This study will establish the preferred dose of lisinopril in men with non-metastatic prostate cancer undergoing radiation treatment. This study will also evaluate the effect of lisinopril on urinary symptoms and the impact of lisinopril on biomarkers and their association with urinary symptoms.

Inclusion Criteria:

• Have a confirmed diagnosis of adenocarcinoma of the prostate and are candidates for curative-intent external beam radiation (with or without androgen deprivation therapy, ADT) at the Wilmot Cancer Institute Department of Radiation Oncology. Radiotherapy may be either primary, adjuvant or salvage. It may be part of combined treatment with androgen deprivation therapy.
• Be stage M0 based on the standard of care staging imaging
• Be able to read English
• Have the psychological ability and general health that permits completion of the study requirements and required follow up
• Be ≥18 and < 70 years of age
• Have ECOG performance status of 0 to 2 within 180 days prior to enrollment
• Have adequate renal function with creatinine clearance > 30 mL/min within 30 days prior to registration
• Have hematologic and hepatic function deemed adequate for planned treatment by the treating investigator within 90 days prior to registration, including:
• hemoglobin ≥9.0 g/dL, independent of transfusion and/or growth factors
• platelet count ≥100,000/µL independent of transfusion and/or growth factors
• Have a baseline systolic blood pressure of >130.

Exclusion Criteria:

• Have received prior pelvic radiotherapy
• Be taking lisinopril or other RAS modifying drug within two months prior to registration
• Have had a prior allergic reaction to lisinopril