the BCG nonresponsive tumour group or between the pretreatment TUR-B specimens of BCG nonresponsive and the BCG responsive groups (p = 0.508, p = 0.708, respectively). Conclusion: Immune escape of tumour cells by PD-1/PD-L1 interaction does not seem to have any role in BCG failure of NMIBCs. Reduced MMR expression may help to determine cases that will respond well to BCG therapy. A better antitumour activity of BCG in NMIBCs with reduced MMR expression may be related to the ongoing accumulation of cancer neoantigens in correlation with increased tumour mutation load as a result of DNA repair defects. [ABSTRACT FROM AUTHOR]

Teaching Point: Benign granulomatous prostatitis mimics prostate cancer on MRI. Peculiar urological history of a patient undergoing prostate MRI helps sorting out that differential, such as a treatment with topic Bacilli Calmette-Guerin instillations.

Teaching point: Mycobacterium bovis spondylodiscitis is a rare, often delayed, complication of intravesical Bacillus Calmette-Guérin therapy for bladder cancer.

Bladder cancer is the 10th most common cancer worldwide. Approximately 75% of patients with bladder cancer will present with non-muscle invasive disease. Patients are usually treated with transurethral resection of bladder tumor (TURBT), in addition to adjuvant intravesical therapy (chemotherapy or anti-cancer immunotherapy with Bacillus Calmette Guerin- BCG) for those at intermediate-risk and high-risk of recurrence and progression. For many years, urine has been thought to be “sterile”; however, advanced microbiological and molecular techniques, including 16S ribosomal RNA (16S rRNA) sequencing, have negated that previous paradigm and confirmed the presence of a urinary microbiome. The urinary microbiome has been associated with several urological diseases, including interstitial cystitis, urgency urinary incontinence, neurogenic bladder dysfunction, and others. More recently, many reports are emerging about the role of the urinary microbiome in urothelial carcinogenesis, including gender disparity in bladder cancer and responses to treatments. The urinary microbiome may serve as a biomarker that can help with risk stratification as well as prediction of the response to intravesical therapies. However, the microbiome literature has been hampered by the lack of a unified standardized methodology for sample collection, type, preservation, processing, as well as bioinformatics analysis. Herein we describe and critique the literature on the association between urinary microbiome and bladder cancer and highlight some of the future directions.

Granulomatous prostatitis (GP) is a rare and benign inflammatory condition of the prostate, often mimicking prostate cancer (PCa) in clinical and radiological evaluations. This study examines the characteristics and diagnostic challenges of GP in a cohort of 12 patients who received Bacillus Calmette-Guérin (BCG) therapy following treatment for non-muscle-invasive bladder urothelial carcinoma. In this case series, we analyze their clinical presentations, MRI findings, and histopathological results. Patients presented with elevated PSA levels and firm or nodular prostates on digital rectal examination, complicating the differentiation from PCa. Multiparametric MRI showed lesions with hypointensity on T2-weighted images, hypersignal on diffusion-weighted imaging and hyposignal on the apparent diffusion coefficient map, further mimicking malignancy. Histopathological examination remains the gold standard for diagnosing GP, distinguishing it from PCa through the identification of granulomas and associated inflammatory cells. This study underscores the importance of awareness and accurate diagnosis of GP to avoid unnecessary biopsies and treatments, highlighting the need for a multidisciplinary approach combining clinical, imaging, and pathological data., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Guerra et al.)

Purpose: To evaluate the outcomes of high-grade T1 non-muscle-invasive bladder cancer treatment (NMIBC) in elderly patients over 80 years of age. Methods: This is a retrospective single tertiary-centre study. Medical records of patients with T1 high-grade NMIBC treated with transurethral resection of the bladder tumour (TURBT) were reviewed. Among 269 patients with high-grade T1 NMIBC, 74 individuals were over 80 years of age at the time of surgery. Finally, 67 patients met the inclusion criteria. Results: Only 47.8% of patients (N = 32) received at least five of the six instillations of the BCG immunotherapy induction course. Oncological outcomes were compared between patients who received at least the induction course of BCG and non-BCG-treated patients matched to each other based on age and Charlson comorbidity index. Thirty case–control pairs were included in the final analysis. Rates of disease recurrence (80% vs. 53%) and cancer-specific mortality (40% vs. 10%) were significantly higher in the group of patients who did not receive BCG. BCG therapy, Charlson comorbidity index, haemoglobin concentration and the number of tumours > 3 in TURBT constituted independent prognostic factors for cancer-specific survival (CSS). Conclusion: BCG should be strongly recommended to patients with T1HG NMIBC despite advanced age and comorbidities. Already BCG induction improves CSS and reduces the recurrence rate in octogenarians with T1HG bladder cancer. [ABSTRACT FROM AUTHOR]

Given the systemic immunogenic effects of Bacillus Calmette-Guérin (BCG) therapy in patients with bladder cancer and its non-specific immunogenic effects in viral respiratory diseases, we aimed to study severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in bladder cancer patients with a history of BCG therapy. In the present study, all bladder cancer survivors with a history of BCG therapy were identified and included in the study according to the data recovered from the UORC (Uro-Oncology Research Center) registry database. These patients were followed up in terms of acquiring coronavirus disease 2019 (COVID-19). Among the studied patients, 102 eligible bladder cancer patients with a history of BCG therapy entered the study. The males constituted the majority of the patients (86.3%), and more than half of the study population (55.9%) were above 65 years old. Among the understudy patients, 12.7% were confirmed for COVID-19. The study results did not show a statistically significant association between the time and number of BCG therapy courses and SARS-CoV-2 infection. Although no statistically significant association was observed between receiving BCG therapy and developing COVID-19, the infection rate in patients who had recently received BCG therapy was lower than those who had received therapy more than a year ago. [ABSTRACT FROM AUTHOR]

Background: Granulomatous prostatitis (GnP) is an interesting complication of bacillus Calmette–Guérin (BCG) therapy as it mimics prostate cancer on clinical, biochemical and imaging examinations. In the era of multiparametric prostate MRI (mpMRI), differentiation of GnP from prostate cancer on imaging is essential. Case presentation: We report a case of post-BCG GnP in a patient with nonmuscle invasive bladder cancer, presenting with a prostate-specific antigen level of 21.6 ng/ml and prostate imaging reporting and data system (PI-RADS) 5 peripheral lesions. A mpMRI performed 6 months before showed a score 2 of PI-RADS. Conclusion: The comparison of mpMRI images before and after BCG administration gives urologists, oncologists and radiologists a precise idea of the mpMRI changes that occur following BCG administration to eventually prevent unnecessary biopsies in future patients.

Introduction: Recurrence of non-muscle-invasive bladder cancer (NMIBC) occurs in 70% of cases, and the risk of progression to muscle-invasive bladder cancer is 20%. Intravesical BCG therapy is indicated in order to increase relapse-free survival in patients with intermediate and high-risk NMIBC. We carried out a survey of Russian urologists on the use of intravesical BCG therapy in the treatment of NMIBC, and also presented the regulatory framework for the use of BCG for the treatment of bladder cancer., Aim: To evaluate the use of intravesical BCG therapy among urologists of the Russian Society of Urology., Results: According to the results of a survey of 145 urologists, 46 (32%) do not prescribe BCG therapy to patients with NMIBC. Most of them (63%) have more than 10 years of experience. The main reasons why urologists do not recommend BCG therapy are the lack of conditions (74%), an absence of the drug (20%), fear of adverse reactions or development of tuberculosis infection of themselves and medical staff (2%), absence of recommendations for BCG therapy from an oncological dispensary (2%). The most commonly prescribed drugs for intravesical instillation areImuron-vac (69%), Uro-BCG-medac (29%), OncoTICE BCG (2%). Only 8% of doctors did not report difficulties during therapy. The most common reason for the refusing from BCG therapy was the lack of conditions in the medical facilities., Conclusions: According to the survey, one third of doctors do not prescribe BCG therapy due to the lack of conditions or a shortage of the drug. An increase of relapse-free survival of patients with NMIBC is possible by providing conditions for intravesical immunotherapy.

Teaching point: Mycobacterium bovis spondylodiscitis is a rare, often delayed, complication of intravesical Bacillus Calmette-Guérin therapy for bladder cancer. [ABSTRACT FROM AUTHOR]

Teaching Point: Benign granulomatous prostatitis mimics prostate cancer on MRI. Peculiar urological history of a patient undergoing prostate MRI helps sorting out that differential, such as a treatment with topic Bacilli Calmette-Guerin instillations. [ABSTRACT FROM AUTHOR]

Many patients with non-muscle-invasive bladder cancer (NMIBC) failed intravesical BCG therapy. Currently, radical cystectomy is the recommended standard of care for those patients. There is unfortunately no effective other second-line therapy recommended. In this review, we present the topics of BCG unresponsive NMIBC; definition, prognosis, and further treatment options: immunotherapy, intravesical chemotherapy, gene therapy, and targeted individualized therapy. There are major challenges of the management of NMIBC who failed BCG therapy as many patients refuse or are unfit for radical cystectomy. Multiple new modalities currently under investigation in ongoing clinical trials to better treat this category of patients. Immunotherapy, especially PD-1/PD-L1 inhibitors, offers exciting and potentially effective strategies for the treatment of BCG unresponsive NMIBC. As the data expands, it is sure that soon there will be established new guidelines for NMIBC. [ABSTRACT FROM AUTHOR]

The authors present the case of a female patient with a tumor of segment VII of the liver, which was postoperatively identified as a tuberculous granuloma. The patient was admitted for elective surgery for a liver tumor, which had been diagnosed a few months before. Computed tomography and nuclear magnetic resonance were performed, based on which focal nodular hyperplasia was suspected. Thirteen years prior to admission the patient had undergone a transurethral resection of superficial bladder carcinoma, followed by adjuvant intravesical Bacillus Calmette-Guérin (BCG-therapy). Upon surgery, segment VII of the liver was resected; postoperative course was uneventful. After the identification of granuloma, the patient was referred to a phthysiatric clinic for further diagnostics and treatment. The authors have deemed this case worthy of reporting primarily due to the exceptionally long period between the completion of BCG therapy and the onset of hepatic tumor. [ABSTRACT FROM AUTHOR]

Summary: To date, intravesical instillation of Bacillus Calmette–Guérin (BCG) is the standard adjuvant treatment for most intermediate- and all high-risk bladder nonmuscle invasive urothelial carcinomas (NMIBC) after complete transurethral resection. Although BCG immunotherapy successfully reduces both recurrence and progression rates in affected patients, there are certain limitations associated with its application. Major issues are the relatively high failure rate in up to 40% of patients, the adverse effects of the instillations, and the shortage in BCG supply, requiring concerted alternative strategies. Furthermore, radical cystectomy, the currently suggested salvage treatment for patients failing BCG therapy, is often an overtreatment for a significant proportion of patients. Checkpoint inhibitor (CKI) immunotherapy has proven to be highly effective in a subset of advanced bladder cancer patients and is currently tested in various clinical scenarios alone and in combination with BCG in the adjuvant setting. CKIs' mechanism is to a large part similar to that reported for BCG—that is, activation of the immune system and elimination of cancer cells in the bladder. Furthermore, CKIs could synergistically enhance the effect of the immune system attracted by BCG and are generally associated with acceptable rates of adverse reactions. Thus, they may represent an ideal alternative to or partner for BCG immunotherapy in NMIBC. In case the recent encouraging results of currently ongoing trials translate into tangible improved outcomes, the combination of CKI and BCG immunotherapy can be expected to represent a valid treatment strategy for well-selected nonmuscle invasive bladder cancer patients in the future. [ABSTRACT FROM AUTHOR]

Abstract The regulation of immune responses occurring during Bacillus Calmette-Guerin (BCG) therapy need to be better scrutinized in order to identify new targetable pathways for non-muscle invasive bladder cancer treatment. Immunoregulatory mechanisms have emerged as key players in various cancers. While T lymphocytes are crucial for the control of tumor growth, they often include regulatory subsets known to restrain their anti-tumor activity. In this prospective study, we assessed conventional regulatory T cells (cTregs) and PD-L1-expressing CD4 T cells (PD-L1+ Tregs) levels in blood and urine of urothelial cancer (UCa) patients undergoing BCG treatment. Local cTregs were found at higher frequencies than their counterpart in the periphery and induced by bladder tumor cells in vitro. Interestingly, while circulating PD-L1+ Tregs were hardly detectable in the blood of healthy donors and UCa patients, substantial levels were found in patients' urine. In vitro experiments suggested that BCG infection of urothelial cells could induce PD-L1+ Tregs, partially via an interferon-β-mediated mechanism. Of note, high level of Tregs in urine was associated with rapid recurrence following BCG therapy. Our findings demonstrate that T lymphocytes recruited during BCG therapy encompass a significant fraction of regulatory cells including a non-classical source of PD-L1 and reinforce treatment strategies combining BCG with PD-1/PD-L1 checkpoint inhibitors as promising approaches for non-muscle invasive bladder cancer. Patient summary We investigated the presence of particular immune cell types in the urine of bladder cancer patients undergoing Bacillus Calmette-Guerin (BCG) therapy. We identified a cell type that is strongly enriched in the urine after BCG instillation and that may favor tumor recurrence. This immune subpopulation might be targeted for bladder cancer treatment. Take Home Message Regulatory T-cell subsets are particularly enriched during Bacillus Calmette-Guerin (BCG) therapy, specifically those expressing PD-L1. In this regard, data provide novel arguments for combining BCG therapy with checkpoint blockade targeting the PD-L1/PD-1 axis to improve non-muscle invasive bladder cancer treatment. [ABSTRACT FROM AUTHOR]

Introduction: Bladder cancer (BCa) is the fifth most frequently diagnosed cancer worldwide and is, in fact, the most expensive cancer on a per-patient to treat basis. There is a critical need to implement new tests into clinical practice to improve the quality of clinical care, decrease unnecessary invasive therapies and ultimately save costs. Currently, no molecular or genetic biomarker has been widely integrated into daily clinical practice. However, major milestones have been achieved in our understanding of the molecular alterations in BCa that will provide the basis for integrating molecular and genetic biomarkers into clinical decision making to guide management. Clinical implementation of such novel molecular and genetic concepts is the cornerstone in an effort to usher the age of precision medicine into patient care. Areas covered: In this review, the authors discuss the emerging role of molecular biomarkers in patients receiving BCG immunotherapy as well as neoadjuvant and adjuvant chemotherapy in BCa. Expert commentary: Molecular predictive and prognostic biomarkers in BCa are promising diagnostic options that will pave the way for molecular-based personalized medicine. [ABSTRACT FROM AUTHOR]

Bacillus Calmette–Guerin (BCG) therapy for non-muscle invasive bladder cancer (NMIBC) can significantly reduce the risk of recurrence and progression. However, BCG therapy may fail in up to a half of treated patients and may also cause toxicities. Biomarkers to predict the effectiveness of BCG therapy are desired to pre-select patients for BCG therapy to maximize efficacy while avoid unnecessary toxicity. Twelve cytokines were measured in 100 blood and 112 urine samples using cytokine antibody array and correlated with recurrence-free survival in overall and BCG-treated NMIBC patients. Of the 12 cytokines, interleukin (IL) -2, IL-8, IL-10, tumor necrosis factor (TNF)-α, granulocyte-macrophage colony-stimulating factor (GM-CSF) and interferon (IFN)-γ were measurable in more than 30% of peripheral blood leukocyte (PBL) samples. Only IL-8 in PBL was found to be significantly associated with tumor recurrence, especially in those who receiving BCG therapy (hazard ratio [HR] = 4.24; 95% confidence interval [95%CI] = 1.65–10.88; p = 0.003). The median recurrence-free survival time for BCG-treated patients with high baseline IL-8 levels were much shorter than those with low IL-8 levels (7.9 vs. >78.4 mo, p = 0.004). Furthermore, consistent associations between urinary IL-8 levels and tumor recurrence in patients receiving BCG therapy were observed in 58 pre-BCG and 54 long-term post-BCG-treated urine samples (both p ≤ 0.005). High urinary baseline IL-8 level also predicted shorter time to tumor recurrence in NMIBC patients (both p ≤ 0.004). By using antibody array-based technology in two separate cohorts of NMIBC patients, we found that PBL and urinary baseline IL-8 levels were significantly associated with tumor recurrence after BCG therapy.

Background: Adjuvant therapy with bacillus Calmette-Guerin (BCG), a live attenuated strain of Mycobacterium bovis, has become the treatment of choice for low-risk superficial bladder carcinoma following transurethral resection of the bladder. Complications following vesical BCG instillations are uncommon but, in some cases, severe side-effects can occur such as sepsis or mycotic aneurysm. Besides usual laboratory techniques used for the diagnosis of Mycobacterium tuberculosis complex (MTBC) infections (smear microscopy and cultures), commercial immunochromatographic assays detecting MBP64, a 24 kDa M. tuberculosis complex-specific secretory protein, can rapidly distinguish MTBC and non-tuberculosis mycobacteria (NTM). MPB64 is found in M. tuberculosis, M. bovis and some but not all substrains of M.bovis BCG. Therefore, these immunochromatographic tests can lead to false negative results and delayed bacteriological diagnosis depending on the presence or absence of MPB64 protein in BCG substrains used for intravesical therapy. Case presentation: We report the case of a 78-year-old male patient who was admitted to the hospital because of a 1-month history of unexplained fever, thrill, weight-loss and general malaise. His past medical history was marked by a non-muscle-invasive bladder carcinoma treated by transurethral resection followed by BCG instillations (Oncotice, Merck, USA). The patient was initially treated for a urinary tract infection but as fever persists after 72 h of antibiotherapy, urinary tract ultrasound was performed and revealed a large abdominal aortic aneurysm confirmed by computed tomography. Surgery was performed after multidisciplinary discussion. Direct smear of perioperative samples revealed acid-fast bacilli and both solid and liquid cultures were massively positive. Rapid identification of the positive mycobacterial culture was performed using an immunochromatographic assay based on the detection of the Mycobacterium tuberculosis MPB 64 antigen. The result was negative for Mycobacterium tuberculosis complex. After review of the medical record, a polymerase chain reaction (PCR) was performed and gave a positive result for M. tuberculosis complex. Anti-tuberculosis therapy was started immediately and the patient evolved favorably. Conclusions: Through this case, we showed how the utilisation of MPB64 immunochromatographic assays can provide misleading information due to the variable presence of this protein among the different BCG strains. This case further illustrates the utility of rapid TB complex-specific PCR assays which provide a more reliable identification of all MTBC species. [ABSTRACT FROM AUTHOR]

Objectives: Immunotherapy with BCG (Bacille Calmette-Guérin) after transurethral resection of the bladder tumor represents a highly effective primary treatment for intermediate and high-risk superficial bladder cancer. The effectiveness of this therapy has been documented, but its mechanism of action is not clear yet. In the present study, we investigated the changes of dendritic cells (DC) numbers in peripheral blood and urine of patients with superficial bladder cancer undergoing BCG intravescical therapy Material and method: We have enumerated plasmacytoid and myeloid DCs in the peripheral blood and in the urine of patients with bladder cancer in order to clarify the role of these cells in the evolution of the disease and the effect of therapy. DCs in blood and urine samples were assessed using the single-platform TruCOUNT assay with monoclonal antibodies. The study population included 37 healthy donors and 13 patients with diagnosis of primitive superficial bladder cancer. Results: At the time of diagnosis a reduction of blood DCs was found in patients as opposed to healthy donors, while DCs were not found in the urine in the same way as in healthy subjects. Six of these patients were followed before and after weekly and monthly instillations of BCG. In the peripheral blood, we observed an immunological recovery of DCs from the third weekly instillation up to the sixth. In the urine of patients, we didn’t find mDCs or pDCs at T0, but we found a statistically significant change from the third instillation up to the sixth. On the contrary, we didn’t find mDCs in urine during monthly instillation. Conclusions: DC Count could be used in the monitoring of patients undergoing BCG therapy. Immunological restoration of mDC numbers in peripheral blood and the efflux in urine could be important for confirming the effectiveness of BCG instillation.

Intravesical bacillus Calmette-Guerin (BCG) therapy is an effective and safe immunotherapy for superficial bladder cancer. However, reactive arthritis (ReA) is reported as an adverse event in about 0.5-1% of patients receiving intravesical BCG therapy. ReA is known as a kind of spondyloarthritis, the main pathological finding of which is enthesitis. Here we report a patient with ReA induced by intravesical BCG therapy for bladder cancer, in whom the diagnosis of ReA was supported by ultrasonographic findings of enthesitis and synovitis. A 69-year-old male was diagnosed with carcinoma in situ of the bladder and treated with intravesical BCG therapy. After the third intravesical BCG injection, pain and swelling appeared in both wrists. Ultrasonographic examination revealed not only intra-articular synovitis in the bilateral wrist joint, wrist flexor tenosynovitis, and wrist extensor tenosynovitis, but also enthesitis of the flexor carpi radialis tendon (FCR). The severe enthesitis of the FCR in both wrists was considered to be an important finding that supported the diagnosis in this patient. Thus, we diagnosed this case as ReA induced by intravesical BCG therapy. In clinical practice, ReA is often difficult to distinguish from seronegative rheumatoid arthritis and other rheumatic diseases. Ultrasonographic findings of enthesitis may support a definitive diagnosis for these patients. [ABSTRACT FROM AUTHOR]

BCG therapy is used as a treatment in bladder cancer. Intravesical administration of Bacillus Calmette-Guérin is used as a treatment method in superficial bladder cancer. While it is commonly effective, some serious side effects may occur. We hereby report a 65-year-old man who developed granulomatous hepatitis as a complication following BCG therapy. He was treated successfully with antitubercular therapy and prednisolone.

Bladder cancer (BCA) is one of the most common cancers. In 2010 in Poland, 6296 people developed bladder cancer and 3110 people died of it. Immunotherapy with BCG (Bacillus Calmette-Guérin) is by far the most effective adjuvant therapy. Noninfiltrating muscle membrane changes, that is, stages Ta, Tis and T1 qualify for BCG immunotherapy. BCG immunotherapy comprises series of bladder instillations, containing attenuated strain of Mycobacterium bovis. The effectiveness of immunotherapy in non-invasive bladder cancer is 70% 5-year survival without recurrence of the tumor. The treatment leads to a reduction of the residual tumor mass, but also to the delay and/or prevention of relapse, disease progression and ultimately death. Cytokines, as key mediators of immune response, play an important role in the pathogenesis of bladder cancer, which occurrence is stimulated by the inflammatory process. BCG immunotherapy provokes an intensive immunological response by the increase of cytokine production. Genetic variants determine inter-individual differences in the incidence of this cancer, as well as the response to the therapy. This is evidenced by the presence of differences in genetic variants of cytokines correlated with the varied risk of bladder cancer incidence. It is believed that concentrations of particular cytokines in urine after installation of BCG may indicate response to the therapy. Increased levels of Th1 cytokines - IFN-γ, IL-2 and TNF-α are correlated with longer survival time without recurrence, whereas high levels of Th2 cytokines such as IL-10, predict unsuccessful BCG therapy. [ABSTRACT FROM AUTHOR]

Objectives: Immunotherapy with BCG (Bacille Calmette-Guérin) after transurethral resection of the bladder tumor represents a highly effective primary treatment for intermediate and high-risk superficial bladder cancer. The effectiveness of this therapy has been documented, but its mechanism of action is not clear yet. In the present study, we investigated the changes of dendritic cells (DC) numbers in peripheral blood and urine of patients with superficial bladder cancer undergoing BCG intravescical therapy Material and method: We have enumerated plasmacytoid and myeloid DCs in the peripheral blood and in the urine of patients with bladder cancer in order to clarify the role of these cells in the evolution of the disease and the effect of therapy. DCs in blood and urine samples were assessed using the single-platform TruCOUNT assay with monoclonal antibodies. The study population included 37 healthy donors and 13 patients with diagnosis of primitive superficial bladder cancer. Results: At the time of diagnosis a reduction of blood DCs was found in patients as opposed to healthy donors, while DCs were not found in the urine in the same way as in healthy subjects. Six of these patients were followed before and after weekly and monthly instillations of BCG. In the peripheral blood, we observed an immunological recovery of DCs from the third weekly instillation up to the sixth. In the urine of patients, we didn't find mDCs or pDCs at T0, but we found a statistically significant change from the third instillation up to the sixth. On the contrary, we didn't find mDCs in urine during monthly instillation. Conclusions: DC Count could be used in the monitoring of patients undergoing BCG therapy. Immunological restoration of mDC numbers in peripheral blood and the efflux in urine could be important for confirming the effectiveness of BCG instillation. [ABSTRACT FROM AUTHOR]

Introduction: Altered p53 gene product correlates with the stage and grade of bladder tumor, but its value as a predictor of BCG response has been disappointing. In order to revisite the prognostic value of pretreatment p53 nuclear overexpression for the BCG response, we studied a large cohort of consecutive patients with superficial bladder cancer treated with BCG.Methods: From 1988 to 2001, 102 patients with a history of multifocal, recurrent, and/or high-risk papillary transitional cell carcinoma or carcinoma in situ, were treated for the first time with BCG. p53 immunostaining was performed on paraffin-embedded tissues using monoclonal antibody DO7 and an automated immunostainer. Special attention was paid to the conditions of tumor fixation. p53 overexpression was defined as more than 20% tumor cells with p53-stained nuclei.Results: Immunostaining was significantly higher for Ta/T1 G3 ± Cis (p<0001), tumoral substage T1b (p=0.001), grade 3 (p=0.0001), and Cis (p=0.02). Times to recurrence, progression and cancer death were shorter among patients with p53 overexpression (p=0.03; p<0.0001; p=0.0003). In multivariate analysis, p53 overexpression was an independent predictor of recurrence (p=0.0003) [RR=0.15; 95%CI, 0.06 to 0.42].Conclusion: Pretreatment p53 nuclear overexpression in superficial bladder tumors is associated with a high risk of disease recurrence, progression and cancer death after BCG therapy. Applying antibody DO7 with an automated immunostainer and stringent fixative conditions, p53 nuclear immunostaining yields clinically relevant information and may be a useful tool for selecting patients with superficial bladder cancer who might be resistant to BCG. [Copyright &y& Elsevier]

The authors report 24 patients presenting a transitional tumor of bladder pT1G3 collected between January 1996 and December 2000. They represent 19% of the superficial tumors of bladder. Two patients had of straightaway a cystectomy after resection for an unverifiable tumor by endoscopy and another after a second resection discovering a real pT2. Only 5 patients received a BCG therapy is 24% of the cases. A recurrence without progression has been noted in 38% of the cases and a progression in 19% of the patients. These last patients had a cystectomy and with a follow-up to 28 months, no recurrence has been noted. [Copyright &y& Elsevier]

Intravesical bacillus Calmette-Guérin (BCG) has been shown to be an effective treatment for superficial transitional cell carcinoma (TCC) of the bladder, but the precise mechanism of action of BCG remains poorly understood. Fibronectin (FN), an important component of the extracellular matrix, has been found to play a role in BCG therapy. Some studies have shown that the soluble form of FN can compete efficiently with the matrix form of binding to the specific receptors on the bacteria and could consequently diminish the effect of BCG treatment. To evaluate a possible correlation between the urinary levels of FN and the efficacy of BCG therapy, we determined prospectively the urinary FN levels in 38 patients with TCC of the bladder and in 25 control subjects without malignancy matched for age and sex. All TCC patients were treated with transurethral tumor resection plus 6 weekly intravesical BCG instillations. After an average follow-up of 30 months, 8 patients (21.1%) had recurrent tumors, while 30 (78.9%) were free of tumor after intravesical BCG therapy. Urinary levels of FN in cancer patients have been shown to be significantly higher than controls (p < 0.001). These elevated levels were not decreased significantly after the operation (p > 0.05). It was also found that the mean urinary FN levels were not statistically significant between patients with recurrence and complete remission. The data suggest that BCG-bladder tumor cell binding is not influenced by soluble fibronectin and urinary FN may not be a ideal marker for selecting patients to BCG therapy.Copyright © 2000 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Among the growing family of inhibitory receptors regulating immunity, sialic acid-binding immunoglobulin domain-containing lectins (Siglecs) have recently emerged as immunoregulatory receptors recognizing sialylated ligands on tumor cell surface. However, their role in the immunoregulation of bladder cancer (BCa) remains unknown. Here, we determined the presence of eight Siglec ligands (SLs) on bladder nontumor and tumor cell lines. S2L, S3L, and S6L were not expressed, and few bladder tumor cell lines expressed S5L and S14L. In contrast, S7L and S10L were upregulated on all bladder tumor cell lines. We found a discrepency in S9L expression by nontumor cell lines, which is however highly expressed by bladder tumor cell lines. Notably, expression of S5L, S6L, and S14L was increased upon bacillus Calmette-Guérin (BCG) infection. Furthermore, we analyzed the expression of Siglecs on T cells from healthy donors and BCa patients. Circulating T cells only expressed Siglec-6, which is upregulated in non-muscle-invasive BCa patients. In addition, BCG therapy induced the overexpression of Siglec-6 by urinary CD8 + T cells. In vitro functional assays suggested that Siglecs may decrease cytotoxic functions of effector CD8 + T cells. Finally, analyses from two BCa datasets (The Cancer Genome Atlas and UROMOL cohorts) showed that Siglec-6 is associated with tumor progression and poor survival. Our findings indicate that Siglec-6 might be a new target for BCa treatments. PATIENT SUMMARY: We investigated the expression of Siglecs, a family of immunoregulatory receptors, in bladder cancer patients. We observed that the expression of Siglec-6 is increased on circulating and urinary T cells of non-muscle-invasive bladder cancer patients. We also showed that Siglec-6 is associated with lower survival in bladder cancer patients and might contribute to bladder cancer recurrence., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Introduction: Intravesical instillations of BCG are recommended for the treatment of high-risk non-muscle-invasive bladder cancer. However, their prolonged use remains limited by the associated potentially serious adverse effects or complications. The purpose of this article was to provide updated recommendations for the diagnosis and management of adverse events (AEs) or complications of intravesical BCG instillations., Materials and Methods: Review of the literature in Medline (http://www.ncbi.nlm.nih.gov) and Embase (http://www.embase.com) using the following MeSH keywords or a combination of these keywords: "bladder," "BCG," "complication," "toxicity," "adverse events," "prevention," and "treatment"., Results: AEs or complications of BCG included genitourinary and systemic symptoms. The most common complications (cystitis, moderate fever) should be treated symptomatically and may require adjustment to allow patients to have the most complete BCG treatment possible. Serious complications are rare but must be identified promptly because of the life-threatening nature of the disease. Their management is based on the combination of anti-tuberculosis treatments, anti-inflammatory drugs and the definitive discontinuation of BCG., Conclusion: The management of BCG AEs requires early identification, rational and effective treatment if necessary, and discussion of the continuation of treatment for each situation., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Immunohistochemical techniques were used to investigate leucocyte subpopulations in the bladders of patients with superficial transitional cell carcinoma treated with BCG Pasteur. Leucocyte subsets were enumerated with a panel of monoclonal antibodies which included CD3, CD4, CD8, TQ1, Leu7, CD15, HLA-DR, CD25, CD22. We demonstrated in the bladders of patients treated with BCG a particular lymphocyte population; the major subset was an inducer (CD4, TQ1) which was activated (CD25, HLA-DR) and associated with polymorphonuclear eosinophils. There was neither inducer of suppression nor major cytotoxic/suppressive subsets. CD8 and NK cells could not be the primary mediators of BCG activity. These data supported the hypothesis of a helper T lymphocyte activity associated with lymphokine production and activation of effector killer cells. [ABSTRACT FROM AUTHOR]

Objective To investigate the expression and importance of the nuclear accumulation of p53 in superficial transitional cell carcinoma (TCC) of the bladder and its role as a predictor of response to treatment. Patients and methods Tumour samples from 30 patients (two women and 28 men, mean age 60.1 years, range 44-75) with pTa/pT1 tumours were assessed immunohistochemically using the Pab1801 monoclonal antibody and standard avidin-biotin peroxidase staining for p53 protein. Results Tumours from six patients (20%) showed nuclear accumulation of p53; five of these patients failed intravesical therapy with bacille Calmette-Guèrin (BCG) and progressed to muscle invasive and/or metastatic disease, in contrast to six of 24 patients with no detectable nuclear oncoprotein. Conclusions The nuclear accumulation of p53 appears to be a prognostic indicator of tumour unresponsive to intravesical treatment, even with the most potent agent (BCG). Therefore, early radical treatment modalities must be seriously considered in this group of patients. [ABSTRACT FROM AUTHOR]

Bladder cancer cells were stimulated with urine obtained from patients with superficial bladder cancer who had received treatment using intravesical bacillus Calmette-Guérin (BCG). The urine from the first 12 h following each of six BCG instillations was collected and examined for its biological effect. We evaluated effects that had previously been attributed to cytokines detected in the urine of such patients. The modulation of MHC class II antigen and intercellular adhesion molecule-1 (ICAM-1) expression were studied. Using neutralizing polyclonal antibodies to interferon γ and tumour factor α the relative contribution of these molecules to the effects investigated were determined. When cells were stimulated for up to 48 h with first-instillation urine, little effect was seen in any of the parameters investigated. Urine from the sixth instillation, however, proved to be a potent immunomodulatory agent, inducing MHC class II molecule and ICAM-1 expression. Urine from instillations two to five mediated increasing immunomodulatory effects. When sixth-instillation urine samples were treated with neutralizing antibodies to interferon γ prior to their addition to the bladder cancer cells, a marked and significant decrease in their potency was observed. Only in urine from one patient did any immunomodulatory capability remain after antibody treatment. Neutralizing antibodies to tumour necrosis factor α, however, failed to reduce the ability of any patient's urine to induce ICAM-1 expression. When both antibodies were used simultaneously no further decrease in potency was observed. These studies demonstrate for the first time the potential immunomodulatory and cytotoxic effects of urine produced by patients receiving intravesical BCG. Furthermore, in all samples tested, the major immunomodulatory component was shown to be interferon γ. Although tumour necrosis factor α is produced as a result of BCG therapy, this cytokine did not appear to contribute to the parameters investigated. namely the induction of HLA class II antigens, and cell-surface ICAM-1. [ABSTRACT FROM AUTHOR]

The bacille Calmette-Guérin, a live attenuated form of Mycobacterium bovis, has been used as anti-cancer immunotherapy for superficial bladder cancer since 1976 [ 1]. It is now the mainstay of therapy for this condition, which is partly attributable to the low complication rate; indeed 95% have no significant side effects [ 2]. However, proven disseminated M. bovis infection has been documented, as is the case with our elderly patient. [ABSTRACT FROM AUTHOR]

Telomerase reverse transcriptase gene promoter (TERTp) mutations are recognized as one of the most frequent genetic events in bladder cancer (BC). No studies have focused on the relevance of TERTp mutations in the specific group of tumors treated with Bacillus Calmette–Guérin (BCG) intravesical therapy. Methods — 125 non muscle invasive BC treated with BCG therapy (BCG-NMIBC) were screened for TERTp mutations, TERT rs2853669 single nucleotide polymorphism, and Fibroblast Growth Factor Receptor 3 (FGFR3) hotspot mutations. Results — TERTp mutations were found in 56.0% of BCG-NMIBC and were not associated with tumor stage or grade. FGFR3 mutations were found in 44.9% of the cases and were not associated with tumor stage or grade nor with TERTp mutations. The TERT rs2853669 single nucleotide polymorphism was associated with tumors of higher grade. The specific c.1-146G>A TERTp mutation was an independent predictor of nonrecurrence after BCG therapy (hazard ratio—0.382; 95% confidence interval—0.150–0.971, p = 0.048). Conclusions — TERTp mutations are frequent in BCG-NMIBC and -146G>A appears to be an independent predictive marker of response to BCG treatment with an impact in recurrence-free survival. [ABSTRACT FROM AUTHOR]

Abstract: Adverse events (AEs) following intravesical bacillus Calmette-Guérin (BCG) therapy are directly related to reduced compliance, leading to treatment cessation and incomplete treatment. Dr Rischmann and his team designed a prospective study to determine whether prophylaxis with ofloxacin could improve the tolerance of BCG in the treatment of transitional cell carcinoma (TCC) of the bladder. A secondary objective was to investigate the effect on efficacy. The use of ofloxacin significantly decreased the incidence of class 2 or higher AEs (moderate or severe) between instillations four and six. With ofloxacin the percentage of class 3 AEs was also significantly decreased between instillations one and nine. Although ofloxacin reduced AEs involving the lower urinary tract, it did not prevent class 1 AEs. Compliance to full BCG treatment was also improved. Ofloxacin did not appear to impair the efficacy of BCG during 12 mo after treatment. The use of prophylactic ofloxacin 200mg given twice after BCG instillations appears to be a simple and practical method of improving BCG tolerability yet maintaining efficacy. [Copyright &y& Elsevier]

The standard of practice set by the SWOG investigation of BCG therapy for superficial bladder cancer has been to evaluate response at 3 months with cystoscopy and bladder biopsy. This study is to determine if all patients require a biopsy post therapy at 3 or 6 months. We reviewed the charts of 43 patients who had received a 6-weekly course of BCG (Connaught strain) for high grade or recurrent Ta, T1, or Tis transitional cell carcinoma of the bladder. The patients with Ta recurrent, T1 or Tis disease received maintenance therapy. All patients were followed through 6 months. At 3 months, 32/43 patients had negative cystoscopies. All 32 patients had corresponding negative biopsies. Eight patients had visible papillary tumors, while three patients had erythematous lesions, which were biopsy negative. At 6 months, eight different patients had visible lesions on cystoscopy that were biopsy proven superficial bladder cancer. The positive predictive value at 3 and 6 months post BCG therapy was 72.6% and 100%, respectively. The false positive rate was 7% at the 3-month checkpoint. Bladder biopsy is not necessary at the 3 or 6 month period following BCG therapy in the face of negative cystoscopic findings. [Copyright &y& Elsevier]

Given the systemic immunogenic effects of Bacillus Calmette-Guérin (BCG) therapy in patients with bladder cancer and its non-specific immunogenic effects in viral respiratory diseases, we aimed to study severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in bladder cancer patients with a history of BCG therapy. In the present study, all bladder cancer survivors with a history of BCG therapy were identified and included in the study according to the data recovered from the UORC (Uro-Oncology Research Center) registry database. These patients were followed up in terms of acquiring coronavirus disease 2019 (COVID-19). Among the studied patients, 102 eligible bladder cancer patients with a history of BCG therapy entered the study. The males constituted the majority of the patients (86.3%), and more than half of the study population (55.9%) were above 65 years old. Among the understudy patients, 12.7% were confirmed for COVID-19. The study results did not show a statistically significant association between the time and number of BCG therapy courses and SARS-CoV-2 infection. Although no statistically significant association was observed between receiving BCG therapy and developing COVID-19, the infection rate in patients who had recently received BCG therapy was lower than those who had received therapy more than a year ago., Competing Interests: No potential conflict of interest relevant to this article was reported., (© Korean Vaccine Society.)

The authors present the case of a female patient with a tumor of segment VII of the liver, which was postoperatively identified as a tuberculous granuloma. The patient was admitted for elective surgery for a liver tumor, which had been diagnosed a few months before. Computed tomography and nuclear magnetic resonance were performed, based on which focal nodular hyperplasia was suspected. Thirteen years prior to admission the patient had undergone a transurethral resection of superficial bladder carcinoma, followed by adjuvant intravesical Bacillus Calmette-Guérin (BCG-therapy). Upon surgery, segment VII of the liver was resected; postoperative course was uneventful. After the identification of granuloma, the patient was referred to a phthysiatric clinic for further diagnostics and treatment. The authors have deemed this case worthy of reporting primarily due to the exceptionally long period between the completion of BCG therapy and the onset of hepatic tumor.

Objectives: To assess whether the initial treatment of non-muscle invasive bladder cancer (NMIBC) was performed according to the guidelines, and to determine the reasons why initial treatment was not provided in nonadherence cases., Materials and Methods: We retrospectively reviewed all patients with NMIBC who underwent their first transurethral resection of bladder tumor (TURBT) at a peripheral hospital, between 2007 and 2016. The treatment offered to the patient was compared to the European Association of Urology guidelines according to risk stratification. For each patient who did not receive the treatment according to the guidelines, one of the following reasons was identified: poor patient compliance, poor patient general health status, urologist's decision, lack of resources., Results: One hundred fifty-nine patients were included with a mean age of 72.2 years at the time of NMIBC diagnosis. The low-risk patients were strictly treated according to the guidelines. Among the intermediate-risk patients, 14% received mitomycin C. Among the high-risk patients, 39% received intravesical Bacillus Calmette-Guerin. In the nonadherence cases (61%), the reasons were related to the patient in 44% of cases (poor compliance, 21%; poor patient general health status, 23%), urologist's decision in 54% of cases, and lack of resources in 2% of cases. Thirty-seven percent of the high-risk patients underwent re-resection., Conclusions: Overall, adherence to NMIBC guidelines was low in all treatment types (intravesical therapy, re-resection, or cystectomy for very high-risk patients), but this finding was similar to that in previous studies. Reasons were mainly related to the urologist's decision or to the patient condition (poor compliance or poor general health status)., Level of Evidence: 3., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)