INTACT: Phase III randomized trial of concurrent chemoradiotherapy with or without atezolizumab in localized muscle invasive bladder cancer—SWOG/NRG1806.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. TPS586-TPS586
Author(s):  
Parminder Singh ◽  
Cathy Tangen ◽  
Jason A. Efstathiou ◽  
Seth P. Lerner ◽  
Sameer G. Jhavar ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Radical Cystectomy ◽  
Residual Disease ◽  
Phase Iii ◽  
Invasive Bladder Cancer ◽  
Event Free Survival ◽  
Muscle Invasive Bladder Cancer ◽  
End Points ◽  
Free Survival ◽  
Muscle Invasive

TPS586 Background: Chemoradiotherapy(CRT) is a SOC for patients with muscle invasive bladder cancer (MIBC) who refuse or are not fit for radical cystectomy. Radiotherapy and chemotherapy are known to increases the PD-L1 expression in bladder cancer. Based on these observations, we hypothesized that addition of atezolizumab to CRT will increase its efficacy. Methods: This is a randomized phase III trial testing CRT with and without atezolizumab for 6 months in 475 patients with MIBC. Pts will be stratified on performance status (0-1 vs. 2); clinical stage (T2 vs T3/T4a, chemotherapy(cisplatin vs 5FU+mitomycin vs gemcitabine); and radiation field (bladder only vs small pelvis). Patients will undergo biopsy 18 week from registration. If they have residual disease they will be taken off protocol treatment and can proceed with alternative SOC option including radical cystectomy. Patients will be followed for 5 years. The primary end point of the study is bladder intact event –free survival (BIEFS). The event is comprised of: recurrence or residual muscle-invasive bladder cancer at 18 weeks or later, clinical evidence of nodal or metastatic disease, radical cystectomy, or death due to any cause. This composite endpoint is reflective of the intent of bladder preservation strategy with radical cystectomy included as one of the outcomes. Secondary end points include overall survival, modified event free survival, pathologic response at 18 weeks, metastasis free survival, cancer specific survival, rate of salvage cystectomy, rate of adverse event and QOL & PRO end points. The expected 3 year BIEFS for the control arm is 52%. The study leadership concluded that a 12% improvement in this endpoint is meaningful for this patient population. With a sample size of 475 patients the study has 85% power to detect the improvement from 52% to 64% in the BIEFS at 3 years (hazard ratio=0.68). The study team will perform translational studies evaluating tumor tissue, whole blood and urine for molecular and immunologic markers of immune response and response to RT. Successful completion of this trial could lead to a new treatment paradigm for patients with muscle invasive bladder cancer. Clinical trial information: NCT03775265.

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.

MP58-04 MUTATION IN MUC6 PREDICTS OVERALL AND RECURRENCE-FREE SURVIVAL FOLLOWING RADICAL CYSTECTOMY FOR MUSCLE-INVASIVE BLADDER CANCER

2015 ◽  
Vol 193 (4S) ◽  
Author(s):  
Brian Cross ◽  
William LaFramboise ◽  
Jeffrey Gingrich ◽  
Somak Roy ◽  
Benjamin Davies ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Radical Cystectomy ◽  
Invasive Bladder Cancer ◽  
Recurrence Free Survival ◽  
Muscle Invasive Bladder Cancer ◽  
Free Survival ◽  
Muscle Invasive

Feasibility and efficacy of gemcitabine and carboplatin neoadjuvant chemotherapy in muscle-invasive bladder cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e16100-e16100
Author(s):  
T. Koie ◽  
H. Yamamoto ◽  
A. Okamoto ◽  
S. Hatakeyama ◽  
A. Momose ◽  
...  
Keyword(s):  
Overall Survival ◽  
Bladder Cancer ◽  
Radical Cystectomy ◽  
Objective Response ◽  
Disease Free Survival ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Free Survival ◽  
Muscle Invasive ◽  
Disease Free

e16100 Background: The neoadjuvant M-VAC followed by radical cystectomy for muscle-invasive bladder cancer has improved survival compared to radical cystectomy alone. Nevertheless, M-VAC has been associated with severe toxicity. The objective of this retrospective study was to evaluate the objective response rate, the impact on overall survival, disease-free survival, disease-free survival and toxicity adverse events of gemcitabine and carboplatin (GC) neoadjuvant chemotherapy in patients with locally advanced bladder cancer. Methods: We reviewed the clinical and pathological data of 140 patients who underwent radical cystectomy and bilateral pelvic lymphadenectomy for T2N0M0 to T4aN0M0 bladder cancer at our institution between January 2001 and August 2008. Seventy patients were treated with neoadjuvant GC followed by cystectomy between March 2005 and August 2008 (GC group), and 70 patients were treated with cystectomy alone between January 2001 and May 2007 (cystectomy alone group). In the GC group, the patients received 2 courses of GC therapy consisted of 800mg/m2 gemcitabine on days 1, 8, and 15 and carboplatin (AUC 4) on day 2. The primary endpoint was the objective response rate, and the secondary endpoints were overall survival, cancer-specific survival, disease free survival, and toxicity. Results: Fifteen patients (23.8%) had a complete response and 26 patients (41.3%) had a partial response in the GC group. At a mean follow-up period of 26.7 months, the overall survival was 85.0% in the GC group and 47.8% in the cystectomy alone group (p = 0.003). The cancer-specific survival was 78.4% in the GC group and 44.6% in the cystectomy alone group (p = 0.0018). The disease-free survival was 82.9% in the GC group and 35.7% in the cystectomy alone group (p = 0.0001). Hematologic toxicities were the main adverse events. Grade 3/4 neutropenia occurred in 26 patients (37.1%) and thrombocytopenia in 15 (21.4%). There was no grade 3/4 gastrointestinal toxicity and no renal function abnormalities. Conclusions: Although this is not a randomized study, the GC neoadjuvant therapy followed by radical cystectomy is feasible and may be associated with improved survival among patients with muscle-invasive bladder cancer. A randomized trial is warranted. No significant financial relationships to disclose.

scholarly journals Radical cystectomy (bladder removal) against intravesical BCG immunotherapy for high-risk non-muscle invasive bladder cancer (BRAVO): a protocol for a randomised controlled feasibility study

BMJ Open ◽  
2017 ◽  
Vol 7 (8) ◽  
pp. e017913 ◽  
Author(s):  
Jamie B Oughton ◽  
Heather Poad ◽  
Maureen Twiddy ◽  
Michelle Collinson ◽  
Victoria Hiley ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
High Risk ◽  
Radical Cystectomy ◽  
Feasibility Study ◽  
Phase Iii ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Phase Iii Trial ◽  
Muscle Invasive ◽  
Randomised Controlled

IntroductionHigh-risk non-muscle invasive bladder cancer (HRNMIBC) is a heterogeneous disease that can be difficult to predict. While around 25% of cancers progress to invasion and metastases, the remaining majority of tumours remain within the bladder. It is uncertain whether patients with HRNMIBC are better treated with intravesical maintenance BCG (mBCG) immunotherapy or primary radical cystectomy (RC). A definitive randomised controlled trial (RCT) is needed to compare these two different treatments but may be difficult to recruit to and has not been attempted to date. Before undertaking such an RCT, it is important to understand whether such a comparison is possible and how best to achieve it.Methods and analysisBRAVO is a multi-centre, parallel-group, mixed-methods, individually randomised, controlled, feasibility study for patients with HRNMIBC. Participants will be randomised to receive either mBCG immunotherapy or RC. The primary objective is to assess the feasibility and acceptability of performing the definitive phase III trial via estimation of eligibility and recruitment rates, assessing uptake of allocated treatment and compliance with mBCG, determining quality-of-life questionnaire completion rates and exploring reasons expressed by patients for declining recruitment into the study. We aim to recruit 60 participants from six centres in the UK. Surgical trials with disparate treatment options find recruitment challenging from both the patient and clinician perspective. By building on the experiences of other similar trials through implementing a comprehensive training package aimed at clinicians to address these challenges (qualitative substudy), we hope that we can demonstrate that a phase III trial is feasible.Ethics and disseminationThe study has ethical approval (16/YH/0268). Findings will be made available to patients, clinicians, the funders and the National Health Service through traditional publishing and social media.Trial registration numberISRCTN12509361; Pre results.

scholarly journals Peri-Operative Morbidity and Outcomes of Radical Cystectomy- Institutional Experience of Single Center

2020 ◽  
Vol 4 (1) ◽  
pp. 107-113
Author(s):  
Amit Mani Upadhyay ◽  
Ashok Kumar Kunwar ◽  
Manik Lama ◽  
Kabir Tiwari ◽  
Sanjesh Bhakta Shrestha ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Radical Cystectomy ◽  
Ileal Conduit ◽  
Invasive Bladder Cancer ◽  
Urinary Bladder Carcinoma ◽  
High Grade ◽  
Muscle Invasive Bladder Cancer ◽  
Operative Morbidity ◽  
Free Survival ◽  
Muscle Invasive

Introduction: The incidence of urinary bladder carcinoma increases distinctly with increasing age. Radicalcystectomy has been the gold standard for the treatment of patients with muscle-invasive bladder cancer or recurrent high-grade non-muscle invasive bladder cancer. Our study aimed to see the peri-operative morbidity and surgical outcomes of the patient who had undergone radical cystectomy in our low volume center. Methods: We retrospectively reviewed the inpatient charts as well as the outpatient records of 10 patients who had undergone radical cystectomy performed in our center for 9 years. A review of the literature on perioperativemorbidity of radical cystectomy was also done using the combination of keywords like mortality, complications, and outcomes of surgery. Results: Age of the patients ranged from 40-80 years. Eight of them were male and two were female. Painlesshematuria (70%) was the commonest presenting symptom, 80% of them were smokers. Three patients received neoadjuvant chemotherapy. Nine patients had radical cystectomy with an ileal conduit, whereas one patient hadradical cystectomy with orthotropic neo-bladder. In postoperative complications, five patients had Clavien-Dindograde I, three patients had grade II, one patient had grade IIIB and one patient had grade V complications. Two years of cancer-free survival was 90% and five years of cancer-free survival was 50%. Conclusions: Radical cystectomy with ileal conduit was still the choice of surgery in muscle-invasive and recurrent high-grade non-muscle invasive bladder cancer.

scholarly journals FOXA1 Gene Expression for Defining Molecular Subtypes of Muscle-Invasive Bladder Cancer after Radical Cystectomy

2020 ◽  
Vol 9 (4) ◽  
pp. 994 ◽  
Author(s):  
Danijel Sikic ◽  
Markus Eckstein ◽  
Ralph M. Wirtz ◽  
Jonas Jarczyk ◽  
Thomas S. Worst ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Radical Cystectomy ◽  
Multivariable Analysis ◽  
Disease Free Survival ◽  
Gene Panel ◽  
The Cancer Genome Atlas ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Free Survival ◽  
Muscle Invasive

It remains unclear how to implement the recently revealed basal and luminal subtypes of muscle-invasive bladder cancer (MIBC) into daily clinical routine and whether molecular marker panels can be reduced. The mRNA expression of basal (KRT5) and luminal (FOXA1, GATA3, KRT20) markers was measured by reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) and correlated to clinicopathological features, recurrence-free survival (RFS), disease-free survival (DFS), and overall survival (OS) in 80 patients with MIBC who underwent radical cystectomy. Additionally, the correlation of single markers with the basal and non-basal subtypes defined by a 36-gene panel was examined and then validated in the TCGA (The Cancer Genome Atlas) cohort. High expression of FOXA1 (p = 0.0048) and KRT20 (p = 0.0317) was associated with reduced RFS. In the multivariable analysis, only FOXA1 remained an independent prognostic marker for DFS (p = 0.0333) and RFS (p = 0.0310). FOXA1 expression (AUC = 0.79; p = 0.0007) was closest to the combined marker expression (AUC = 0.79; p = 0.0015) in resembling the non-basal subtype defined by the 36-gene panel. FOXA1 in combination with KRT5 may be used to distinguish the basal and non-basal subtypes of MIBC.

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