Metastatic Castration-Sensitive Prostate Cancer: Evolving Management With New Data from ASCO 2025 - Episode 11
Suboptimal PSA Response: What Are the Best Next Steps?
Panelists discuss how managing patients with suboptimal prostate-specific antigen (PSA) response or rising PSA requires careful consideration of PSA kinetics, doubling time, duration of prior response, and imaging findings to determine whether to continue monitoring, add therapy, or transition to castration-resistant treatment approaches.
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Managing patients with suboptimal PSA response requires careful distinction between those with declining but inadequate PSA reduction vs those experiencing actual PSA progression. For patients whose PSA continues to decline but fails to reach optimal nadir levels, close monitoring without immediate treatment changes remains appropriate, as current evidence does not support adding therapies for suboptimal but ongoing responses. However, the upcoming TRIPLESWITCH trial results may guide treatment intensification in this population, potentially establishing evidence-based approaches for patients not achieving target PSA reductions at specified timepoints.
PSA progression represents a different clinical scenario requiring prompt evaluation and intervention. Clear criteria from prostate cancer working groups define PSA progression and early castration-resistant disease development. When PSA begins rising, comprehensive assessment including prostate-specific maturation antigen (PSMA) PET imaging helps characterize progression patterns, distinguishing between oligoprogression amenable to stereotactic body radiation therapy vs polyprogression requiring systemic therapy changes. The kinetics of PSA rise, including doubling time and absolute increase rate, significantly influence treatment decisions.
Treatment selection for PSA progression depends on multiple factors, including prior response duration, PSA kinetics, and progression volume. Patients with prolonged prior responses and slow PSA rises may benefit from local therapies for oligoprogression, whereas those with rapid PSA doubling times or widespread progression require systemic interventions like chemotherapy or lutetium PSMA therapy. The “art of medicine” becomes crucial in these gray zones where level 1 evidence is lacking, requiring clinicians to integrate multiple clinical variables to optimize individual patient outcomes while avoiding both undertreatment and overtreatment scenarios.
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