RESUMO
Objective: This study aimed to evaluate the relative efficacy and safety of first-line treatment options for metastatic castration-resistant prostate cancer (mCRPC). Methods: We systematically searched electronic databases, including PubMed and Web of Science, for studies published from their inception to April 3rd, 2023. Inclusion criteria were: 1) Completed Phase III or IV randomized controlled trials (RCTs) registered on ClinicalTrials.gov; 2) Patients with a confirmed diagnosis of mCRPC who had not previously received chemotherapy or novel endocrine therapies. We conducted a network meta-analysis using R software (version 3.4.0). Network graphs and risk of bias graphs were generated using Stata 14.0 and RevMan 5.4, respectively. The primary outcome was overall survival (OS), and the secondary outcome was the incidence of severe adverse events (SAEs). Results: Seven RCTs encompassing 6,641 patients were included. The network meta-analysis revealed that both docetaxel+prednisone (DP) and cabazitaxel+prednisone (CP) significantly improved OS compared to abiraterone. Compared to placebo, DP showed comparable results to both cabazitaxel 20 mg/m^2+prednisone (C20P) and cabazitaxel 25 mg/m^2+prednisone (C25P) in terms of OS. For SAEs, both DP and C20P were superior to C25P, with no statistical difference between C20P and DP. The probability ranking plots indicated that C25P ranked highest for OS, while DP ranked highest for SAEs. Conclusions: Based on our network meta-analysis, we recommend cabazitaxel 20 mg/m^2+prednisone (C20P) as the primary choice for first-line management of mCRPC, followed by DP. Enzalutamide and abiraterone are suggested as subsequent options. Radium-223 may be considered for patients presenting with bone metastases. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023443943.
RESUMO
Several observational studies have reported an association between obesity and primary liver cancer (PLC), while the causality behind this association and the comparison of the risk effects of different obesity indicators on PLC remain unclear. In this study, we performed two-sample Mendelian randomization (MR) analyses to assess the associations of genetically determined liver fat, visceral adipose tissue (VAT), and body mass index (BMI) with the risk of PLC. The summary statistics of exposures were obtained from two genome-wide association studies (GWASs) based on the UK Biobank (UKB) imaging cohort and the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort. GWAS summary statistics for PLC were obtained from FinnGen consortium R7 release data, including 304 PLC cases and 218 488 controls. Inverse-variance weighted (IVW) was used as the primary analysis, and a series of sensitivity analyses were performed to further verify the robustness of these findings. IVW analysis highlighted a significant association of genetically determined liver fat (OR per SD increase: 7.14; 95% CI: 5.10-9.99; P = 2.35E-30) and VAT (OR per SD increase: 5.70; 95% CI: 1.32-24.72; P = .020) with PLC but not of BMI with PLC. The findings were further confirmed by a series of MR methods. No evidence of horizontal pleiotropy between these associations existed. Our study suggested that genetically determined liver fat and VAT rather than BMI were associated with an increased risk of PLC, which suggested that visceral fat distribution is more predictive of the clinical risk of PLC than common in vitro measures.
