Concurrent gemcitabine and radiotherapy for the treatment of muscle-invasive bladder cancer: A pooled individual data analysis of eight phase I-II trials.
Abstract Purpose Although radical cystectomy is still considered the standard of care for most localized muscle-invasive bladder cancer (MIBC) patients, bladder-sparing strategies with chemoradiotherapy have demonstrated comparable local control and survival rates when adjusting for tumor stage. We present a pooled analysis of individual patient data out of published trials with gemcitabine-based chemoradiotherapy for MIBC. Methods and materials Individual patient data were collected from Institutions that enrolled patients into trials that evaluated gemcitabine-based chemoradiotherapy for MIBC. Results We identified eight studies published on gemcitabine-based radiochemotherapy and 190 patients were included in this analysis. A complete response (CR) was observed in 166 patients (93%). After a median follow up of 44.5months, 36 patients (18.9%) presented a bladder recurrence and 14 subsequently underwent cystectomy. The 5-year overall survival (OS), disease-specific survival (DSS), and cystectomy-free survival (CFS) rates were 59%, 80.9%, and 93.3%, respectively. The achievement of CR after chemoradiotherapy was the main prognostic variable which was associated with improved OS, DSS, and CFS. The treatment was well tolerated. Conclusion This pooled analysis strengthens the evidence that chemoradiotherapy regimens with concurrent gemcitabine are feasible and well tolerated. Prospective randomized controlled trials are on-going to definitively assess the efficacy of gemcitabine-based chemoradiotherapy for MIBC.
Purpose Multiple prospective Radiation Therapy Oncology Group (RTOG) protocols have evaluated bladder-preserving combined-modality therapy (CMT) for muscle-invasive bladder cancer (MIBC), reserving cystectomy for salvage treatment. We performed a pooled analysis of long-term outcomes in patients with MIBC enrolled across multiple studies. Patients and Methods Four hundred sixty-eight patients with MIBC were enrolled onto six RTOG bladder-preservation studies, including five phase II studies (RTO...
Background We conducted a phase I trial of gemcitabine (gem) with concurrent radiotherapy in patients with muscle-invasive bladder cancer (BC) ineligible for surgery or cisplatin or refusing organ loss. Patients and methods Patients with urothelial cancer, cT2-T4, cN0-1, M0, ineligible for surgery due to local tumor extension, PS, age or co-morbidities or who refused surgery were included. After maximal transurethral resection, the treatment schedule included: twice-weekly i.v. infusion of gem [...
Abstract Context Aims of bladder preservation in muscle-invasive bladder cancer (MIBC) are to offer a quality-of-life advantage and avoid potential morbidity or mortality of radical cystectomy (RC) without compromising oncologic outcomes. Because of the lack of a completed randomised controlled trial, oncologic equivalence of bladder preservation modality treatments compared with RC remains unknown. Objective This systematic review sought to assess the modern bladder-preservation treatment modal...
The aim of this study was to determine the prognostic and predictive values of ribonucleoside reductase subunit M1 (RRM1) and excision repair cross-complementation group 1 (ERCC1) expression in patients with muscle-invasive bladder cancer treated with chemoradiotherapy. The expression of RRM1 and ERCC1 in pretreatment tumor samples of retrospectively identified patients was determined by immunohistochemical analysis. A total of 39 patients were included in this study; 49% were treated with neoad...
CONTEXT: The European Association of Urology (EAU) guidelines panel on Muscle-invasive and Metastatic bladder cancer (BCa) updates its guidelines yearly. This updated summary provides a synthesis o ...
Although radical cystectomy is still the treatment of choice for patients with infiltrating bladder cancer, there is growing evidence of the effectiveness of a conservative approach. Developed as a treatment of need for elderly or unfit patients unable to undergo radical cystectomy, conservative therapy is becoming a true alternative to surgery for highly selected patients. Although transurethral bladder resection, external radiotherapy and systemic chemotherapy can control the disease as single...
Last. David I. Quinn(SC: University of Southern California)H-Index: 72
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Abstract Context We present a summary of the Second International Consultation on Bladder Cancer recommendations on chemotherapy for the treatment of bladder cancer using an evidence-based strategy. Objective To review the data regarding chemotherapy in patients with clinically localized and metastatic bladder cancer with a focus on its use for patients in the neoadjuvant and adjuvant settings. Evidence acquisition Medline databases were searched for original articles published prior to April 1,...
Purpose Concomitant treatment with radiation therapy and cisplatin (CDDP) remains the gold standard for bladder preservation in the treatment of muscle-invasive bladder cancer (MIBC). We present the long-term results of a phase 1 clinical trial to assess the association of twice-weekly gemcitabine with CDDP and radiation therapy in this setting. Methods and Materials Patients with pT2-pT4N0M0 MIBC without hydronephrosis or diffuse carcinoma in situ were enrolled in this study. After maximal tran...
In this multicenter, phase 3 trial, we randomly assigned 360 patients with muscleinvasive bladder cancer to undergo radiotherapy with or without synchronous chemotherapy. The regimen consisted of fluorouracil (500 mg per square meter of bodysurface area per day) during fractions 1 to 5 and 16 to 20 of radiotherapy and mitomycin C (12 mg per square meter) on day 1. Patients were also randomly assigned to undergo either whole-bladder radiotherapy or modified-volume radiotherapy (in which the volum...
Abstract Tolerability to gemcitabine radiochemotherapy was evaluated in 33 patients with inoperable, locally advanced transitional-cell bladder cancers. The dose of 75mg/m 2 gemcitabine once a week, concurrently with standard radiotherapy of 60Gy/6weeks, was found to be acceptable. Eighty-one percentage of 3-year local progression-free survival suggests efficiency warranting further studies.
Last. A. Mabudi(SUT: Sahand University of Technology)
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Abstract Human Serum Albumin (HSA) is introduced as one of the ideal protein-based nanoparticles for drug delivery due to some of its unique performances such as non-toxic, non-immunogenic, biocompatible, and biodegradable. Besides, the HSA has gained considerable attention owing to high compatibility without any severe side effects and extraordinary binding capacity of various drugs on its Sudlow sites (Ⅰ and Ⅱ). Hence, this study tries to explore and discuss the interactions between two Sudlow...
Introduction: Urothelial cancers (UC) include tumors of the bladder, upper tract, and proximal urethra. Bladder cancer (BC) arises from urothelial cells lining the bladder and accounts for 90-95% of UC. BC is responsible for approximately 500,000 new cases and has a dismal prognosis with 200,000 deaths annually globally. However, immune checkpoint inhibitors (ICIs) and antibody-drug conjugates are rapidly changing the treatment landscape. Novel therapies are building on this success and are bein...
#1V. Kong(Princess Margaret Cancer Centre)H-Index: 1
#1Adham Hijab(ICR: Institute of Cancer Research)H-Index: 1
Last. Brian C. Baumann(WashU: Washington University in St. Louis)H-Index: 16
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Technological advancement has facilitated patient-specific radiotherapy in bladder cancer. This has been made possible by developments in image-guided radiotherapy (IGRT). Particularly transformative has been the integration of volumetric imaging into the workflow. The ability to visualise the bladder target using cone beam computed tomography and magnetic resonance imaging initially assisted with determining the magnitude of inter- and intra-fraction target change. It has led to greater confide...
Purpose Definitive radiation therapy (RT), with or without concurrent chemotherapy, is an alternative to radical cystectomy for patients with localized, muscle-invasive bladder cancer (MIBC) who are either not surgical candidates or prefer organ preservation. We aim to synthesize an evidence-based guideline regarding the appropriate use of RT. Methods and Materials We performed a Preferred Reporting Items for Systematic Reviews and Meta-analyses literature review using the PubMed and Embase data...
In this study we compared three different microbubble-based approaches to the delivery of a widely used chemotherapy drug, gemcitabine: (i) co-administration of gemcitabine and microbubbles (Gem+MB); (ii) conjugates of microbubbles and gemcitabine-loaded liposomes (GemlipoMB); and (iii) microbubbles with gemcitabine directly bound to their surfaces (GembioMB). Both in vitro and in vivo investigations were carried out, respectively, in the RT112 bladder cancer cell line and in a murine orthotopic...
Introduction Daily radiotherapy delivered with radiosensitisation offers patients with muscle invasive bladder cancer (MIBC) comparable outcomes to cystectomy with functional organ preservation. Most recurrences following radiotherapy occur within the bladder. Increasing the delivered radiotherapy dose to the tumour may further improve local control. Developments in image-guided radiotherapy have allowed bladder tumour-focused ‘plan of the day’ radiotherapy delivery. We aim to test within a rand...
Bladder cancer is among the top ten most common cancer types in the world. Around 25% of all cases are muscle-invasive bladder cancer, for which the gold standard treatment in the absence of metastasis is the cystectomy. In recent years, trimodality treatment associating maximal transurethral resection and radiotherapy combined with concurrent chemotherapy is increasingly used as an organ-preserving alternative. However, the use of this treatment is still limited by the lack of biomarkers predic...
INTRODUCTION Radical cystectomy (RC) is the current mainstay for muscle-invasive bladder cancer (MIBC). Concerns regarding morbidity, mortality and quality of life have favored the introduction of bladder sparing strategies. Trimodal therapy, combining transurethral resection, chemotherapy and radiotherapy is the current standard of care for bladder preservation strategies in selected patients with MIBC. EVIDENCE ACQUISITION A comprehensive search of the Medline and Embase databases was performe...
Last. Fadil Akyol(Hacettepe University)H-Index: 18
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Abstract Purpose Cisplatin based chemoradiation has been commonly used as a definitive treatment for muscle-invasive bladder cancer (MIBC). The aim of the current study is to evaluate oncologic results and toxicity profile of bladder-sparing treatment with external beam radiotherapy (EBRT) and gemcitabine chemotherapy (ChT) in patients with MIBC. Materials and Methods Between April 2005 and November 2018 44 patients with nonmetastatic and N0 MIBC were treated with transurethral resection of blad...