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- Malmström, Per-Uno, et al.
(författare)
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An individual patient data meta-analysis of the long-term outcome of randomised studies comparing intravesical mitomycin C versus bacillus Calmette-Guérin for non-muscle-invasive bladder cancer
- 2009
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Ingår i: European Urology. - : Elsevier BV. - 0302-2838 .- 1873-7560. ; 56:2, s. 247-56
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Patients with non-muscle-invasive bladder cancer with an intermediate or high risk need adjuvant intravesical therapy after surgery. Based largely on meta-analyses of previously published results, guidelines recommend using either bacillus Calmette-Guérin (BCG) or mitomycin C (MMC) in these patients. Individual patient data (IPD) meta-analyses, however, are the gold standard. OBJECTIVE: To compare the efficacy of BCG and MMC based on an IPD meta-analysis of randomised trials. DESIGN, SETTING, AND PARTICIPANTS: Trials were searched through Medline and review articles. The relevant trial investigators were contacted to provide IPD. MEASUREMENTS: The drugs were compared with respect to time to recurrence, progression, and overall and cancer-specific death. RESULTS AND LIMITATIONS: Nine trials that included 2820 patients were identified, and IPD were obtained from all of them. Patient characteristics were 71% primary, 54% Ta, 43% T1, 25% G1, 58% G2, and 16% G3, and 7% had prior intravesical chemotherapy. Based on a median follow-up of 4.4 yr, 43% recurred. Overall, there was no difference in the time to first recurrence (p=0.09) between BCG and MMC. In the trials with BCG maintenance, a 32% reduction in risk of recurrence on BCG compared to MMC was found (p<0.0001), while there was a 28% risk increase (p=0.006) for BCG in the trials without maintenance. BCG with maintenance was more effective than MMC in both patients previously treated and those not previously treated with chemotherapy. In the subset of 1880 patients for whom data on progression, survival, and cause of death were available, 12% progressed and 24% died, and, of those, 30% of the deaths were due to bladder cancer. No statistically significant differences were found for these long-term end points. CONCLUSIONS: For prophylaxis of recurrence, maintenance BCG is required to demonstrate superiority to MMC. Prior intravesical chemotherapy was not a confounder. There were no statistically significant differences regarding progression, overall survival, and cancer-specific survival between the two treatments.
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- Schultz, Iman J, et al.
(författare)
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Gene expression analysis for the prediction of recurrence in patients with primary Ta urothelial cell carcinoma
- 2007
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Ingår i: European Urology. - : Elsevier BV. - 0302-2838 .- 1873-7560. ; 51:2, s. 416-423
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Tidskriftsartikel (refereegranskat)abstract
- Objectives The individual recurrence-free period after primary surgery of patients with Ta urothelial cell carcinoma (UCC) cannot be predicted accurately. This study aims at discriminating between patients with primary Ta UCC and long or short recurrence-free periods. Methods We investigated mRNA expression of 23 genes in 44 primary Ta tumours (23 and 21 tumours were from patients with long [≥4 yr] or short [≤2 yr] recurrence-free periods, respectively), using real-time quantitative polymerase chain reaction. The genes were selected from previously published studies and showed a relationship with tumour recurrence in patients with UCC. Results Differential mRNA expression between the two patient groups indicated statistical significance only for the gene survivin (p = 0.0011). Its recurrence predictive value could not be increased by a combination with any of the other genes. Comparison of the receiver operating characteristic curves for survivin expression between patients with long or short recurrence-free intervals revealed an area under the curve of 0.79 (95%CI, 0.65–0.92). Using the median expression (0.84) as cut-off level, survivin identified 71.4% (95%CI, 47.8–88.7) and 69.6% (95%CI, 47.1–86.8) of the patients with long or short recurrence-free periods, respectively. Conclusions Our study identifies survivin as the most promising candidate to distinguish between patients with primary Ta UCC and long or short recurrence-free intervals. Therefore, survivin mRNA expression analysis might help the urologist to individualise patient treatment and prevent unnecessary cystoscopies in a subgroup of these patients.
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- Schultz, Iman J., et al.
(författare)
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Prediction of recurrence in Ta urothelial cell carcinoma by real-time quantitative PCR analysis : a microarray validation study
- 2006
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 119:8, s. 1915-1919
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Tidskriftsartikel (refereegranskat)abstract
- Accurate prediction of tumor recurrence in patients with superficial urothelial cell carcinoma (UCC) might result in a significant reduction of invasive follow-up cystoscopies. A recent study identified a panel of 26 genes from a large cDNA microarray analysis of bladder tumors that discriminated between early- and late-recurring patients with superficial Ta tumors (Dyrskjot et al., Nat Genet 2003;33:90-6). We aimed to validate this panel of genes in 44 primary Ta UCCs (23 and 21 tumors from patients with short or prolonged recurrence-free periods, respectively), by real-time quantitative PCR. Statistical analysis showed marginal significant different mRNA expression levels between the 2 patient groups. To evaluate a supplementary effect of genes for the identification of patients with short or prolonged recurrence-free intervals, forward logistic regression analysis was applied. This revealed that a combination of the expression profiles of the genes HNRPK, LTB4DH and ANP32B resulted in the best performance, although the combination only marginally increased the predictive value of HNRPK alone. Comparing the receiver-operating-characteristic curves for HNRPK expression among patients with short or prolonged recurrence-free periods, revealed an area under the curve of 0.696 (95% CI, 0.537-0.855). Using the median HNRPK expression level as cut-off, a sensitivity of 69.6% and a specificity of 71.4% were obtained for the identification of patients with short or prolonged recurrence-free periods, respectively. In conclusion, we were not able to confirm the microarray gene expression pattern of the 26 genes shown by Dyrskjot et al. The discovery of accurate recurrence predictive markers, therefore, remains a challenge.
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| 5. |
- Schultz, Iman J., et al.
(författare)
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Simultaneous proteomic and genomic analysis of primary Ta urothelial cell carcinomas for the prediction of tumor recurrence
- 2007
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Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 27:2, s. 1051-1058
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Tidskriftsartikel (refereegranskat)abstract
- Background: The prediction of tumor recurrence in patients with Ta urothelial cell carcinoma is inaccurate and new prognostic markers are desirable. Materials and Methods: Surface-enhanced laser-desorption ionization time-of-flight mass spectrometry (SELDI-TOF MS) was performed on 33 primary Ta tumors (16 and 17 tumors were from patients with long and short recurrence-free periods, respectively) and data were compared to previously obtained mRNA expression profiles of 49 genes. Results: The intensities of a protein peak at m/z 33331 varied most significantly between the two patient groups (p=0.0048). This was comparable to survivin, whose mRNA expression differed most significantly (p=0.0042) of the 49 genes. ROC analysis revealed an area under the curve for protein peak 33331 and survivin of 0.78 (95% CI, 0.62-0.94) and 0.79 (95% CI, 0.63-0.94), respectively. Protein peak 33331 and survivin identified 3 (17%) and 8 (47%) patients with a recurrence-free period of at least 4 years, respectively, without generating false-negatives. Conclusion: These findings indicate that SELDI-TOF MS and real-time Q-PCR analysis on the same tissue can result in the identification of markers with comparable differential expression. Such combined analyses may yield combinations of several markers that might improve disease prognosis.
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- Schultz, Iman J., et al.
(författare)
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The Prognostic Role of the STK15 T91A Polymorphism and of STK15 mRNA Expression in Patients with Urothelial Cell Carcinoma
- 2007
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Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 27:2, s. 1025-1030
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Tidskriftsartikel (refereegranskat)abstract
- Background: The prognostic role of the STK15 T91A polymorphism and of STK15 mRNA expression was investigated in patients with urothelial cell carcinoma (UCC). Materials and Methods: The STK15 genotype with respect to the T91A polymorphism was assessed by restriction fragment length polymorphism in 135 patients. STK15 mRNA expression was measured in tumor tissues of 103 patients, using real-time quantitative PCR. Results: The T91A polymorphism lacked any prognostic information in our patient cohort. Interestingly though, STK15 mRNA expression was increased in invasive and high-grade tumors (p-values of 0.009 and 0.0001, respectively). Additionally, patients with superficial UCC (n=82) who had a tumor recurrence in the first year after surgery displayed elevated STK15 mRNA expression levels (p=0.009). Kaplan-Meier survival analysis revealed an increased risk of tumor progression for patients with Ta tumors (n=62) and high STK15 expression (log-rank p=0.04). Furthermore, a decreased overall (log-rank p=0.006) and UCC-specific survival (log-rank p=0.001) were shown for patients with elevated STK15 mRNA levels. Conclusion: Patients with UCC and elevated levels of STK15 mRNA generally showed a more adverse disease course than patients with low levels. This may help in identifying patients in need of more aggressive treatment.
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| 7. |
- Wu, Xifeng, et al.
(författare)
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Genetic variation in the prostate stem cell antigen gene PSCA confers susceptibility to urinary bladder cancer.
- 2009
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 41:9, s. 991-5
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Tidskriftsartikel (refereegranskat)abstract
- We conducted a genome-wide association study on 969 bladder cancer cases and 957 controls from Texas. For fast-track validation, we evaluated 60 SNPs in three additional US populations and validated the top SNP in nine European populations. A missense variant (rs2294008) in the PSCA gene showed consistent association with bladder cancer in US and European populations. Combining all subjects (6,667 cases, 39,590 controls), the overall P-value was 2.14 x 10(-10) and the allelic odds ratio was 1.15 (95% confidence interval 1.10-1.20). rs2294008 alters the start codon and is predicted to cause truncation of nine amino acids from the N-terminal signal sequence of the primary PSCA translation product. In vitro reporter gene assay showed that the variant allele significantly reduced promoter activity. Resequencing of the PSCA genomic region showed that rs2294008 is the only common missense SNP in PSCA. Our data identify rs2294008 as a new bladder cancer susceptibility locus.
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