The study will be conducted at multiple centers across Europe. Participation in the study will comprise a screening period, where the screening assessments must be completed before subjects are enrolled and randomized (only for Phase 3 subjects). Eligible, consenting subjects will then undergo treatment according to their assigned study phase and treatment group, to occur over up to 96 weeks (24 months) with a post-treatment follow-up period to monitor safety and efficacy. The study will be closed when 96 events have been registered for the primary endpoint, which is expected to be at 7-8 years from the time of randomization of the first subject. conditions: Prostate Cancer studyType: INTERVENTIONAL phases: PHASE2 phases: PHASE3 allocation: RANDOMIZED interventionModel: PARALLEL interventionModelDescription: Phase 2: non randomised, 1 treatment arm, open label Phase 3: randomized 1:1 between two treatment arms, blinded primaryPurpose: TREATMENT masking: QUADRUPLE maskingDescription: Phase 3 trial: blinded Phase 2 trial: open label whoMasked: PARTICIPANT whoMasked: CARE_PROVIDER whoMasked: INVESTIGATOR whoMasked: OUTCOMES_ASSESSOR count: 493 type: ESTIMATED name: Darolutamide name: Darolutamide matched placebo name: Radiotherapy name: Zoladex 3.6Mg Implant name: Zoladex LA name: Decapeptyl sustained release 22.5 mg name: Decapeptyl sustained release 11.25 mg name: Depo-Eligard 45 mg name: Depo-Eligard 22.5 mg name: Depo-Eligard 7.5 mg name: Firmagon 120 MG Injection name: Firmagon 80 MG Injection name: Docetaxel measure: Phase 3: PSMA PET metastasis free survival (ppMFS) measure: Phase 2: quality of life (sexual subdomain) measure: Phase 2: quality of life (hormonal subdomain) measure: Overall survival measure: Prostate-cancer specific survival measure: Biochemical progression-free survival measure: Time to next systemic therapy measure: Frequency and severity of adverse events sex: MALE minimumAge: 18 Years stdAges: ADULT stdAges: OLDER_ADULT facility: GZA Sint-Augustinus status: RECRUITING city: Wilrijk state: Antwerp zip: 2610 country: Belgium name: Piet Ost, MD, PhD role: CONTACT email: cancertrials@gza.be name: Piet Ost role: PRINCIPAL_INVESTIGATOR lat: 51.16734 lon: 4.39513 facility: OLVZ Aalst status: NOT_YET_RECRUITING city: Aalst zip: 9300 country: Belgium name: Samuel Br role: CONTACT name: Samuel Bral role: PRINCIPAL_INVESTIGATOR lat: 50.93604 lon: 4.0355 facility: AZ Sint-Jan status: NOT_YET_RECRUITING city: Brugge zip: 8000 country: Belgium name: Sabine Meersschout role: CONTACT name: Sabine Meersschout role: PRINCIPAL_INVESTIGATOR lat: 51.20892 lon: 3.22424 facility: Saint Luc status: NOT_YET_RECRUITING city: Bruxelles zip: 1200 country: Belgium name: Ad Vanderm role: CONTACT name: Ad Vandermeulen role: PRINCIPAL_INVESTIGATOR lat: 50.85045 lon: 4.34878 facility: UZA status: NOT_YET_RECRUITING city: Edegem zip: 2600 country: Belgium name: Karen Fransis role: CONTACT name: Karen Fran role: PRINCIPAL_INVESTIGATOR lat: 51.15662 lon: 4.44504 facility: UZ Gent status: NOT_YET_RECRUITING city: Gent zip: 9000 country: Belgium name: Valérie Fonteyne role: CONTACT name: Valérie Fonteyne role: PRINCIPAL_INVESTIGATOR lat: 51.05 lon: 3.71667 facility: AZ Sint-Lucas status: NOT_YET_RECRUITING city: Gent zip: 900 country: Belgium name: Lien Van De Voorde role: CONTACT name: Lien Van De Voor role: PRINCIPAL_INVESTIGATOR lat: 51.05 lon: 3.71667 facility: AZ Groeninge status: NOT_YET_RECRUITING city: Kortrijk zip: 8500 country: Belgium name: Nick Liefhooghe role: CONTACT name: Nick Liefhooghe role: PRINCIPAL_INVESTIGATOR lat: 50.82803 lon: 3.26487 facility: CHU Liège status: NOT_YET_RECRUITING city: Liège zip: 4000 country: Belgium name: Brieuc Suatois role: CONTACT name: Brieuc Sautois role: PRINCIPAL_INVESTIGATOR lat: 50.63373 lon: 5.56749 facility: AZ Delta status: NOT_YET_RECRUITING city: Roeselare zip: 8800 country: Belgium name: Benedikt Engels role: CONTACT name: Benedikt Enge role: PRINCIPAL_INVESTIGATOR lat: 50.94653 lon: 3.12269 facility: VITAZ status: NOT_YET_RECRUITING city: Sint-Niklaas zip: 9100 country: Belgium name: Bart De Troyer role: CONTACT name: Bart De Troyer role: PRINCIPAL_INVESTIGATOR lat: 51.16509 lon: 4.1437 hasResults: False