Geriatric Assessment-Based Stratification to Evaluate Treatment Intensity, Quality of Life, and Survival in Older Patients With Metastatic Colorectal Cancer: Protocol for a Prospective Observational Study.

Abstract

Background: Older patients with metastatic colorectal cancer (mCRC) are a heterogeneous population with wide variability in functional status, frailty, cognition, nutritional reserve, and comorbidity burden. Treatment decisions are often guided primarily by chronological age and performance status, which may not adequately capture vulnerability or patient-centered outcomes in this population.

Objective: The primary aim of this study is to prospectively evaluate the association of baseline geriatric assessment (GA)-derived frailty with overall survival in older patients with mCRC receiving first-line systemic therapy in routine clinical practice; secondary aims are to evaluate the associations of frailty with initial treatment intensity and early changes in quality of life (QOL).

Methods: Baseline GA includes activities of daily living, instrumental activities of daily living, the Clinical Frailty Scale, the Mini-Cog, nutritional assessment, the Charlson Comorbidity Index (excluding cancer-related items), and the Eastern Cooperative Oncology Group (ECOG) performance status. Blood-based prognostic biomarkers, including the prognostic nutritional index and neutrophil-to-lymphocyte ratio, are also collected. Initial treatment intensity is defined according to the first-line systemic regimen selected at baseline, whereas subsequent local therapies are recorded separately. QOL is assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) at baseline and 8 to 12 weeks after treatment initiation.

Results: This study was registered in the UMIN Clinical Trials Registry (UMIN000060489) on April 1, 2026. This study received no external funding. Participant recruitment began on April 1, 2026 (the first participant enrolled in June 2026) and is planned to continue for approximately 2.5 years (projected completion: October 2028), with an anticipated sample size of approximately 100 participants; an early QOL follow-up is scheduled for 8 to 12 weeks after treatment initiation for each participant. As of the submission of this revised manuscript (August 2026), 4 participants had been enrolled, baseline QOL assessments had been completed for all 4 participants, and the 8- to 12-week follow-up QOL assessments had been completed for 3 participants; no outcome data were available. Analysis of the primary outcome will be conducted after final survival follow-up, with the main results anticipated for publication in 2030.

Conclusions: This protocol describes a pragmatic GA-based observational framework to examine associations between pretreatment vulnerability, initial treatment intensity, survival outcomes, and patient-reported QOL in older patients with mCRC. Given the exploratory, hypothesis-generating design, the study is expected to generate clinically relevant hypotheses for individualized, patient-centered treatment strategies and future geriatric oncology research.

Trial registration: UMIN Clinical Trials Registry UMIN000060489; https://tinyurl.com/3mn563er.

International registered report identifier (irrid): DERR1-10.2196/94561.