Below the Belt Award

This study will test the benefit of monthly testosterone injections for metastatic prostate cancer (cancer which has spread outside the prostate) patients on long-term testosterone reducing drugs. Benefits may include an anti-cancer effect, improvements in quality of life and potential for cancer cells to respond positively to drugs that have failed previously. The research will test the possible benefits and increase understanding about this treatment. Additionally, the study aims to improve the ability to select patients who can benefit most from this treatment due to changes in their tumour that might make them more responsive. Androgen deprivation therapy (ADT) remains the mainstay of prostate cancer treatment. Though an effective therapy initially, the side effects of ADT are numerous and treatment resistance is inevitable. Castrate-refractory prostate cancer (CRPC) progresses via adaptive mechanisms that allow ongoing androgen receptor (AR) signaling despite castrate levels of androgens. Preclinical data suggest these adaptive mechanisms may be exploited through the administration of supraphysiologic levels of testosterone, which has been shown to inhibit growth in some androgen-receptor expressing prostate cancer cells. Men with germline and/or somatic DNA repair defects may be particularly sensitive to this treatment. This study aims to explore the effect of bipolar androgen therapy (BAT) with testosterone enanthate on PSA responses in men with advanced castrate-refractory prostate cancer (CRPC) and DNA repair defects identified on screening circulating tumour DNA (ctDNA) or tumour biopsy. The research will test the hypothesis while information on treatment effects may be key to appropriate patient selection.