The effect of a phytoestrogen intervention and impact of genetic factors on tumor proliferation markers among Swedish patients with prostate cancer: study protocol for the randomized controlled PRODICA trial

Abstract

Background A high intake of phytoestrogens, found in soy, rye, and seeds, is associated with a reduced risk of a prostate cancer diagnosis. Previously, we found that the overall decreased risk of prostate cancer diagnosis in males with a high intake of phytoestrogens was strongly modified by a nucleotide sequence variant in the estrogen receptor-beta (ERβ) gene. However, we do not know if phytoestrogens can inhibit the growth of prostate cancer in males with established diseases. If there is an inhibition or a delay, there is reason to believe that different variants of the ERβ gene will modify the effect. Therefore, we designed an intervention study to investigate the effect of the addition of foods high in phytoestrogens and their interaction with the ERβ genotype on prostate tumor proliferation in patients with prostate cancer. Method The PRODICA trial is a randomized ongoing intervention study in patients with low- and intermediate-risk prostate cancer with a Gleason score < 8, prostate-specific antigen (PSA) < 20, and scheduled for radical prostatectomy. The study is conducted at Sahlgrenska University Hospital in Gothenburg, Sweden. The intervention consists of a daily intake of soybeans and flaxseeds (~ 200 mg of phytoestrogens) until the surgery, approximately 6 weeks. The aim is to recruit 200 participants. The primary outcome is the difference in the proliferation marker Ki-67 between the intervention and the control groups. The genotype of ERβ will be investigated as an effect-modifying factor. Secondary outcomes include, e.g., concentrations of PSA and steroid hormones in the blood. Discussion The results of the PRODICA trial will contribute important information on the relevance of increasing the intake of phytoestrogens in patients with prostate cancer who want to make dietary changes to improve the prognosis of their cancer. If genetic factors turn out to influence the effect of the intervention diet, dietary advice can be given to patients who most likely benefit from it. Dietary interventions are cost-effective, non-invasive, and result in few mild side effects. Lastly, the project will provide basic pathophysiological insights which could be relevant to the development of treatment strategies for patients with prostate cancer. Trial registration. ClinicalTrials.gov NCT02759380. Registered on 3 May 2016.

Effects on Serum Hormone Concentrations after a Dietary Phytoestrogen Intervention in Patients with Prostate Cancer: A Randomized Controlled Trial

“…The design of the PRODICA (the impact of DIet and individual genetic factors on tumor proliferation rate in men with PROstate CAncer) study and the randomization process have been described in detail elsewhere [ 23 ]. Men diagnosed with prostate cancer cT1–cT2 (prostate-specific antigen (PSA) < 20, International Society of Urological Pathology (ISUP) grade < 4) and scheduled for radical prostatectomy were invited to participate in the study at the Department of Urology at Sahlgrenska University Hospital in Gothenburg, Sweden.…”

“…The patients were recruited between 1 February 2016, and 12 October 2022, and the last blood sample was collected in November 2022. In the PRODICA study, tumor proliferation is the primary outcome and hormone concentrations are predeclared secondary outcomes [ 23 ]. The study was registered at ClinicalTrials.gov (NCT02759380, ; accessed on 26 March 2023) on 3 May 2016 after our pilot study ( n = 10) was finished.…”

“…The study was registered at ClinicalTrials.gov (NCT02759380, ; accessed on 26 March 2023) on 3 May 2016 after our pilot study ( n = 10) was finished. Except for some administrative changes, we made no major changes to the study protocol after the pilot study [ 23 ]. The study was approved by the Ethical Review Board in Gothenburg (registration number 410–14, amendment numbers T124-15; 2020-02471; 2021-03320, 2021-05878-02).…”

“…During the inclusion meeting, the participants in the intervention group were provided with the amounts of soybeans and flaxseeds that were planned to suffice until the scheduled surgery. The participants received a schedule on the amounts of the intervention foods to eat [ 23 ], serving suggestions, and recipes. Intake of the food items was gradually increased during the first nine days and thereafter included a daily intake of 28 g flaxseeds, 47 g green soybeans, and 28 g roasted yellow soybeans (corresponding to an estimated amount of 100 mg isoflavones and 100 mg of lignans and thus 200 mg of phytoestrogens [ 25 ]).…”

Correction: The effect of a phytoestrogen intervention and impact of genetic factors on tumor proliferation markers among Swedish patients with prostate cancer: study protocol for the randomized controlled PRODICA trial

“…The original publication of this article [1] contained a typo on page 2. The incorrect and correct information is shown below.…”