Randomized, controlled intervention study of soy protein isolate in men at high risk for biochemical recurrence after radical prostatectomy: Design and accrual

B38 Various lines of evidence suggest that soy intake may prevent prostate cancer and be beneficial for men with prostate cancer and soy constituents inhibit development of prostate cancer in animal models. We designed a double-blind, randomized placebo-controlled clinical trial to determine whether intervention with soy protein reduces biochemical recurrence (PSA failure) in men who are at high risk for such failure in the first two years after radical prostatectomy. To be eligible, subjects must fulfill one or more of the following characteristics: high Gleason sum (≥8), established extra-prostatic extension, seminal vesicle invasion, established positive surgical margins, positive lymph nodes, and/or preoperative PSA of ≥20 ng/ml. Using a review of current literature and recent historical data from NYU, it was estimated that the two-year PSA failure rate in subjects fulfilling one or more of these criteria is approx. 30%. Other eligibility criteria are a baseline PSA of less than 0.07 ng/ml and confirmation of pathological characteristics by centralized slide review. Exclusionary factors include: regular soy intake at baseline, recent history of soy or milk protein allergy, iron deficiency anemia, diabetes, thyroid disease, or frequent substantive constipation. Biochemical recurrence was defined a priori as reaching a PSA of ≥0.07 ng/ml using an ultra-sensitive assay (Tosoh), confirmed twice at ≥1 month intervals. With a sample size of 256 evaluable subjects, this study will have 80% power to detect a 50% reduction in two-year PSA failure rate at a 2-sided significance level of 0.05. To accommodate a known drop-out of 13%, the accrual goal is 284. Thus far, 173 men have been randomized to soy protein isolate or a casein-based placebo (Solae) that are identical in composition, except for protein source, and provide 20 g protein/day with the soy preparation containing ~24-26/day genistein and ~40-43/day total isoflavones. Self-reported compliance is excellent, and serum isoflavones (including equol) are being measured by HPLC with electrochemical detection as an independent compliance measure. Of 123 subjects with detectable serum genistein levels from whom equol values were determined thus far, 31% did not have detectable serum equol (less than 1 ng/ml), 41% had equol levels between 1 and 10 ng/ml, and 28% had equol level above 10 ng/ml (range 11-417 ng/ml). Besides UIC and NYU, 2 other academic medical centers and 2 VA Medical Centers are involved in this study. Thus far, 160 men have completed two years of intervention or developed PSA failure. No treatment-related adverse events were observed, except two cases of transient constipation. Of 33 men thus far identified with biochemical failure (PSA ≥0.07) 22 developed further evidence of recurrence while the other man is being followed for this. Continued accrual is ongoing at six US institutions. (Supported in part by NIH Grants No. CA27790 and CA116195 by the Fremont Family Foundation. The past donation of the intervention materials by The Solae Company is gratefully acknowledged.)