We performed a double blind, randomized, clinical trial to evaluate the effect of a soy product, QC, on PSA in patients with PCa prior to RP. We found no statistically significant difference in PSA changes in patients treated with QC compared to Placebo. We also found no difference in surgical specimens (including Gleason score, surgical margins, clinical stage, extracapsular extension, lymph node or semivesical invasion) or laboratory parameters (free, total and bioavailable testosterone, amylase, CRP, C-reactive protein, HDL, LDL, Lipase, ESR, TSH, triglycerides) in patients treated with QC. Furthermore, we found no changes in quality of life for patients treated with QC compared to placebo. There were no serious adverse events directly attributed to QC during the trial period. Although the trial had low recruitment, to our knowledge this is the first randomized control trial to evaluate a fermented soy product’s effect on PSA and surgical parameters in patients with PCa undergoing RP. Even though the study was terminated prematurely due to inability to recruit, and thus did not achieve the design power, contributes to a growing body of literature aimed toward evaluating low-toxicity interventions on PCa.

Soy isoflavones have been previously investigated for their relationship with PCa. In terms of risk of PCa, a systematic review and metanalysis summarized the results of 30 studies investigating soy product intake and PCa risk. The metanalysis included studies with patient self reported soy intake and studies which included soy products as an intervention. The metanalysis found a significant association of soy intake with reduced risk of PCa (Total soy food (p < 0.001), genistein (p = 0.008), daidzein (p = 0.018), and unfermented soy food (p < 0.001)) [13]. In patients with PCa, a recent systematic review assessed the role of genistein in PCa parameters, where the effect of genistein supplementation was investigated in two studies [14]. Lazarevic et al. investigated the effect of 30 mg of genistein daily for three to six weeks prior to RP compared to placebo in a randomized phase 2 clinical trial of 54 men with localized PCa. Compared to placebo, patients who were given genistein had statistically insignificant change in PSA (p = 0.051), however they had a significant difference in cellular response (p = 0.033), and cell proliferation (p < 0.001) [15]. However, this trial was evaluated and was found to have a high (completeness of outcome data) or unclear (allocation concealment, blinding of personell and outcome assessor) risk of bias on 4 out of 7 criteria but low risk of bias for sequence generation and blinding as well as selective outcome reporting. In contrast, in a relatively low risk of bias trial, randomization of 60 mg of genistein daily versus placebo for 12 weeks in men enrolled in watchful waiting, yielded no impact on mean change in PSA [16]. Similar to the findings of our clinical trial on fermented soy, Hamilton-Reeves et al. performed a double-blind, randomized, placebo-controlled trial to examine the effects of soy isoflavone capsules in patients with localized PCa for 6 weeks prior to RP. There was no statistically significant difference in change in PSA, testosterone, estrogen, or total cholesterol [17]. Unlike the in-vivo studies including our study and Hamilton-Reeves et al., Q-CAN has been shown to reduces viability and increase apoptosis of cancer cells in a fermentation, concentration and time dependent manner. This suggests that fermentation of soy results in the production of metabolites that can reduce cancer cell viability, and induce cellular apoptosis. Interestingly, it was shown, in-vitro, that these actions occurred independent of genistein content [18].

An important distinction of our study from the current available literature on PCa and soy, is that our trial investigated the fermented soy product QC specifically in a randomized control setting. Strengths of our study include the strict inclusion criteria and its randomized prospective nature. Additionally, unlike prior trials on soy and PCa, our study captured PSA results, laboratory values, surgical parameters, and quality of life measures.

There are several important limitations to note. Most significantly, this trial included a small sample size due to early terminiation and failed to achieve the protocol determined sample size. Therefore, adequate statistical power was not reached to assess the prespecified study endpoints. As additional considerations we did not account for longer-term outcomes or data regarding continued patient exposure to QC post-treatment. The trial also did not include feasibility measurements including patient acceptance and site demographics. Additionally, PSA is a surrogate measure which may not adequately represent cancer risk or response and may fail to identify a variety of antitumor effects. In addition, the length of the exposure was relatively short (a minimum of 2 weeks), which may also be inadequate to lead to measurable differences in clinical parameters. To account for these limitations, further trials should be cognizant of potential sample size limitations, considerations of exposure length, and should incorporate a wider range of clinical and biological endpoints. These findings of poor accrual highlight specific areas for feasibility assessment that should be conducted in future clinical trials of nutritional interventions in prostate cancer.