Association Between the Preoperative Modified Frailty Index-5 and Cumulative Morbidity After Colorectal Cancer Resection: A Single-Center Retrospective Cohort Study Based on the Comprehensive Complication Index

Objective: This study evaluated the association between the preoperative 5-factor Modified Frailty Index (mFI-5) and in-hospital cumulative postoperative morbidity, as measured by the Comprehensive Complication Index (CCI), in patients undergoing colorectal cancer resection. Methods: This retrospective, single-center cohort study included 455 patients who underwent resection for colorectal cancer between January 2015 and April 2021. Patients were classified as mFI-5 = 0, mFI-5 = 1, or mFI-5 ≥ 2. The primary outcome was high cumulative morbidity during the index hospitalization, defined as CCI ≥ 26.2. Associations with categorical outcomes were evaluated using multivariable logistic regression. Deviation from a linear trend was assessed using a likelihood ratio test, and sensitivity analyses were performed after excluding patients who died, restricting the analysis to elective patients, and using Firth penalized logistic regression. An exploratory interaction between categorical mFI-5 and emergency surgery was assessed using Firth penalized logistic regression. Results: Of the patients, 230 (50.5%) had mFI-5 = 0, 96 (21.1%) had mFI-5 = 1, and 129 (28.4%) had mFI-5 ≥ 2. The rates of CCI ≥ 26.2 were 17.8%, 12.5%, and 28.7%, respectively, and did not demonstrate a linear gradient across categories. Compared with mFI-5 = 0, mFI-5 ≥ 2 was associated with higher odds of CCI ≥ 26.2 after adjustment (OR 2.17, 95% CI 1.21–3.89; p = 0.010), whereas no association was observed for mFI-5 = 1 (OR 0.71, 95% CI 0.34–1.48; p = 0.364). A deviation from the linear trend was observed for CCI ≥ 26.2 (p = 0.025). In exploratory analyses, the adjusted OR was 2.43 (95% CI 1.30–4.54) among in-hospital survivors and 1.79 (95% CI 0.96–3.33) in the elective-only cohort. Firth analyses yielded similar results. The joint interaction test yielded p = 0.012, although the emergency subgroup contained a zero-event cell. Conclusions: mFI-5 ≥ 2 was associated with higher adjusted odds of high cumulative postoperative morbidity, whereas mFI-5 = 1 did not show an intermediate increase in risk. The non-monotonic pattern and attenuation of the association in the elective-only cohort support cautious interpretation of mFI-5 ≥ 2 as an exploratory risk indicator requiring external validation.