Understanding PSA Threshold in Metastatic Castration-Sensitive Prostate Cancer

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Response assessment in mCSPC requires a multifaceted approach IRONMAN represents a landmark global collaboration providing crucial insights into PSA threshold significance in metastatic castration-sensitive prostate cancer. This worldwide effort, spanning North America, Europe, Africa, and Australia, demonstrates the power of international cooperation in advancing prostate cancer research. The registry data confirm that patients achieving a best PSA response below 0.2 ng/mL experience significantly better progression-free and overall survival than those with PSA ≥ 0.2 ng/mL, regardless of whether they received doublet or triplet therapy, or specific ARPI selection.

These findings have immediate clinical implications for trial design and patient counseling. The clear prognostic distinction at the 0.2-ng/mL threshold supports designing clinical trials for patients experiencing suboptimal PSA responses, as current practice lacks evidence-based interventions for this population. Additionally, the data suggest potential for treatment de-escalation strategies in patients achieving very low PSA thresholds, although this requires careful prospective validation. The TRIPLESWITCH trial exemplifies the practical application of these concepts, using PSA response to guide treatment intensification decisions.

The PSA threshold research builds upon historical foundations from trials like SWOG, which first established PSA nadir as a prognostic indicator with thresholds between 0.2 and 0.4 ng/mL. Current data refine these thresholds further, with ultralow PSA levels (≤ 0.02 ng/mL) showing even greater prognostic value. This granular understanding of PSA kinetics enables more precise patient counseling about prognosis and treatment expectations, while supporting the development of risk-adapted treatment strategies that optimize outcomes while minimizing unnecessary treatment burden.