scholarly journals Review of Experimental Studies to Improve Radiotherapy Response in Bladder Cancer: Comments and Perspectives

Cancers ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 87
Author(s):  
Linda Silina ◽  
Fatlinda Maksut ◽  
Isabelle Bernard-Pierrot ◽  
François Radvanyi ◽  
Gilles Créhange ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Systematic Reviews ◽  
Bladder Tumour ◽  
Experimental Studies ◽  
Tumour Response ◽  
Predictive Biomarkers ◽  
Therapeutic Index ◽  
In Vivo Studies ◽  
Molecular Characteristics ◽  
Bladder Preservation

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 predicting tumour response and by a lack of targeted radiosensitising drugs that can improve the therapeutic index, especially by limiting side effects such as bladder fibrosis. In order to improve the bladder-preserving treatment, experimental studies addressing these main issues ought to be considered (both in vitro and in vivo studies). Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for systematic reviews, we conducted a literature search in PubMed on experimental studies investigating how to improve bladder cancer radiotherapy with different radiosensitising agents using a comprehensive search string. We made comments on experimental model selection, experimental design and results, formulating the gaps of knowledge still existing: such as the lack of reliable predictive biomarkers of tumour response to chemoradiation according to the molecular tumour subtype and lack of efficient radiosensitising agents specifically targeting bladder tumour cells. We provided guidance to improve forthcoming studies, such as taking into account molecular characteristics of the preclinical models and highlighted the value of using patient-derived xenografts as well as syngeneic models. Finally, this review could be a useful tool to set up new radiation-based combined treatments with an improved therapeutic index that is needed for bladder preservation.

scholarly journals Selective organ preservation with neo-adjuvant chemotherapy for the treatment of muscle invasive transitional cell carcinoma of the bladder

2015 ◽  
Vol 112 (10) ◽  
pp. 1626-1635 ◽  
Author(s):  
S Hafeez ◽  
A Horwich ◽  
O Omar ◽  
K Mohammed ◽  
A Thompson ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Adjuvant Chemotherapy ◽  
Organ Preservation ◽  
Bladder Tumour ◽  
Poor Responders ◽  
Bladder Preservation ◽  
Platinum Based Chemotherapy ◽  
Neo Adjuvant Chemotherapy ◽  
Muscle Invasive

Abstract Background: Radiotherapy for muscle invasive bladder cancer (MIBC) aims to offer organ preservation without oncological compromise. Neo-adjuvant chemotherapy provides survival advantage; response may guide patient selection for bladder preservation and identify those most likely to have favourable result with radiotherapy. Methods: Ninety-four successive patients with T2-T4aN0M0 bladder cancer treated between January 2000 and June 2011 were analysed at the Royal Marsden Hospital. Patients received platinum-based chemotherapy following transurethral resection of bladder tumour; repeat cystoscopy (±biopsy) was performed to guide subsequent management. Responders were treated with radiotherapy. Poor responders were recommended radical cystectomy. Progression-free survival (PFS), disease-specific survival (DSS) and overall survival (OS) were estimated using Kaplan–Meier method; univariate and multivariate analyses were performed using the Cox proportional hazard regression model. Results: Response assessment was performed in 89 patients. Seventy-eight (88%) demonstrated response; 53 (60%) achieved complete response (CR); 74 responders had radiotherapy; 4 opted for cystectomy. Eleven (12%) demonstrated poor response, 10 received cystectomy. Median survival for CR was 90 months (95% CI 64.7, 115.9) compared with 16 months (95% CI 5.4, 27.4; P<0.001) poor responders. On multivariate analysis, only response was associated with significantly improved PFS, OS and DSS. After a median follow-up of 39 months (range 4–127 months), 14 patients (16%) required salvage cystectomy (8 for non-muscle invasive disease, 5 for invasive recurrence, 1 for radiotherapy related toxicity). In all, 82% had an intact bladder at last follow-up after radiotherapy; 67% had an intact bladder at last follow-up or death. Our study is limited by its retrospective nature. Conclusions: Response to neo-adjuvant chemotherapy is a favourable prognostic indicator and can be used to select patients for radiotherapy allowing bladder preservation in >80% of the selected patients.

1254: Bladder Preservation in Invasive Bladder Cancer with Chemotherapy after Radical Transurethral Resection Bladder Tumour: Long-Term Followup

2006 ◽  
Vol 175 (4S) ◽  
pp. 403-403
Author(s):  
Juan Patou ◽  
Oscar Rodriguez ◽  
Josep Segarra ◽  
Jorge Huguet ◽  
Eugenio Marcuelto ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Transurethral Resection ◽  
Bladder Tumour ◽  
Invasive Bladder Cancer ◽  
Bladder Preservation

scholarly journals Predictive Biomarkers of Bacillus Calmette-Guérin Immunotherapy Response in Bladder Cancer: Where Are We Now?

2012 ◽  
Vol 2012 ◽  
pp. 1-17 ◽  
Author(s):  
Luís Lima ◽  
Mário Dinis-Ribeiro ◽  
Adhemar Longatto-Filho ◽  
Lúcio Santos
Keyword(s):  
Bladder Cancer ◽  
Tumour Progression ◽  
Therapeutic Option ◽  
Bladder Tumour ◽  
Predictive Biomarkers ◽  
Bacillus Calmette Guerin ◽  
Exclusion Criteria ◽  
Effective Therapeutic Option ◽  
Intravesical Instillations

The most effective therapeutic option for managing nonmuscle invasive bladder cancer (NMIBC), over the last 30 years, consists of intravesical instillations with the attenuated strain Bacillus Calmette-Guérin (the BCG vaccine). This has been performed as an adjuvant therapeutic to transurethral resection of bladder tumour (TURBT) and mostly directed towards patients with high-grade tumours, T1 tumours, andin situcarcinomas. However, from 20% to 40% of the patients do not respond and frequently present tumour progression. Since BCG effectiveness is unpredictable, it is important to find consistent biomarkers that can aid either in the prediction of the outcome and/or side effects development. Accordingly, we conducted a systematic critical review to identify the most preeminent predictive molecular markers associated with BCG response. To the best of our knowledge, this is the first review exclusively focusing on predictive biomarkers for BCG treatment outcome. Using a specific query, 1324 abstracts were gathered, then inclusion/exclusion criteria were applied, and finally 87 manuscripts were included. Several molecules, including CD68 and genetic polymorphisms, have been identified as promising surrogate biomarkers. Combinatory analysis of the candidate predictive markers is a crucial step to create a predictive profile of treatment response.

339: Selective Bladder Preservation by Transurethral Layer-Section in T2 Muscle-Invasive Bladder Cancer

2007 ◽  
Vol 177 (4S) ◽  
pp. 114-115
Author(s):  
Young Deuk Choi ◽  
Kang Su Cho ◽  
Soung Yong Cho ◽  
Hyun Min Choi ◽  
Nam Hoon Cho
Keyword(s):  
Bladder Cancer ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Bladder Preservation ◽  
Muscle Invasive

Comparative Study of Highly Pathogenic Avian Infl uenza Strains Isolated in Ukraine in 2005 and 2008

2014 ◽  
Vol 1 (1) ◽  
pp. 68-71
Author(s):  
A. Gerilovych ◽  
B. Stegniy ◽  
A. Stegniy ◽  
M. Stegniy ◽  
K. Smietanka ◽  
...  
Keyword(s):  
Western Europe ◽  
Rna Extraction ◽  
Experimental Studies ◽  
Molecular Characteristics ◽  
Eastern European ◽  
Highly Pathogenic ◽  
Genetic Lineages ◽  
Phylogenetic Studies ◽  
Polymerase Chain ◽  
Pathogenic H5n1

Objective. To research the molecular characteristics of two HPAI strains – A/Ch/Syvash/02/05/H5N1 and A/Ch/Krasnogvardeysk/58/08/H5N1, which were identifi ed as representatives of the highly pathogenic H5N1 viruses. Methods. RNA extraction, real-time polymerase chain reaction (PCR). Results. The phylogenetic studies revealed that the above mentioned strains belong to two various genetic lineages originated from the Eastern European strains isolated in 2005, but differ from the viruses introduced to the Central and Western Europe in 2005/2006, and also the lineages consisting of H5N1 viruses isolated in the Europe and Middle East in late 2007. Conclusions. Relying on experimental studies, it can be concluded that the strains of A/Ch/Syvash/02/05/H5N1 and A/Ch/Krasnogvardeysk/58/08/H5N1 are highly pathogenic.

scholarly journals Complications of intravesical BCG therapy in non-muscle invasive bladder cancer: our tertiary care centre experience

2020 ◽  
Vol 26 (1) ◽  
Author(s):  
Vivek Sharma ◽  
Avinash P. S. Thakur ◽  
Vasantharaja Ramasamy ◽  
Pushpendra Kumar Shukla ◽  
Fanindra Singh Solanki ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Adverse Effects ◽  
Bladder Carcinoma ◽  
Bladder Tumour ◽  
The Body ◽  
Bcg Therapy ◽  
Intravesical Bcg ◽  
Urothelial Bladder ◽  
Muscle Invasive ◽  
Intravesical Bcg Therapy

Abstract Background Urothelial bladder carcinoma accounts for around 3.9% cases of all the male cancers in India. Non-muscle-invasive bladder carcinoma (NMIBC) is predominant group which constitute approximately three fourth of the urothelial bladder cancer. Intravesical BCG immunotherapy is the corner stone of today’s NMIBC management. However, as with any other therapy it has its own complications and its interruption due to these adverse effects is a major cause of suboptimal efficacy. The aim of this study was to assess the complications of intravesical BCG therapy and their management in NMIBC patients. Methods This was a retrospective descriptive study conducted between October 2016 and November 2019; a backward review of 149 patients with diagnosis of NMIBC that undergone intravesicle BCG therapy was performed. Patient’s demographical, clinical, diagnostic and procedural data regarding bladder tumour, BCG therapy, its complications and management were collected and analysed. Results Total 149 patients were analysed, comprising 116 males and 33 females. The mean age was of 57.2 ± 6.7 years. Total 85.23% were primary and 14.76% were recurrent tumours. Total 96 patients (64.42%) completed the planned course, while 53 (35.57%) interrupted. The reasons for BCG interruption includes adverse effects (15.4%), progression of disease (6.7%), disease refractory to BCG (4.6%) and disease recurrence during BCG (3.3%). Most of the adverse events occurred in first 6 months and most interruptions occurred after the induction period. Cystitis was the most common observed adverse effect seen in 39.6% patients. Frequency, urgency, haematuria were common presentation. Radical cystectomy was the most common (16.10%) further treatment with patients whose treatment was interrupted. Conclusion BCG is an indispensable therapy available for NMIBC, but it is associated with array of adverse effects and complications, which are the main reasons for poor compliance to BCG therapy. Although BCG-related complications can affect any organ in the body, potentially life-threatening systemic BCG-related infections are encountered in only < 5% of patients. There are some difficulties in diagnosis of the BCG complications because acid-fast staining, culture and PCR test are not always positive; tissue biopsies should be indicated sometimes to evaluate histopathology and presence of M. bovis. A persistently monitored multidisciplinary approach with high index of suspicion and prompt anti-TB therapy can help to derive the maximum benefits while keeping the complications at check.

scholarly journals Circulating Cell-Free DNA in Liquid Biopsies as Potential Biomarker for Bladder Cancer: A Review

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1448
Author(s):  
Raquel Herranz ◽  
Julia Oto ◽  
Emma Plana ◽  
Álvaro Fernández-Pardo ◽  
Fernando Cana ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Progression ◽  
Specific Treatment ◽  
Predictive Biomarkers ◽  
Liquid Biopsies ◽  
Cell Free Dna ◽  
Specific Patient ◽  
Free Dna ◽  
Potential Biomarker ◽  
Cancer Types

Bladder cancer (BC) is among the most frequent cancer types in the world and is the most lethal urological malignancy. Presently, diagnostic and follow-up methods for BC are expensive and invasive. Thus, the identification of novel predictive biomarkers for diagnosis, progression, and prognosis of BC is of paramount importance. To date, several studies have evidenced that cell-free DNA (cfDNA) found in liquid biopsies such as blood and urine may play a role in the particular scenario of urologic tumors, and its analysis may improve BC diagnosis report about cancer progression or even evaluate the effectiveness of a specific treatment or anticipate whether a treatment would be useful for a specific patient depending on the tumor characteristics. In the present review, we have summarized the up-to-date studies evaluating the value of cfDNA as potential diagnostic, prognostic, or monitoring biomarker for BC in several biofluids.

scholarly journals Inhibition of Androgen Signalling Improves the Outcomes of Therapies for Bladder Cancer: Results from a Systematic Review of Preclinical and Clinical Evidence and Meta-Analysis of Clinical Studies

Diagnostics ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 351
Author(s):  
Massimiliano Creta ◽  
Giuseppe Celentano ◽  
Luigi Napolitano ◽  
Roberto La Rocca ◽  
Marco Capece ◽  
...  
Keyword(s):  
Systematic Review ◽  
Bladder Cancer ◽  
Relative Risk ◽  
Clinical Studies ◽  
Clinical Evidence ◽  
Meta Analysis ◽  
Bladder Tumour ◽  
Signalling Pathways ◽  
Reductase Inhibitors ◽  
The Impact

Bladder cancer (BCa) is an endocrine-related tumour and the activation of androgen signalling pathways may promote bladder tumorigenesis. We summarized the available preclinical and clinical evidence on the implications of the manipulation of androgen signalling pathways on the outcomes of BCa therapies. A systematic review was performed in December 2020. We included papers that met the following criteria: original preclinical and clinical research; evaluating the impact of androgen signalling modulation on the outcomes of BCa therapies. Six preclinical and eight clinical studies were identified. The preclinical evidence demonstrates that the modulation of androgen receptor-related pathways has the potential to interfere with the activity of the Bacillus Calmette Guerin, doxorubicin, cisplatin, gemcitabine, and radiotherapy. The relative risk of BCa recurrence after transurethral resection of the bladder tumour (TURBT) is significantly lower in patients undergoing therapy with 5 alpha reductase inhibitors (5-ARIs) or androgen deprivation therapy (ADT) (Relative risk: 0.50, 95% CI: 0.30–0.82; p = 0.006). Subgroup analysis in patients receiving 5-ARIs revealed a relative risk of BCa recurrence of 0.46 (95% CI: 0.22–0.95; p = 0.040). A significant negative association between the ratio of T1 BCa patients in treated/control groups and the relative risk of BCa recurrence was observed. Therapy with 5-ARIs may represent a potential strategy aimed at reducing BCa recurrence rate, mainly in patients with low stage disease. Further studies are needed to confirm these preliminary data.

scholarly journals 92 Reshaping the Diagnostic Pathways for Investigation of Haematuria During and After The COVID-19 Pandemic: Diagnostic Accuracy of Strategies for Detection of Bladder Cancer from The IDENTIFY Cohort Study

2021 ◽  
Vol 108 (Supplement_2) ◽  
Author(s):  
S Khadhouri ◽  
K Gallagher ◽  
K MacKenzie ◽  
T Shah ◽  
C Gao ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cohort Study ◽  
Test Performance ◽  
Bladder Tumour ◽  
Healthcare Services ◽  
Diagnostic Strategies ◽  
Flexible Cystoscopy ◽  
Resource Limited ◽  
Diagnostic Test Performance ◽  
Diagnostic Pathways

Abstract Introduction Diagnostic haematuria services have been reduced due to the COVID-19 pandemic, compromising patient care, and necessitating a more pragmatic pathway. Method The IDENTIFY study was an international, prospective, multicentre cohort study of over 11,000 patients referred to secondary care for investigation of haematuria. Using this data, we developed strategies using combinations of imaging and cytology as triage tests to maximise cancer detection within a pragmatic pathway. Results 8112 patients (74·4%) received an ultrasound or a CT urogram, with or without cytology. 5737 (70·7%) patients had visible haematuria (VH) and 2375 (29·3%) had non-visible haematuria (NVH). Diagnostic test performance was used to determine optimal age cut-offs for four proposed strategies. We recommended proceeding directly to transurethral resection of bladder tumour for patients of any age with positive triage tests for cancer. Patients with negative triage tests under 35-years-old with VH, or under 50-years-old with NVH can safely be discharged without undergoing flexible cystoscopy. The remaining patients may undergo flexible cystoscopy, with a greater priority for older patients to capture high risk bladder cancer. Conclusions We suggest diagnostic strategies in patients with haematuria, which focus on detection of bladder cancer, whilst reducing the burden to healthcare services in a resource-limited setting.

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