Aim: Identifying the best care for a patient can be extremely challenging. To support the creation of multifactorial Decision Support Systems (DSSs), we propose an Umbrella Protocol, focusing on prostate cancer. Materials & methods: The PRODIGE project consisted of a workflow for standardizing data, and procedures, to create a consistent dataset useful to elaborate DSSs. Techniques from classical statistics and machine learning will be adopted. The general protocol accepted by our Ethical Committee can be downloaded from cancerdata.org. Results: A standardized knowledge sharing process has been implemented by using a semi-formal ontology for the representation of relevant clinical variables. Conclusion: The development of DSSs, based on standardized knowledge, could be a tool to achieve a personalized decision-making.