Magnetic Resonance-Guided Stereotactic Body Radiation Therapy for the Treatment of Prostate Cancer

Inclusion Criteria:

* Documented informed consent of the participant and/or Legally Authorized Representative

  * Assent, when appropriate, will be obtained and documented for adults lacking capacity per institutional guidelines
* Age: ≥ 18 years
* Eastern Cooperative Oncology Group (ECOG) ≤ 2
* National Comprehensive Cancer Network (NCCN) low-risk or intermediate-risk prostate cancer, defined as:

  * Low-risk: Prostate-specific antigen (PSA) \< 10 ng/mL AND grade group 1 (Gleason score 3+3) AND clinical stage T1-T2a
  * Intermediate-risk (one or more of the following intermediate risk factors \[IRFs\]): PSA 10-20 ng/mL, grade group 2 or 3 (Gleason 3+4 or 4+3), or clinical stage T2b-T2c

    * Favorable intermediate-risk (all of the following): 1 IRF, grade group 1 or 2, \< 50% cores positive
    * Unfavorable intermediate-risk (one or more of the following): 2 or 3 IRFs, grade group 3, ≥ 50% cores positive

      * Biopsies from a single region of interest (ROI) are counted as a single sample
* Diagnostic multiparametric MRI (mpMRI) of the prostate (within 6 months prior to enrollment) with MRI-visible dominant lesion defined as Prostate Imaging-Reporting and Data System (PI-RADS) ≥ 3
* Prostate biopsy, including targeted and systematic biopsy. All PI-RADS ≥ 3 lesions must be sampled by MRI-targeted biopsy. Biopsy results must confirm concordance between the MRI-visible lesion and histologically confirmed prostate adenocarcinoma. Patients with any positive biopsy core (any grade group) from a region not attributable to the MRI-defined PI-RADS ≥ 3 lesion(s) are excluded
* Unilateral disease, defined as: the MRI-visible dominant lesion(s) and all biopsy-confirmed prostate cancer confined to one prostatic lobe. Multiple lesions are permitted provided they can be encompassed within a single focal treatment planning volume
* Agreement by males of childbearing potential to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 4 months after the last dose of protocol therapy

  * Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for \> 1 year (women only)

Exclusion Criteria:

* Chemotherapy, biological therapy, immunotherapy within 21 days or five half-lives (whichever is shorter) prior to day 1 of protocol therapy
* Current or planned androgen deprivation therapy (ADT), including leutenizing hormone-releasing hormone (LHRH) agonists, LHRH antagonists, antiandrogens, or prior bilateral orchiectomy. Prior 5-alpha reductase inhibitor use is permitted if discontinued ≥ 90 days prior to baseline PSA assessment or if the corrected PSA value (measured PSA × 2) meets protocol risk group eligibility criteria (≤ 20 ng/mL)
* Prior focal therapy for prostate cancer, including but not limited to high intensity focused ultrasound (HIFU), cryotherapy, irreversible electroporation (IRE), laser ablation, or photodynamic therapy
* Prior pelvic radiation therapy
* Prior prostate procedures for BPH (including but not limited to transurethral resection of the prostate \[TURP\], UroLift, Aquablation, Rezūm, prostate artery embolization) that, in the opinion of the treating radiation oncologist, have significantly altered prostatic anatomy such that focal SBRT treatment planning would be compromised or leads to increased risk of treatment-related toxicity
* For patients with severe baseline lower urinary tract symptoms (International Prognostic Scoring System \[IPSS\] ≥ 20), the treating radiation oncologist should confirm that the patient's baseline urinary function and location/volume of target does not, in their clinical judgment, represent an unacceptable risk for treatment-related urinary morbidity
* Clinically significant uncontrolled illness. Patients that are known to be HIV-infected that are on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
* Patient has baseline grade ≥ 3 gastrointestinal (GI) or genitourinary (GU) toxicity
* History of prior rectal surgery (e.g., low anterior resection, abdominoperineal resection) or other pelvic surgery that, in the opinion of the treating radiation oncologist, would significantly alter normal pelvic anatomy and compromise safe treatment delivery
* Active inflammatory bowel disease (ulcerative colitis or Crohn's disease) involving the rectum or sigmoid colon
* Contraindication to magnetic resonance imaging, including but not limited to:

  * Implanted metallic devices not certified as MRI-conditional (e.g., non-MRI-conditional cardiac pacemakers, defibrillators, neurostimulators, cochlear implants, metallic foreign bodies)
  * Severe claustrophobia not manageable with anxiolytic medication and/or supportive measures
  * Inability to tolerate supine positioning for the duration of MR-guided treatment delivery (approximately 30-45 minutes per fraction)
* Other active malignancy. Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
* Any other condition that would, in the Investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures
* Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)