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

Inclusion Criteria:

• Pathologically proven adenocarcinoma of the prostate with NCCN high-risk disease orNCCN unfavorable intermediate-risk disease.

• Patients with unfavorable intermediate-risk disease must meet the followingcriteria:

• 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 theprostate/seminal vesicles. PET/CT which is found to display activity n the prostateconsistent 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 ADTbegins 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 theopinion of the treating physician.

• Able to understand and willing to sign an IRB approved written informed consentdocument.

Exclusion Criteria:

• Definitive radiologic evidence of nodal (cN+) or metastatic (cM1) disease onconventional imaging (bone scan) or prostate cancer-specific PET/CT scan (NaFPET/CT, Axumin PET/CT, fluciclovine, choline, or PSMA PET/CT scan). Patients withlymph nodes ≥ 1 cm on short axis are ineligible unless the lymph node is read asbenign by Radiology.

• Prior androgen deprivation therapy. (If the onset of androgen ablation is ≤ 60 daysprior to treatment start, the patient is eligible.) Baseline PSA and testosteronemust 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, orhigh-intensity focused ultrasound (HIFU) to the prostate.

• Prior pelvic radiotherapy.

• Presence of baseline CTCAE grade ≥ 2 GI or GU toxicity that does not resolve tograde 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 atleast 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 toregistration.

• Uncontrolled intercurrent illness precluding RT and/or ADT including, but notlimited to, seizures, myocardial infarction in the past 6 months, current severe orunstable angina pectoris, congestive heart failure requiring hospitalization in thepast 6 months, uncontrolled active infection, uncontrolled hypertension, or anycondition that in the opinion of the investigator would preclude participation inthe study.

• History of uncontrolled inflammatory bowel disease, including ulcerative colitis andCrohn's disease.

• Presence of anal fissure or history of bowel or bladder fistula.

• Scleroderma. Patients who are moderately symptomatic from other autoimmune diseasesor patients on biologic therapies for autoimmune diseases are also excluded.

• Known history of HIV or chronic hepatitis B or C. Testing to evaluate for thepresence of HIV and/or hepatitis B or C is not required in patients who do not carrythe diagnosis.

• Poorly visualized bladder and bowel on diagnostic CT or CT simulation (either due tobody habitus or artifact).

• Unable to spend 30 minutes lying on the radiation therapy treatment couch due tosignificant urinary frequency/urgency or other comorbidities.