SUrGery With or Without dARolutamide in High-risk and/or Locally Advanced Prostate Cancer

Inclusion Criteria:

1. Age ≥18 years

2. Histologically confirmed adenocarcinoma of the prostate

3. High-risk and/or locally advanced prostate cancer diagnosis defined by: One of the following criteria is sufficient to define a high-risk and/or locallyadvanced prostate cancer:

• ISUP grade 4 or 5 on biopsies

• cN1 disease in MRI or PET-Scan

• T3b disease in MRI If these criteria are not being identified, two of the following criteria arenecessary to define high-risk and/or locally advanced prostate cancer:

• PSA value >20 ng/ml

• ≥ 50% of the core of biopsies need to be positive for adenocarcinoma ISUP grade 3

• T3a disease in MRI

4. No distant metastasis confirmed by imaging (i.e., MRI/CT-Scan and Bone Scintigraphyor PET-Scan)

5. Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0-1

6. Patient eligible for radical prostatectomy as per the investigator

7. Adequate organ function within 28 days prior to start of treatment determined by thefollowing central laboratory values:

• Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and totalbilirubin less than the upper limit of normal (ULN; note that in subjects withGilbert's syndrome, if total bilirubin is >1.5 X ULN, measure direct andindirect bilirubin. If direct bilirubin is ≤1.5 X ULN, the subject may beeligible);

• Serum creatinine <1.5 mg/dL;

• Platelets ≥75,000/uL, without transfusion and/or growth factors within 1 monthprior to randomization;

• Hemoglobin >12.0 g/dL (7.4 mmol), without transfusion and/or growth factorswithin 1 month prior to randomization;

• Adequate renal function: creatinine clearance/eGFR within normal limits tobaseline assessed as per local standard method;

• Normal cardiac function according to local standard by 12-leadElectrocardiogram (ECG) (complete, standardized 12-lead recording).

8. Patient able to receive darolutamide for up to 9 months as per the investigator

9. Patient able to swallow whole study drug tablets

10. Life expectancy more than 5 years

11. Men engaged in sexual activity with a woman of childbearing potential should accept (or female partners of men enrolled in the study who are of childbearing potentialor are pregnant) to use an highly effective contraception during darolutamidetreatment and at least one week after the end of the investigational product

12. Signed informed consent

13. Patient able to participate and willing to give informed consent prior performanceof any study-related procedures and to comply with the study protocol for theduration of the study, including undergoing treatment and scheduled visits andexaminations including follow up

14. Patient affiliated to a Social Health Insurance in France.

Exclusion Criteria:

1. Distant metastasis (clinical stage M1). Nodal disease below the iliac bifurcation (clinical stage N1) is not an exclusion.

2. Pathological finding consistent with small cell, ductal or neuroendocrine carcinomaof the prostate

3. Prior treatment for prostate cancer

4. Castrated men (Bilateral orchiectomy or other)

5. History of any pelvic radiation

6. Any of the following concurrent illness within 6 months prior to first dose of studydrug: severe or unstable angina, myocardial infarction, symptomatic congestive heartfailure, arterial or venous thromboembolic events (eg, pulmonary embolism,cerebrovascular accident including transient ischemic attacks), or clinicallysignificant ventricular arrhythmias or New York Heart Association Class II to IVheart disease; uncomplicated deep vein thrombosis is not considered exclusionary

7. Uncontrolled hypertension as indicated by a systolic blood pressure (BP) ≥ 160 mmHgor diastolic BP ≥ 100 mmHg at screening despite medical management. Participantswith hypertension can enroll provided BP is stable and controlled byanti-hypertensive treatment

8. HIV-positive patient with one or more of the following: Not receiving highly activeantiretroviral therapy; Had a change in antiretroviral therapy within 6 months ofthe start of screening; Receiving antiretroviral therapy that may interfere withstudy drug; CD4 count <350 at screening; AIDS-defining opportunistic infectionwithin 6 months of start of screening

9. Active or symptomatic viral hepatitis or chronic liver disease; ascites or bleedingdisorders secondary to hepatic dysfunction

10. Gastrointestinal conditions affecting absorption

11. Known or suspected contraindications or hypersensitivity to darolutamide

12. Treatment with strong CYP3A4 inducers and P-gp inducers within 2 weeks or 5drug-elimination half-lives, whichever is longer, prior to initiation of study drug

13. Major surgery within 28 days before first dose of study treatment

14. Any psychological, familial, geographic or social situation, according to thejudgment of investigator, potentially preventing the provision of informed consentor compliance to study procedure

15. Patient who has forfeited his/her freedom by administrative or legal award or who isunder legal protection (curatorship and guardianship, protection of justice)

16. Concurrent enrolment in another interventional therapeutic clinical study.

17. Patients with a history of another malignancy at high risk of recurrence within 5years and with a concurrent malignancy requiring active treatment or having requiredanticancer treatment within 6 months prior to inclusion.