Effect of soy protein isolate supplementation on biochemical recurrence of prostate cancer after radical prostatectomy: a randomized trial

Abstract

Importance: Soy consumption has been suggested to reduce risk or recurrence of prostate cancer, but this has not been tested in a randomized trial with prostate cancer as the end point.

Objective: To determine whether daily consumption of a soy protein isolate supplement for 2 years reduces the rate of biochemical recurrence of prostate cancer after radical prostatectomy or delays such recurrence.

Design, setting, and participants: Randomized, double-blind trial conducted from July 1997 to May 2010 at 7 US centers comparing daily consumption of a soy protein supplement vs placebo in 177 men at high risk of recurrence after radical prostatectomy for prostate cancer. Supplement intervention was started within 4 months after surgery and continued for up to 2 years, with prostate-specific antigen (PSA) measurements made at 2-month intervals in the first year and every 3 months thereafter.

Intervention: Participants were randomized to receive a daily serving of a beverage powder containing 20 g of protein in the form of either soy protein isolate (n=87) or, as placebo, calcium caseinate (n=90).

Main outcomes and measures: Biochemical recurrence rate of prostate cancer (defined as development of a PSA level of ≥0.07 ng/mL) over the first 2 years following randomization and time to recurrence.

Results: The trial was stopped early for lack of treatment effects at a planned interim analysis with 81 evaluable participants in the intervention group and 78 in the placebo group. Overall, 28.3% of participants developed biochemical recurrence within 2 years of entering the trial (close to the a priori predicted recurrence rate of 30%). Among these, 22 (27.2%) occurred in the intervention group and 23 (29.5%) in the placebo group. The resulting hazard ratio for active treatment was 0.96 (95% CI, 0.53-1.72; log-rank P = .89). Adherence was greater than 90% and there were no apparent adverse events related to supplementation.

Conclusion and relevance: Daily consumption of a beverage powder supplement containing soy protein isolate for 2 years following radical prostatectomy did not reduce biochemical recurrence of prostate cancer in men at high risk of PSA failure.

Trial registration: clinicaltrials.gov Identifier: NCT00765479.

Figure 1. Participant Flow

NYU indicates New York University; PSA, prostate-specific antigen. ^aExclusionary medical factors included recent or current history of anemia, iron deficiency problems or subclinical iron deficiency at baseline, diabetes or insulin resistance requiring use of medication, thyroid disease, significant renal impairment, need for a sodium-restricted diet, substantive tendency to be constipated (grade ≥2 experienced regularly), a medical problem precluding the consumption of soy or casein such as allergies to soy or milk protein, and postoperative PSA of 0.07 ng/mL or higher. Fifty-four patients had diabetes, 8 had thyroid disease, 4 had anemia or low iron status, 2 had other malignancies, 1 had renal disease, and 1 had mental disease. ^bThe 4-month postsurgery deadline had passed for these patients before pathology review could occur. ^cPreviously undetected exclusionary medical factors included 4 patients who had diabetes, 1 who had thyroid disease, 1 who had anemia, 2 who had protein allergies, 1 who had recurrent constipation, 1 who had a restricted diet, and 1 who had mental disease. ^dEight eligible participants were referred to the study by participating clinical sites other than NYU and the Manhattan VA; 1 eligible participant was referred to the study by a urologist in private practice. All 9 participants were confirmed to be at high risk by pathology review. ^eThe median time between surgery and randomization was identical in both groups (14 weeks; 95% CI, 13.1–14.1; range, 7 or 8 to 18 weeks).

Figure 2

Biochemical Recurrence-Free Survival