BackgroundSecond-generation androgen receptor inhibitors (ARIs) have been developed and approved for treating castration-resistant prostate cancer (CRPC). There is a lack of direct comparison of the therapeutic effects and adverse events between the conventional ARI (bicalutamide) and three second-generation ARIs (enzalutamide, apalutamide and darolutamide).MethodsOur network meta-analysis evaluated therapeutic effects and adverse events of the conventional ARI (bicalutamide) and the second-generation ARIs in treating CRPC. We systematically searched the Pubmed, Cochrane library and Embase databases for studies published until October 2022 and only randomized clinical trials (RCTs) were included. The progression-free survival, prostate-specific antigen (PSA) progression-free survival, overall survival (PFS/PSA-PFS/OS), PSA response rate and relative adverse events (AEs) of CRPC patients were collected and synthesized. We then performed subgroup analysis. The non-metastatic and metastatic CRPC (nm/mCRPC) observations were analyzed separately. Data analyses were performed using R software (4.2.1) based on Bayesian framework.Results6,993 subjects from seven eligible RCTs were analyzed. Enzalutamide, apalutamide and darolutamide were more effective than bicalutamide in treating CRPC, and the performance of darolutamide was slightly worse than the other two second-generation ARIs. Similar adverse events rate were observed among the second-generation ARIs and bicalutamide. Apalutamide showed a slightly higher rate of Grade 3+ AEs, percentages of AE-related drug withdrawals and AE-related mortality. Patients receiving enzalutamide had significantly higher rate of hypertension and fatigue. In subgroup analysis, enzalutamide showed better therapeutic effects compared with bicalutamide in both nmCRPC and mCRPC groups. In nmCRPC group, enzalutamide and apalutamide had more benefits on PFS and PSA-PFS compared with darolutamide. We displayed the probability ranking map of PFS, PSA-PFS, OS, time to cytotoxic chemotherapy, PSA response rate and relative AE outcomes.ConclusionThe current network meta-analysis indicated that the second-generation ARIs were superior to the conventional ARI, bicalutamide. The three second-generation ARIs showed incomplete equivalence on CRPC treatment. The darolutamide was slightly less effective compared with enzalutamide and apalutamide. The adverse events of apalutamide were worse than the others, but no statistical significance was observed among these vital AEs. All ARIs were generally well-tolerated. These results may provide reference to clinical decision and further direct comparison trials.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO, identifier CRD42022370842.

Objective The purpose of this network meta-analysis was to compare the effectiveness and adverse effects of limited, standard, extended, and super-extended pelvic lymph node dissection (PLND) following radical prostatectomy. Methods This study followed the PRISMA 2020 statement. Clinical trials were searched from three electronic databases, including PubMed, the Cochrane Library, and Embase from the database’s inception to April 5, 2022. The lymph node-positive rate, biochemical recurrence-free rate, lymphocele rate, thromboembolic rate, and overall complication rate were compared by meta-analysis. Data analyses were performed using R software based on the Bayesian framework. Results Sixteen studies involving 15,269 patients were included. All 16 studies compared the lymph node-positive rate; 5 studies compared the biochemical recurrence-free rate; 10 studies compared the lymphocele rate; 6 studies compared the thromboembolic rate, and 9 studies compared the overall complication rate. According to Bayesian analysis, the lymph node-positive rate, lymphocele rate, and overall complication rate were significantly associated with the extension of the PLND range. The limited, extended, and super-extended PLND templates showed a similar but lower biochemical recurrence-free rate and a higher thromboembolic rate than the standard template. Conclusions The extension of the PLND range is associated with an elevated lymph node-positive rate; however, it does not improve the biochemical recurrence-free rate and correlates with an increased risk of complications, especially lymphocele. The selection of the PLND range in clinical practice should consider the oncological risk and adverse effects. Trial registration PROSPERO (CRD42022301759).

BackgroundOrchiectomy has been replaced by medication represented by luteinizing hormone-releasing hormone (LHRH) agonist as the first-line therapy for androgen deprivation therapy (ADT). After the wide application of LHRH agonist, the side-effects of long-term ADT were noticed. It is time to reconsider the role of medication and surgeries in the treatment of prostate cancer.MethodsEmbase, Pubmed, Web of science and Cochrane library were searched for relevant trials. Quality of the studies and risk of bias were assessed by using the Newcastle-Ottawa Scale (NOS). Therapeutic and adverse effects, as well as long-term metabolic adverse effects were extracted from the selected studies. The data synthesized in meta-analyses were performed with R software (4.2.1). Risk ratio (RR) with its 95% confidence interval (CI) was calculated by combining outcome data including complete and partial response rate, progression rate, death rate and adverse effects such as hot flash and increase in pain. Descriptive analysis was performed among the prostate specific antigen (PSA), testosterone and metabolic adverse effects due to a lack of homogeneity of frailty measures.Results1,711 participants from 11 studies were included in our systematic review. 1,258 patients from six studies were included in the meta-analysis. Based on the meta-analysis, the therapeutic and adverse outcomes included overall response rate, complete response rate, partial response rate, stable rate, progression rate, death rate and hot flashes. No statistical significance was observed between LHRH agonists and orchiectomy. Compared with surgery, LHRH agonist elevated the risk of the increase in pain. In descriptive analysis, it was shown that the therapeutic effects between PSA and testosterone also showed no significant difference. Both groups had lipid and glucose metabolic disorders, and a few studies reported worse lipid metabolic performance in orchiectomy group and worse insulin resistance in LHRH agonist group.ConclusionWe found that the therapeutic outcomes were similar between the two options. The results of lipid and glucose metabolic abnormality were controversial in existing studies. The direct comparison studies on metabolic adverse effects should be performed in the future. The therapeutic, metabolic, psychological and economical effects should be considered before applying ADT methods.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42022365891.