The researchers are doing this study to find out if stereotactic body radiation therapy (SBRT) without androgen deprivation therapy (ADT) is an effective treatment approach for people with unfavorable intermediate-risk prostate. The researchers will see whether SBRT can prevent participants' cancer from coming back and/or spreading to other parts of the body. In addition, they will look closely at how safe and effective it is to rely on Decipher test results for determining which patients would benefit from more extensive radiation treatments

Inclusion Criteria:

• Pathologically proven diagnosis of prostate adenocarcinoma within 12 months of enrollment

• Unfavorable intermediate risk prostate cancer by NCCN 2021 risk stratification guidelines, including any of the following clinicopathologic features:

• Gleason Score 4+3

• ≥ 50% biopsy cores positive

• Two or more of the following risk factors:

  • Grade Group 2 or 3
  • cT2b-T2c
  • PSA 10 - 20 ng/mL

• Able to undergo MRI for initial staging and MR based radiation planning

• Sufficient biopsy tissue available for Decipher genomic testing

• Prostate volume < 90cc

• IPSS ≤ 20

• Age ≥ 18

• KPS ≥ or ECOG 0-2

• Estimated life expectancy >5 years

• Willing and able to provide written informed consent and Authorization for Use and Release of Health and Research Study Information (HIPAA authorization)

Exclusion Criteria:

• Radiographic T3-T4 detected on staging mpMRI

  °Must be "consistent with" (>90% probability) or suspicious for/probable/probably (75%-90% probability) ofT3-T4 disease determined by the reading radiologist.

• Evidence of distant metastases as determined by MRI, PET, or CT imaging

• Evidence of pelvic lymph node involvement as determined by MRI, PET, or CT imaging

• Prior treatment for prostate cancer including chemotherapy, surgery, or hormonal therapy

• Prior pelvic radiation

• Active second malignancy or past history of malignancies diagnosed within the last 2 years that requires active therapy and/or in remission, with the exception of resected non-melanoma skin cancers, non-muscle invasive bladder cancer, stage I head and neck cancer, or stage I colorectal cancer

• TURP or greenlight PVP within 6 months of enrollment

• History of Crohn's Disease or Ulcerative Colitis

Prostate cancer

Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.