Folate Study in Men With Advanced Prostate Cancer

Inclusion Criteria

• •1. Provision of signed and dated informed consent form.
• •2. Stated willingness to comply with all study procedures and availability for the duration of the study.
• •3. Age ≥ 18 years.
• •4. Proven diagnosis of prostate cancer (intermediate unfavorable risk, high risk, very high risk localized per the 2025 NCCN guidelines), or metastatic hormone-sensitive prostate cancer with confirmation by pathology report and most recent prostate biopsy procedure note.
• •5. Prostate cancer treatment naïve.
• •6. Commencing androgen deprivation therapy for prostate cancer within 4 weeks of enrollment in the study. Note that radiotherapy and androgen receptor pathway inhibitors, apart from abiraterone, are allowed in both arms.
• •7. Hemoglobin ≥ 11 g/dL.
• •8. Red blood cell folate \> 750 nmol/L.
• •9. Homocysteine \< 15 micromol/L.
• •10. Creatine clearance within the normal range.
• •11. Eastern Cooperative Oncology Group performance status 0-1
• •12. Stated willingness to abstain from consumption of any supplements or medications containing folic acid or potassium.
• •13. Ability to take oral medications and be willing to adhere to trimethoprim and androgen deprivation therapy regimens.
• •14. For participants able to cause a pregnancy: use of condoms or other methods to ensure effective contraception with partner.
• •15. Agreement to adhere to lifestyle considerations described in the protocol throughout study duration.