Can Bcl-XL expression predict the radio sensitivity of Bilharzial-related squamous bladder carcinoma? a prospective comparative study

Abstract

BackgroundLocal pelvic recurrence after radical cystectomy for muscle invasive bilharzial related squamous cell carcinoma accounts for 75% of treatment failures even in organ confined tumors. Despite the proven value of lymphadenectomy, up to 60% of patients undergoing cystectomy do not have it. These factors are in favor of adjuvant radiotherapy reevaluation. objectives: to evaluate the effect of adjuvant radiotherapy on disease free survival in muscle invasive bilharzial related squamous cell carcinoma of the urinary bladder and to test the predictability of radio-sensitivity using the anti apoptotic protein Bcl-XL.MethodsThe study prospectively included 71 patients, (47 males, 24 females) with muscle invasive bilharzial related squamous cell carcinoma of the bladder (Stage pT2a-T3N0-N3M0) who underwent radical cystectomy in Assiut university hospitals between January 2005 and December 2006. Thirty eight patients received adjuvant radiotherapy to the pelvis in the dose of 50Gy/25 fractions/5 weeks (Group 1), while 33 patients did not receive adjuvant radiotherapy (group 2). Immunohistochemical characterization for bcl-xL expression was done. Follow up was done every 3 months for 12 to 36 months with a mean of 16 ± 10 months. All data were analyzed using SPSS version 16. Three years cumulative disease free survival was calculated and adjusted to Bcl-XL expression and side effects of the treatment were recorded.ResultsThe disease free cumulative survival was 48% for group 1 and 29% for group 2 (log rank p value 0.03). The multivariate predictors of tumor recurrence were the positive Bcl-XL expression (odd ratio 41.1, 95% CI 8.4 - 102.3, p < 0.0001) and radiotherapy (odd ratio 0.19, 95% CI 0.05 - 0.78, p < 0.02). With Cox regression, the only independent multivariate predictor of radio-sensitivity was the Bcl-XL expression with odd ratio 4.6 and a p value < 0.0001. All patients tolerated the treatment with no life threatening or late complications during the period of follow up.ConclusionsAdjuvant radiotherapy for muscle invasive bilharzial related squamous cell carcinoma of the urinary bladder has potential effectiveness and minor side effects. Moreover, Bcl-XL expression is a valuable tool for predicting those who might not respond to this adjuvant treatment.

Squamous cell carcinoma of the urinary bladder: Systematic review of clinical characteristics and therapeutic approaches

“…Adjuvant radiotherapy has historically been associated with serious side-effects including intestinal obstruction and urinary fistulae. In B-SCC, a recent study of patients determined that those not receiving adjuvant radiotherapy had a DFS of 29% compared to 48% for those who received adjuvant radiotherapy [41] . Given advances in radiation techniques and other promising contemporary studies of B-SCC [42] , postoperative radiotherapy for SCC should also be revisited.…”

Disruption of STAT3 by Niclosamide Reverses Radioresistance of Human Lung Cancer

“…It has been reported that multiple signal transduction pathways, including the PI3K/AKT, MAPK/ERK, ATM and EGFR pathways, can reduce radiation efficacy by promoting DNA repair in tumor cells (34, 35). Overexpression of Bcl2 and Bcl-XL resulted in resistance of tumor cells to apoptosis induced by radiation (36–39). Here we discovered that radiation induces activation of the JAK2/STAT3 survival signaling pathway, leading to upregulation of its downstream transcriptional effectors, Bcl2/Bcl-XL, in various human lung cancer cells (Figs.…”

NRAS mutant melanoma: biological behavior and future strategies for therapeutic management

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