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Background Maintaining functional status is among the most important patient-centered outcomes for older adults with cancer. This study investigated the association between comprehensive geriatric assessment (CGA) and progressive disease or decline of IADL-independence 1 year after chemotherapy, overall survival (OS), and premature termination of chemotherapy. CGA-based functional status and quality of life (QOL) 1 year after chemotherapy are also described. Methods This prospective cohort study involved patients aged ≥65 years treated with chemotherapy for any cancer type. CGA and the G8-screening tool were performed before and after the completion of chemotherapy. Analyses were adjusted for tumor type and treatment intent: (a) indolent hematological malignancies, (b) aggressive hematological malignancies, c) solid malignancies treated with curative intent, and (d) solid malignancies treated with palliative intent. Results All 291 included patients lived in The Netherlands; 193 (67.4%) lived fully independent prior to chemotherapy. The median age was 72 years; 164 (56.4%) were male. IADL independence, CGA-based functional status, and QOL were maintained in half of the patients 1 year after chemotherapy. An abnormal G8-score before chemotherapy was a higher risk for progressive disease or a decline of IADL-independence (OR 3.60, 95% CI, 1.98-6.54, P  < .0001), prematurely terminated chemotherapy (OR 2.12, 95% CI, 1.24-3.65, P  = .006), and shorter median OS (HR 1.71, 95% CI, 1.16-2.52, P  = .007). The impact of an abnormal G8-score differed across tumor type (oncological or hematological) and treatment indication (adjuvant or palliative). Conclusion An abnormal G8 score before chemotherapy is associated with progressive disease and functional decline after chemotherapy and shorter median OS, especially in patients with solid malignancies. [ABSTRACT FROM AUTHOR]