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. 2025 Oct;16(5):e70076.
doi: 10.1002/jcsm.70076.

The Prognostic Role of Frailty and Its Recognition With Simple FRAIL and Fried Frailty Questionnaires in Advanced Cancer Patients

Pia Weinländer  1   2   3 , Sara Hadzibegovic  1   2   4 , Jan Porthun  1   3   5 , Lucie Kretzler  1   3   4 , Ruben Evertz  6   7 , Alessia Lena  1   2   4 , Laura-Carina Lück  1   2   3 , Jonathan L Hella  1   2   3 , Ursula Wilkenshoff  1   4 , Andrea Stroux  8 , Kalliopi Keramida  9   10 , Anne Letsch  11   12 , Dominik Paul Modest  12   13   14 , Lars Bullinger  12   13   14   15 , Ulrich Keller  12   13   14   15 , Mahir Karakas  16   17 , Youssef S Abdelwahed  1   2   4 , Philipp Attanasio  1   4 , Ursula Rauch  1   2   4 , Carsten Skurk  1   4 , Wolfram Doehner  2   18   19   20 , Ulf Landmesser  1   2   4   21 , Stephan von Haehling  6   7 , Markus S Anker  1   2   4   22
Affiliations

The Prognostic Role of Frailty and Its Recognition With Simple FRAIL and Fried Frailty Questionnaires in Advanced Cancer Patients

Pia Weinländer et al. J Cachexia Sarcopenia Muscle. 2025 Oct.

Abstract

Background: Patients with advanced cancer frequently suffer from frailty associated with vulnerability and adverse outcomes. Our aim was to assess the prevalence of frailty and elucidate the utility of two commonly used frailty questionnaires in an advanced cancer population.

Methods: The Fried Frailty Phenotype (FFP) and Simple FRAIL Questionnaire (SFQ) were assessed in hospitalized patients with mostly advanced cancer. Patients were classified by both questionnaires as frail (3-5 points), pre-frail (1-2 points) and robust (0 points) and followed up for all-cause mortality. Utility was evaluated with correlation and survival analysis.

Results: From 11/2017 to 02/2020, 251 mostly advanced cancer patients (61 ± 13 years, 53% men, BMI 25.3 ± 4.8 kg/m2, 78% cancer stage ≥ 3) were prospectively enrolled. In cancer patients, according to the FFP and SFQ, 17%/13% were frail, 52%/41% prefrail and 31%/47% robust. The correlation between both scores was strong (rs = 0.65, p < 0.001). Both scores were predictors of mortality of cancer patients in univariable and multivariable Cox proportional hazards analyses (multivariable adjusted: per 1 point: FFP: HR 1.36, 95% CI, 1.15-1.61, p < 0.001; SFQ: HR 1.29, 95% CI, 1.09-1.52, p = 0.003-adjustment for age, cancer stage/type, anti-cancer therapy naïve, sex, BMI, CKD and anaemia). The time-dependent multivariable adjusted area under the receiver operating characteristic curve for 6-/24-month survival follow-up for the FFP was 0.78 (95% CI, 0.70-0.86)/0.92 (95% CI, 0.87-0.98) and for the SFQ was 0.79 (95% CI, 0.69-0.88)/0.90 (95% CI, 0.83-0.97).

Conclusion: Frailty and pre-frailty as assessed by FFP and SFQ are commonly found in advanced stage cancer patients. Both questionnaires have a strong correlation and are associated with all-cause mortality in this population. Since the SFQ is easier and quicker to perform, it can be used remotely, and with untrained staff, it might facilitate earlier preventive measures and initiate further actions to mitigate its impact.

Keywords: Fried Frailty Phenotype; Simple FRAIL Questionnaire; cancer; frailty; mortality.

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Conflict of interest statement

U.W. is supported by a Clinical Fellowship Grant from the Berlin Institute of Health and has received speaker fees and/or contributions to congresses from Abbott, AstraZeneca, Bayer, Berlin Chemie, Bristol Myers Squibb, GE Healthcare, Pfizer, Philips and Servier, all outside the submitted work. D.P.M.: speaker fees and honoraria: Servier, Amgen, Merck, Sanofi, MSD, AstraZeneca, Pierre Fabre, GSK, Seagen, G1, Onkowissen, COR2ED, Taiho, Takeda, Incyte, Cureteq, 21up, Medscape, Aptitude Health, Regeneron. Funding (inst): Servier, Amgen. L.B. has received honoraria from AbbVie, Amgen, Astellas, Bristol Myers Squibb, Celgene, Daiichi‐Sankyo, Gilead, Hexal, Janssen, Jazz Pharmaceuticals, Menarini, Novartis, Pfizer, Roche, Sanofi and Seattle Genetics and has received research support from Bayer and Jazz Pharmaceuticals. U.K. has served on advisory boards for Roche, Janssen‐Cilag, Celgene, Takeda, Bristol Myers Squibb, Gilead, Hexal, Pfizer, AstraZeneca and Pentixapharm, has received clinical research support from Janssen‐Cilag, Novartis, Takeda, Bristol Myers Squibb, Roche and Pfizer and has received travel support from Roche, Bristol Myers Squibb, Gilead, Takeda, Janssen‐Cilag and Celgene. M.K. is supported by a Clinician Scientist Professorship Grant from the Else Kroener‐Fresenius‐Foundation and has received personal fees and grant support from Daiichi‐Sankyo, Adrenomed, Sphingotec and Vifor Pharma, all outside the submitted work, and is a part‐time employee of 4TEEN4 Pharmaceuticals. U.L. has received institutional research grants from Amgen, Bayer and Novartis and has received speaker or consulting honoraria from AstraZeneca, Bayer, Boehringer, Amgen, Sanofi, Novartis and Novo Nordisk. S.v.H. has been a paid consultant for and/or received honoraria payments from AstraZeneca, Bayer, Boehringer Ingelheim, BRAHMS, Chugai, Grünenthal, Helsinn, Hexal, Novartis, Pharmacosmos, Respicardia, Roche, Servier, Sorin and Vifor. He also reports research support from Amgen, AstraZeneca, Boehringer Ingelheim, Innovative Medicines Initiative (IMI) and the German Center for Cardiovascular Research (DZHK). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Figures

FIGURE 1
FIGURE 1
(A) Fried Phenotype and the Simple FRAIL Questionnaire responses in points separated by sex. (B) Venn diagram with the distribution of cancer patients in the categories Robust/Prefrail/Frail according to the Fried Phenotype and the Simple FRAIL Questionnaire (n = 251).
FIGURE 2
FIGURE 2
(A) Cumulative survival of all cancer patients (n = 251) according to the Fried Phenotype. (B) Cumulative survival of all cancer patients (n = 251) according to the Simple FRAIL Questionnaire. (C) Comparison of hazard ratios including confidence intervals from survival analysis according to the Fried Phenotype and the Simple FRAIL Questionnaire (n = 251). *Multivariable adjusted for age, cancer stage and type, anti‐cancer therapy naïve, sex, body mass index, chronic kidney disease and anaemia.
FIGURE 3
FIGURE 3
(A) Time‐dependent ROC curves according to the Fried Phenotype and the Simple FRAIL Questionnaire (n = 251). *Multivariable adjusted for age, cancer stage and type, anti‐cancer therapy naïve, sex, body mass index, chronic kidney disease and anaemia. (B) Time‐dependent area under the curve according to the Fried Phenotype and the Simple FRAIL Questionnaire (n = 251). *Multivariable adjusted for age, cancer stage and type, anti‐cancer therapy naïve, sex, body mass index, chronic kidney disease and anaemia.
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