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.

Can neoadjuvant gemcitabine plus carboplatin followed by immediate cystectomy improve survival in patients with cisplatin-ineligible muscle-invasive bladder cancer?

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15565-e15565
Author(s):  
Takuya Koie ◽  
Yuichiro Suzuki ◽  
Yuki Tobisawa ◽  
Tohru Yoneyama ◽  
Kazuyuki Mori ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Propensity Score ◽  
Propensity Score Analysis ◽  
Disease Free Survival ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Score Analysis ◽  
Treatment Type ◽  
Grade 3 ◽  
Muscle Invasive

e15565 Background: Standard neoadjuvant chemotherapy has not yet been established for patients with muscle-invasive bladder cancer (MIBC) who are ineligible for cisplatin based chemotherapy. In the present study, we conducted a propensity score analysis to elucidate the clinical significance of neoadjuvant gemcitabine and carboplatin chemotherapy (GCarbo) for cisplatin-ineligible patients with MIBC. Methods: The cohort of the neoadjuvant group consisted of 51 patients with MIBC, treated between March 2005 and June 2011, who were ineligible for cisplatin. Patients received 2 courses of GCarbo consisting of 800 mg/m2gemcitabine on days 1, 8, and 15, and carboplatin with an AUC of 4 on day 2. After GCarbo, radical cystectomy (RC) and bilateral pelvic lymph node dissection (PLND) were performed at an interval of 1 month. The cohort of RC alone included 59 cisplatin-ineligible MIBC patients treated with RC and bilateral PLND between June 1998 and February 2010. Propensity score matching was used to adjust for potential selection biases associated with treatment type. The endpoints were overall (OS) and disease-free survival (DFS). Results: Of the 51 patients who received GCarbo and RC, 6 (11.8%) RC specimens were found to be cancer free. Grade 3/4 neutropenia occurred in 17 patients (33.3%) and thrombocytopenia in 11 patients (21.6%). There were no patients who experienced grade3/4 nephrotoxicity or nausea. Propensity score-matched analysis indicated 45 matched pairs from both groups. The median follow-up period was 35.3 months. The 3-year OS rate was 86.5% for neoadjuvant GCarbo vs. 50.6% for the RC alone group (P < 0.0001). The DFS rate was 78.8% for neoadjuvant GCarbo vs. 44.8% for RC alone (P= 0.001). Multivariate analysis revealed that the neoadjuvant GCarbo regimen was an extremely strong and independent predictor of the longer OS and DFS. Conclusions: Although the present study is non-randomized, neoadjuvant GCarbo chemotherapy followed by immediate RC achieved significantly longer OS and DFS than cystectomy alone. The clinical usefulness of the present treatment for cisplatin-ineligible patients with MIBC should be verified by further trials.

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.

scholarly journals Stromal LAG-3+cells infiltration defines poor prognosis subtype muscle-invasive bladder cancer with immunoevasive contexture

2020 ◽  
Vol 8 (1) ◽  
pp. e000651 ◽  
Author(s):  
Han Zeng ◽  
Quan Zhou ◽  
Zewei Wang ◽  
Hongyu Zhang ◽  
Zhaopei Liu ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
T Cells ◽  
Immune Checkpoint ◽  
Cox Regression ◽  
Mrna Level ◽  
Disease Free Survival ◽  
The Cancer Genome Atlas ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Muscle Invasive

BackgroundLymphocyte activation gene 3 (LAG-3) is a promising immune checkpoint therapeutic target being evaluated in clinical trials. We assessed the LAG-3+cells distribution, its association with clinical outcomes and immune contexture and its role in the landscape of muscle-invasive bladder cancer (MIBC) treatment.Methods141 patients with MIBC from Zhongshan Hospital were included for survival and adjuvant chemotherapy (ACT) benefit analyses. 32 fresh resected samples of MIBC were collected to detect CD8+T cells functional state. The molecular classification analyses were based on 391 patients with MIBC from The Cancer Genome Atlas. Immunohistochemistry and flow cytometry were performed to characterize various immune cells infiltration.ResultsIn Kaplan-Meier analyses and Cox regression models, stromal LAG-3+cells enrichment was consistently associated with inferior overall survival and disease-free survival, and indicated suboptimal responsiveness to ACT. Patents with high stromal LAG-3+cells possessed increased protumor cells, immunosuppressive cytokines and immune checkpoint expression. The phenotypic analyses of CD8+T cells correlated its dysfunctional state with LAG-3+cells. Besides, LAG-3 mRNA level was linked to luminal and basal subtypes of MIBC. LAG-3-high tumors exhibited limited FGFR3 mutation and signaling signature, and displayed activated immunotherapeutic and EGFR-associated pathway.ConclusionsStromal LAG-3+cells abundance indicated an immunoevasive contexture with dysfunctional CD8+T cells, and represented an independent predictor for adverse survival outcome and ACT resistance in MIBC. LAG-3 expression could potentially be a novel biomarker for FGFR3-targeted and EGFR-targeted therapies and immunotherapy. The crucial role of LAG-3+cells in the therapeutic landscape of MIBC needs further validation retrospectively and prospectively.

Using radiologic response to predict prognosis in patients with muscle-invasive bladder cancer undergoing carboplatin-based neoadjuvant chemotherapy.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 361-361
Author(s):  
Shingo Hatakeyama ◽  
Hayato Yamamoto ◽  
Akiko Okamoto ◽  
Atsushi Imai ◽  
Takahiro Yoneyama ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Multivariate Analysis ◽  
Neoadjuvant Chemotherapy ◽  
Radical Cystectomy ◽  
Cox Regression ◽  
Disease Free Survival ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Contrast Enhanced Ct ◽  
Muscle Invasive

361 Background: Prognosis and tumor responses of carboplatin-based neoadjuvant chemotherapy for muscle invasive bladder cancer (MIBC) are not well documented. To assess the usefulness of carboplatin-based neoadjuvant chemotherapy, we examined the correlation between radiological responses and pathologic down staging on radical cystectomy (RCx) specimens, disease free survival (DFS), and overall survival (OS). Methods: Between March 2005 and June 2013, we performed carboplatin-based neoadjuvant chemotherapy followed by radical cystectomy in 115 patients with T2-4NxM0 MIBC. After diagnostic TUR biopsy, all participants received two courses of Gemcitabine plus Carboplatin therapy. Baseline and post chemotherapy tumor size from contrast enhanced CT were reviewed. The patients were divided in two groups between responders (CR+PR), and non-responders (SD+PD). RCx and bilateral pelvic lymphadenectomy were performed approximately within a month after cessation of chemotherapy. DFS and OS distributions within radiologic response subgroups were estimated with the Kaplan-Meier method and compared using the log-rank test. To evaluate independent predictor for DFS and OS, age, gender, performance status, pathological T and N stage, down-staging, tumor grade, renal function, and radiological responses were applied by Cox-regression multivariate analysis. Results: No significant differences were observed in patient backgrounds between the groups. Radiologic responses were observed in 75 (65%) patients with 69±24% decrease in responder group, whereas tumor response was 2.8±14% in non-responders. The rate of pathological down staging to <pT2 was 37 (49%) in responders, 5 (13%) in non-responders group. Radiologic response was a strong predictor of DFS and OS. A 5-year advantages of DFS and OS in responders vs. non-responders were 88% and 86% vs. 64% and 69%, respectively (P=0.021 and P=0.013). Multivariate analysis showed radiologic response was the independent factor for DFS and OS. Conclusions: Radiological response post carboplatin-based neoadjuvant chemotherapy is associated with OS in patients with MIBC.

Effectiveness of platinum-based adjuvant chemotherapy for muscle-invasive bladder cancer: A weighted propensity score analysis.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 392-392
Author(s):  
Fumitaka Shimizu ◽  
Satoru Muto ◽  
Masataka Taguri ◽  
Takeshi Ieda ◽  
Takatsugu Okegawa ◽  
...  
Keyword(s):  
Overall Survival ◽  
Bladder Cancer ◽  
Propensity Score ◽  
Propensity Score Analysis ◽  
Rank Test ◽  
Muscle Invasive Bladder Cancer ◽  
Log Rank Test ◽  
Score Analysis ◽  
Subgroup Analyses ◽  
Muscle Invasive

392 Background: The clinical evidence of adjuvant chemotherapy (AC ) is less robust than neoadjuvant chemotherapy (NAC). However, several surveys suggest that urologists prefer to use AC more frequently than NAC. We evaluate the clinical benefit of adjuvant platinum based chemotherapy following radical cystectomy (RC) for muscle-invasive bladder cancer (BCa) in routine clinical practice. Methods: This observational study was conducted to compare the effectiveness of AC versus observation postcystectomy in patients with clinicallymuscle-invasive BCa. Cancer-specific survival (CSS) and overall survival (OS) between the AC group and RC alone group were compared using Kaplan-Meiyer method and log-rank test. After adjusting for background factors using propensity score weighting, differences in CSS and OS between these two groups were compared. Subgroup analyses by the pathological characteristics were performed. Results: In total, 322 patients were included in this study. Of these, 23% received AC postcystectomy. Clinicopathological characteristics showed that patients in the AC group were pathologically more advanced and were at higher risk than the RC alone group. In the unadjusted population, although it is not significantly, the AC group had lower overall survival (3-years OS; 61.5% vs 73.6%, HR 1.44, p = 0.243, log-rank test, AC vs RC alone). In the weighted propensity score analysis, although it is not significantly, AC group were superior than RC alone groups (OS: HR 0.65, 95%CI 0.39-1.09, p = 0.099, log-rank test, AC vs RC alone). Subgroup analyses showed that AC significantly reduced the hazard ratio of OS and CSS in ≥ pT3, pN+, ly+, and v+ subgroups. Conclusions: The weighted propensity score analyses showed that platinum-based AC might be associated with increased CSS and OS in patients with high-risk invasive BCa.

scholarly journals GSTT1as a Prognosticator for Recurrence and Progression in Patients with Non-Muscle-Invasive Bladder Cancer

2010 ◽  
Vol 29 (2) ◽  
pp. 81-87 ◽  
Author(s):  
Yun-Sok Ha ◽  
Chunri Yan ◽  
Min Su Lym ◽  
Pildu Jeong ◽  
Won Tae Kim ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cox Regression ◽  
Prognostic Significance ◽  
Invasive Bladder Cancer ◽  
Clinicopathological Parameters ◽  
Rank Test ◽  
Glutathione S Transferase ◽  
Muscle Invasive Bladder Cancer ◽  
Gstt1 Null Genotype ◽  
Muscle Invasive

Although polymorphisms in glutathione S-transferase (GST) have been associated with the risk of bladder cancer (BC), few reports provide information about the development of BC. The aim of the present study was to investigate the effect of homozygous glutathione S-transferase-μ (GSTM1) and glutathione S-transferase-&phis; (GSTT1) deletions as prognostic markers in non-muscle-invasive bladder cancer (NMIBC). A total of 241 patients with primary NMIBC were enrolled in this study. GSTM1 and GSTT1 polymorphisms were analyzed by multiplex polymerase chain reaction (PCR) using blood genomic DNA. The results were compared with clinicopathological parameters. The prognostic significance of the GSTs was evaluated by Kaplan-Meier and multivariate Cox regression model. A statistically significant association between genotype and histopathological parameter was not observed. The patients with the GSTT1-positive genotype had significantly reduced recurrence- and progression-free survival than those with the GSTT1-null genotype (log-rank test,p< 0.05, respectively). Recurrenceand progressionfree survival were not related to the GSTM1 genotypes. In multivariate regression analysis, the GSTT1positive genotype was the independent predictor for recurrence [hazard ratio (HR), 1.631;p= 0.043] and progression (HR, 3.418;p= 0.006). These results suggested that the GSTT1 genotype could be a useful prognostic marker for recurrence and progression in 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.

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