Phase I/Ib, single arm trial of Two-Fraction Stereotactic Body Radiation Therapy (SBRT) with an MRI directed, dominant intraprostatic lesion (DIL), simultaneous integrated boost (SIB) based on genomic classification in the treatment of localized prostate cancer. The primary purpose of this study is to determine the feasibility and safety of two fraction SBRT in patients with localized prostate cancer.

Inclusion Criteria:

• Patient age greater than or equal 18

• Localized adenocarcinoma of the prostate

• Biopsy-proven diagnosis of prostate adenocarcinoma

• Low to intermediate risk National Comprehensive Cancer Network (NCCN) disease

  • TX-T2c-8th addition staging
  • PSA<20 ng/ml
  • Grade group 3 or less

• Proper rectal space replacement required as determined by the treating radiation oncologist

• Prostate size less than 60cc defined at time of simulation based on MRI

• Patient ability to undergo MRI and documented dominant Prostate Imaging Reporting and Data System (PI-RADS) 3 or higher lesion

  -- Exception is very low risk, low risk, or favorable intermediate risk with a low to intermediate decipher score in which case an SIB is not utilized

• Androgen-deprivation therapy (ADT) is left to the discretion of the treating radiation oncologist

• Agreement to use effective contraceptive methods such as condoms and spermicidal foam, intrauterine device, or for their partner to use prescription birth control pills

• Ability to give informed consent

Exclusion Criteria:

• High risk disease

• Pelvic lymph node involvement

• Prophylactic lymph node irradiation requirement as determined by the treating radiation oncologist

• Evidence of clinical or radiological extracapsular extension or seminal vesicle invasion

• Prior radiation to the pelvis

• Prior malignancies within the last 5 years

• Inability to meet pre-specified 2 fraction DVH constraints

• Prostate size > 60cc as measures at treatment planning MRI

• Active significant inflammatory bowel disease (IBD) or rheumatological disease

• Prior prostate surgeries

  • Previous uro lift
  • Transurethral resection of the prostate (TURP) within 6 months of SBRT

• "Reasonable" urinary, bowel, and erectile function as defined by the pre-treatment EPIC questionnaire (>50 overall summary score for each domain)

• Men of reproductive potential may not participate unless they agree to use an effective contraceptive method

The de-identified participant data from the final research dataset used in the published manuscript will be shared upon reasonable request beginning 9 months and ending 36 months following article publication or as required by a condition of awards and agreements supporting the research provided the investigator who proposes to use the data executes a data use agreement with NYU Langone Health. Requests may be directed to: [Vianca.santos@nyulangone.org]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.

Beginning 9 months and ending 36 months following article publication or as required by a condition of awards and agreements supporting the research.

The investigator who proposed to use the data will be granted access upon reasonable request. Requests should be directed to Vianca.santos@nyulangone.org. To gain access, data requestors will need to sign a data access agreement.