The role of frailty in modifying physical function and quality of life over time in older men with metastatic castration-resistant prostate cancer

Introduction: As treatment options for metastatic castration-resistant prostate cancer (mCRPC) expand and its patient population ages, consideration of frailty is increasingly relevant. Using a novel frailty index (FI) and two common frailty screening tools, we examined quality of life (QoL) and physical function (PF) in frail versus nonfrail men receiving treatment for mCRPC.Materials and Methods: Men aged 65+ starting docetaxel chemotherapy, abiraterone, or enzalutamide for mCRPC were enrolled in a multicenter prospective cohort study. QoL, fatigue, pain, and mood were measured with the Functional Assessment of Cancer Therapy-General scale, the Edmonton Symptom Assessment System tiredness and pain subscales, and the Patient Health Questionnaire-9. PF was evaluated with grip strength, four-meter gait speed, five times Sit-to-Stand Test, and instrumental activities of daily living. Frailty was determined using the Vulnerable Elders Survey (VES-13), the Geriatric 8 (G8), and an FI constructed from 36 variables spanning laboratory abnormalities, geriatric syndromes, functional status, social support, as well as emotional, cognitive, and physical deficits. We categorized patients as non-frail (FI <= 0.2, VES < 3, G8 > 14), pre-frail (FI > 0.20, <= 0.35), or frail (FI > 0.35, VES >= 3, G8 <= 14); assessed correlation between the three tools; and performed linear mixed-effects regression analyses to examine longitudinal differences in outcomes (0, 3, 6 months) by frailty status. A sensitivity analysis with worst-case imputation was conducted to explore attrition.Results: We enrolled 175 men (mean age 74.9 years) starting docetaxel (n = 71), abiraterone (n = 37), or enzalutamide (n = 67). Our FI demonstrated moderate correlation with the VES-13 (r = 0.607, p < 0.001) and the G8 (r = -0.520, p < 0.001). Baseline FI score was associated with worse QoL (p < 0.001), fatigue (p < 0.001), pain (p < 0.001), mood (p < 0.001), PF (p < 0.001), and higher attrition (p < 0.01). Over time, most outcomes remained stable, although pain improved, on average, regardless of frailty status (p = 0.007), while fatigue (p = 0.045) and mood (p = 0.015) improved in frail patients alone.Discussion: Among older men receiving care for mCRPC, frailty may be associated with worse baseline QoL and PF, but over time, frail patients may experience largely similar trends in QoL and PF as their non-frail counterparts. Further study with larger sample size and longer follow-up may help elucidate how best to incorporate frailty into treatment decision-making for mCRPC.