Association between Geriatric 8 frailty and overall survival, treatment intensity, and treatment tolerance in older patients with cancer (PROGNOSIS-G8)

Introduction Frailty is frequent among older adults with cancer and may affect treatment tolerance. Frailty screening is recommended to help guide clinical decision-making. This study evaluates the association between frailty, assessed with the Geriatric 8 (G8), and first-line oncologic treatment intensity, treatment tolerance within nine months, and one-year overall survival in older adults with various cancers. Materials and methods This prospective cohort study at Odense University Hospital, Denmark included older adults age ≥ 70 years with solid cancers who underwent G8 screening at their initial oncology consultation between June 1, 2020-October 15, 2021. Clinical and survival data were extracted from medical records. Guideline treatment was defined as regimens consistent with national guidelines for first-line oncologic treatment, allowing add-on protocol treatment, while reduced-intensity treatment referred to regimens not among first choices. Treatment tolerance was defined as the absence of discontinuations, dose reductions after treatment initiation, or un-administered treatments (excluding delays). Associations between G8 frailty (G8 ≤ 14/17 points) and outcomes were analyzed using adjusted multivariate logistic regression and Cox proportional hazards regression. Results Among the 1398 patients screened, 65% were frail. Non-frail patients were more likely to receive guideline treatment (OR 1.98, 95%CI 1.28–3.06) and had better first-line treatment tolerance, irrespective of treatment intensity, compared to frail patients (OR 2.38, 95%CI 1.49–3.81), though this effect was more pronounced when receiving guideline treatment (OR 3.08, 95%CI 1.72–5.52). Frailty was associated with twice the risk of one-year mortality (HR 2.03, 95%CI 1.47–2.78), with an absolute mortality risk of 40%, compared to 10% for non-frail patients. Frail patients able to tolerate reduced-intensity treatment had a 68% lower mortality risk compared to frail patients who were unable to tolerate guideline treatment (HR 0.32, 95%CI 0.21–0.49). Discussion G8 screening identifies older adults at a higher risk of treatment intolerance and mortality. Our findings support the need for clinical trials investigating the effects of initially reduced-intensity treatments with potential escalation in frail older adults receiving systemic treatment. Study registration The study is registered at clinicaltrials.gov [ NCT04644874 ].