BCG Therapy Research Articles

Nadofaragene firadenovec: a new gold standard for BCG-unresponsive bladder cancer?

High-risk non-muscle-invasive bladder cancer unresponsive to BCG therapy is notoriously difficult to treat, recurs at an extremely high rate, and can progress to muscle invasion and metastases. Radical cystectomy is curative in 80–85% of patients when offered early in the disease course.1 However, many patients seek alternatives in an attempt to preserve their bladder, or simply have too many comorbidities and are therefore ineligible for cystectomy, which carries substantial morbidity and mortality.

Adjuvant intravesical chemotherapy with titanium glycerosolvate aquacomplex versus BCG therapy in patients with high risk nonmuscle-invasive bladder cancer

Objective: to compare recurrence rate, progression rate and recurrence-free survival in patients with high-risk non-muscle-invasive bladder cancer (NMIBC) after adjuvant intravesical chemotherapy (IVCT) with titanium glycerosolvate aquacomplex (TGA) versus intravesical BCG therapy.Material and methods. In a retrospective multicenter clinical study initially were included 126 patients with NMIBC. Of all 126 patients, 94 patients with high-risk NMIBC were selected and divided into 2 groups using a pseudo randomization with propensity score matching to minimize systematic differences in the process of forming groups. The treatment group (n = 55) consisted of patients with high-risk NMIBC who received a 6-week course of adjuvant IVCT with TGA. In the control group (n = 39) patients received an induction 6-week course of adjuvant intravesical BCG therapy, 19 (49 %) of 39 patients received maintenance therapy. Both methods were compared according to recurrence rate, progression rate and recurrence-free survival. Significance of difference was set at p <0.05.Results. The compared groups of patients were well balanced in terms of clinical and morphological characteristics and the main risk factors for recurrence and progression of non-muscle-invasive bladder cancer, no significant differences were found between the groups (p >0.5). The recurrence rate in treatment and control groups was 33 % and 23 %, respectively (p = 0.31). The disease progression was observed in 1 (2 %) patient in the treatment group and in 4 (13 %) patients in the control group (p = 0.08). The median disease-free survival in both groups of patients was not reached at the time of analysis. Three- and five-year recurrence-free survival in the treatment group of patients were 71 % and 62 %, respectively; in the control group — 76 % and 72 %, respectively. There were no significant differences between recurrence-free-survival curves of the treatment and control groups (p = 0.58).Conclusion. Adjuvant IVCT with TGA has demonstrated a clinical effectiveness comparable to intravesical BCG therapy and it can be used as an alternative method of treatment in patients with high-risk NMIBC.

COVID-19 infection threat in patients with high-risk non-muscle invasive bladder cancer receiving intravesical BCG therapy.

AimWe evaluated the COVID‐19 infection threat in patients receiving intravesical BCG therapy which has immunotherapeutic effects and is of vital importance in most of the individuals with high‐risk non‐muscle‐invasive bladder cancer (NMIBC) and investigated the need for postponement of this therapy.MethodsA total of 71 patients, who were diagnosed with high‐risk NMIBC and on intravesical BCG treatment regularly (induction or maintenance), were enrolled in the study. The patients were classified into two groups depending on whether they were diagnosed with COVID‐19 during the pandemic period or not.ResultsOf 71 patients, 26 underwent a COVID‐19 polymerase chain reaction test with clinical suspicion during the pandemic period. Of these 26 patients, 4 were diagnosed with COVID‐19. Age of the patients, working status (working/retired), compliance with containment measures against the pandemic, number of BCG courses, adverse effects after BCG therapy and systemic immune‐inflammation index, which is an inflammation‐related parameter, were not different between groups (P > .05). Neutrophil/lymphocyte ratio was significantly higher in the COVID‐19 positive group (P < .05). COVID‐19 positivity was higher in age groups 50‐64 (6.6%) and 65‐80 (5.8%) years than that in similar age groups of the normal population.ConclusionEvery effort should be made to administer intravesical BCG treatment in high‐risk NMIBC patients even during the pandemic period. However, increased risk of COVID‐19 transmission should be kept in mind and protective measures against COVID‐19 for healthcare providers and patients before the procedure should be taken optimally. The procedure should be postponed in patients with lymphopenia in recent complete blood count.

ROLE OF AGE, GENDER, AND TOBACCO IN CAUSING BLADDER CANCER AND PATHOLOGICAL STUDY OF BLADDER CANCER IN KPK.

Objective:&#x0D; To determine assocation of age, gender &amp; tabbaco in causing bladder carcinoma and its causative factors. &#x0D; Materials and Methods:&#x0D; This was a retrospective audit on individuals suffering from bladder carcinoma. All the enrolled individuals in our research study were diagnosed and treated in our set up under strict criteria.&#x0D; Results:&#x0D; Total 156 affected individuals suffering from bladder cancer were diagnosed and treated in our setup. Out of 156 patients, 111 were characterized by isolated painless total hematuria. Bladder carcinoma is associated with age so in 70 patients (age &gt; 60 year) were characterized by high grade cancer with a p = 0.04, while the remaining patients (age &lt;60 years), were characterized by both high and low-grade cancers. The risk of tumor relapse is considerably less in those individuals who take adjuvant BCG therapy or mitomycin C therapy, and the difference between the two groups is statistically significant, with a P &lt; 0.0001.&#x0D; Conclusion:&#x0D; The incidence rate of bladder carcinoma is increasing. Tobacco is one of the most common causative factors for bladder carcinoma in kpk.

Abstract A07: A marker to optimize BCG dosing schedules for immunotherapy

Abstract Background: BCG immunotherapy is the standard for non-muscle invasive bladder cancer (NMIBC) and there has been no change in therapy schedules, though some patients cannot tolerate repeated dosing. This study evaluates the potential of the GST theta 2 (GSTT2) gene that modulates BCG survival in bladder cancer cell lines to modulate patient response to therapy. Our hypothesis is that better intracellular BCG survival should correlate with better immune activation. GSTT2, a member of the glutathione-S-transferase family, lies on chromosome 22q. In man, a 37kb deletion removes a pseudogene (GSTT2B) and the 5' flanking region of the GSTT2 gene, resulting in low/no expression of GSTT2. This deletion is a reliable marker of GSTT2 gene expression. GSTT2B is deleted in 34% of Caucasians and 29.2% of Asians. Our aim was to genotype NMIBC patients who had received BCG immunotherapy to determine if their response correlates with their GSTT2B status and to evaluate the role of GSTT2 in immune activation. Methods: The GSTT2B deletion and the promoter region of GSTT2 were analyzed by PCR in patients (n=201) and controls (n=150). The impact of BCG instillation on recurrence was analyzed. GSTT2 overexpression was performed in U937 macrophages (GSTT2B homozygous deleted) and bacterial survival determined. GSTT2 knockout mice were generated. Bone marrow-derived dendritic cells (DC) from GSTT2 knockout and wild-type mice were exposed to BCG, and immune activation in terms of cytokine production was examined. Data were analyzed using SPSS 23.0 and p&amp;lt;0.05 was taken to be significant. The institutional animal care and use committee approved animal work and the institutional review board approved patient sample analysis (NHG DSRB: 2012/00475). Results: Overexpressing GSTT2 in U937 cells decreased BCG survival at 2h (p&amp;lt;0.05). SNPs in the GSTT2 promoter were not associated with response to BCG except for the GSTT2B deletion. Patients were segregated by the number of BCG instillations they received, namely 9 or more BCG instillations (n=135) or 8 or fewer BCG instillations (n=39). Patients with the GSTT2B homozygous deletion who received 8 or fewer BCG instillations (74% received 6 instillations), were 90% recurrence free (p&amp;lt;0.05). For those who received 9 or more BCG instillations, the recurrence incidence was 35.5% and recurrence occurred within 2 years. Patients with GSTT2B full-length genotype did better with more BCG instillations. DC from GSTT2 knockout mice produced a 3-fold increase in IL6 production but similar TNFα and IL10 levels as wild-type DC in response to BCG. Conclusions: GSTT2B deletion was associated with lower likelihood of recurrence for patients who received 8 or fewer BCG instillations, while for GSTT2B full-length patients, those who received 9 or more BCG instillations had reduced recurrence compared to those who received fewer instillations. GSTT2 expression modulates immune activation by modulating BCG survival. Hence, GSTT2B absence may be a marker for patients who might do well with less BCG therapy. Citation Format: Juwita N. Rahmat, Kah Wei Tan, Ting Li Ong, Sin Mun Tham, Chong Wen Tsung, Yiong Huak Chan, Lata Raman, Edmund Chiong, Kesavan Esuvaranathan, Ratha Mahendran. A marker to optimize BCG dosing schedules for immunotherapy [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2019 May 18-21; Denver, CO. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(15_Suppl):Abstract nr A07.

Abstract A12: Bladder cancer-derived extracellular vesicles and immune activation

Abstract Background: Bladder tumors occur on the luminal surface of the bladder, and cancer cells and cellular components are shed in urine, which permits the isolation of an enriched population of bladder cancer-specific extracellular vesicles (EVs). EVs contain proteins, miRNA, mRNA, and cellular metabolites, which may serve as stimulators of immune cells. The objective of this study was to evaluate the immune potential of tumor-derived EVs (TEVs) produced on exposure to BCG using a murine bladder cancer cell line and immune cells. Methods: TEVs were isolated by differential high-speed centrifugation of cell culture supernatants. They were confirmed to be extracellular vesicles by electron microscopy and size measurement using nanoparticle tracking analysis. Unstimulated murine bladder cancer cells (MB49) were used to prepare TEV1. The cells were then exposed to BCG Tokyo (MOI 4) and TEVs were isolated after 2 hours (TEV2). BCG was then washed off and the cells were allowed to grow in complete media for 2 days before isolation of the third sample, TEV3. EVs from BCG (BEV) were collected to serve as a control. Bone marrow-derived cells were obtained from C57BL/6J mice to generate dendritic cells (DC) and neutrophils. These cells were untreated or treated with 1ug of TEVs or BEV or BCG (MOI 5) for 24 hours. The supernatants were analyzed for cytokine production and the DCs and neutrophils were analyzed for activation markers by flow cytometry. The institutional animal care and use committee approved the use of mice. Results: DCs treated with TEV2 had significantly higher expression of CD86 (at similar levels when DCs were treated with BCG) and MHC2, both of which enhanced the DC's capacity to present antigens to T cells, when compared to TEV1 or TEV3. While neutrophils induced by BCG expressed significantly higher levels of costimulatory molecules CD80, CD83, CD86, and MHC2, TEV2 induced significant expression of CD80 and CD86. BCG caused a massive release of proinflammatory cytokines (IL6, TNFa, and IL12p70) and the anti-inflammatory cytokine IL10. Cytokine production induced by TEV2 was not as high as that induced by direct BCG stimulation, but it was significantly higher than that produced by untreated cells or TEV1 and TEV3. Unlike BCG, TEV2 did not significantly stimulate IL10 production. Conclusion: Our results demonstrate that tumor cells treated with BCG for 2 hours produce EVs that are able to cause significant modulation of DCs and neutrophils. TEVs generated during BCG immunotherapy have immunostimulatory potential. Therefore, TEVs represent a promising source of material to increase immune activation and efficacy of BCG therapy. This could reduce the number of instillations and adverse effects associated with BCG therapy. Citation Format: Sin Mun Tham, Kesavan Esuvaranathan, Ratha Mahendran. Bladder cancer-derived extracellular vesicles and immune activation [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2019 May 18-21; Denver, CO. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(15_Suppl):Abstract nr A12.

Trained immunity as a molecular mechanism for BCG immunotherapy in bladder cancer.

Intravesical BCG instillation is the gold-standard adjuvant immunotherapy for patients with high-risk non-muscle-invasive bladder cancer. However, the precise mechanism of action by which BCG asserts its beneficial effects is still unclear. BCG has been shown to induce a non-specific enhancement of the biological function in cells of the innate immune system, creating a de facto heterologous immunological memory that has been termed trained immunity. Trained immunity or innate immune memory enables innate immune cells to mount a more robust response to secondary non-related stimuli after being initially primed (or trained) by a challenge such as BCG. BCG-induced trained immunity is characterized by the metabolic rewiring of monocyte intracellular metabolism and epigenetic modifications, which subsequently lead to functional reprogramming effects, such as an increased production of cytokines, on restimulation. Results from BCG vaccination studies in humans show that trained immunity might at leastpartly account for the heterologous beneficial effects of BCG vaccination. Additionally, immunity might have a role in the effect of BCG immunotherapy for bladder cancer. Based on these indications, we propose that trained immunity could be one of the important mechanisms mediating BCG immunotherapy andcould provide a basis for further improvements towards a personalized approach to BCG therapy in non-muscle-invasive bladder cancer.

BCGitis of the wrist after intravesical BCG therapy: A case report

Septic arthritis of the wrist can result in joint destruction, making timely diagnosis crucial for initiating empiric antibiotics and surgical intervention. Mycobacterium is a rare cause of this disorder. A 47-year-old man with bladder cancer was treated surgically and received BCG intravesical therapy. Eleven months later, this patient developed severe carpal BCGitis requiring total carpal resection. The first step was addition of a cement spacer and radiometacarpal stabilisation (Masquelet technique). Secondary infections occurred aggravating the prognosis. This case emphasises the importance of taking into account the patient's medical history. Tuberculosis of the wrist is a rare etiology for septic arthritis; delayed treatment leads to severe complications and functional sequelae.

Phase II trial of atezolizumab in BCG-unresponsive non-muscle invasive bladder cancer: SWOG S1605 (NCT #02844816).

5022 Background: Radical cystectomy (RC) is the standard of care for patients with BCG-unresponsive high risk non-muscle invasive bladder cancer (NMIBC), but many patients are unfit for surgery or elect bladder preservation. Based on the reported efficacy of atezolizumab in metastatic urothelial carcinoma and the known expression of PD-L1 in NMIBC after BCG therapy, this trial was designed to evaluate the activity of atezolizumab in BCG-unresponsive high risk NMIBC. Methods: This single arm phase II registration trial testing systemic atezolizumab (1200 mg IV) every 3 weeks for one year aimed to enroll 135 (70 CIS and 65 non-CIS) eligible patients with histologically proven BCG-unresponsive high risk NMIBC who were unfit for or declined RC. Here we report on the subset with CIS (with or without concomitant Ta/T1) among patients who received at least one protocol treatment. The primary endpoint was pathological complete response (CR) rate at 6 months as defined by mandatory biopsy with a null hypothesis of 30% and alternative of 50% with a 1-sided alpha = 0.05 and 96% power. The 3 month CR rate, defined by cytology, cystoscopy and for-cause biopsy, is reported here as a secondary endpoint, in addition to safety. Results: Seventy-five eligible CIS patients were enrolled. Two received no treatment and are not evaluable. Of 73, median patient age was 73.4 years and median number of prior BCG doses was 12. Concomitant Ta/T1 tumor was found in 30 (41.1%) patients, including T1 disease in 16 (21.9%). A CR was observed in 30 (41.1%; 95% CI 29.7%, 53.2%) patients at 3 months and 19 (26.0%; 95% CI 16.5%, 37.6%) at 6 months. Any possibly or probably treatment-related adverse event (AE) was observed in 61 (83.6%) patients. The most frequent AEs were fatigue 36 (49.3%), pruritis 8 (11.0%), hypothyroidism 8 (11.0%), and nausea 8 (11.0%). Grade 3-5 AEs occurred in 9 (12.3%) patients and there was one treatment-related death (myasthenia gravis with respiratory failure and sepsis). Conclusion: The observed response to atezolizumab at 3 and 6 months in patients with BCG-unresponsive CIS was similar to that reported in recent similar trials and meets the benchmark for initial CR defined by the FDA guidance. This trial provided no new safety concerns. The duration of response will determine if this is a suitable treatment option for patients with BCG-unresponsive high risk CIS. Clinical trial information: 02844816 .

PD03-07 A MULTI-INSTITUTIONAL EVALUATION OF RESCUE THERAPY WITH INTRAVESICAL GEMCITABINE AND DOCETAXOL FOR NON-MUSCLE INVASIVE BLADDER CANCER AFTER BCG FAILURE

INTRODUCTION AND OBJECTIVE:After the recurrence of NMIBC following BCG therapy, risk stratified management directs patients toward radical cystectomy, clinical trial enrollment, and off-label use o...

MP73-08 INTRAVESICAL GEMCITABINE AND DOCETAXOL IN HEAVILY PRE-TREATED PATIENTS WITH NON-MUSCLE INVASIVE BLADDER CANCER (NMIBC)

You have accessJournal of UrologyBladder Cancer: Non-invasive IV (MP73)1 Apr 2020MP73-08 INTRAVESICAL GEMCITABINE AND DOCETAXOL IN HEAVILY PRE-TREATED PATIENTS WITH NON-MUSCLE INVASIVE BLADDER CANCER (NMIBC) Adele Caruso*, Roshan Ravishankar, Keith VanArsdalen, and Stanley Malkowicz Adele Caruso*Adele Caruso* More articles by this author , Roshan RavishankarRoshan Ravishankar More articles by this author , Keith VanArsdalenKeith VanArsdalen More articles by this author , and Stanley MalkowiczStanley Malkowicz More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000959.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Therapeutic options are limited for BCG resistant/ refractory NMIBC patients who are unfit or refuse radical cystectomy. Combination chemotherapy is not regularly used due to additive toxicity. The non-desiccant properties of Gemcitabine allow for combined therapy not previously employed. Docetaxol as a single agent demonstrates significant activity with acceptable toxicity. The objective of this study was to evaluate combination intravesical chemotherapy for its initial response and therapeutic durability in those patients heavily pre-treated with BCG. METHODS: Patients who had failed or were intolerant to BCG therapy were offered combination intravesical therapy per the following regimen 1000 mg of GEM in 100 cc’s of saline instilled for two hours followed by bladder emptying and reinstallation of 37.5 mg DOC in 50 mls saline. This was done weekly for 6 weeks. At twelve weeks patients underwent cystoscopy with full bladder mapping and cytology. Cystoscopy was performed every 3 months for one year and at 3 months or 6 months thereafter. Further biopsiy or resection was performed for positive cytology, distinct recurrent tumor or suspicious areas on cystoscopy. Failure was defined as positive cytology, tumor recurrence or distant failure. RESULTS: Between 12/2015 and 6/2019, thirty patients were recruited. 26 are eligible for evaluation and had a mean of 3.2 prior induction courses of intravesical therapy. There were 20 men and 6 women with a mean age of 77 (range 68-94). Twenty four of 26 patients demonstrated an initial negative evaluation. 16/26 patients recurred during this time period with a mean disease free interval of 12.45 months (range 3-34 months). Ten patients are NED for a mean of 9.6 months (range 3-15 months) 11 failures were local (2 muscle invasive progression), 4 cytology only, 1 pelvic lymph node progression. The regimen was well tolerated per patient complaints and AUA voiding scores. CONCLUSIONS: Sequential, combination Gemcitabine and Docetaxol intravesical chemotherapy is an active regimen in BCG pretreated patients who are unfit or unwilling to undergo cystectomy. A near universal initial response with a complete response maintained for over one year in responders suggests a role for maintenance therapy and supports continued study of this intravesical regimen. Source of Funding: NONE © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e1124-e1124 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Adele Caruso* More articles by this author Roshan Ravishankar More articles by this author Keith VanArsdalen More articles by this author Stanley Malkowicz More articles by this author Expand All Advertisement PDF downloadLoading ...

PD12-12 PATIENT MATCHED GENOMIC ANALYSIS OF HIGH-GRADE NON-MUSCLE INVASIVE BLADDER CANCER SPECIMENS PRE- AND POST-BCG IMMUNOTHERAPY

INTRODUCTION AND OBJECTIVE: High-grade non-muscle invasive bladder cancer (NMIBC) is treated with intravesical BCG immunotherapy. Unfortunately, 40% of patients develop recurrence with a subset progressing. Identification of genomic alterations associated with response to BCG could identify novel approaches to prevent or delay recurrence. To explore tumor evolution under the selective pressure of BCG therapy, we utilized targeted exon capture sequencing (IMPACT) to compare tumor collected pre- and post-BCG treatment. METHODS: High-grade NMIBC patients treated with BCG had IMPACT performed on pre- and post-treatment tumor. Patients were classified as having BCG unresponsive or late-relapsing disease. BCG unresponsive tumors were those with recurrent high-grade disease within 12 months after completion of adequate BCG. BCG late-relapsing tumors were those with high-grade recurrence over 12 months after BCG treatment. The association between patient characteristics, genomic profiles and tumor mutational burden (TMB) with high-grade recurrence following BCG was estimated. TMP pre- and post-treatment was compared using a paired Wilcoxon test. RESULTS: Matched specimens from 18 patients were analyzed. The median age at diagnosis was 60 years (IQR 50-75) and 15 (83%) were male. 11 patients (61%) were cTa, 6 (33%) cT1 and 1 cTis. The mutational concordance between pretreatment and posttreatment BCG specimens was 80% (IQR 65-96) (Figure 1). TMB between matched specimens was not significantly different with median 7 in both (p=0.88). Notably three patients gained a potentially actionable mutation post-BCG like patient 10 with a gain of a FGFR3 mutation after FACETS analysis. Univariable analysis did not detect statistically significant differences in BCG-unresponsive vs late-relapsing with respect to age, gender, number of tumors, smoker, tumor size or cT-stage. Comparing genomic alterations, a significant difference in the present of a CREBBP mutation was detected between these two cohorts (p=0.03). As a chromatin modifying gene, mutations in CREBBP may potentially be actionable with histone deacetylase inhibitors. CONCLUSIONS: With recurrent BCG shortages, further knowledge of resistance patterns can help guide clinical practice. We found a high concordance between tumor pre- and post-BCG treatment. The cohort identified here was small but there were some notable differences between pre- and post-treatment specimens, especially with gain of actionable mutations in post-BCG specimens. While we examined only patients with BCG recurrences, there were a number of actionable mutations that could serve as potential targets for novel therapies.Source of Funding: This work was supported by the Sidney Kimmel Center for Prostate and Urologic Cancers, the Michael and Zena Wiener for Therapeutics Program in Bladder Cancer, Pin Down Bladder Cancer, Cycle for Survival, the Marie-Josee and Henry R. Kravis Center for Molecular Oncology, NIH/NCATS Grant Number UL1-TR002384, the National Cancer Institute Cancer Center Core Grant Number P30-CA008748 and by SPORE in Bladder Cancer P50-CA221745.

Outcomes of patients with high-risk non-muscle invasive bladder cancer (NMIBC) who undergo radical cystectomy after BCG and subsequent salvage intravesical therapy.

483 Background: We evaluate the impact of salvage intravesical therapy on survival in patients with NMIBC previously treated with BCG who ultimately underwent radical cystectomy (RC). Methods: We retrospectively identified patients with NMIBC who received at least 1 complete induction course of BCG and subsequently underwent RC for bladder cancer between 2000-2018. Patients were stratified by receipt of salvage intravesical therapy following BCG prior to RC. Oncologic outcomes were compared using Cox proportional hazards regression analysis and the Kaplan-Meier method. Results: We identified 371 patients who underwent RC after receiving BCG, of whom 55 (15%) received salvage intravesical therapy, most commonly Mitomycin C (n = 26), Valrubicin (n = 8), Gemcitabine (n = 7), and CG0070 (n = 6). Median follow-up among survivors was 1.1 (IQR 0-4.3) years. Patients who received salvage intravesical therapy were more likely to initially present with CIS (27% vs 17%) and less likely to present with T1 disease (33% vs 50%, both p &lt; 0.05). Receipt of salvage intravesical therapy was not associated with increased risk of adverse pathology (≥pT2 or pN+) at RC (33% vs 41%, p = 0.27). Furthermore, on Kaplan-Meier analysis, receipt of salvage intravesical therapy was not associated with cancer-specific or overall survival. On multivariable Cox proportional hazards regression, clinical stage prior to RC, but not receipt of salvage intravesical therapy, was associated with inferior cancer-specific survival and overall survival. Conclusions: Our results suggest that RC following carefully managed salvage intravesical therapy after BCG is not associated with inferior oncologic outcomes, which can improve patient counseling. [Table: see text]

Role of tumor microenvironment in the efficacy of BCG therapy.

Despite its significant overall efficacy, BCG fails to benefit a substantial proportion of bladder cancer (BlCa) patients. Here, we review recent data highlighting the role of tumor microenvironment (TME) in limiting antitumoral activity of BCG treatment and emerging opportunities to target TME to enhance the overall outcomes in BCG-treated BlCa patients.

Comparison of Abnormal Prostate MRI and Histopathology of Prostatic Biopsy after Intravesical BCG Therapy for Non-Muscle Invasive Bladder Cancer

Comparison of Abnormal Prostate MRI and Histopathology of Prostatic Biopsy after Intravesical BCG Therapy for Non-Muscle Invasive Bladder Cancer

Prognostic Role of mRNA-Expression of Aquaporins (AQP) 3, 4, 7 and 9 in Stage pT1 Non-Muscle-Invasive Bladder Cancer.

AQP proteins show a variety of functions in human cell metabolism. The role of different AQP subtypes in tumor metabolism and prognosis are subject of ongoing research. To investigate the mRNA expression of Aquaporin (AQP) 3, 4, 7 and 9 in pT1 non-muscle-invasive bladder cancer (NMIBC) and its prognostic value in therapeutic decision making. Formalin-fixed-paraffin-embedded (FFPE) tissues from transurethral resection of the bladder (TURB) from 112 patients with initial diagnosis of stage pT1 NMIBC were analyzed retrospectively together with clinical data and therapeutic approaches. mRNA expression of AQP3, 4, 7 and 9 was measured and quantified using RT-qPCR. Of the 112 patients (83.9%male, median age 72 years), 40 had a recurrence (35.7%), 16 a progression (14.3%) and 14 patients (12.5%) died tumor-related. mRNA expression for AQP3 was detected in 99.1%, AQP4 in 46.4%, AQP7 in 86.6%and AQP9 in 97.3%. Spearman analysis revealed statistically significant correlations between AQP3, AQP7 and AQP9 mRNA expression with adverse clinical and histopathological parameters (WHO1973 grade 3, concomitant Cis or multifocality). High AQP9 mRNA expression was associated with worse PFS in the total cohort (p = 0.034) and in Grade 3 tumors (p = 0.003) in Kaplan-Meier analysis. In patients with bladder sparing approach, high AQP3 mRNA expression was significantly associated with worse CSS in patients receiving BCG therapy (p = 0.029). mRNA expression of AQP3, 7 and 9 correlates with adverse clinical and pathological parameters. AQP3 and 9 may help to identify a subgroup of highest risk patients who may be considered for early cystectomy.

Optimisation de la prise en charge du cancer de la vessie chez les patients âgés

To define and present potential improvements for the management of bladder cancer in older patients. Bibliographical search was performed from the Medline bibliographic database (NLM Pubmed tool) and Embase focused on: bladder cancer, treatment, BCG, chemotherapy, cystectomy, and elderly. The oncological principles of medico-surgical management of bladder cancer do not differ according to age. On the other hand, the patient comorbidities have been likely to alter the tolerance of these treatments. At the NMIBC stages, no adaptation of the standard treatment has demonstrated any interest. At the MIBC stages, the prognosis was improved by geriatric multidisciplinary perioperative management. The indications and principles of surgical treatments must be identical regardless of the patient age. At the NMIBC stages, adjuvant therapy, including BCG therapy, should not be questioned because of the age of the patient. On the other hand, at the localized MIBC stages, neoadjuvant and adjuvant chemotherapy should not be considered as a standard and their indications assessed individually after geriatric assessment.

Re: Disseminated Mycobacterium bovis Infection Post-Kidney Transplant following Remote Intravesical BCG Therapy for Bladder Cancer

Re: Disseminated Mycobacterium bovis Infection Post-Kidney Transplant following Remote Intravesical BCG Therapy for Bladder Cancer

Protocol for phase I study of pembrolizumab in combination with Bacillus Calmette-Guérin for patients with high-risk non-muscle invasive bladder cancer

IntroductionThe initial treatment for high-risk non-muscle invasive bladder cancer (NMIBC) is endoscopic resection of the tumour followed by BCG therapy. In those who develop recurrence, the standard treatment is radical...

Role of heat shock proteins in bladder cancer: potential biomarkers for treatment response and oncological prognosis

Transurethral resection of bladder tumor (TURBT) and BCG intravesical instillation have been the gold standard for non-muscle invasive bladder cancer (NMIBC) treatment in patients with intermediate and high-risk disease (1,2). However, patients with T1 high grade (T1HG) disease still have relatively poor outcomes with 11.4 and 19.8% of patients experiencing disease progression at 1 and 5 years, respectively and disease specific mortality rates of 4.8% and 11.2%, respectively (3). The identification of biomarkers that could appropriately select patients who will benefit from BCG therapy would be greatly beneficial for optimizing outcomes and minimizing overtreatment.