Adaptive Stereotactic Body Radiation Therapy to the Prostate and Pelvic Nodes With Simultaneous Integrated Boost to the MR-detected Nodule for Patients With High-risk and Unfavorable Intermediate-risk Prostate Cancer

Eligibility Criteria

• * Pathologically proven adenocarcinoma of the prostate with 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):
• * PSA 10-20 ng/mL
• * cT2b-c (AJCC 8th ed.)
• * 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 n 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.
• * 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 IRB approved written informed consent document.
• * Definitive radiologic evidence of nodal (cN+) or metastatic (cM1) disease on conventional imaging (bone scan) or prostate cancer-specific PET/CT scan (NaF PET/CT, Axumin PET/CT, fluciclovine, choline, or 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 ≥ 20
• * 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 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.