Soy Protein in Preventing Recurrent Cancer in Patients Who Have Undergone Surgery for Stage II Prostate Cancer

Soy Protein in Preventing Recurrent Cancer in Patients Who Have Undergone Surgery for Stage II Prostate Cancer

Randomized Placebo-Controlled Adjuvant Study of Prevention of Prostate Cancer Recurrence After Radical Prostatectomy by Soy Protein Isolate

RATIONALE: Soy protein may help prevent prostate cancer recurrence in patients who have undergone surgery for prostate cancer. PURPOSE: This randomized phase II/III trial is studying how well soy protein works and compares it to a placebo in preventing recurrent cancer in patients who have undergone surgery for stage II prostate cancer.

OBJECTIVES: Determine whether soy protein isolate reduces the PSA failure rate and time to PSA failure within 2 years following radical prostatectomy in patients who are at high risk for prostate cancer recurrence. Determine the effects of soy protein isolate on intermediate biomarkers of steroid hormone axis (testosterone, estradiol, and SHBG) and thyroid activity (T3 and T4). Determine the effects of soy protein isolate on intermediate biomarkers of apoptosis (soluble Fas and Fas-ligand), angiogenesis (VEGF and bFGF), antioxidant activity (8-isoprostanes), and IGF axis (IGF-1 and IGFBP-3). Compare patients who are equol producers to those who are non-producers. OUTLINE: This is a multicenter study. Patients are stratified according to hospital/clinic site (NYU vs UIC or Jesse Brown VA Medical Center vs other sites), number of high-risk characteristics (1 vs > 1), and race (African American vs non-African American [i.e., non-Hispanic White, Hispanic, Asian, and other]). Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive an oral soy protein isolate beverage once daily. Arm II: Patients receive an oral casein placebo beverage once daily. Treatment in both arms continues for up to 2 years in the absence of disease progression or unacceptable toxicity. Blood samples are collected periodically for biomarker laboratory studies. Samples are analyzed to measure PSA levels by Tosoh PSA assay; cholesterol levels; isoflavone and equol concentrations by HPLC and ESA; and indicators of steroid hormone axis (testosterone, estradiol, and SHBG), indicators of thyroid activity (T3 and T4), indicators of apoptosis (soluble Fas and Fas-ligand), indicators of angiogenesis (VEGF and bFGF), indicators of oxidative stress (8-isoprostanes), and indicators of IGF axis (IGF-1 and IGFBP-3) by ELISA.

DISEASE CHARACTERISTICS: Diagnosis of prostate cancer Clinically localized (T1c or T2) disease At high risk for recurrence, as defined by ≥ 1 of the following: Preoperative PSA > 20.0 ng/mL Seminal vesicle invasion Extracapsular extension (excluding the bladder neck) Positive surgical margins (excluding apical margins) Micrometastases in any removed pelvic lymph nodes Final Gleason score of ≥ 8 Must have undergone radical prostatectomy for prostate cancer within the past 4 months Must have an undetectable PSA (< 0.07 ng/mL) at baseline, as measured by Tosoh PSA assay No clinical evidence of locally recurrent or metastatic disease PATIENT CHARACTERISTICS: No significant intake of soy (i.e., more than once a week) at baseline including, but not limited to, any of the following: Vegetarians who regularly consume soy products (e.g., tofu) Individuals with customary Asian dietary habits, including regular intake of soy products Individuals who use soy-based milk replacements No anemia, iron deficiency problems, or subclinical iron deficiency at baseline No diabetes No thyroid disease No requirement for a sodium-free diet No substantive tendency to be constipated (i.e., ≥ grade 2 constipation experienced regularly) No medical problem that would preclude the consumption of the soy containing beverage powder, including allergies against soy (or milk protein) No concurrent major disease, including major mental disease or major substance abuse problems No significant side effects from medication PRIOR CONCURRENT THERAPY: See Disease Characteristics No concurrent radiotherapy or hormonal therapy No other concurrent adjuvant therapy for prostate cancer

Bosland MC, Enk E, Schmoll J, Schlicht MJ, Randolph C, Deaton RJ, Xie H, Zeleniuch-Jacquotte A, Kato I. Soy protein supplementation in men following radical prostatectomy: a 2-year randomized, placebo-controlled clinical trial. Am J Clin Nutr. 2021 Apr 6;113(4):821-831. doi: 10.1093/ajcn/nqaa390.

Bosland MC, Huang J, Schlicht MJ, Enk E, Xie H, Kato I. Impact of 18-Month Soy Protein Supplementation on Steroid Hormones and Serum Biomarkers of Angiogenesis, Apoptosis, and the Growth Hormone/IGF-1 Axis: Results of a Randomized, Placebo-Controlled Trial in Males Following Prostatectomy. Nutr Cancer. 2022;74(1):110-121. doi: 10.1080/01635581.2020.1870706. Epub 2021 Jan 12.

Bosland MC, Kato I, Zeleniuch-Jacquotte A, Schmoll J, Enk Rueter E, Melamed J, Kong MX, Macias V, Kajdacsy-Balla A, Lumey LH, Xie H, Gao W, Walden P, Lepor H, Taneja SS, Randolph C, Schlicht MJ, Meserve-Watanabe H, Deaton RJ, Davies JA. Effect of soy protein isolate supplementation on biochemical recurrence of prostate cancer after radical prostatectomy: a randomized trial. JAMA. 2013 Jul 10;310(2):170-8. doi: 10.1001/jama.2013.7842.