ASCO 2024: Debunking the Frailty-Sarcopenia-ADT Axis in Metastatic Prostate Cancer with Multicomponent Exercise: The FIERCE Trial

(UroToday.com) The 2024 American Society of Clinical Oncology (ASCO) annual meeting featured a session on prostate cancer trials in progress, and a presentation by Dr. Christina Dieli-Conwright discussing the trial design of the FIERCE trial, debunking the frailty-sarcopenia-ADT axis in metastatic prostate cancer with multicomponent exercise. Metastatic prostate cancer incidence is growing despite a decrease in the prevalence of prostate cancer. ADT, the mainstay treatment for metastatic prostate cancer, is accompanied by a number of side effects, such as decline in muscle mass and physical function, leading to the exacerbation of age-related conditions including frailty and sarcopenia.

Notably, prostate cancer patients who received ADT are 3 times more likely to develop frailty compared to patients who never received ADT and 2 times more likely to develop sarcopenia compared to men without cancer.  Frailty is characterized by a loss of functional reserve, where frail men with metastatic prostate cancer have a worse prognosis. Sarcopenia refers to a decrease in muscle mass, strength, and function, and is associated with increased mortality in men with metastatic prostate cancer. Exercise plays a key role in ameliorating or preventing further deterioration of ADT-related side effects and improving muscle mass, fitness, and strength. However, while there is a number of exercise studies in men with prostate cancer, those with metastatic prostate cancer have been vastly understudied, with a lack of studies focusing on frailty and sarcopenia and the mechanisms of how exercise could address such outcomes. Thus, Dr. Dieli-Conwright and colleagues designed the FIERCE trial to assess the effects of a 16-week multicomponent exercise intervention, encompassing resistance, aerobic, and functional training on frailty and sarcopenic status and their potential mechanistic biomarkers, and disease progression. The trial design of the FIERCE trial is as follows:
The FIERCE trial is a prospective study aiming to recruit 80 pre-frail/frail men with metastatic prostate cancer receiving ADT who will be randomized to an exercise or attention control group at the Dana Farber Cancer Institute. The 16-week exercise intervention will include 3x weekly clinic supervised, resistance and functional exercise circuit training, and self-directed home-based aerobic exercise:
The attention control group will receive a stretching program and will be offered the exercise program following the study period. The primary outcome will be frailty, measured by the Fried Frailty phenotype (i.e., muscle loss, exhaustion, physical activity, gait speed, and strength) and frailty-associated biomarkers (IL-6, TNF-α, CRP). Secondary outcomes include sarcopenia, measured using computerized tomography scans, and sarcopenia-associated muscle biopsy-driven biomarkers (myokines and insulin pathway markers). An exploratory outcome will assess the effect of exercise on cancer cell line growth (LNCaP cell line). To date, eight out of planned 80 patients have been enrolled in this trial. 

The originality of the FIERCE Trial lies in the following aspects:

1. Focuses on a vulnerable, understudied population of men with prostate cancer who are pre-frail/frail, sedentary, and diagnosed with metastatic disease by
2. Implementing a non-pharmacologic approach, exercise, to improve the frailty-sarcopenia-ADT axis that
3. Includes multicomponent exercise training supervised by a certified cancer exercise trainer to maximize benefits and maintain intervention fidelity, with
4. Exploration on the mechanistic biomarkers related to skeletal muscle and disease progression 

Clinical trial information: NCT06040125.

Presented by: Christina M. Dieli-Conwright, PhD, MPH, Associate Professor of Medicine, Harvard Medical School and Dana-Farber Cancer Institute, Boston, MA

Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago, IL, Fri, May 31 – Tues, June 4, 2024.