This trial evaluated the efficacy of isoflavone in patients with prostate-specific antigen (PSA) recurrent prostate cancer after prior therapy. Researchers postulated that isoflavone therapy would slow the rate of rise of serum PSA. Twenty patients with rising PSA after prior local therapy were enrolled in this open-label, Phase II, non-randomised trial. They were treated with soy milk containing 47 mg of isoflavonoid per 8 oz serving three times per day for 12 months. Serum PSA, testosterone, lipids, isoflavone levels (genistein, daidzein and equol) and QoL were measured at various time-points from 0 to 12 months. PSA outcome was evaluated. Within the mixed regression model, it was estimated that PSA had increased 56% per year before study entry and only increased 20% per year for the 12-month study period. Specifically, the slope of PSA after study entry was significantly lower than that before study entry in six patients and the slope of PSA after study entry was significantly higher than before study entry in two patients. For the remaining 12 patients, the change in slope was statistically insignificant. Nearly two-thirds of the patients were noted to have significant levels of free equol in their serum while on therapy.