Frailty and mortality in patients with cancer: A systematic review and meta-analysis of 191 observational studies

Frailty is increasingly recognized as a marker of vulnerability in patients with cancer yet not performed in routine oncology care due to practical barriers, including lack of knowledge and limited human, temporal and spatial resources. Additionally, a comprehensive pan-cancer synthesis across all validated instruments is currently lacking. Consequently, the magnitude and consistency of the association across different demographic, clinical, cancer (types, disease stages, treatment modalities), and frailty instruments characteristics have not been comprehensively quantified. Therefore, we aimed to examine the association between frailty and all-cause and cancer-specific mortality in patients with cancer and to explore demographic, clinical, and treatment-related factors that may affect this relationship.

In this systematic review, PubMed, EMBASE, CINAHL, Web of Science, LILACS, and SciELO were searched from inception to August 2025. Observational studies assessing the association between frailty and mortality in adults (≥18 years) with cancer were included. Screening was performed independently by multiple reviewers. The methodological quality was evaluated using the Newcastle-Ottawa Quality Assessment Scale (NOS) for cohort studies. Random-effects meta-analyses, subgroup and meta-regression analyses were undertaken.

A total of 191 studies comprising over 626,975 patients (median age, 72.0 years; 40.0% male) were included. Regarding the quality assessment, 160 studies (83.8%) scored 9 points in the Newcastle-Ottawa Scale, with scores ranging from 7 to 9. Frailty was independently associated with higher all-cause mortality (n = 162; adjusted HR, 1.98; 95% CI, 1.85-2.09), with consistent findings after sensitivity analyses. Frailty was also associated with higher cancer-specific mortality (n = 18; adjusted HR, 1.84; 95% CI, 1.58-2.15). Subgroup and meta-regression analyses did not identify significant association of age, sex, body mass index, cancer stage, performance status, or treatment modalities with frailty and mortality.

Frailty is a consistent and independent prognostic factor for mortality in patients with cancer. These findings support the integration of frailty assessment into routine oncology practice to improve risk stratification and inform more individualised treatment decision-making beyond traditional clinical indicators.