The association of blood biomarkers with treatment response and adverse health outcomes in older patients with solid tumors: A systematic review

Blood biomarkers are potentially useful prognostic markers and may support treatment decisions, but it is unknown if and which biomarkers are most useful in older patients with solid tumors. The aim of this systematic review was to evaluate the evidence on the association of blood biomarkers with treatment response and adverse health outcomes in older patients with solid tumors. A literature search was conducted in five databases in December 2022 to identify studies on blood biomarkers measured before treatment initiation, not tumor specific, and outcomes in patients with solid tumors aged ≥60 years. Studies on any type or line of oncologic treatment could be included. Titles and abstracts were screened by three authors. Data extraction and quality assessment, using the Quality in Prognosis Studies (QUIPS) checklist, were performed by two authors. Sixty-three studies were included, with a median sample size of 138 patients (Interquartile range [IQR] 99–244) aged 76 years (IQR 72–78). Most studies were retrospective cohort studies (63%). The risk of bias was moderate in 52% and high in 43%. Less than one-third reported geriatric parameters. Eighty-six percent examined mortality outcomes, 37% therapeutic response, and 37% adverse events. In total, 77 unique markers were studied in patients with a large variety of tumor types and treatment modalities. Neutrophil-to-lymphocyte ratio (20 studies), albumin (19), C-reactive protein (16), hemoglobin (14) and (modified) Glasgow Prognostic Score ((m)GPS) (12) were studied most often. The vast majority showed no significant association of these biomarkers with outcomes, except for associations between low albumin and adverse events and high (m)GPS with mortality. Most studies did not find a significant association between blood biomarkers and clinical outcomes. The interpretation of current evidence on prognostic blood biomarkers is hampered by small sample sizes and inconsistent results across heterogeneous studies. The choice for blood biomarkers in the majority of included studies seemed driven by availability in clinical practice in retrospective cohort studies. Ageing biomarkers are rarely studied in older patients with solid tumors. Further research is needed in larger and more homogenous cohorts that combine clinical parameters and biomarkers before these can be used in clinical practice.