The primary purpose of this study is to determine whether a tumor test recently developed by GenomeDx Biosciences known as Decipher® can predict aggressive prostate cancer with the same accuracy in African-American men (AAM) as in non-African-American men (NAAM). The Decipher® test was developed from samples derived mainly from men of European origins and little is known about its performance in AAM. It is important to study whether this test can be used in AAM who are known to experience the highest rates of prostate cancer as well as death from prostate cancer. The use of the Decipher® test result to predict how well a patient will do before treatment may make it possible for doctors to distinguish aggressive disease from low risk prostate cancer and modify treatment accordingly. Thus, patients that do not need additional therapies may be spared from unnecessary side effects and those that are at risk may be provided with more aggressive therapy to improve survival. This study is being done to learn whether the Decipher test can really affect these outcomes.

This is a multisite, prospective validation trial. Based on a population consisting of 25% AAM and 75% NAAM, investigators will actively recruit participants and aim to achieve a 1:1 enrollment ratio of AAM to NAAM. To achieve this, low risk AAM will be accrued first and then matching NAAM will be enrolled. NAAM men will be matched to AAM on prostate specific antigen (PSA) at diagnosis.

There will be no treatment intervention beyond standard of care (SOC), and therefore participants will be allowed to choose their definitive treatment option. The intent is to enroll low risk and high volume disease (burden) patients to limit the accrual of patients that would select active surveillance (AS).

Inclusion Criteria:

• Adult patients with Karnofsky Performance Status >70
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1
• Pathologically (histologically) proven diagnosis of prostate cancer (PCa) undergoing their first line of treatment
• Meet National Comprehensive Cancer Network (NCCN) criteria for either: Low risk PCa (defined as Gleason score 6 in ≥ 3 cores; T-stage T1c- T2a); Intermediate risk PCa (defined as Gleason score 7, or prostatic specific antigen (PSA) ≥ 10 ng/ml & < 20 ng/ml, or T-stage ≤ T2c)
• Eligible for either radical prostatectomy (RP) or definitive radiation therapy (RT) (+/- short-term androgen deprivation therapy (ADT))
• Age > 18 years
• Biopsy specimen available

Exclusion Criteria:

• Inability to acquire biopsy or prostatectomy tissue
• History of prior PCa directed chemotherapy or pelvic irradiation (prior to study enrollment)
• Documented distant metastatic disease or pelvic lymphadenopathy
• Prior radical prostatectomy (RP) or cryosurgery for prostate cancer or bilateral orchiectomy
• Targeted for active surveillance after diagnostic biopsy
• Selecting ADT alone after diagnostic biopsy
• On active surveillance for > 6 months after diagnosis

Men diagnosed with localized prostate cancer.