Stereotactic Body Radiation Therapy With Boost Using Urethral-Sparing Intensity-Modulated Radiation Therapy Planning in Treating Patients With Prostate Cancer

This phase I/II trial studies the side effects and best dose of stereotactic body radiation therapy while using intensity-modulated radiation therapy (IMRT) planning to help avoid radiation to normal tissue in patients with prostate cancer. Stereotactic body radiation therapy is a specialized radiation therapy that sends x-rays directly to the tumor using small, high doses of radiation over several days and may cause less damage to normal tissue. This treatment schedule allows for a higher dose of radiation to be administered over a shorter overall treatment period in comparison to standard radiation therapy.

PRIMARY OBJECTIVES:

I. To evaluate the incidence of genitourinary (GU) and gastrointestinal (GI) acute and late toxicity for patients treated with prostate stereotactic body radiotherapy (SBRT) with simultaneous integrative boost, urethral ring sparing, and enhanced prostate localization (magnetic resonance imaging \[MRI\\-computed tomography \[CT\] fusion).

II. To also evaluate the incidence of GU and GI acute and late toxicity for patients treated with prostate stereotactic body radiotherapy (SBRT) with a more conventional and uniformly delivered dose of 7.25 Gy/fraction to the prostate.

III. Disease-free survival: disease-free failure events include local progression, distant progression, biochemical failure as defined by the Radiation Therapy Oncology Group (RTOG) Phoenix definition, and death from any cause.

SECONDARY OBJECTIVES:

I. Evaluate patient quality of life (QOL) using the Expanded Prostate Cancer Index Composite 26 (EPIC-26) for evaluation of the QOL for up to 3 years after the completion of SBRT.

OUTLINE: Participants are assigned to 1 of 2 treatment arms. Participants unable to undergo MRI, whose MRI proves technically inadequate for delineating needed anatomic structures, or who decline to enroll on Arm A are assigned to Arm B.

ARM A: (n = 120) Participants undergo 5 fractions of moderate dose SBRT with simultaneous integrated boost (SIB) every other day for 10 days following urethral-sparing IMRT planning.

ARM B: (n = 40) Participants undergo 5 fractions of uniform dose SBRT every other day for 10 days following undergo urethral-sparing IMRT planning.

After completion of study treatment, patients are followed up at 4-8 weeks, at 4, 8, and 12 months, every 4 months for 1 year, every 6 months for 3 years, and then every 12 months thereafter.

Per protocol amendment in December 2023, the follow up time period for data collection will change to 3 years after the last participant completed treatment.

Eligibility Criteria:
Inclusion Criteria:

* Histologically confirmed diagnosis of adenocarcinoma of the prostate and most recent biopsy within 180 days of study enrollment
* History/physical examination with digital rectal examination of the prostate within 90 days prior to study enrollment
* Gleason score =\< 7, no tertiary pattern \>= 5
* Clinical stage =\< T2b (American Joint Committee on Cancer \[AJCC\] 7th Edition Staging Manual) and no radiographic evidence of T3 or T4 disease
* Clinical stage N0, M0
* Most recent prostate specific antigen (PSA) within 60 days of enrollment
* Maximum PSA =\< 20 ng/ml (not within 20 days after biopsy)
* Eastern Cooperative Oncology Group (ECOG) performance status 0-1
* American Urological Association (AUA) =\< 18 with or without medical management
* Up to a total of year of androgen deprivation allowed.
* Participant signs study specific informed consent prior to study enrollment

Exclusion Criteria:

* FOR ARM A: Inability to obtain a planning MRI or a planning MRI of sufficient quality to allow identification of the peripheral zone and urethra, or inability to adequately fuse the MRI to the planning CT scan
* FOR BOTH ARM A AND ARM B:
* Prior or concurrent invasive malignancy (except non-melanomatous skin cancer) or lymphomatous/hematogenous malignancy unless continually disease free for a minimum of 5 years; (for example, carcinoma in situ of the bladder or oral cavity is permissible)
* Prosthetic implants in the pelvic region that the investigator feels will impede treatment, planning, or delivery (e.g., an artificial hip)
* =\< 3 months from a transurethral resection of the prostate (TURP) procedure
* Significant urinary obstruction (i.e. AUA symptom score \> 18)
* Previous pelvic irradiation, prostate brachytherapy
* Previous radical surgery (prostatectomy) or cryosurgery for prostate cancer
* Severe, active comorbidity, defined as follows:

  * Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
  * Crohn's disease or ulcerative colitis
  * Scleroderma