Active Surveillance With or Without Apalutamide Treatment in Low Risk Prostate Cancer

Inclusion Criteria:

1. Out-patient aged ≥ 18 years old

2. With life expectancy of more than 5 years

3. With ECOG performance status = 0 or 1

4. Having read, understood, signed and dated the informed consent,

5. With a Localized prostate cancer diagnozes within less than 7 months and defined by:

• Clinical Stage: T1c or T2a

• Sampled biopsy with less of 3 positive cores and tumor length < 3 mm per core (<7mm for targeted cores)

• Gleason score < 7 (3+4 for patients >70years if small volume tumor)

• PSA levels ≤ 10 ng/ml or PSA density <0.2ng/ml/ml

6. Clinical laboratory values at screening:

7. Hemoglobin ≥9.0 g/dL, independent of transfusion and/or growth factors within 3months prior to randomization

8. Platelet count ≥100,000 x 109/µL independent of transfusion and/or growth factorswithin 3 months prior to randomization

9. Serum albumin ≥3.0 g/dL

10. Serum creatinine <2.0 × upper limit of normal (ULN)

11. Serum potassium ≥3.5 mmol/L

12. Serum total bilirubin ≤1.5 × ULN (Note: In subjects with Gilbert's syndrome, iftotal bilirubin is >1.5 × ULN, measure direct and indirect bilirubin and ifdirect bilirubin is ≤1.5 × ULN, subject may be eligible)

13. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) <2.5 × ULN

14. Medications known to lower the seizure threshold (see list in appendix 2) must bediscontinued or substituted at least 4 weeks prior to study entry.

15. Agrees to use a condom (even men with vasectomies) and another effective method ofbirth control if he is having sex with a woman of childbearing potential or agrees touse a condom if he is having sex with a woman who is pregnant while on study drug andfor 3 months following the last dose of study drug. Must also agree not to donatesperm during the study and for 3 months after receiving the last dose of study drug.

16. Having accepted the principle of active surveillance

17. Who is willing to participate to the study for a minimum period of 36 months

18. Able to swallow the study drug and comply with study requirements

19. Patient affiliated to the national "Social Security" regimen or beneficiary of thisregimen.

Exclusion Criteria:

1. Prior treatment for prostate cancer with surgery or radiotherapy or including 5-alphareductase inhibitor (finasteride or dutasteride) and antiandrogen

2. Absolute neutrophil count < 1,500/μL,

3. Seizure or known condition that may pre-dispose to seizure (including but not limitedto prior stroke, transient ischemic attack, loss of consciousness within 1 year priorto randomization, brain arteriovenous malformation; or intracranial masses such asschwannomas and meningiomas that are causing edema or mass effect)

4. Any prior malignancy (other than adequately treated basal cell or squamous cell skincancer, superficial bladder cancer, or any other cancer in situ currently in completeremission) within 5 years prior to randomization

5. Severe/unstable angina, myocardial infarction, symptomatic congestive heart failure,arterial or venous thromboembolic events (e.g., pulmonary embolism, cerebrovascularaccident including transient ischemic attacks), or clinically significant ventriculararrhythmias within 6 months prior to randomization

6. Uncontrolled hypertension (SBP≥160 mmHg or DBP≥90 mmHg). Patients with a history ofuncontrolled hypertension are allowed provided blood pressure is controlled byanti-hypertensive treatment.

7. Gastrointestinal disorder affecting absorption

8. Active infection (eg, human immunodeficiency virus [HIV] or viral hepatitis) or othermedical condition that would make prednisone/prednisolone (corticosteroid) usecontraindicated

9. Any other condition that, in the opinion of the Investigator, would impair thepatient's ability to comply with study procedures

10. Mental deficiency or any other reason that may hinder the understanding or the strictapplication of the Protocol

11. Patient placed under judicial protection, tutorship, or curatorship

12. Patient unlikely to attend control visits

13. Patient currently enrolled in an investigational study or having participated toanother investigational study within the past 3 months