Frailty and adverse clinical outcomes in prostate cancer patients: An analysis from the RADICAL-PC cohort.
Authors: Baro Vila Rocio Consuelo , Pinthus Jehonathan H. , Karampatos Sarah , Cano Garcia Cristina , Mian Rajibul , Lopez-Lopez Jose , Kann Ariel Galapo , Violette Philippe , V surya Prakash , Fradet Vincent , Anderson Patrick , Villareal Trujillo Nicolas , Tan Li Ling , Sabbagh Robert , Lavallee Luke , Oliveira Lívia , Leong Darryl 
Published: February 2025

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Background:
As a disease of older individuals, prostate cancer (PC) may feature physical frailty. Most related studies are retrospective and focus on short-term surgical outcomes.
Methods:
We conductedan analysis of a prospective study of PC patients either diagnosed within the past year, treated with androgen deprivation therapy (ADT) for the first time within the past six months, or scheduled to initiate ADT within a month
.
Frailty was assessed using Fried's criteria which includes five domains [Handgrip strength, gait speed, physical activity, unintentional weight loss (>4 kg/year) and exhaustion (≥3 days/week)]. Patients were classified as frail (≥3 criteria), pre-frail (1-2 criteria), or robust (0 criteria). Participants were followed annually to ascertain the occurrence of mortality, new metastases, major adverse cardiovascular events (MACE: myocardial infarction, stroke, cardiovascular death, stroke, heart failure, peripheral arterial disease, venous thromboembolism or arterial revascularization) and hospitalization. The relationship between frailty and these events was evaluated by Cox proportional hazards models adjusted for age at enrolment, education, race, tobacco and alcohol use, diabetes, past history of cardiovascular disease, estimated glomerular filtration rate, PC risk, metastatic disease and ADT exposure.
Results:
We studied 4304 participants (mean age 69±8 years) from 9 countries: 1429 (33%) were robust, 2394 (56%) pre-frail and 481 (11%), frail. During a median 2.4 years, 336 (8%) died, 161 (4%) died from PC or developed new metastases, 506 (12%) were hospitalized and 262 (6%) experienced MACE. Being prefrail or frail was associated with a higher risk of death, hospitalization and MACE but not PC death or new metastases (Table).
Conclusions:
Pre-frailty and frailty are common among patients with PC. Frailty is associated with approximately a two-fold increase in mortality, hospitalization or MACE in PC patients independent of a wide range of prognostic factors.

Relationship between frailty and clinical outcomes.

Characteristic
Death
Hospitalization
PC death or new metastases
MACE

Hazard ratio (95% confidence interval)

p-value

Hazard ratio (95% confidence interval)

p-value

Hazard ratio (95% confidence interval)

p-value

Hazard ratio (95% confidence interval)

p-value

Frailty Robust Pre-frail Frail
Ref1.54(1.13-2.00)2.90(2.00-4.21)
0.007<0.001
Ref1.39(1.10-1.74)2.29(1.70-3.09)
0.005<0.001
Ref1.05(0.70-1.57)1.47(0.85-2.52)
0.830.17
Ref1.44(1.05-1.97)2.21(1.46-3.34)
0.023<0.001

Estimates are from Cox proportional hazards models adjusted for age at enrolment, education, race, tobacco and alcohol use, diabetes, past history of cardiovascular disease, estimated glomerular filtration rate, PC risk, metastatic disease and ADT exposure.