ASCO GU 2021: The Potential Role of Frailty in Modifying Quality-of-Life Related Outcomes in Metastatic Castration-Resistant Prostate Cancer Patients Receiving Docetaxel, Abiraterone, Enzalutamide, and Radium 223

( The field of advanced prostate cancer has rapidly progressed over the past 15 years. Prior to the publication of TAX-327, there were no proven life-prolonging therapies for patients with metastatic castration-resistant prostate cancer (mCRPC). Since that time, there have been many new agents that have proven survival benefits including taxane-based chemotherapy, agents targeting the androgen axis, and bone-targeting agents. Treatment selection in this context is not entirely clear, however, frailty-informed care is emerging as a strategy for tailoring management decisions though there are limited data to support this approach. In a plenary abstract presentation in the Poster Highlights Session: Prostate Cancer session at the 2021 ASCO GU Cancers Symposium, Dr. Kim and colleagues examined patient-reported outcomes, stratified by a validated frailty index (FI), for patients with mCRPC receiving treatment with docetaxel chemotherapy, abiraterone, enzalutamide, or radium 223.

The authors performed a multicenter, prospective cohort study among older (aged 65+) men starting one of four approved therapies for mCRPC. The authors assessed patients’ mood, fatigue, pain, and QoL with PHQ-9, ESAS tiredness, ESAS pain, and FACT-G total as well as subscale scores. They subsequently used linear mixed effect models to determine the change in each outcome over time (at 0, 3, 6 months). At end of treatment, patients were administered the Decisional Regret Scale.

Using 34 variables that span laboratory abnormalities, geriatric syndromes, instrumental activities of daily living, social support, as well as emotional, cognitive, and physical deficits, the authors constructed a FI. Following established cut-offs, they categorized patients as non-, pre-, and frail, then performed stratified linear mixed-effects regression analyses to identify differences in outcomes by frailty status.

The authors identified a total of 198 men (mean age 75.1) who were starting docetaxel (n = 70), abiraterone (n = 38), enzalutamide (n = 67), and radium-223 (n = 29). Among these, rates of frailty were 9.6%, 1.5%, 5.6%, and 2.5%, respectively, with only a modest correlation between frailty and age (Pearson r = 0.27).

Independent of frailty status, baseline quality of life-related measures were similar between treatment groups, with the exceptions of mood (p = 0.033) and pain (p = 0.034). Over time, no significant change in QoL was reported, although all four therapies resulted in generally low levels of decisional regret and similar trends of improved pain but worsened mood (p = 0.006 and 0.02, respectively).


At baseline, frailty status was correlated with worse FACT-G total (p < 0.001), functional well-being (p < 0.001), and depression scores (p < 0.001). In an analysis stratified by frailty index, frail patients experienced treatment-related effects on quality of life-related outcomes as fit patients for all measures aside from mood (p < 0.001).


The authors conclude that frail elderly men receiving systemic therapy for mCRPC experience similar outcomes to non-frail men though frailty status is independently associated with worse functional status.

Presented by: Seungyeon Kim, Medical Student, the University of Toronto, Toronto, ON, Canada; University Health Network, Toronto, ON, Canada

Written by: Christopher J.D. Wallis, Urologic Oncology Fellow, Vanderbilt University Medical Center Twitter @WallisCJD during the 2021 ASCO Genitourinary Cancers Symposium (ASCO GU), February 11th to 13th, 2021