Statin Use Is Associated with Better Prognosis of Patients with Prostate Cancer after Definite Therapies: A Systematic Review and Meta-Analysis of Cohort Studies.

Objective: Although the prognostic effect of statins on patients with prostate cancer (PCa) has been frequently evaluated, a consistent result is still lacking. We aimed to evaluate the association between statin use and mortality among patients with PCa after definite therapies. Methods: A systematic search of PubMed and other databases for cohort studies about the effect of statins on patients with PCa was performed until April 2022. Meta-analysis was performed using R software version 4.1.2. Results: 24 cohort studies involving 369, 206 participants were finally included. We found statin use significantly reduced the risk of prostate cancer-specific mortality (PCSM) with a pooled hazard ratio (pHR) = 0.76 (95% CI: 0.69-0.84, 18 studies), especially for postdiagnostic statin users: pHR = 0.81 (95% CI: 0.77-0.85) and patients who accepted androgen deprivation therapy (ADT): pHR = 0.69 (95% CI: 0.59-0.81). Statin use was also associated with a 24% reduction in the risk of all-cause mortality (ACM): pHR = 0.76 (95% CI: 0.68-0.85, 17 studies), especially for postdiagnostic statin users: pHR = 0.81 (95% CI: 0.78-0.85) and patients treated with ADT: pHR = 0.72 (95% CI: 0.63-0.82) or radiotherapy (RT): pHR = 0.68 (95% CI: 0.50-0.93). Conclusion: In conclusion, the use of statins could promote the prognosis of patients with PCa, especially for postdiagnostic users. For patients who received either ADT or radical prostatectomy (RP), statin use could decrease the PCSM. As for those who received either ADT or RT, statin use could decrease the ACM.

Toll-Like Receptor 4 as a Favorable Prognostic Marker in Bladder Cancer: A Multi-Omics Analysis.

BACKGROUND: The toll-like receptor 4 (TLR4) agonist, Bacille Calmette-Guérin, has exhibited gratifying effects in treating bladder cancer. The study aims to explore the expression pattern, prognostic value, and potential mechanism of TLR4 in bladder cancer. METHODS: The transcriptome file from the GSE13507 dataset in the Gene Expression Omnibus database and the promoter methylation file from the bladder cancer dataset in The Cancer Genome Atlas database were downloaded for analysis. The prognostic value of the TLRs was assessed by univariate Cox regression. Immunohistochemistry was applied to verify the expression of TLR4 in bladder cancer. The drug response is estimated through the R package "pRRophetic." The CIBERSORT algorithm was carried out to estimate the infiltrating immune cells of samples. Gene Set Enrichment Analysis (GSEA) was performed to identify the pathways involved under varied TLR4 expression levels. RESULTS: TLR4 is decreased in tumor tissues compared with surrounding tumor tissues or normal tissue, which is also positively correlated to the overall survival rate (hazard ratio [HR] = 0.38) and cancer-specific survival rate (HR = 0.15) of patients with bladder cancer. Low expression of TLR4 is observed in tumors with malignant performance (high pathological grade, higher tumor stage, and progression). Patients with low TLR4 levels are more sensitive to gemcitabine rather than cisplatin. The promoter methylation level of TLR4 is positively associated with TLR4 expression (P < 0.001). The cg14629571 methylation site largely contributes to the overall methylation level. The CIBERSORT analysis shows that high TLR4 expression is associated with lower levels of plasma cells, M0 macrophages, and M1 macrophages. The GSEA results indicate that the TGF-ß pathway and apoptosis are activated in high TLR4 bladder cancer, while G2M checkpoint and E2F targets pathways are enriched in low TLR4 bladder cancer. CONCLUSION: This research discusses the abnormal expression and prognostic value of TLR4 in bladder cancer. The TLR4 expression can effectively predict oncological outcomes and drug sensitivity of bladder cancer patients. TLR4 is also associated with infiltrating immune cell variation and cancer pathway dysregulation. The results provide a novel prognostic marker and potential drug targets for bladder cancer.

Efficacy and toxicity in scheduled intravesical gemcitabine versus Bacille Calmette-Guérin for Ta and T1 bladder cancer: a systematic review and meta-analysis.

BACKGROUND: We conducted a meta-analysis to compare the efficacy and toxicity of scheduled intravesical gemcitabine (GEM) and Bacille Calmette-Guérin (BCG) for Ta and T1 non-muscle invasive bladder cancer (NMIBC). METHODS: The database search was performed in Ovid Medline, Embase, Web of Science, Cochrane Library from the commencement of the database to July 7, 2020. Trials using immediate instillation were excluded and we present the included studies in accordance with the PRISMA 2020 reporting checklist. The data extracted was analyzed using Stata 11.0 software. RESULTS: Six studies of 466 patients comparing GEM and BCG were finally included. No significant difference was detected between GEM and BCG group in recurrence free survival [hazard ratio (HR) =0.80, 95% confidence interval (95% CI), 0.46-1.37, P=0.410], progression free survival (HR =0.82, 95% CI, 0.38-1.77, P=0.621), and total adverse events [odds ratio (OR) =0.70, 95% CI, 0.38-1.29, P=0.253). However, patients receiving GEM treatment are less likely to develop urinary adverse events, such as dysuria (OR =0.50, 95% CI, 0.29-0.87) and hematuria (OR =0.40, 95% CI, 0.18-0.91). We performed subgroup analysis and found that the effects of GEM and BCG were similar even on patients with high recurrence risk tumor. Sensitivity analysis showed the robustness of the results. DISCUSSION: Scheduled intravesical GEM instillation has a similar effect with BCG instillation in preventing NMIBC recurrence and progression, but GEM therapy causes a lower incidence of dysuria and hematuria than BCG. GEM may be an alternative therapy for BCG. However, the results should be treated with caution due to the low to moderate quality of the included studies.

Efficacy of intravesical therapies on the prevention of recurrence and progression of non-muscle-invasive bladder cancer: A systematic review and network meta-analysis.

Intravesical instillation therapy is the mainstay of prophylaxis of tumor recurrence and progression in non-muscle-invasive bladder cancer. However, there is no study evaluating the superiority of monotherapy. The aim of this study is to compare the efficacy of preventing recurrence and progression of intravesical monotherapies via network meta-analysis (NMA) of randomized controlled trials. Database searches were conducted on Embase, Ovid Medline, Web of Science, ScienceDirect, Cochrane Library, and ClinicalTrials.com from the time of establishment to February 6, 2020. The monotherapies included Bacille Calmette-Guérin (BCG), mitomycin C (MMC), interferon (IFN), adriamycin, epirubicin, gemcitabine (GEM), and thiotepa (THP). A Bayesian consistency network model was generated under a random-effects model. The superiority of therapy was identified based on the surface under the cumulative ranking curve (SUCRA). Fifty-seven studies with 12462 patients are included. NMA shows that GEM (SUCRA = 0.92), BCG (SUCRA = 0.82), and IFN (SUCRA = 0.78) are the top three effective drugs to reduce recurrence. GEM (SUCRA = 0.87) is the most effective therapy to prevent progress, followed by BCG, MMC, THP, and IFN with similar efficacy. Subgroup analysis of pairwise meta-analysis and NMA was performed on publication year, trial initiation year, study origin, center involvement, sample size, drug schedule, tumor characteristics, and trial quality to address confounding factors, which suggests the robustness of the results with stable effect sizes. Network meta-regression also indicates consistent rank by analyzing year, sample size, and quality. Compared with BCG, GEM is also a promising therapy with favorable efficacy to reduce tumor recurrence and progression. IFN and MMC could be alternative therapies for BCG with slightly inferior efficacy in recurrence prevention and similar efficacy in progression prevention. However, the results of this study should be treated with caution since most of the included studies are of moderate to high risk of bias.

Effect of preexercise glycemic-index meal on running when CHO-electrolyte solution is consumed during exercise.

PURPOSE: This study examined the effect of consuming carbohydrate- (CHO) electrolyte solution on running performance after different-glycemic-index (GI) meals. METHODS: Nine men completed 3 trials in a randomized counterbalanced order, with trials separated by at least 7 days. Two hours before the run after an overnight fast, each participant consumed a high-GI (GI = 83) or low-GI (GI = 36) CHO meal or low-energy sugar-free Jell-O (GI = 0, control). The 2 isocaloric GI meals provided 1.5 g available CHO/kg body mass. During each trial, 2 ml/kg body mass of a 6.6% CHO-electrolyte solution was provided immediately before exercise and every 2.5 km after the start of running. Each trial consisted of a 21-km performance run on a level treadmill. The participants were required to run at 70% VO2max during the first 5 km of the run. They then completed the remaining 16 km as fast as possible. RESULTS: There was no difference in the time to complete the 21-km run (high-GI vs. low-GI vs. control: 91.1 +/- 2.0 vs. 91.8 +/- 2.2 vs. 92.9 +/- 2.0 min, n.s.). There were no differences in total CHO and fat oxidation throughout the trials, despite differences in preexercise blood glucose, serum insulin, and serum free-fatty-acid concentrations. CONCLUSION: When a CHO-electrolyte solution is consumed during a 21-km run, the GI of the preexercise CHO meal makes no difference in running performance.