Soy supplementation had no effect on the risk of biochemical (PSA) recurrence after radical prostatectomy in high-risk patients, investigators in a randomized trial reported.
The study ended early after an interim analysis showed a PSA recurrence rate of 27.2% in men who took the soy supplement versus 29.5% in men who received a calcium-derived control therapy. The results did not change in an analysis limited to adherent patients.
Despite the negative outcome, the investigators emphasized that the results apply only to a specific patient population.
'The lack of protective activity of soy against prostate cancer recurrence observed in this study was limited to men at above-average risk of recurrence within the first 2 years after surgery and to the soy protein dose tested,' Maarten C. Bosland, DVSc, PhD, of the University of Illinois at Chicago, and co-authors concluded in an article published online in JAMA.
'The findings of this study may therefore not be generalizable to prostate cancer patients at average risk of recurrence.'
The trial had limitations that go beyond generalizability, said Derek Raghavan, MD, PhD, of Carolinas HealthCare System in Charlotte, N.C., who was not involved in the trial.
'This is a really disappointing study, because it was poorly designed and executed, and I don't think it tells us anything new,' Raghavan told MedPage Today.
'Half of the patients got what appears to be a poorly characterized soy product and the other half got a calcium caseinate product, which in other contexts is used as a source of energy in diet supplementation. It was meant to be a placebo, yet it was actually a mechanism for giving calories.'
The trial included men with various levels of risk, required 13 years to conduct, and enrolled relatively few men despite screening thousands of patients, he added.
'It's really impossible to figure out whether those confounding factors would have made the study null and void,' said Raghavan.
The reduced prevalence of prostate cancer in Asian versus Western nations has helped focus attention on dietary factors that might influence risk. Because of the increased consumption of soy products in Asian nations, some researchers have hypothesized that consumption of soy might reduce prostate cancer risk. However, the hypothesis has no supporting evidence, the authors noted in their introduction.
Most prostate cancers detected by PSA testing are indolent and highly unlikely to become fatal. Focusing an intervention on men with high-risk disease has the most potential to reduce the risk of prostate cancer-specific mortality, the authors continued.
Several previous studies had examined the effect of soy protein on PSA levels in various populations of healthy men, men enrolled in surveillance for presumably indolent prostate cancer, men with high-grade prostatic intraepithelial neoplasia, and men with untreated prostate cancer. Collectively, the trials produced mixed and inconsistent results.
No prior studies had evaluated soy's effect on biochemical recurrence after radical prostatectomy. To address the issue, Bosland and colleagues at seven centers in the U.S. enrolled patients who had localized prostate cancer (T1c or T2) and a PSA value <0.07 ng/mL after radical prostatectomy.
Eligible patients had one or more high-risk features: PSA >20 ng/mL, final Gleason score ≥8, positive surgical margins, extracapsular extension, seminal vesicle invasion, or micrometastases in pelvic lymph nodes.
The patients were randomized to a soy protein isolate or a caseinate-based product incorporated into a beverage powder, which was consumed daily.
The primary endpoint was the 2-year rate of biochemical recurrence and time to recurrence. The investigators defined recurrence as a serum PSA value ≥0.07 ng/mL, confirmed by two subsequent tests at least 1 month apart. Adherence was self-reported and monitored by serial measurement of serum genistein.
Investigators randomized 177 patients from July 1997 to May 2010. The trial design called for an interim analysis after 45 biochemical recurrences. At the interim analysis, 22 of 81 (27.2%) evaluable patients in the soy arm had recurrence compared with 23 of 78 (29.5%) in the control group.
The authors reported that 11 adherent participants discontinued treatment before the interim analysis but remained in follow-up. Exclusion of those patients in a per-protocol analysis did not change the results, nor did censoring of 13 participants considered possibly nonadherent because of serum genistein levels.
The groups had similar rates of adverse events, and the principal reasons for discontinuation related to the taste and palatability of assigned treatment.
The study was supported by the National Institutes of Health, the Prevent Cancer Foundation, and the United Soybean Board. Solae provided intervention products.
Bosland reported no relevant disclosures. Co-author Samir S. Taneja disclosed relationships with Eigen, Gtx, Bayer, Janssen, Elsevier, and Steba.
Primary source: Journal of the American Medical Association Source reference: Bosland MC, et al 'Effect of soy protein isolate supplementation on biochemical recurrence of prostate cancer after radical prostatectomy. A randomized trial' JAMA 2013; DOI: 10.1001/jama.2013.7842.
