Background: Recent randomized clinical trials have examined the efficacy of different combinations of systemic and local treatment approaches for metastatic hormone-sensitive prostate cancer (mHSPC). We compared the efficacy of these combined regimens in order to identify the optimal therapy for specific patient subgroups.Methods: The treatments were abiraterone (ABI), apalutamide (APA), docetaxel (DOC), enzalutamide (ENZ), and radiotherapy (RT) combined with androgen-deprivation therapy (ADT). Five electronic databases were searched up to May 7, 2020 for relevant trials. The risk of bias in the included trials was evaluated with the Cochrane tool. The hazard ratio (HR) with 95% confidence interval (CI) was determined for the included trials and indirect comparisons were performed using the R software.Results: In total, 10 randomized, controlled trials with 11,194 patients were included in the meta-analysis. ADT + RT was superior to ADT monotherapy in terms of overall survival (HR = 0.96, 95% CI: 0.85-1.1) and conferred a survival benefit in a subgroup of low-volume patients (HR = 0.68, 95% CI: 0.54-0.87). Combined systemic treatments were significantly superior to ADT monotherapy in comparisons of survival and prostate-specific antigen response, including in the high-volume subgroup; meanwhile, in the low-volume subgroup only ADT + ENZ (HR = 0.38, 95% CI 0.21-0.69) showed a significant clinical benefit. In the Gleason score <8 subgroup, all combined systemic treatments were superior to ADT monotherapy, but the results were only significant for ADT + APA (HR = 0.56, 95% CI: 0.33-0.95) and ADT + DOC (HR = 0.71, 95% CI: 0.54-0.92). In the Gleason score ≥8 subgroup, ADT monotherapy was inferior (albeit not significantly) to combined treatments. In a ranking of performed comparisons, Wang et al.Combined Therapies for Prostate Cancer ADT + ENZ was the optimal regimen, although this was non-significant. Combined therapies also demonstrated superiority in quality-of-life indicators such as time to skeletal events and pain progression. Conclusion:ADT + radiotherapy led to superior outcomes in mHSPC patients with low-volume disease. While all combined systemic regimens confer a survival advantage over ADT monotherapy, the optimal treatment approach for certain mHSPC patient subgroups remains to be determined.

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Reactivation of the androgen receptor signaling pathway in the emasculated environment is the main reason for the occurrence of castration-resistant prostate cancer (CRPC). The immunophilin FKBP51, as a co-chaperone protein, together with Hsp90 help the correct folding of AR. Rapamycin is a known small-molecule inhibitor of FKBP51, but its effect on the FKBP51/AR signaling pathway is not clear. In this study, the interaction mechanism between FKBP51 and rapamycin was investigated using steady-state fluorescence quenching, X-ray crystallization, MTT assay, and qRT-PCR. Steady-state fluorescence quenching assay showed that rapamycin could interact with FKBP51. The crystal of the rapamycin-FKBP51 complex indicated that rapamycin occupies the hydrophobic binding pocket of FK1 domain which is vital for AR activity. The residues involving rapamycin binding are mainly hydrophobic and may overlap with the AR interaction site. Further assays showed that rapamycin could inhibit the androgen-dependent growth of human prostate cancer cells by down-regulating the expression levels of AR activated downstream genes. Taken together, our study demonstrates that rapamycin suppresses AR signaling pathway by interfering with the interaction between AR and FKBP51. The results of this study not only can provide useful information about the interaction mechanism between rapamycin and FKBP51, but also can provide new clues for the treatment of prostate cancer and castration-resistant prostate cancer.

Aims Emerging evidence has related inflammation-based biomarkers to numerous carcinomas, including bladder carcinoma (BC). However, the role of inflammatory biomarkers in the prognosis of BC remains inconclusive. This study aimed to compare preoperative plasma fibrinogen (PF) and other inflammatory biomarkers such as the platelet–lymphocyte ratio (PLR), neutrophil–lymphocyte ratio (NLR), lymphocyte–monocyte ratio (LMR), C-reactive protein (CRP) level, and serum albumin level to predict the prognosis of patients with BC. Methods This article focused on a retrospective analysis of 175 patients with newly diagnosed BC who were admitted to our hospital from March 2005 to March 2016. Of these BC patients, 136 had undergone radical cystectomy (RC). Results According to multivariate analysis, high PF level was an independent predictor of overall survival (OS) in 136 BC patients receiving RC (HR = 3.759; P = 0.011), but not for all 175 BC patients. Combining the NLR and PF values showed higher predictive accuracy for OS than NLR or PF alone (P < 0.05). Additionally, for 136 BC patients who had undergone RC, a close relationship was found between high PF levels (≥3.39 g/L) and lymph node metastasis (P = 0.011) and clinical T stage (P = 0.015). Furthermore, PF was a superior prognostic factor compared with the LMR, PLR, CRP, and albumin values in 136 BC patients who had undergone RC (P < 0.001). Conclusions The preoperative PF level may be a prognostic biomarker; and when combined with the NLR, it can improve the predictive ability of the survival of BC patients, particularly of BC patients who underwent RC.

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