The project produced a comprehensive systematic review and network meta‑analysis of bone‑modifying agents for patients with prostate cancer and bone metastases. The primary aim was to identify all randomized trials that compared bisphosphonates, RANK‑Ligand inhibitors, or other bone‑targeted drugs for the prevention of skeletal‑related events (SREs) such as fractures, spinal cord compression, or hypercalcaemia. Using Cochrane methodology, the team searched MEDLINE, Embase, and CENTRAL with highly sensitive strategies, screened titles and abstracts independently, and extracted patient‑ and study‑specific data into a standardized form. Two reviewers assessed risk of bias with the Cochrane tool, and disagreements were resolved by a third expert. The extracted data were entered into a network of trials, and a Bayesian network meta‑analysis was performed, incorporating both direct and indirect comparisons. The analysis was conducted with the CINeMA software, which evaluates consistency, transitivity, and the overall confidence in each estimate. Although the report does not yet present numerical effect sizes, the methodology allows the ranking of treatments for clinically relevant outcomes such as reduction in SREs, overall survival, quality of life, and adverse events. Previous systematic reviews have shown that bisphosphonates and denosumab reduce skeletal complications, but the comparative efficacy and safety of individual agents remain unclear. By combining all available evidence, the network meta‑analysis will provide clinicians with a hierarchy of options, informing guideline recommendations and individual treatment decisions.

The project was carried out within the Cochrane Haematological Malignancies (CHM) group, which is affiliated with the Department of Internal Medicine I at the University of Cologne. This affiliation ensured close interaction with haematology‑oncology specialists, allowing the findings to be interpreted in a clinical context. The statistical analysis was performed in collaboration with the Institute for Medical Statistics and Bioinformatics at the university’s medical faculty, where statisticians Anne Adams and Kathrin Kuhr led the data preparation and modelling. Clinical expertise was provided by Prof. Dr. Dr. Axel Heidenreich, director of the prostate cancer centre at the University Hospital Cologne, who maintained regular contact with the research team. The project was funded under the German Federal Ministry of Education and Research grant 01KG1709, which covered personnel, database access, and statistical software. The protocol was published in the Cochrane Library in 2018, and the final manuscript was submitted for peer review in May 2019, with plans for publication in the Cochrane Library and presentation at international oncology conferences. The results will be disseminated to clinicians and incorporated into evidence‑based guidelines, thereby supporting personalized treatment decisions for patients with metastatic prostate cancer.