scholarly journals Non-maintenance intravesical Bacillus Calmette–Guérin induction therapy with eight doses in patients with high- or highest-risk non-muscle invasive bladder cancer: a retrospective non-randomized comparative study

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Makito Miyake ◽  
◽  
Kota Iida ◽  
Nobutaka Nishimura ◽  
Tatsuki Miyamoto ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Propensity Score ◽  
Invasive Bladder Cancer ◽  
Rank Test ◽  
Bacillus Calmette Guerin ◽  
Muscle Invasive Bladder Cancer ◽  
Free Survival ◽  
Landmark Analyses ◽  
Muscle Invasive ◽  
Group B

Abstract Background To explore possible solutions to overcome chronic Bacillus Calmette–Guérin (BCG) shortage affecting seriously the management of non-muscle invasive bladder cancer (NMIBC) in Europe and throughout the world, we investigated whether non-maintenance eight-dose induction BCG (iBCG) was comparable to six-dose iBCG plus maintenance BCG (mBCG). Methods This observational study evaluated 2669 patients with high- or highest-risk NMIBC who treated with iBCG with or without mBCG during 2000–2019. The patients were classified into five groups according to treatment pattern: 874 (33%) received non-maintenance six-dose iBCG (Group A), 405 (15%) received six-dose iBCG plus mBCG (Group B), 1189 (44%) received non-maintenance seven−/eight-dose iBCG (Group C), 60 (2.2%) received seven−/eight-dose iBCG plus mBCG, and 141 (5.3%) received only ≤5-dose iBCG. Recurrence-free survival (RFS), progression-free survival, and cancer-specific survival were estimated and compared using Kaplan–Meier analysis and the log-rank test, respectively. Propensity score-based one-to-one matching was performed using a multivariable logistic regression model based on covariates to obtain balanced groups. To eliminate possible immortal bias, 6-, 12-, 18-, and 24-month conditional landmark analyses of RFS were performed. Results RFS comparison confirmed that mBCG yielded significant benefit following six-dose iBCG (Group B) in recurrence risk reduction compared to iBCG alone (groups A and C) before (P < 0.001 and P = 0.0016, respectively) and after propensity score matching (P = 0.001 and P = 0.0074, respectively). Propensity score-matched sequential landmark analyses revealed no significant differences between groups B and C at 12, 18, and 24 months, whereas landmark analyses at 6 and 12 months showed a benefit of mBCG following six-dose iBCG compared to non-maintenance six-dose iBCG (P = 0.0055 and P = 0.032, respectively). There were no significant differences in the risks of progression and cancer-specific death in all comparisons of the matched cohorts. Conclusions Although non-maintenance eight-dose iBCG was inferior to six-dose iBCG plus mBCG, the former might be an alternative remedy in the BCG shortage era. To overcome this challenge, further investigation is warranted to confirm the real clinical value of non-maintenance eight-dose iBCG.

Intravesical rad-IFNα/Syn3 for patients with high-grade, bacillus Calmette-Guérin (BCG) refractory or relapsed non-muscle invasive bladder cancer: A phase II randomized study.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 279-279 ◽  
Author(s):  
Stephen A. Boorjian ◽  
Neal D. Shore ◽  
Daniel Canter ◽  
Kenneth Ogan ◽  
Lawrence Ivan Karsh ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Phase Ii ◽  
Invasive Bladder Cancer ◽  
High Grade ◽  
Recurrence Free Survival ◽  
Bacillus Calmette Guerin ◽  
Efficacy And Safety ◽  
Muscle Invasive Bladder Cancer ◽  
Free Survival ◽  
Muscle Invasive

279 Background: While bacillus Calmette-Guérin (BCG) is the most effective intravesical treatment for reducing recurrence and progression for high-risk non-muscle invasive bladder cancer (NMIBC), many patients are either refractory to treatment or relapse. We assessed the efficacy and safety of rAd-IFNα/Syn 3 (Instiladrin, FKD Finland), a replication deficient recombinant adenovirus gene transfer vector, for patients with high-grade (HG) BCG refractory or relapsed NMIBC. Methods: In this open-label, US multicenter (n=13), parallel-arm Phase II study (NCT01687244), 43 patients with HG BCG refractory or relapsed NMIBC were randomized 1:1 to receive intravesical rAd-IFNα/Syn3 at 1x1011 or 3x1011viral particles/mL. Patients responding at months 3, 6, and 9 were re-treated at months 4, 7, and 10. Most patients (n=21) had a primary tumor classification of carcinoma in situ (CIS); 9 had both CIS and Ta/T1 disease and 10 had Ta/T1 disease alone. The primary endpoint was 12-month HG recurrence-free survival (RFS). All patients receiving at least one dose were included in efficacy and safety analyses. Results: Forty patients received rAd-IFNα/Syn3 (1 x 1011 vp/mL: n=21; 3 x 1011vp/mL: n=19) between November 2012 and April 2015. Fourteen patients (35.0%; 90% CI 22.6%, 49.2%) remained free of HG tumor recurrence 12 months after initial treatment. Comparable 12 month HG RFS was noted between dosage arms, as well as between patients with refractory and relapsed NMIBC. Interestingly, the 12 month HG recurrence-free survival for patients with Ta/T1-only disease was 50% (5/10). rAd-IFNα/Syn3 was well-tolerated, with no Grade 5 adverse events (AEs), one Grade 4 AE (COPD; unrelated to treatment), and no patient discontinuing treatment due to an adverse event. The most frequently reported AEs were micturition urgency (n=16), dysuria and pollakiuria (n=13 each), fatigue (n=9), and nocturia (n=10). Conclusions: rAd-IFNα/Syn3 was well tolerated and demonstrated promising efficacy for patients with HG NMIBC after BCG therapy who are unable or unwilling to undergo radical cystectomy. A phase III trial utilizing this novel agent is ongoing. Clinical trial information: 01687244.

scholarly journals A Molecular Signature Determines the Prognostic and Therapeutic Subtype of Non-Muscle-Invasive Bladder Cancer Responsive to Intravesical Bacillus Calmette-Guérin Therapy

2021 ◽  
Vol 22 (3) ◽  
pp. 1450
Author(s):  
Seon-Kyu Kim ◽  
Seong-Hwan Park ◽  
Yeong Uk Kim ◽  
Young Joon Byun ◽  
Xuan-Mei Piao ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Molecular Subtypes ◽  
Molecular Signature ◽  
Invasive Bladder Cancer ◽  
Diagnostic Tools ◽  
Bacillus Calmette Guerin ◽  
Muscle Invasive Bladder Cancer ◽  
Free Survival ◽  
Bcg Therapy ◽  
Muscle Invasive

Non-muscle-invasive bladder cancer (NMIBC) is clinically heterogeneous; thus, many patients fail to respond to treatment and relapse. Here, we identified a molecular signature that is both prognostic and predictive for NMIBC heterogeneity and responses to Bacillus Calmette-Guérin (BCG) therapy. Transcriptomic profiling of 948 NMIBC patients identified a signature-based subtype predictor, MSP888, along with three distinct molecular subtypes: DP.BCG+ (related to progression and response to BCG treatment), REC.BCG+ (related to recurrence and response to BCG treatment), and EP (equivocal prognosis). Patients with the DP.BCG+ subtype showed worse progression-free survival but responded to BCG treatment, whereas those with the REC.BCG+ subtype showed worse recurrence-free survival but responded to BCG treatment. Multivariate analyses revealed that MSP888 showed independent clinical utility for predicting NMIBC prognosis (each p = 0.001 for progression and recurrence, respectively). Comparative analysis of this classifier and previously established molecular subtypes (i.e., Lund taxonomy and UROMOL class) revealed that a great proportion of patients were similar between subtypes; however, the MSP888 predictor better differentiated biological activity or responsiveness to BCG treatment. Our data increase our understanding of the mechanisms underlying the poor prognosis of NMIBC and the effectiveness of BCG therapy, which should improve clinical practice and complement other diagnostic tools.

scholarly journals Clinical Evaluation of Patients with Mixed Low-and-High Grade Non-muscle Invasive Bladder Cancer with EORTC Risk Scores

2020 ◽  
Author(s):  
Tianjie Lan ◽  
Yuhong Li ◽  
Yi Lu ◽  
Chuanfeng Liu ◽  
Gaoteng Lin ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Invasive Bladder Cancer ◽  
Risk Scores ◽  
Rank Test ◽  
High Grade ◽  
Muscle Invasive Bladder Cancer ◽  
Free Survival ◽  
Log Rank Test ◽  
Muscle Invasive

Abstract Background: To evaluate the recurrence and progression rate of patients with mixed low-and-high grade (MG) non-muscle invasive bladder cancer (NMIBC), and compare these outcomes with the European Cancer Research and Treatment Organization (EORTC) prognostic risk scores.Methods: A retrospective analysis was performed based on the data from 68 MG NMIBC patients undergoing transurethral resection of bladder treatment (TUR-BT) from October 2013 to November 2018 in our hospital. The patients received intravesical treatment, and the follow-up protocols, including cystoscopy, ultrasound and urinary cytology, for the mean follow-up period of 33±10.7 months. The patients were divided into 4 groups according to the EORTC risk scores, and the recurrence rate and progression scores of tumors in each group were calculated and compared with the estimated rates based on EORTC risk scores. The log-rank test and multivariable analysis were used to analyze the possible differences between the risk groups and to identify independent prognostic factors.Results: Among the 68 patients, averagely 67.6 years (32-86 years), 42 patients were of Stage Ta and 26 were of Stage T1; the tumor recurrence was noted in 15 patients (22.1%), 11 as LG (low grade) and 4 as HG (high grade); and tumor progression in 4 patients (5.9%), 2 stages of progression. The Kaplan-Meier curve showed a real recurrence-free survival (RFS) difference rates between Group 1-4 and Group 5-9 (P=0.0362<0.05, log-rank test); while for Group 0, Group 2-6 and Group 7-13, the real progression-free survival (PFS) was statistically different (P=0.0077<0.01, log-rank test)． Conclusions: The pathology and clinical behavior of MG are “benign” prior to LG even if the patients did not receive overly aggressive intravesical instillations. The EORTC risk scores can be applied to the short-term prognostic assessment of recurrence and progression risk in MG patients of the cohort. However, the value and applicability of long-term prognosis assessment are to be confirmed in further studies in the future.

scholarly journals Preoperative aspartate transaminase/alanine transaminase ratio as a prognostic biomarker in primary non-muscle-invasive bladder cancer: a propensity score-matched study

BMC Urology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xiaofeng Cheng ◽  
Xiaochen Zhou ◽  
Ming Yi ◽  
Song Xu ◽  
Cheng Zhang ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Propensity Score ◽  
Prognostic Biomarker ◽  
Alanine Transaminase ◽  
Invasive Bladder Cancer ◽  
Aspartate Transaminase ◽  
Muscle Invasive Bladder Cancer ◽  
Free Survival ◽  
Cox Regression Analysis ◽  
Muscle Invasive

Abstract Purpose To evaluate the prognostic value of the aspartate transaminase/alanine transaminase (AST/ALT) ratio in primary non-muscle-invasive bladder cancer (NMIBC) using propensity score matching (PSM) analysis. Methods We retrospectively collected the clinical and pathological data from 314 patients with primary NMIBC who underwent transurethral resection of bladder tumor. The full cohorts were divided into a low AST/ALT ratio group and a high AST/ALT ratio group according to the optimal cut-off value which was obtained based on the analysis of the receiver operating characteristic curve for the 3-year recurrence-free survival (RFS). After 1:1 PSM, the correlation between preoperative AST/ALT ratio and survival prognosis was evaluated by Kaplan–Meier analysis with log-rank tests. The independent prognostic factors for RFS and progression-free survival (PFS) were also analyzed. Results The optimum cutoff value of the preoperative AST/ALT ratio was 1.40. Before PSM, a high AST/ALT ratio was correlated with the larger proportion of age > 60 years (P = 0.007) and the worse pathological T stage (P < 0.001). After PSM, patients with a high AST/ALT ratio had poorer RFS and PFS than patients with a low AST/ALT ratio (all P < 0.001). In addition, multivariate Cox regression analysis indicated that preoperative AST/ALT ratio was considered as an independent prognostic factor of RFS (HR 2.865; 95%CI 1.873–4.381; P < 0.001) and PFS (HR 4.771; 95%CI 2.607–8.734; P < 0.001) in patients with primary NMIBC. Conclusions The high AST/ALT ratio group tended to have poorer RFS and PFS than the low AST/ALT ratio group. Our results also indicated that the elevated preoperative AST/ALT ratio could be seen as a useful prognostic biomarker for predicting early disease recurrence and progression in patients with primary NMIBC.

scholarly journals Intravesical bacillus Calmette-Guérin versus chemohyperthermia for high-risk non-muscle-invasive bladder cancer

2015 ◽  
Vol 9 (5-6) ◽  
pp. 278 ◽  
Author(s):  
Rahmi Gokhan Ekin ◽  
Ilker Akarken ◽  
Ferruh Zorlu ◽  
Huseyin Tarhan ◽  
Ulku Kucuk ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
High Risk ◽  
Propensity Score ◽  
Cox Regression ◽  
Invasive Bladder Cancer ◽  
Bacillus Calmette Guerin ◽  
Muscle Invasive Bladder Cancer ◽  
Free Interval ◽  
Significant Difference ◽  
Muscle Invasive

Introduction: Patients with high-risk non-muscle invasive bladder cancer (NMIBC) need adjuvant intravesical treatment after surgery. Although bacillus Calmette-Guérin (BCG) is highly effective, new adjuvant treatments to decrease recurrences and toxicity have been studies. We performed a retrospective propensity score-matched study to compare the efficacy of BCG and chemohyperthermia (C-HT).Methods: We included 1937 patients diagnosed with bladder cancer between January 2004 and January 2014. The primary efficacy endpoint was recurrence-free interval. Patients treated with C-HT were matched with patients treated with BCG using propensity score- matched analysis. Cox-regression models were used to estimate the association between intravesical treatments and the presence of recurrence and progression.Results: Of the 710 patients treated with intravesical treatments, 40 and 142 were eligible for inclusion in C-HT and BCG groups, respectively. Following case matching, there were no differences in patient or tumour characteristics between treatment groups. The 2-year recurrence-free interval in C-HT and BCG groups were 76.2% and 93.9%, respectively (p = 0.020). C-HT treatment (hazard ratio [HR] 5.42; 95% confidence interval [CI] 1.11–26.43; p = 0.036) and high-grade tumour (HR 4.60; 95% CI 1.01–20.88; p = 0.048) are associated with an elevated odds of tumour recurrence. In multivariate Cox-regression analysis, there was no significant difference between C-HT and BCG in the odds of recurrence (p = 0.054). There were no differences in progression between C-HT and BCG.Conclusion: C-HT is not as effective treatment as BCG in high-risk NMIBC patients who are BCG-naive. Although, there were no significant difference in the odds of recurrence, recurrence-free interval is significantly improved by the administration of BCG.

Neoadjuvant gemcitabine and carboplatin followed by immediate radical cystectomy for muscle-invasive bladder cancer patients ineligible for cisplatin-based chemotherapy: A propensity score-matched analysis.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 375-375
Author(s):  
Takuya Koie ◽  
Chikara Ohyama ◽  
Atsushi Imai ◽  
Shingo Hatakeyama ◽  
Takahiro Yoneyama ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Propensity Score ◽  
Cox Regression ◽  
Propensity Score Analysis ◽  
Strong Predictor ◽  
Disease Free Survival ◽  
Invasive Bladder Cancer ◽  
Rank Test ◽  
Muscle Invasive Bladder Cancer ◽  
Muscle Invasive

375 Background: Standard neoadjuvant chemotherapy has not yet been established for patients with muscle-invasive bladder cancer (MIBC) who are ineligible for cisplatin (CDDP)-based chemotherapy. We conducted a propensity score analysis to evaluate the clinical significance of neoadjuvant gemcitabine and carboplatin (GCarbo) chemotherapy for CDDP-ineligible patients with MIBC. Methods: We enrolled 381 patients with MIBC, and retrospectively compared two cohorts of CDDP-ineligible patients with MIBC. The GCarbo cohort consisted of 63 patients, who received 2 courses of GCarbo consisting of 800 mg/m2 gemcitabine on days 1, 8, and 15 and carboplatin with an area under the curve of 4 on day 2, prior to RC. The RC alone cohort consisted of 56 patients receiving RC without neoadjuvant or adjuvant chemotherapy. The endpoints were overall (OS), cancer-specific (CSS), and disease-free survival (DFS). The oncological outcomes were analyzed using log-rank test and multivariate Cox regression model. Results: Propensity score-matched analysis indicated 56 matched pairs from both groups. The 3-year OS rates were 77.9% for the GCarbo cohort and 50.7% for the RC alone cohort (P = 0.002). The 3-year CSS rates were 92.8% for the GCarbo cohort and 52.6% for RC alone group (P < 0.001). The 3-year DFS rates were 80.6% for the GCarbo cohort and 48.1% for the RC alone cohort (P = 0.005). Multivariate analysis revealed that GCarbo was an extremely strong predictor of improved survival. Conclusions: Although the present study is non-randomized, neoadjuvant GCarbo chemotherapy followed by immediate RC significantly improved OS, CSS, and DFS in CDDP-ineligible MIBC patients.

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