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Management of non-metastatic castration-resistant prostate cancer (nmCRPC) has undergone a paradigm shift with next-generation androgen receptor inhibitors. However, direct comparative data are not available to inform treatment decisions and/or guideline recommendations. Therefore, we performed network meta-analysis to indirectly compare the efficacy and safety of currently available treatments. Multiple databases were searched for articles published before June 2020. Studies that compared overall and/or metastasis-free and/or prostate-specific antigen (PSA) progression-free survival (OS/MFS/PSA-PFS) and/or adverse events (AEs) in nmCRPC patients were considered eligible. Three studies (n = 4117) met our eligibility criteria. Formal network meta-analyses were conducted. For MFS, apalutamide, darolutamide, and enzalutamide were significantly more effective than placebo, and apalutamide emerged as the best option (P score: 0.8809). Apalutamide [hazard ratio (HR): 0.85, 95% credible interval (CrI): 0.77–0.94] and enzalutamide (HR: 0.86, 95% CrI: 0.78–0.95) were both significantly more effective than darolutamide. For PSA-PFS, all three agents were statistically superior to placebo, and apalutamide emerged as the likely preferred option (P score: 1.000). Apalutamide (HR: 0.71, 95% CrI: 0.69–0.74) and enzalutamide (HR: 0.76, 95% CrI: 0.74–0.79) were both significantly more effective than darolutamide. For AEs (including all AEs, grade 3 or grade 4 AEs, grade 5 AEs, and discontinuation rates), darolutamide was the likely best option. Apalutamide and enzalutamide appear to be more efficacious agents for therapy of nmCRPC, while darolutamide appears to have the most favorable tolerability profile. These findings may facilitate individualized treatment strategies and inform future direct comparative trials.

To determine the predictive and prognostic value of a panel of systemic inflammatory response (SIR) biomarkers relative to established clinicopathological variables in order to improve patient selection and facilitate more efficient delivery of perioperative systemic therapy.

Diagnostic and methodological evaluation of studies on the urinary shedding of SARS-CoV-2, compared to stool and serum: A systematic review and meta-analysis.

Purpose: Androgen deprivation therapy is a standard therapy for some patients with localized and almost all patients with metastatic prostate cancer. Although several clinical cohort studies have identified an impact of androgen deprivation therapy on cognitive function, the previous reviews were not able to perform a well designed quantitative synthesis to summarize the risk of dementia and/or Alzheimer disease. Consequently there is still a lack of systematic review and meta-analysis regarding the impact of this risk including more recent studies. Materials and Methods: We conducted a systematic review and meta-analysis of the literature assessing the differential incidence of dementia and/or Alzheimer disease as outcomes in patients with prostate cancer who did vs did not receive androgen deprivation therapy. We queried PubMedÒ and Web of ScienceÔ databases from January 1 to 3, 2020. We used random or fixed effects meta-analytic models in the presence or absence of heterogeneity per the I 2 statistic. We performed 6 meta-analyses for all cause dementia, Alzheimer disease and all cause dementia or Alzheimer disease according to the duration of androgen deprivation therapy (up to 12 or more than 12 months). Results: A total of 14 studies were selected after considering inclusion and exclusion criteria. Nine of them reported all cause dementia (ie all types of dementia including Alzheimer disease), with 8 reporting Alzheimer disease. Five studies assessed these outcomes according to the duration of androgen deprivation therapy. The risk of new onset dementia (all cause) and Alzheimer disease was higher in patients with prostate cancer who received androgen deprivation therapy compared to those who did not (HR 1.21, 95% CI 1.11e1.33 and HR 1.16, 95% CI 1.09e1.24). The risk of dementia (all cause) was higher in patients with prostate cancer who received androgen deprivation therapy for more than 12 months (HR 1.36, 95% CI 1.07e1.72); however, for those who had less than 12 months of androgen deprivation therapy exposure the difference was not statistically significant 1.06 (95% CI 0.77e1.28). There was no association between the androgen deprivation therapy duration and the risk of Alzheimer disease (HR 1.21, 95% CI 0.97e1.51 for exposure up to 12 months and HR 1.39, 95% CI 0.69e2.79 for exposure greater than 12 months).

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Objectives To perform a systematic review and network meta‐analysis to compare the efficacy and safety of currently available treatments for the management of metastatic hormone‐sensitive prostate cancer (mHSPC), as there has been a paradigm shift with the use of next‐generation androgen receptor inhibitors (ARIs) and docetaxel. Methods Multiple databases were searched for articles published before May 2020 according to the Preferred Reporting Items for Systematic Review and Meta‐analysis extension statement for network meta‐analysis. Studies comparing overall/progression‐free survival (OS/PFS) and/or adverse events (AEs) in patients with mHSPC were eligible. Results Nine studies (N = 9960) were selected, and formal network meta‐analyses were conducted. Abiraterone (hazard ratio [HR] 0.83, 95% credible interval [CrI] 0.76–0.90), docetaxel (HR 0.90, 95% CrI 0.82–0.98), and enzalutamide (HR 0.85, 95% CrI 0.73–0.99) were associated with significantly better OS than androgen‐deprivation therapy (ADT), and abiraterone emerged as the best option. Abiraterone (HR 0.71, 95% CrI 0.67–0.76), apalutamide (HR 0.73, 95% CrI 0.65–0.81), docetaxel (HR 0.84, 95% CrI 0.78–0.90), and enzalutamide (HR 0.67, 95% CrI 0.63–0.71) were associated with significantly better PFS than ADT, and enzalutamide emerged as the best option. Abiraterone (HR 0.85, 95% CrI 0.78–0.93), apalutamide (HR 0.87, 95% CrI 0.77–0.98), and enzalutamide (HR 0.80, 95% CrI 0.73–0.88) were significantly more effective than docetaxel. Regarding AEs, apalutamide was the likely best option among the three ARIs. In patients with low‐volume mHSPC, enzalutamide was the best option in terms of OS and PFS. Conclusions All three ARIs are effective therapies for mHSPC; apalutamide was the best tolerated. All three seemed more effective than docetaxel. These findings may facilitate individualised treatment strategies and inform future comparative trials.

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