Germline DNA copy number polymorphism to predict the efficacy of BCG therapy for non-muscle invasive bladder cancer.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 431-431
Author(s):  
Yoshiaki Yamamoto ◽  
Sho Ozawa ◽  
Masahiro Samoto ◽  
Junichi Mori ◽  
Ryo Inoue ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Copy Number ◽  
Progression Free Survival ◽  
Japanese Patients ◽  
Intravesical Instillation ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Free Survival ◽  
Bcg Therapy ◽  
Muscle Invasive

431 Background: Bacillus Calmette-Guerin (BCG) intravesical instillation is the most effective immunotherapy for non-muscle-invasive bladder cancer (NMIBC), however there are few reliable markers to elucidate the efficacy of BCG therapy. Germline copy number polymorphisms (CNPs) are expected to affect various diseases including human malignancies, but the significance of CNPs in NMIBC treated with BCG therapy remains unclear. FAM81A located on 15q22.2 was reported as one of tumor-associated ETS shared target genes in prostate cancer. PCSK6 located on 15q26.3 was reported to regulate proliferation and tumor progression in several cancers. The purpose of this study is to determine the prognostic value of CNPs for NMIBC treated with BCG therapy. To our knowledge, this is the first report to confirm CNPs as a potential biomarker for assessing the efficacy of immunotherapy. Methods: Array comparative genomic hybridization (CGH) was performed to search for candidate whole genome-wide CNPs related to NMIBC susceptibility. Next, quantitative real-time polymerase chain reaction was carried out to evaluate the effect of BCG therapy for 57 Japanese patients with NMIBC treated with BCG intravesical instillation. Results: Eleven CNPs were associated with NMIBC risk in array CGH. FAM81A and PCSK6 copy number according to those CNPs examined showed significant relationship with disease progression in NMIBC treated with BCG. The means of the relative copy numbers of patients with CNP and those without it were 1.58 and 2.10 for FAM81A ( P < 0.0001), and 1.06 and 1.80 for PCSK6 ( P < 0.0001), respectively. Univariate Cox proportional hazards regression analysis showed that FAM81A ( P = 0.0022), and PCSK6 ( P = 0.0147) copy number had a significant effect on progression-free survival. In multivariate analyses, FAM81A copy number was an independent prognostic factor for progression-free survival ( P = 0.0419, RR = 7.59, 95% CI, 1.07–153.42). The combination of FAM81A or PCSK6 CNP was the most significant prognostic biomarker to predict the efficacy of BCG therapy for NMIBC ( P = 0.0002). Conclusions: Germline DNA CNPs may be a potential new biomarker for estimating the efficacy of BCG therapy in Japanese patients with NMIBC.

scholarly journals Tumour stage on re-staging transurethral resection predicts recurrence and progression-free survival of patients with high-risk non-muscle invasive bladder cancer

2014 ◽  
Vol 8 (5-6) ◽  
pp. 306 ◽  
Author(s):  
Mohamed Bishr ◽  
Jean-Baptiste Lattouf ◽  
Mathieu Latour ◽  
Fred Saad
Keyword(s):  
Bladder Cancer ◽  
High Risk ◽  
Transurethral Resection ◽  
Progression Free Survival ◽  
Invasive Bladder Cancer ◽  
Tumour Stage ◽  
Muscle Invasive Bladder Cancer ◽  
Free Survival ◽  
Bcg Therapy ◽  
Muscle Invasive

Introduction: To identify patients who should be considered for early radical cystectomy, we evaluated the clinical and pathological variables affecting the outcome of patients with high-risk non-muscle invasive bladder cancer (NMIBC) who underwent re-staging transurethral resection (re-TUR).Methods: We reviewed the clinical data of 453 patients treated for urothelial carcinoma between 2006 and 2010. In total, 94 patients underwent re-TUR after their initial TUR. Of these, 72 were not upstaged to muscle invasive disease and were therefore included in our study.Results: On re-TUR, 31 patients had no residual tumour (T0) and 41 patients had residual NMIBC. A statistically significant difference was noted between patients with pT0 and patients with residual NMIBC on re-TUR in regard to tumour recurrence and progression (39% vs. 83%, p < 0.001) (6% vs. 34%, p = 0.005), respectively. On multivariate analysis, tumour stage on re-TUR and the regimen of intravesical bacillus Calmette-Guérin (BCG) therapy (induction vs. maintenance) remained independent predicting factors for recurrence-free survival (RFS) (p = 0.001, hazard ratio [HR]: 1.77), (p < 0.001 HR: 0.16) and progression-free survival (PFS) (p = 0.014, HR: 2.11), (p = 0.008, HR: 0.097), respectively.Conclusions: The presence of T0 on re-TUR is associated with better RFS and PFS and could be a predictive factor for candidates for conservative management. Patients with persistent NMIBC on re-TUR require close follow-up and, in some cases, could be considered for early cystectomy. Maintenance intravesical BCG therapy can improve RFS and PFS in patients with high-risk NMIBC. This study is limited by its retrospective nature and the relatively small number of patients in the cohort.

Effectiveness and safety of valrubicin in non–muscle-invasive bladder cancer following reintroduction: Results from a medical chart review study.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 296-296
Author(s):  
Michael S. Cookson ◽  
Christine Francis Lihou ◽  
Samira Q. Harper ◽  
Thomas Li ◽  
Surya Chitra ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Radical Cystectomy ◽  
Concomitant Medication ◽  
Disease Free Survival ◽  
Progression Free Survival ◽  
The United States ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Free Survival ◽  
Muscle Invasive

296 Background: Valrubicin was approved in the United States in 1998, removed from the market in 2002 because of manufacturing issues, and reintroduced in 2009. We report secondary outcomes and concomitant medication use from a US multicenter, observational, retrospective study. Methods: Medical records of adult patients with non–muscle-invasive bladder cancer (NMIBC) who used valrubicin were abstracted (March–September 2011). Kaplan-Meier analyses were performed for disease-free survival (DFS), progression-free survival (PFS), worsening-free survival (WFS), cystectomy-free survival (CFS), and time to cystectomy. Results: 113 patients (mean age, 73.7 years) received intravesical valrubicin (median, 6 instillations [range, 2–18]). 107 patients (94.7%) received >3 instillations; 97 (85.8%) completed the full course of therapy (≥6 instillations). DFS was 51.6% (95% CI, 40.9%–61.3%) at 3 months, 30.4% (95% CI, 20.4%–41.1%) at 6 months, and median DFS was 3.5 months (95% CI, 2.5–4.0). PFS was 97.6% (95% CI, 90.9%–99.4%) at 3 months, 87.2% (95% CI, 75.4%–93.5%) at 6 months, and median PFS was 18.2 months (95% CI, 17.2–19.0). WFS was 47.4% (95% CI, 37.2%–57.0%) at 3 months and 28.1% (95% CI, 18.8%–38.2%) at 6 months. CFS was 98.0% (95% CI, 92.2%–99.5%) at 3 months and 93.7% (95% CI, 85.2%–97.4%) at 6 months. Median CFS was not reached; only 13.3% of patients underwent radical cystectomy after starting valrubicin. 56 patients (49.6%) experienced ≥1 local adverse reaction; the most common were hematuria and pollakiuria (both 17.7%), micturition urgency (15.9%), and bladder spasm (14.2%). 55 patients (48.7%) used ≥1 concomitant medication for local adverse reactions; the most commonly used were urinary antispasmodics (21.2%), fluoroquinolones (14.2%), and other urologicals (14.2%). Conclusions: In patients with NMIBC treated with intravesical valrubicin, median DFS and PFS were 3.5 and 18.2 months, respectively, and median CFS was not reached as only 13% of patients underwent radical cystectomy. Valrubicin was well tolerated, and most patients received the full course of 6 instillations. Funding: Research and abstract were supported by Endo Pharmaceuticals Inc.

Efficacy and safety of valrubicin in non–muscle-invasive bladder cancer in older and younger patients.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 309-309
Author(s):  
Michael S. Cookson ◽  
Christine Francis Lihou ◽  
Samira Q. Harper ◽  
Thomas Li ◽  
Surya Chitra ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Progression Free Survival ◽  
The United States ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Serious Adverse Event ◽  
Free Survival ◽  
Kaplan Meier ◽  
Muscle Invasive ◽  
Funding Research

309 Background: Valrubicin was approved in the United States in 1998, removed from the market in 2002 because of manufacturing issues, and reintroduced in 2009. We report the effectiveness and safety of valrubicin, stratified by patient age, from a US multicenter, observational, retrospective study. Methods: Medical records of adults with non–muscle-invasive bladder cancer (NMIBC) who used valrubicin were abstracted between March and September 2011. The median age (75 [range 42–95] years) was the stratification cutoff. Kaplan-Meier analyses were performed for event-free survival (EFS), worsening-free survival (WFS), and progression-free survival (PFS). Results: 113 patients (mean age, 73.7 years) received intravesical valrubicin (median, 6 [range, 2–18] instillations). Median EFS, WFS, and PFS were similar in patients ≤75 vs >75 years old (see Table); 1-year rates were 17.8% vs 15.4%, respectively, for EFS; 16.1% vs 14.3% for WFS; and 80.2% vs 81.4% for PFS. 11 (19%) patients aged ≤75 years vs 4 (7%) aged >75 years underwent radical cystectomy; 28 (48%) vs 28 (51%), respectively, experienced ≥1 local adverse reaction; 3 (5%) vs 4 (7%) experienced ≥1 serious adverse event; and 4 (7%) vs 1 (2%) discontinued as a result. Conclusions: In patients with NMIBC treated with intravesical valrubicin, effectiveness and safety are similar in patients aged ≤75 and >75 years. Funding: Research and abstract were supported by Endo Pharmaceuticals Inc. [Table: see text]

scholarly journals Prognostic value of prostate volume in non-muscle invasive bladder cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Won Sik Ham ◽  
Jee Soo Park ◽  
Won Sik Jang ◽  
Young Deuk Choi ◽  
Jongchan Kim
Keyword(s):  
Bladder Cancer ◽  
Prostate Volume ◽  
Progression Free Survival ◽  
Invasive Bladder Cancer ◽  
Intravesical Therapy ◽  
Recurrence Free Survival ◽  
Muscle Invasive Bladder Cancer ◽  
Free Survival ◽  
Muscle Invasive ◽  
Group 1

AbstractThere is evidence that a history of benign prostatic hyperplasia increases the incidence of bladder cancer, and treatment with 5-alpha reductase inhibitor or androgen deprivation therapy reduces recurrence of non-muscle invasive bladder cancer. We aimed to evaluate whether prostate volume affects its prognosis. We reviewed medical records of men who underwent transurethral resection of bladder tumor due to non-muscle invasive bladder cancer from January 2012 to December 2017. Patients were divided into two groups based on prostate volume measured by computed tomography (group 1: 264 patients with ≤ 30 mL, group 2: 124 patients with > 30 mL). Propensity score matching analysis was used for adjust selection bias, and then assessed recurrence-free survival and progression-free survival. With a median follow up duration of 52 months, group 1 showed higher 5-year recurrence-free and progression-free survival (69.3% vs 47.0%, p = 0.001; 96.7% vs 87.7%, p = 0.002). Further, cox-regression analysis showed that tumor size (HR = 1.292 p < 0.001), multifocal tumor (HR = 1.993, p < 0.001), adjuvant intravesical therapy (chemotherapy: HR = 0.580, p = 0.037 and bacillus Calmette–Guérin: HR = 0.542, p = 0.004) and prostate volume (HR = 2.326, p < 0.001) were significant predictors of recurrence-free survival. Prostate volume (HR = 2.886, p = 0.014) was also associated with PFS with age (HR = 1.043, p = 0.044) and tumor grade (HR = 3.822, p = 0.013). We conclude higher prostate volume is associated with worse recurrence and progression-free survival in non-muscle invasive bladder cancer.

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.

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