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.

The proportion of participants achieving pathologic response rate (pRR: pathologic complete response [pCR] or minimal residual disease [MRD])

Time frame · 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.

Proportion of participants with pathologic complete response (pCR)

Time frame · 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)

Time frame · 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)

Time frame · 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

Time frame · 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

Time frame · 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])

Time frame · 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.