Background: A major challenge in the care of older cancer pts is identification of who might benefit from adjuvant chemotherapy (CT). Frail pts (FP) typically tolerate CT poorly and/or die from causes other than cancer. It is crucial to identify FP to spare them toxicities of potentially non beneficial and non cost-effective therapy. Fried Frailty Criteria (FFC), based on the Cardiovascular Health Study (CHS) tool, and Balducci Frailty Criteria (BFC), based on several components of a comprehensive geriatric assessment (CGA), are the two most commonly used measures to identify FP. Recently a VES-13 score of ≥7 has been suggested as a means to identify FP. Methods: Early-stage cancer pts aged ≥ 70 years who were candidates for adjuvant therapy were classified as frail/ not frail at baseline based on CHS assessment, CGA and VES-13 score. As FP are at risk of disability and death, pts were seen 6-monthly to assess for functional decline (FD), defined as either a change from no impaired activities of daily living (ADL) or instrumental ADL (IADL) to any IADL or ADL impairment, or a decrease of ≥2 or ≥1 in IADL or ADL score, respectively, confirmed at two consecutive reviews. Date and cause of death were also captured. To avoid cancer itself confounding the ability of the evaluated tools to identify FP, the main analysis included only tumor-independent events; that is, events occurring in pts without cancer recurrence. A baseline blood sample was taken to assess if analysis of serum metabolomic spectra could identify a metabolic “frailty” signature. Results: 185 pts, median age 77 years (range 70-91), were enrolled. Most pts had breast (65%) or colorectal cancer (30%). Median follow-up was 36 months. The incidence of tumor-independent events in relation to frailty according to VES-13, BFC and FFC and accuracy of each tool are reported in the table. Conclusions: VES-13 score ≥7 may more accurately identify older patients at risk of health deterioration than FFC or BFC. Data comparing metabolomics with other tools to identify FP will be presented.