Prostate Cancer is the most common cancer in European men. Despite the dramatic improvements in early diagnostic and local treatment, one out of five prostate cancer patients will die from their disease. Therefore, it remains critical to improve the present strategy for advanced and metastatic prostate cancer. In the DE-ESCALATE project, we will evaluate whether intermittent intensified androgen deprivation treatment (iADT) in metastatic prostate cancer is not inferior to continuous treatment in terms of oncological benefit while minimizing side effects and resource utilization and improving patient quality of life. The proposed clinical trial is designed to detect early if iADT has a negative impact on overall survival compared to continuous therapy. If successful, the outcomes of the project will define a new evidence-based standard of care for metastatic hormone-sensitive prostate cancer. The proposed research could lead to improved patient survival and quality of life but also improve health system sustainability. We are a multidisciplinary and multistakeholder consortium involving clinical oncologists, surgeons, health economists and patient representatives. The study design was successfully discussed with patients. This action is part of the Cancer Mission cluster of projects on ‘Diagnosis and treatment'.