A phase II randomized placebo‐controlled trial of pomegranate fruit extract in men with localized prostate cancer undergoing active surveillance

Introduction or Objective Men with favorable‐risk prostate cancer (PCa) on active surveillance may benefit from intervention strategies to slow or prevent disease progression and the need for definitive treatment. Pomegranate and its extracts have shown antiproliferative and proapoptotic effects in cell lines and animal models, but its effect on human prostate cancer as a target tissue remain unclear. Objectives of this trial include pomegranate's ability to alter serum and prostate tissue biomarkers and the ability of an active surveillance cohort to adhere to a chemoprevention trial for 1 year. Methods Men with organ‐confined, favorable‐risk PCa on AS were randomly assigned to receive pomegranate fruit extract (PFE) 1000 mg (n = 15) or placebo (n = 15) once daily for twelve months. Prostate biopsies were performed at study entry and upon completion of the 1‐year intervention. Plasma and urinary biomarkers were analyzed utilizing immunoassays and HPLC. Tissue proteins were assessed by immunohistochemistry (IHC) and measured by automated quantitation. Results PFE was well‐tolerated with no significant toxicities. One patient withdrew before study initiation and 29 completed the 1‐year intervention. No differences in plasma insulin‐like growth factor‐1 (IGF‐1) levels, prostate‐specific antigen doubling time, or biopsy kinetics were observed. Metabolites including urolithin A and urolithin A‐gluc were detected more frequently in the PFE arm in both urine and plasma (p