Adaptive Stereotactic Body Radiation Therapy to the Prostate and Pelvic Nodes with Simultaneous Integrated Boost to the MR-Detected Nodule for the Treatment of Patients with High-Risk and Unfavorable Intermediate-Risk Prostate Cancer

Inclusion Criteria

• Pathologically proven adenocarcinoma of the prostate with National Comprehensive Cancer Network (NCCN) high-risk disease or NCCN unfavorable intermediate-risk disease
• Patients with unfavorable intermediate-risk disease must meet the following criteria: *At least one intermediate risk factor (IRF) **Prostate specific antigen (PSA) 10-20 ng/mL **cT2b-c (American Joint Committee on Cancer [AJCC] 8th edition) **Gleason score 7 *At least one “unfavorable” intermediate-risk identifier: **> 1 IRF **Gleason score 4+3 **>= 50% of biopsy cores positive *NO high-risk features
• Patients with high-risk disease must meet at least one of the following criteria: *cT3a-T3b *PSA > 20 *Gleason score >= 8
• MRI scan of the prostate with at least one MR-detectable lesion in the prostate/seminal vesicles. PET/CT which is found to display activity in the prostate consistent with prostate cancer may be substituted per investigator discretion
• Planning to undergo concurrent whole-pelvis SBRT and androgen deprivation therapy (ADT). ADT may be initiated at any time per institutional standard, so long as ADT begins within 60 days of the start of radiotherapy
• At least 18 years of age
• Eastern cooperative oncology group (ECOG) performance status =< 1
• Agreement to adhere to Lifestyle Considerations throughout study duration
• Able to complete relevant patient-reported quality-of-life questionnaires in the opinion of the treating physician
• Able to understand and willing to sign an institutional review board (IRB) approved written informed consent document
• Men and transgender women who have prostate cancer and members of all races and ethnic groups are eligible for this trial
• Patients must agree to use condoms (even if status post [S/P] vasectomy) and another effective method of birth control if engaging in heterosexual intercourse with a woman of childbearing potential. Patients must agree to use condoms if engaging in heterosexual intercourse with a woman who is pregnant. These restrictions are in place throughout treatment and for 3 months following the last radiation treatment.

Exclusion Criteria

• Definitive radiologic evidence of nodal (cN+) or metastatic (cM1) disease on conventional imaging (bone scan) or prostate cancer-specific PET/CT scan (Sodium Fluoride [NaF] PET/CT, Axumin PET/CT, fluciclovine, choline, or prostate-specific membrane antigen [PSMA] PET/CT scan). Patients with lymph nodes >= 1 cm on short axis are ineligible unless the lymph node is read as benign by Radiology
• Prior androgen deprivation therapy. (If the onset of androgen ablation is =< 60 days prior to treatment start, the patient is eligible.) Baseline PSA and testosterone must be obtained prior to start of treatment
• Systemic chemotherapy within 3 years prior to treatment start
• Prior radical prostatectomy, pelvic lymph node dissection, prostate cryotherapy, or high-intensity focused ultrasound (HIFU) to the prostate
• Prior pelvic radiotherapy
• Presence of baseline CTCAE grade >= 2 GI or GU toxicity that does not resolve to grade 1 or less with appropriate intervention
• cT4 disease
• American Urologic Association (AUA) urinary symptom score > 15
• Prostate gland measuring > 90 cc
• Unable to get prostate fiducial markers placed for image guided radiation treatment. Rectal hydrogel is optional and is left to the discretion of the treating physician
• Hip prosthetic that does not allow for treatment planning visualization
• Prior malignancy (except for non-melanoma skin cancer) unless disease-free for at least 2 years. Patients are not eligible if they have had a prior pelvic malignancy (e.g. bladder cancer, rectal cancer)
• Prior transurethral resection of the prostate (TURP) within 3 months prior to registration
• Uncontrolled intercurrent illness precluding RT and/or ADT including, but not limited to, seizures, myocardial infarction in the past 6 months, current severe or unstable angina pectoris, congestive heart failure requiring hospitalization in the past 6 months, uncontrolled active infection, uncontrolled hypertension, or any condition that in the opinion of the investigator would preclude participation in the study
• History of uncontrolled inflammatory bowel disease, including ulcerative colitis and Crohn’s disease
• Presence of anal fissure or history of bowel or bladder fistula
• Scleroderma. Patients who are moderately symptomatic from other autoimmune diseases or patients on biologic therapies for autoimmune diseases are also excluded
• Known history of human immunodeficiency virus (HIV) or chronic hepatitis B or C. Testing to evaluate for the presence of HIV and/or hepatitis B or C is not required in patients who do not carry the diagnosis
• Poorly visualized bladder and bowel on diagnostic CT or CT simulation (either due to body habitus or artifact)
• Unable to spend 30 minutes lying on the radiation therapy treatment couch due to significant urinary frequency/urgency or other comorbidities