scholarly journals Application of a multiplex urinalysis test for the prediction of intravesical BCG treatment response: A pilot study

2021 ◽  
pp. 1-7
Author(s):  
Kaoru Murakami ◽  
Ashish M. Kamat ◽  
Yunfeng Dai ◽  
Ian Pagano ◽  
Runpu Chen ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
High Risk ◽  
Treatment Response ◽  
Clinical Laboratory ◽  
Model Performance ◽  
Roc Curves ◽  
Disease Recurrence ◽  
Bcg Therapy ◽  
Intravesical Bcg ◽  
Urinary Levels

BACKGROUND: Intravesical Bacillus Calmette-Guerin (BCG), a live attenuated tuberculosis vaccine that acts as a non-specific immune system stimulant, is the most effective adjuvant treatment for patients with intermediate or high-risk non-muscle-invasive bladder cancer (NMIBC). However, to date, there are no reliable tests that are predictive of BCG treatment response. In this study, we evaluated the performance of OncuriaTM, a bladder cancer detection test, to predict response to intravesical BCG. METHODS: OncuriaTM data was evaluated in voided urine samples obtained from a prospectively collected cohort of 64 subjects with intermediate or high risk NMIBC prior to treatment with intravesical BCG. The OncuriaTM test, which measures 10 cancer-associated biomarkers was performed in an independent clinical laboratory. The ability of the test to identify those patients in whom BCG is ineffective against tumor recurrence was tested. Predictive models were derived using supervised learning and cross-validation analyses. Model performance was assessed using ROC curves. RESULTS: Pre-treatment urinary concentrations of MMP9, VEGFA, CA9, SDC1, PAI1, APOE, A1AT, ANG and MMP10 were increased in patients who developed disease recurrence. A combinatorial predictive model of treatment outcome achieved an AUROC 0.89 [95% CI: 0.80–0.99], outperforming any single biomarker, with a test sensitivity of 81.8% and a specificity of 84.9%. Hazard ratio analysis revealed that patients with higher urinary levels of ANG, CA9 and MMP10 had a significantly higher risk of disease recurrence. CONCLUSIONS: Monitoring the urinary levels of a cancer-associated biomarker panel enabled the discrimination of patients who did not respond to intravesical BCG therapy. With further study, the multiplex OncuriaTM test may be applicable for the clinical evaluation of bladder cancer patients considering intravesical BCG treatment.

scholarly journals Management of hepatic granulomatous tuberculosis complicating intravesical BCG for superficial bladder cancer

2012 ◽  
Vol 1 (3) ◽  
Author(s):  
Vincent Fradet ◽  
Christiane Gaudreau ◽  
Paul Perrotte ◽  
Jean Côté ◽  
Jean-Marie Paquin
Keyword(s):  
Bladder Cancer ◽  
High Risk ◽  
Mycobacterium Bovis ◽  
Superficial Bladder Cancer ◽  
Granulomatous Hepatitis ◽  
Bacille Calmette Guerin ◽  
Systemic Complications ◽  
Bcg Therapy ◽  
Intravesical Bcg ◽  
Management Alternatives

Intravesical bacille Calmette-Guérin (BCG) therapy is the most effective treatmentfor high-risk superficial bladder cancer. Severe systemic complications are rare, but may occur in approximately 1% of cases. We report a severe complicationof intravesical BCG: a disseminated Mycobacterium bovis infectionwith biopsy-proven granulomatous hepatitis in a patient with bladder cancer. We also elaborate on the different management alternatives.

A phase II, randomized study of nivolumab (nivo) or nivo plus BMS-986205 with or without intravesical Bacillus Calmette-Guerin (BCG) in BCG-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC): CheckMate 9UT.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. TPS493-TPS493 ◽  
Author(s):  
Noah M. Hahn ◽  
Sam S. Chang ◽  
Maxwell Meng ◽  
Neal D. Shore ◽  
Badrinath R. Konety ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
High Risk ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Locally Advanced ◽  
Unmet Need ◽  
Clinical Activity ◽  
Free Survival ◽  
Bcg Therapy ◽  
Intravesical Bcg

TPS493 Background: Immune checkpoint inhibitors, including nivo (anti–PD-1), have demonstrated favorable tolerability and efficacy profiles, ushering in a new treatment (tx) paradigm for advanced bladder cancer (advBC). However, an unmet need exists for new effective tx options in earlier stages of disease, specifically for patients (pts) with BCG-unresponsive, high-risk NMIBC. Increased IDO and PD-L1 expression in NMIBC tumors (Inman, et al. Cancer 2007; Hudolin, et al. Anticancer Res 2017), support the combination of anti–PD-1 and IDO1 inhibition in NMIBC. BMS-986205, a selective, potent, once-daily IDO1 inhibitor that works early in the IDO1 pathway, has demonstrated clinical activity in combination with nivo in pts with immunotherapy-naive advBC who received ≥ 1 prior line of therapy (objective response rate, 37%; Tabernero, et al. J Clin Oncol 2018;36(suppl) [abstr 4512]). These findings provide a rationale for investigation of nivo + BMS-986205 ± intravesical BCG therapy in BCG-unresponsive high-risk NMIBC. Here we describe a phase 2, randomized, open-label study assessing the safety and efficacy of nivo ± BMS-986205 ± intravesical BCG in pts with BCG-unresponsive, high-risk NMIBC. Methods: Pts aged ≥ 18 years with BCG-unresponsive (per February 2018 FDA guidance), high-risk NMIBC, defined as carcinoma-in-situ (CIS) with or without papillary component, any T1, or Ta high-grade lesions, will be enrolled. Pts must have urothelial carcinoma as the predominant histological component (>50%). Key exclusion criteria include locally advanced or metastatic BC, upper urinary tract disease within 2 years, prostatic urethral disease within 1 year, and prior immunotherapy. Using a novel adaptive-type design, pts will be randomized to 1 of 4 tx arms with nivo ± BMS-986205 ± BCG. Primary endpoints include proportion of pts with CIS with complete response (CR), duration of CR in pts with CIS, and event-free survival for all pts without CIS. Secondary endpoints are progression-free survival and safety. This global study in 13 countries is underway, with a target enrollment of 436 pts. ( Clinical trial information: NCT03519256.

scholarly journals The Recovery of an intravesical BCG-induced arthritis after RITUXIMAB treatment

2021 ◽  
Author(s):  
Nejla El amri ◽  
Héla Zeglaoui ◽  
Salma Hmila ◽  
dhouha khalifa ◽  
Sadok Lataoui ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
High Risk ◽  
Rare Case ◽  
Superficial Bladder Cancer ◽  
Standard Of Care ◽  
Severe Form ◽  
Bcg Therapy ◽  
Intravesical Bcg ◽  
Risk Of Relapse

BCG intra-vesical instillation is the standard of care for superficial bladder cancer at high risk of relapse and progression. Yet, this treatment can cause dysimmune complications. Osteoarticular manifestations related to BCG therapy are rare and frequently mild. We report a rare case of a severe form successfully treated with Rituximab.

Tumor mutational burden (TMB) and BCG responsiveness in high-risk non-muscle invasive bladder cancer (NMIBC).

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 442-442 ◽  
Author(s):  
Diogo Assed Bastos ◽  
Mariana Lima ◽  
Romulo Loss Mattedi ◽  
Filipe Ferreira dos Santos ◽  
Vanessa Buzatto ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
High Risk ◽  
Proportional Hazards ◽  
Significant Proportion ◽  
Unmet Need ◽  
Predictive Biomarkers ◽  
Predictive Biomarker ◽  
Cox Proportional Hazards ◽  
Bcg Therapy ◽  
Intravesical Bcg

442 Background: Despite optimal management of NMIBC with transurethral resection of bladder tumor (TURBT) and intravesical BCG therapy, a significant proportion of patients (pts) will eventually present with disease recurrence or progression. To date, there is no validated predictive biomarker to guide patient selection for the most appropriate therapy in this setting. Methods: We retrospectively identified pts with high-risk NMIBC treated with TURBT, repeat TUR and intravesical BCG (≥ 6 instillations) from 2009 to 2016. Patients were classified as BCG-responsive (BCG-R) and BCG-unresponsive (BCG-UR) based on the International Bladder Cancer Group criteria. Whole exome sequencing was performed using archival FFPE tumor tissue from pre-BCG TURBT samples. Association of genomic variables and outcomes was evaluated by Cox proportional hazards survival analysis and likelihood ratio tests. Results: Thirty-five patients were included (BCG-R = 17, BCG-UR = 18). Median follow-up was 46 months for BCG-R and 52 months for BCG-UR pts. The majority of pts was male (91.4%), former smoker (60%), and presented with high-grade urothelial carcinoma (85.7%) and/or T1 staging (71.4%). Median time for relapse and progression was 10.5 and 19 months, respectively, in the BCG-UR group. In this cohort, TMB was significantly different in BCG-R and BCG-UR groups, with a median TMB of 5.53 +- 4.60 and 3.17 +- 1.82 mutations/Mb, respectively ( P= 0.045). TMB was also associated with relapse-free survival (RFS), with a median RFS of 38 and 15 months in high versus low TMB groups, respectively ( P= 0.0092). Intratumoral genetic heterogeneity assessed by mutant-allele tumor heterogeneity (MATH) was not statistically different between the groups, with a median MATH score of 31.8 and 21.9 for BCG-R and BCG-UR ( P= 0.14), respectively. On multivariate analysis, age and TMB were independently associated with RFS. Conclusions: In this exploratory biomarker study, high TMB was associated with benefit from immunotherapy with BCG for NMIBC. The identification of predictive biomarkers in this setting is an important unmet need and integrative analysis of TMB with other potential predictive biomarkers should be assessed in larger datasets.

A phase II, randomized study of nivolumab (NIVO), NIVO plus linrodostat mesylate, or NIVO plus intravesical bacillus Calmette-Guerin (BCG) in BCG-unresponsive, high-risk, nonmuscle invasive bladder cancer (NMIBC): CheckMate 9UT.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS5090-TPS5090
Author(s):  
Noah M. Hahn ◽  
Sam Chang ◽  
Maxwell Meng ◽  
Neal D. Shore ◽  
Badrinath R. Konety ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
High Risk ◽  
Checkpoint Inhibitors ◽  
Randomized Study ◽  
Objective Response ◽  
Locally Advanced ◽  
Unmet Need ◽  
Clinical Activity ◽  
Bcg Therapy ◽  
Intravesical Bcg

TPS5090 Background: Immune checkpoint inhibitors, including NIVO (anti–PD-1), have demonstrated favorable tolerability and efficacy profiles, ushering in a new treatment (tx) paradigm for advanced bladder cancer (advBC). However, an unmet need exists for new effective tx options in earlier stages of disease, specifically for patients (pts) with BCG-unresponsive, high-risk NMIBC. Increased IDO and PD-L1 expression in NMIBC tumors (Inman, et al. Cancer 2007; Hudolin, et al. Anticancer Res 2017), support the combination of anti–PD-1 and IDO1 inhibition in NMIBC. Linrodostat mesylate, a selective, potent, once-daily IDO1 inhibitor, has demonstrated clinical activity in combination with NIVO in pts with immunotherapy-naive advBC who received ≥ 1 prior line of therapy (objective response rate, 37%; Tabernero, et al. J Clin Oncol 2018;36(suppl) [abstr 4512]). Furthermore, high levels of PD-L1 expression have been reported in patients not responding to BCG tx. These findings provide a rationale for investigation of NIVO ± linrodostat ± intravesical BCG therapy in BCG-unresponsive high-risk NMIBC. Here we describe a phase 2, randomized, open-label study assessing the safety and efficacy of NIVO ± linrodostat ± intravesical BCG in pts with BCG-unresponsive, high-risk NMIBC (NCT03519256). Methods: Pts aged ≥ 18 years with BCG-unresponsive (per February 2018 FDA guidance), high-risk NMIBC, defined as carcinoma-in-situ (CIS) with or without papillary component, any T1, or Ta high-grade lesions, will be enrolled. Pts must have urothelial carcinoma as the predominant histological component ( > 50%). Key exclusion criteria include locally advanced or metastatic BC, upper urinary tract disease within 2 years, prostatic urethral disease within 1 year, and prior immunotherapy. Using a novel adaptive-type design, pts will be randomized to 1 of 4 tx arms with NIVO ± linrodostat ± BCG. Primary endpoints include proportion of pts with CIS with complete response (CR) and duration of CR in pts with CIS. Secondary endpoints are progression-free survival and safety. This global study in 14 countries is underway, with a target enrollment of 436 pts. Clinical trial information: NCT03519256 .

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

2020 ◽  
Vol 16 (3) ◽  
pp. 126-134
Author(s):  
A. V. Zamyatin ◽  
V. O. Mager ◽  
A. S. Orlov ◽  
K. A. Il'in ◽  
S. E. Zavatskiy ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Treatment Group ◽  
High Risk ◽  
Recurrence Rate ◽  
Control Group ◽  
Recurrence Free Survival ◽  
Free Survival ◽  
Bcg Therapy ◽  
Intravesical Bcg ◽  
Intravesical Bcg Therapy

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.

scholarly journals KEYNOTE-676: Phase III study of BCG and pembrolizumab for persistent/recurrent high-risk NMIBC

2020 ◽  
Vol 16 (10) ◽  
pp. 507-516 ◽  
Author(s):  
Ashish M Kamat ◽  
Neal Shore ◽  
Noah Hahn ◽  
Shaheen Alanee ◽  
Hiroyuki Nishiyama ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
High Risk ◽  
Treatment Options ◽  
Cancer Recurrence ◽  
Disease Recurrence ◽  
Current Treatment ◽  
Phase Iii ◽  
Bcg Therapy ◽  
Registration Number ◽  
Phase Iii Study

Background: Nonmuscle-invasive bladder cancer (NMIBC) is the most common form of bladder cancer, with high rates of disease recurrence and progression. Current treatment for high-risk NMIBC involves Bacillus Calmette-Guérin (BCG) therapy, but treatment options are limited for patients with recurrent or BCG-unresponsive disease. Aberrant programmed death 1 signaling has been implicated in BCG resistance and bladder cancer recurrence and progression, and pembrolizumab has shown efficacy in patients with BCG-unresponsive high-risk NMIBC. Aim: To describe the rationale and design for the randomized, comparator-controlled Phase III KEYNOTE-676 study, which will evaluate the efficacy and safety of pembrolizumab in combination with BCG in patients with persistent/recurrent high-risk NMIBC after BCG induction therapy. Trial registration number: NCT03711032

scholarly journals A retrospective analysis of patients treated with intravesical BCG for high-risk nonmuscle invasive bladder cancer

2019 ◽  
Vol 11 ◽  
pp. 175628721983305 ◽  
Author(s):  
Julie Mariam Joshua ◽  
Meenu Vijayan ◽  
Ginil Kumar Pooleri
Keyword(s):  
Bladder Cancer ◽  
High Risk ◽  
Disease Free Survival ◽  
Invasive Bladder Cancer ◽  
Progression Rate ◽  
Therapeutic Effects ◽  
Free Survival ◽  
Bcg Therapy ◽  
Intravesical Bcg ◽  
Nonmuscle Invasive Bladder Cancer

Background: Adjuvant intravesical immunotherapy with Bacillus Calmette–Guerin (BCG) is considered as the first-line agent in patients with high-risk nonmuscle invasive bladder cancer (NMIBC) after surgery. There are no data in India where there is a high prevalence of tubercle bacillus and inherent immunity against Bacillus sp. The present study aims to evaluate the outcomes of intravesical BCG in the Indian population. Methods: A retrospective study of 101 patients who underwent intravesical BCG for high-risk NMIBC between January 2006 and December 2015 was carried out in a single centre. We compared the recurrence-free rate and progression rate of patients who received induction alone and induction with maintenance BCG therapy. The safety profile of intravesical BCG therapy was also assessed in the study. Results: After a median follow up of 2 years, the disease-free survival (DFS) rates of the induction group and maintenance group were 82% and 88% respectively ( p = 0.233). There was no difference in progression-free survival (PFS) rates at 2 years in those who receive maintenance BCG (95%) and those with induction BCG (94.7%; p = 0.721). A total of 69.36% of our patients had local adverse events. Conclusion: Our results suggest that maintenance therapy does not enhance the therapeutic effects of BCG in patients who respond favourably to 6 weeks of induction. Additional prospective studies are warranted in those countries where tuberculosis exposure is prevalent.

Effectiveness of the Moreau strain of Bacillus Calmette-Guerin (BCG) for nonmuscle invasive bladder cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 4539-4539 ◽  
Author(s):  
Daher Cezar Chade ◽  
Andre Machado ◽  
Ricardo Waksman ◽  
Guilherme Garcia ◽  
Paulo Esteves ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
High Risk ◽  
Disease Progression ◽  
Disease Recurrence ◽  
Intravesical Instillation ◽  
Bacillus Calmette Guerin ◽  
Free Survival ◽  
Instillation Therapy ◽  
Bcg Therapy ◽  
Muscle Invasive

4539 Background: Intravesical instillation therapy of Bacillus Calmette-Guerin (BCG) for intermediate and high-risk non-muscle invasive bladder cancer (NMIBC) after complete transurethral resection has been widely shown to be more effective than any other adjuvant treatment. However, there are several different BCG strains not appropriately evaluated in clinical setting, but in current use. BCG Moreau is by far the most utilized strain in Brazil and has been recently introduced to the European market to cover the issue of BCG shortage, but there is insufficient data regarding its oncologic efficacy. Methods: We retrospectively analyzed 336 consecutive patients, who received adjuvant intravesical instillation therapy with BCG Moreau for intermediate- and high-risk NMIBC between January 2005 and February 2015 at a single institution. The end points of this study were time to first recurrence and progression to muscle-invasive disease. Results: Median age was 62 years (interquartile range 54-76, mean 64.3 years). In addition to induction BCG therapy, 228 (67.9%) patients received maintenance BCG. However, 35 (15.4%) patients interrupted maintenance BCG due to toxicity. Overall, after at least a complete induction BCG therapy, 87 (25.9%) patients presented with disease recurrence and 33 (9.8%) patients had disease progression. When analyzing on patients who received BCG maintenance in addition to induction therapy, 31 (13.6%) patients had disease recurrence and 10 (4.4%) had disease progression. The 5-year recurrence-free survival and progression-free survival rate was 69.8% (95% CI 52.8-77.2) and 86.2% (95% CI 69.9-93.2), respectively. Conclusions: BCG Moreau has shown to be safe and effective as adjuvant intravesical treatment in intermediate and high-risk NMIBC patients. Since results are comparable to other strains, wider use of BCG Moreau may be encouraged and prospective clinical trials stimulated for higher level of evidence.

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