StatinT-reg Function Changes: a Novel Immune Regulatory Effect Underlying Benefit of Statin Use on Lethal Prostate Cancer

Inclusion Criteria:

1. Men with pathologically-confirmed localized prostate cancer determined to be intermediate (stage T2b, or Gleason 7, or PSA 10-20 ng/mL) or high risk (stage T2c, or PSA >/=20 ng/mL, or Gleason >/=8) of biochemical recurrence at the time of biopsy
2. Electing to undergo prostatectomy;
3. Ability to provide written informed consent and willing to complete study procedures.

Exclusion Criteria:

1. Current statin use or use of non-statin lipid-lowering drug (fibrates, bile acid sequestrants, or niacin);
2. Current use of medications contraindicated for concomitant use with 40mg simvastatin:

• Gemfibrozil
• Cyclosporine
• Danazol
• CYP3A4 inhibitors: itraconazole; ketoconazole; posaconazole; erythromycin; clarithromycin; telithromycin; HIV protease inhibitors; boceprevir; telaprevir; nefazodone

3. Current use of medications requiring lower dose of simvastatin not already listed as exclusions criteria:

• Verapamil
• Diltiazem
• Amiodarone
• Ranolazine
• Calcium channel blockers: verapamil; diltiazem; amlodipine

4. Men with low-density lipoprotein cholesterol <50mg/dL
5. Statin use in the previous 12 months;
6. Discontinued statin use because of statin-related adverse event;
7. Evidence or suspicion of metastases;
8. Prior neoadjuvant or adjuvant chemotherapy, hormone therapy, or radiation therapy;
9. History of non-prostate cancer other than non-melanoma skin cancer in the last 24 months;
10. Diagnosed diabetes or currently taking diabetes medications
11. Prior myocardial infarction or stroke
12. Chronic liver disease (hepatitis or cirrhosis) or abnormal liver function (>1.5x clinical laboratory's upper limit of normal alanine aminotransferase);
13. Stage 4 or 5 chronic kidney disease (Creatinine clearance / estimated glomerular filtration rate < 30 mL/min calculated by Cockgroft-Gault formula);
14. History of myopathy or inflammatory muscle disease (>3x clinical laboratory's upper limit of normal creatine kinase).