Highlights on prostate cancer 1

Prof Piet Dirix, radiation oncologist at the Iridium Network in Antwerp highlights the most interesting presentations from the oral abstract session on prostate cancer (PCa).

Extensive preclinical data suggest that metformin, a well-known anti-glycemic agent, delays PCa progression in the localised setting. The MAST trial, a randomized, double-blind, placebo-controlled study on active surveillance, involved approximately 500 PCa patients, with or without metformin. The trial results were negative, showing no statistical difference between the treatment and control groups for PFS, and a detrimental effect on patients with a BMI over 30. These findings undermine the use of metformin for preventing PCa progression.

In the high-risk biochemical recurrence setting after local treatment with or without radiotherapy, both the EMBARK and PRESTO trials focused on HRQoL after ADT. The EMBARK trial demonstrated that ADT combined with enzalutamide delayed metastasis-free survival compared to placebo while maintaining high global HRQoL. Updated results presented at ASCO 2024 showed that after treatment suspension at week 37 (if PSA ≤ 0.2 ng/mL), HRQoL did not improve, indicating the treatment was well tolerated. Therefore, treatment intensification is feasible and effective without deteriorating patients’ QoL.

Similarly, the PRESTO trial found that intensified AR blockade for 52 weeks (ADT plus apalutamide, or ADT plus apalutamide and abiraterone) prolonged PSA PFS compared to ADT alone. There was no detrimental effect on general or specific QoL, including sexual function and hormonal side effects. Triple therapy (combining apalutamide and abiraterone) did not improve efficacy outcomes, confirming that triple therapy is unnecessary despite not decreasing QoL.

Many patients progress to develop CRPC. The CHAARTED trial demonstrated a significant survival benefit from early chemo-hormonal therapy (ADT + docetaxel). The CHAARTED2 trial investigated whether these patients would benefit from additional treatment with abiraterone plus cabazitaxel versus abiraterone alone. The primary endpoint, rPFS, showed a clear five-month benefit, and the treatment was well tolerated. This is undoubtedly a viable treatment option, although its applicability needs further establishment.

Lastly, the efficacy of ¹⁷⁷Lu-PSMA-617 in taxane-naïve mCRPC patients who progressed on ARPI was investigated. Patients were randomized 1:1 to either a second-line ARPI or ¹⁷⁷Lu-PSMA-617. Since nearly 80% of patients with confirmed radiographic progression on ARPI crossed over to ¹⁷⁷Lu-PSMA-617, this study effectively compares immediate versus delayed ¹⁷⁷Lu-PSMA-617 treatment. The rPFS outcomes were impressive, although OS did not show a clear benefit. The treatment significantly delayed the time to worsening pain and HRQoL by 4-5 months, indicating it is a valid treatment choice, not only for end-of-life patients as in the VISION trial.