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.

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.

Significance of prophylactic urethrectomy at the time of radical cystectomy for bladder cancer

2020 ◽  
Author(s):  
Kyohei Hakozaki ◽  
Eiji Kikuchi ◽  
Koichiro Ogihara ◽  
Keisuke Shigeta ◽  
Takayuki Abe ◽  
...  
Keyword(s):  
Overall Survival ◽  
Bladder Cancer ◽  
Survival Rate ◽  
Neoadjuvant Chemotherapy ◽  
Radical Cystectomy ◽  
Carcinoma In Situ ◽  
Bladder Tumour ◽  
Overall Survival Rate ◽  
Definitive Evidence

Abstract Background Prophylactic urethrectomy at the time of radical cystectomy is frequently recommended for patients with bladder cancer at a high risk of urethral recurrence without definitive evidence. The present study attempted to clarify the survival benefits of performing prophylactic urethrectomy. Methods We identified 214 male patients who were treated by radical cystectomy with an incontinent urinary diversion in our seven institutions between 2004 and 2017. We used propensity score matching and ultimately identified 114 patients, 57 of whom underwent prophylactic urethrectomy (prophylactic urethrectomy group) and 57 who did not (non-prophylactic urethrectomy group). Results No significant differences were observed in the 5-year overall survival rate between the prophylactic urethrectomy and non-prophylactic urethrectomy groups in the overall. However, the local recurrence rate was significantly lower in the prophylactic urethrectomy group than in the non-prophylactic urethrectomy group (P = 0.015). In the subgroup of 58 patients with multiple tumours and/or concomitant carcinoma in situ at the time of transurethral resection of bladder tumour, the 5-year overall survival rate was significantly higher in the prophylactic urethrectomy group than in the non-prophylactic urethrectomy group (P = 0.021). A multivariate analysis revealed that performing prophylactic urethrectomy was the only independent predictor of the overall survival rate (P = 0.016). In those patients who were treated without neoadjuvant chemotherapy (n = 38), the 5-year overall survival rate was significantly higher in the prophylactic urethrectomy group than in the non-prophylactic urethrectomy group (P = 0.007). Conclusions Prophylactic urethrectomy at the time of radical cystectomy may have a survival benefit in patients with multiple tumours and/or concomitant carcinoma in situ, particularly those who do not receive neoadjuvant chemotherapy.

scholarly journals Histopathological Changes in Adjacent Non-Tumour Mucosa in Trans Urethral Resection of Bladder Tumour Specimens of Bladder Carcinoma

2021 ◽  
Vol 10 (13) ◽  
pp. 962-967
Author(s):  
Divya Renjini ◽  
Muthukrishnan Chirayil Ponnappan ◽  
Vasudevan Sambu Potty
Keyword(s):  
Bladder Cancer ◽  
Bladder Carcinoma ◽  
Carcinoma In Situ ◽  
Bladder Tumour ◽  
Residual Tumour ◽  
P53 Expression ◽  
Thin Sections ◽  
Adjacent Mucosa ◽  
Multiple Biopsies

BACKGROUND Urinary bladder cancer is associated with high morbidity and mortality rates if not treated optimally. One of the causes of tumour recurrence is undiscovered residual tumour, and the existence of macroscopically invisible premalignant and malignant lesions of urothelium during the primary resection which can be detected by taking biopsy from apparently normal mucosa in the vicinity of the tumour during trans urethral resection of bladder tumour (TURBT). The primary objective was to estimate the proportion of bladder tumour showing changes in adjacent non tumour mucosa in TURBT specimens, within a period of six months. The secondary objectives were to study the association between changes in non-tumour bladder mucosa with the recurrence, seen after six months, and to study the expression of P53 in adjacent non tumour mucosa of bladder cancer. METHODS All cases of bladder carcinoma from trans urethral resection of bladder tumour which were sent along with adjacent non tumour mucosa and received at Department of Pathology, MCH, Trivandrum, for a period of six months were included in the study. Adjacent mucosa sent along with TURBT specimen received at our department was collected. After processing, tissue is embedded in paraffin blocks and thin sections of 4 - 5 m thickness was taken and stained with haematoxylin and eosin (H & E). Using light microscopy, changes in adjacent mucosa were assessed for any abnormal changes and findings were correlated with collected data. P53 expression was studied in the adjacent mucosa. All details were entered in the proforma. Details collected were entered in Excel and analysed using SPSS software. RESULTS Out of 37 TURBT cases that were sent along with adjacent mucosa, 12 cases showed changes in adjacent mucosa accounting for 32.4 %. P53 positivity accounting for 18.9 %, was seen in abnormal mucosa change with carcinoma in situ and dysplasia. On follow up, 8 % of cases with positive biopsy finding showed recurrence. CONCLUSIONS Multiple biopsies from adjacent non tumour mucosa is not necessary for all patients with superficial bladder tumour. Positive findings in adjacent mucosa does not have significant correlation with tumour stage / grade, and tumour size, number of lesions or histopathological findings. Adjacent mucosa may be useful in detecting concomitant carcinoma in situ (CIS), which can be helpful in therapeutic approach. KEY WORDS Normal Looking Mucosa, TURBT, Bladder Cancer

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