With people living longer after being treated for prostate cancer, quality of life has become a concern when considering the treatment plan. Sometimes after radiation therapy, patients may experience problems that affect the urinary and bowel systems, along with sexual function.

Stereotactic body radiotherapy (SBRT) is a type of radiation technique that delivers five high doses of radiation. At University of California at Los Angeles (UCLA), we have the option to administer SBRT in both our CT-guided and MRI-guided radiation machines.

This trial aims to determine the most effective method for protecting the nerves and blood vessels essential for erectile function, utilizing a technique known as neurovascular sparing.

This technique uses images (i.e., MRI) to map the neurovascular bundles of nerves and blood vessels, which are crucial for erectile function. "Adapting" the radiotherapy treatment for each of these five treatment sessions could enable a more precise delivery of your radiation treatment that is customized based on your internal anatomy immediately before the treatment starts. This is also a standard and low-risk intervention used in many different types of cancer. However, it is a very labor-intensive and time-consuming procedure that requires a team of experts to work together before each of your radiotherapy sessions. We are unsure if the increased complexity associated with this adaptive treatment reduces side effects.

The mechanism implicated in sexual function decline following radiotherapy involves injury to vascular structures surrounding the prostate which are critical for normal erectile function, namely the corpora cavernosa, internal pudendal arteries, and neurovascular bundles. These structures are all in close proximity to the prostate gland and are often included at least partially within the planning target volume margin of treatment plans. As noted above, these planning target volume (PTV) expansions were historically large due to the need to ensure adequate coverage of the target volume to achieve disease control although this likely came at the cost of higher rates of treatment-related toxicity. With enhanced technology for target visualization and intra-fraction motion management, it is technically feasible to reduce margins and spare surrounding normal tissue from receiving the full prescription dose while still treating the target volume with high confidence.

Beyond reducing the isometric PTV expansion due to increased precision in radiation delivery with modern techniques, however, it is now technically feasible to crop out these sensitive Organs-at-risk (OARs) from the final PTV volume in order to further spare them from receiving excess dose. This process, referred to as neurovascular-sparing (NV-sparing), involves the fusion of an MRI and/or MR angiogram to standard radiation planning images to allow accurate contouring of the internal pudendal arteries and neurovascular bundles so that these can be intentionally spared. Daily online adaptive replanning may also play a role in ensuring appropriate coverage of the target volume and sparing of OARs as intended by the treatment plan. To date, no investigations have reported on the clinical or dosimetric outcomes of patients treated with an NV approach in conjunction with these other methods. Furthermore, specific dose constraints for these structures are largely unknown due to the lack of empiric evidence to guide selection.

Inclusion Criteria:

1. Age ≥ 18.

2. Histologically confirmed, clinically localized adenocarcinoma of the prostate.

3. Staging workup as recommended by the National Comprehensive Cancer Network (NCCN) on the basis of risk grouping.

   a. Advanced imaging studies (i.e. prostate-specific membrane antigen [PSMA] positron emission tomography [PET]/CT and fluciclovine PET/CT scan) can supplant a bone scan if performed first.

4. No evidence of metastatic disease in lymph nodes above the bifurcation of the renal arteries, or in bones or visceral organs (nodal disease identified on a PSMA PET/CT scan below the bifurcation of the renal arteries is allowable).

5. Eastern Cooperative Oncology Group (ECOG) performance status ≤2.

6. Ability to undergo magnetic resonance angiography (MRA) of the pelvis.

7. No indication for urgent or emergent radiation.

8. Written informed consent obtained from participant or participant's legal representative and ability for participant to comply with the requirements of the study.

Exclusion Criteria:

1. Patients with neuroendocrine or small cell carcinoma of the prostate.
2. Patients with any evidence of distant metastases except that evidence of lymphadenopathy below the level of the renal arteries can be deemed locoregional per the discretion of the investigator.
3. Evidence of intraprostatic lesion by biopsy, MRI, or PSMA PET/CT within the middle third, or both lateral thirds of the prostate gland.
4. History of whole-gland cryosurgery, high-intensity focused ultrasound (HIFU), brachytherapy, or other ablative treatments of the whole prostate.
5. Prior pelvic radiotherapy.
6. History of Crohn's disease, ulcerative colitis, or ataxia telangiectasia.
7. Penile prosthesis or implant present prior to treatment.

Prostate is required to treat

single blind