Frailty and outcomes in adults undergoing systemic anti-cancer treatment: a systematic review and meta-analysis

It is increasingly recognised that frailty should be assessed and considered in treatment decision-making in patients with cancer. This review and meta-analysis synthesises existing evidence evaluating the association between baseline frailty and Systemic Anti-Cancer Treatment (SACT) outcomes in adults with cancer. Five databases were systematically searched from database inception to January 2023 to identify prognostic factor studies (cohort/case-control design) reporting the associations between validated frailty assessments (pre-treatment) and follow-up outcomes in adults with solid-organ malignancy undergoing SACT. Risk of bias (RoB) was assessed via Quality of Prognosis Studies in Systematic Reviews tool. Where appropriate, associations between frailty and outcomes (survival, toxicity, treatment tolerance, functional decline/quality of life and hospitalisation) were synthesised in meta-analysis and presented as forest plots. 58 studies met inclusion criteria. They were undertaken in a range of tumour sites and mainly in older patients and advanced disease/palliative settings. Most had low/moderate RoB. Nine frailty assessment tools were evaluated. Four outcomes were synthesised in meta-analysis, which demonstrated the prognostic value of two tools: Geriatric-8 (G8; survival, treatment tolerance, hospitalisation) and Vulnerable Elders Survey-13 (VES13; survival, toxicity, treatment tolerance). Overall pooled estimates indicate that frailty conveys an increased risk of mortality (hazard ratio (HR) 1.68, 95% confidence interval 1.41-2.00), toxicity (odds ratio (OR) 1.83, 1.24-2.68), treatment intolerance (OR 1.68, 1.32-2.12) and hospitalisation (OR 1.94, 1.32-2.83). Simple, brief frailty assessments including G8 and VES13 are prognostic for a range of important outcomes in patients undergoing SACT. Risk estimates should be used to support shared decision-making.