Intravesical bacille Calmette-Guérin versus mitomycin C in superficial bladder cancer: formal meta-analysis of comparative studies on tumor progression.
ABSTRACT To compare the therapeutic efficacy of intravesical bacille Calmette-Guérin (BCG) with mitomycin C (MMC) on progression of Stage Ta and T1 bladder carcinoma.
Combined published and unpublished data from comparative studies on BCG versus MMC in superficial bladder carcinoma were analyzed, considering possible confounding factors. Odds ratios (ORs) and 95% confidence intervals (CIs) were used as the primary effect size estimate. Tumor progression was defined as progression to a higher tumor stage or the development of metastatic disease.
In nine eligible clinical trials, 1277 patients were treated with BCG and 1133 with MMC. Within the overall median follow-up of 26 months, 7.67% of the patients in the BCG group and 9.44% of the patients in the MMC group developed tumor progression. In all nine individual studies and in the combined results, no statistically significant difference in the ORs for progression between the BCG and MMC-treated groups was found (combined OR = 0.77; 95% CI 0.57 to 1.03; P = 0.081). In the subgroup with BCG maintenance, the combined result of the five individual studies showed a statistically significant superiority of BCG over MMC (OR = 0.66; 95% CI 0.47 to 0.94; P = 0.02). In the four studies without BCG maintenance, the combined result indicated no statistically significant difference between the two treatments (OR = 1.16; 95% CI 0.65 to 2.07; P = 0.612). Potential confounders, such as tumor risk status, duration of follow-up, BCG strain, BCG and MMC treatment regimen, and year of publication did not significantly influence these results.
The results demonstrated statistically significant superiority for BCG compared with MMC for the prevention of tumor progression only if BCG maintenance therapy was provided.
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ABSTRACT: Aim. To evaluate whether tumor infiltrating lymphocytes (TIL) in biopsy specimens are associated with the clinical outcome of non-muscle invasive bladder cancer. Methods. We retrieved tumor specimens from 115 patients with solitary papillary non-muscle invasive bladder cancer treated between 1996 and 2006 and constructed tissue microarrays. Patients were divided in two groups: those with recurrent disease (N=69) and those without recurrent disease (N=46) during the follow up of minimum 5 years. All patients were treated with initial transurethral resection and none received adjuvant therapy. Immunhistochemical staining was performed with anti-CD3, CD4, CD8, and Granzyme B (GrB). The CD4+:CD8+ and GrB+:CD8 ratios were determined. Results. Tumor infiltrating lymphocytes were predominantly observed within cancer stroma, and only rare individual cells were observed intraepithelially. The group without recurrent disease had lower levels of CD3+ and CD8+ lymphocytes than the group with recurrent disease (P=0.0001, P=0.0002, respectively). The CD4+:GrB+ and GrB+:CD8+ ratios were significantly higher in patients without recurrent disease (P=0.0002, P=0.039, respectively). Conclusion. This study revealed a possible connection between TIL number and bladder cancer recurrence. TIL subset ratio showed different patterns in recurrent and non-recurrent tumors, which is why it could become a useful a prognostic clinical index if our findings are confirmed in randomized trials.Croatian Medical Journal 12/2012; 53(6):598-604. · 1.25 Impact Factor
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ABSTRACT: To explore the necessity of maintenance, efficacy of low-dose and superiority of various combination therapies of Bacillus Calmette-Guerin (BCG) in treatment of superficial bladder cancer (BCa). Comprehensive searches of electronic databases (PubMed, Embase, and the Cochrane Library) were performed, then a systematic review and cumulative meta-analysis of 21 randomized controlled trials (RCTs) and 9 retrospective comparative studies were carried out according to predefined inclusion criteria. Signicantly better recurrence-free survivals (RFS) were observed respectively in patients who received BCG maintenance, standard-dose and BCG plus epirubicin therapy comparing to those received induction, low-dose and BCG alone. BCG maintenance therapy was also associated with significantly better progression-free survival (PFS), but there were more incidences of adverse events. Pooled results showed no remarkable advantage of BCG combined with Mitomycin C or with interferon alpha-2b in improving oncologic outcomes. Sensitivity-analyses stratified by study-design and tumor stage led to very similar overall results and often to a decrease of the between-study heterogeneity. Our data confirmed that non-RCT only affected strength rather than direction of the overall results. All patients with superficial BCa should be encouraged to accept BCG maintenance therapy with standard-dose if well tolerated. Patients can benefit from BCG combined with epirubicin but not from BCG combined with Mitomycin C or interferon alpha-2b.BMC Cancer 07/2013; 13(1):332. · 3.33 Impact Factor
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ABSTRACT: Bladder cancer stem cell research is rapidly expanding based on the knowledge of cancer stem cells from various cancer types and normal stem cells as models. In various cancer types, cancer stem cells have been implicated in therapeutic resistance and relapse after initial therapy. Understanding how cancer stem cells differ from bulk cancer cells and how cancer stem cells contribute to relapse and resistance are essential to develop novel therapeutics to target cancer stem cells effectively. Here we review the latest information on bladder cancer stem cells, their biological characteristics, including their response to treatment, recurrence, immune context and technical problems encountered in bladder cancer stem cell research.Current Stem Cell Research & Therapy 11/2013; · 2.96 Impact Factor