Frailty and [¹⁷⁷Lu]Lu-PSMA-617 therapy: tools and strategies for older men with metastatic castration-resistant prostate cancer

The prognosis of metastatic castration-resistant prostate cancer is dismal. [¹⁷⁷Lu]Lutetium-prostate-specific membrane antigen (PSMA)-617 ([¹⁷⁷Lu]Lu-PSMA-617) is the new standard of care for PSMA-positive mCRPC previously treated with ARPI and taxane-based chemotherapy. The efficacy and safety of [¹⁷⁷Lu]Lu-PSMA-617 have been confirmed by phase 2 (TheraP [NCT03392428]) and phase 3 (VISION study [NCT02511664] and PSMAfore trial [NCT04689828]) clinical trials. A substantial proportion of patients with mCRPC are older adults; however, chronological age alone should not be considered a contraindication to [¹⁷⁷Lu]Lu-PSMA-617 therapy. Instead, therapeutic decisions must be guided by a comprehensive evaluation of life expectancy, comorbidities, and frailty. Here we review the effectiveness and safety data for [¹⁷⁷Lu]Lu-PSMA-617, present tools for the geriatric and frailty assessments in clinical practice and discuss its utility and therapeutic indications in patients with different types of frailty.