High-risk prostate cancer represents the most aggressive form of the disease worldwide. In the past it was largely treated without curative intent but during the last years there has been a paradigm shift with an increase of curative procedures (particularly radical prostatectomy) for high-risk patients and, vice versa, active surveillance for low-risk disease. For this reason the high-risk group represents the novel target for contemporary research. The pre-operative risk groups are considered homogeneous in terms of prognosis and therapeutic response but there are grey zones within each group that have not been adequately studied. The main hypothesis of this PhD thesis (ISBN-NUMBER: 9789082757606 for the printed version and 9789082757613 for the e-version) is that not all high-risk prostate cancer patients have the same outcomes after surgery and also not the same response to multimodality therapies. In this context, novel treatments or their combinations should be tested. We analysed the largest high-risk database in the world demonstrating that not all high-risk patients after surgery have the same outcome according to their postoperative pathologic features. The European Multicentre Prostate Cancer Clinical and Translational Research group classifier was then defined as three different prognostic groups to predict cancer specific death. Interestingly, patients in these groups did not respond homogenously to adjuvant radiotherapy and/or androgen deprivation therapy. We also analysed the survival impact of neoadjuvant hormonal therapy before surgery, showing that patients who need adjuvant radiotherapy and were exposed to neoadjuvant hormonal therapy have the best prognosis. This outcome opens new perspectives for neoadjuvant treatment with or without other treatment combinations. The ARNEO trial is a phase II randomised, double blind, placebo controlled trial to study the association of apalutamide and degarelix before surgery for intermediate and high-risk disease.

(BELG J MED ONCOL 2018:12(3):130–132)