Weighing HRQOL and Tolerability in Metastatic Castration-Sensitive Prostate Cancer Care

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Health-related quality of life (HRQOL) represents a fundamental consideration in mCSPC management, ranking second to cancer control in patient priorities while significantly impacting daily treatment decisions. The ARANOTE trial demonstrated that patients achieving ultralow PSA levels experienced superior QOL outcomes in a stepwise fashion, mirroring cancer control benefits. Notably, darolutamide plus androgen deprivation therapy (ADT) appeared to extend the time patients maintained good QOL and showed superior QOL preservation compared with ADT alone, with numerically lower fatigue rates despite being an additional therapy.

QOL assessment requires validated instruments combined with clinical observation of patient functional status, ambulation, and daily activities. Darolutamide’s unique pharmacological profile, including minimal blood-brain barrier penetration and reduced GABA receptor interaction, translates to improved tolerability in clinical practice. Unlike other androgen receptor pathway inhibitor trials, darolutamide studies didn’t exclude patients with seizure history or cerebrovascular accidents, reflecting its favorable central nervous system safety profile. Drug-drug interaction considerations become particularly important in older patients with polypharmacy, where darolutamide’s minimal interaction profile offers advantages.

Integrating QOL data into treatment decisions requires balancing cancer control with day-to-day patient experience. As patients live longer with advanced prostate cancer, maintaining functional independence and cognitive clarity becomes increasingly important. The ARASEC trial, comparing darolutamide outcomes in US patients with charter trial ADT monotherapy using FDA-approved matched adjusted indirect comparison methodology, will provide additional real-world evidence for treatment selection. Successful long-term mCSPC management depends on selecting therapies that optimize oncologic outcomes and patient-reported QOL measures.