A review of pomegranate in prostate cancer

BACKGROUND: Preclinical studies showing that pomegranate juice and its components inhibit prostate cancer led to multiple clinical trials to determine whether pomegranate products could slow the growth of prostate cancer. This review summarizes the preclinical data and discusses the results of the clinical trials. METHODS: Trials targeted patients on active surveillance, neoadjuvant patients, patients with biochemical recurrence (BCR) following local therapy for prostate cancer, and patients with metastatic castration-resistant prostate cancer (mCRPC). RESULTS: In the BCR patient population, early phase II trials of both pomegranate juice and extract showed significant lengthening of PSA doubling time (PSADT), and confirmed the safety of pomegranate products. While a placebo-controlled phase III trial determined that pomegranate extract did not significantly prolong PSADT in BCR patients, a preplanned subset analysis of patients with the manganese superoxide dismutase (MnSOD) AA genotype showed greater PSADT lengthening on the pomegranate extract arm. In the neoadjuvant population, a large trial demonstrated a significant increase in urolithin A and a non-significant reduction in 8-hydroxy-2-deoxyguanosine, a marker of oxidation in prostate cancer tissue, on the pomegranate arm vs the placebo arm. In addition, a randomized clinical trial of a polyphenol-rich multicomponent food supplement that included a 31.25% pomegranate extract found significant slowing of PSA increase in the food supplement arm vs placebo in men on active surveillance and those experiencing BCR. CONCLUSIONS: Pomegranate juice and extract are safe but did not significantly improve outcomes in BCR patients in a large placebo-controlled trial. However a subset of BCR patients with the MnSOD AA genotype appear to respond positively to the antioxidant effects of pomegranate treatment. Phase II trials of 100% pomegranate products in neoadjuvant patients and patients with mCRPC were negative. A multicomponent food supplement showed promising results in a phase II study in active surveillance and BCR patients.