A Study to Learn How Well a Combination of Darolutamide and Androgen Deprivation Therapy (ADT) Works as a Treatment Before Surgery for Men Who Have High-risk Localized Prostate Cancer.

• Darolutamide (Drug): Oral tablets of 600 mg twice daily (BID).
• ADT (Drug): Goserelin acetate implant (ZOLADEX), at a dose of 10.8 mg, will be administered subcutaneously every 12 weeks into the anterior abdominal wall below the navel line.

Primary outcomes

• The proportion of participants achieving pathologic response rate (pRR: pathologic complete response [pCR] or minimal residual disease [MRD]) [Completion of Follow-up 1, 30 days after last dose of study drug]: pRR is defined as the proportion of participants with either condition of pCR or MRD at week 12 or 24 in corresponding arm. Proportion of participants with pCR is defined as the proportion of participants with no residual tumor detected in radical prostatectomy (RP) specimens following 12 or 24 weeks of neoadjuvant treatment of darolutamide and ADT per randomization. Proportion of participants with MRD is defined as the proportion of participants that have residual cancer burden (RCB) ≤0.25 cm\^3 in the RP specimens.

Secondary outcomes

• Proportion of participants with pathologic complete response (pCR) [Completion of Follow-up 1, 30 days after last dose of study drug]: Proportion of participants with pCR is defined as the proportion of participants with no residual tumor detected in radical prostatectomy (RP) specimens following 12 or 24 weeks of neoadjuvant treatment of darolutamide and ADT per randomization.
• Percentage of participants with tumor downstaging (e.g. clinical T3 to pathologic T2) [At baseline and immediately after radical prostatectomy]: The pathology review will compare the T stage of tumor tissue at baseline (Screening) with the T stage of radical prostatectomy (RP) specimen at RP and calculate the proportion of participants whose tumor stage has decreased from the baseline T stage.
• Percentage of participants with positive surgical margin (PSM) [Immediately after radical prostatectomy]: PSM is defined as the presence of cancer cells at the edge of the tissue removed during surgery.
• Biochemical complete response (CR) rate prior to radical prostatectomy (RP) and at landmark timepoints post-RP [At pre-RP, at 5 weeks, 12 weeks post-RP, and every 3 months after that until Year 2 after RP or end of follow up]: Biochemical CR rate is defined as participants who attain serum prostate-specific antigen (PSA) level below 0.1 ng/mL (PSA <0.1 ng/mL).
• Biochemical recurrent free survival since radical prostatectomy (RP) among participants with prostate-specific antigen (PSA) <0.1 ng/mL after RP [From RP to biochemical recurrence or death whichever occurs first, up to 2.5 years]: Biochemical recurrent free survival is defined as time from RP to biochemical recurrence or death, whichever occurs first. The endpoint will be assessed only among participants with PSA <0.1 ng/mL after RP. Biochemical recurrence is defined as PSA ≥0.1 ng/mL in 2 consecutive measurements after RP. The date of the first measurement defines the date of biochemical recurrence.
• Incidence and severity of treatment-emergent adverse events (TEAEs) (including treatment-emergent serious adverse events [TESAEs]) [From first dose of study drug up to 30 days after the end of study drug administration]: TEAEs are defined as AEs with an onset date on or after the first dose of study drug and up to the end-of-study drug plus 30 days or with an onset date prior to the first dose of study drug but worsening in intensity after the study drug. Events with missing onset dates will be included as treatment-emergent.

Sex: Male, ages: 18 Years to any

Inclusion Criteria:

* Participants must be 18 years or older at the time of signing the informed consent.
* Darolutamide-naïve participants who are with localized prostate adenocarcinoma who plan to receive radical prostatectomy (RP) and defined as high risk with National Comprehensive Cancer Network (NCCN) criteria (version 1.2025).
* No evidence of distant metastasis based on computed tomography (CT), magnetic resonance imaging (MRI), and whole body bone scan (WBBS) within 42 days prior to start of study treatment.
* Candidate for RP with pelvic lymph node dissection (PLND) or extended PLND (ePLND) as per the investigator.
* Participants must have at least one of the following features according to NCCN definition of high-risk:

  * Biopsy Gleason score ≥8, and/or
  * Prostate-specific antigen (PSA) >20 ng/mL measured during Screening and prior to randomization, or
  * Clinical stage ≥ T3a.
* Participants with pelvic lymph node involvement (N1) can be included.
* Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.

Exclusion Criteria:

* Prostate cancer with known neuroendocrine (NE) differentiation or small cell features.
* Evidence of metastatic disease. Minimum imaging requirements to exclude metastatic disease are diagnostic quality imaging of the chest, pelvis, and the abdomen (CT or MRI with intravenous \[IV\] contrast), and WBBS. Nodal disease below the iliac bifurcation (clinical stage N1) is not an exclusion.
* Intolerant to darolutamide or androgen deprivation therapy (ADT) treatment.
* History of

  * Loss of consciousness or transient ischemic attack or stroke within 6 months prior to randomization, or
  * Significant cardiovascular disease within 6 months prior to randomization.
  * Any contraindications for RP.
* Uncontrolled or treatment-resistant hypertension.
* History of another malignancy within 5 years prior to randomization.