Preoperative 5-Factor Modified Frailty Index and Index-Hospitalization Cumulative Morbidity After Esophagectomy: An Exploratory Comprehensive Complication Index–Based Cohort Study

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Background and Objectives: The Comprehensive Complication Index (CCI) integrates the number and severity of postoperative complications into a continuous measure. We evaluated the association between the 5-factor modified frailty index (mFI-5) and index-hospitalization cumulative morbidity quantified using the CCI after esophagectomy. Materials and Methods: This retrospective cohort study included 50 patients undergoing esophagectomy between March 2011 and April 2026. Patients were categorized as mFI-5 < 2 (n = 34) or mFI-5 ≥ 2 (n = 16). Complications occurring during the index hospitalization were defined using Esophagectomy Complications Consensus Group criteria, graded by the Clavien–Dindo classification, and summarized using the CCI. The primary outcome was index-hospitalization cumulative morbidity measured using the CCI. The association between mFI-5 ≥ 2 and CCI was assessed using exploratory linear regression with age as the primary adjustment variable; ASA class was additionally evaluated in a sensitivity model. A death-excluded sensitivity analysis was also performed. Results: Median CCI was higher in the mFI-5 ≥ 2 group than in the mFI-5 < 2 group (30.8 [27.8–60.0] vs. 22.6 [20.9–34.6]; p = 0.043). In the age-adjusted model, mFI-5 ≥ 2 was associated with a 14.65-point higher CCI, although the confidence interval included the null (95% CI, −2.12 to 31.43; p = 0.085). Additional adjustment for ASA class further attenuated the estimate (β = 10.98; 95% CI, −10.49 to 32.45; p = 0.309), with ASA class III occurring exclusively in the mFI-5 ≥ 2 group (62.5% vs. 0%). After exclusion of deaths, the between-group difference in CCI was no longer statistically significant (p = 0.188). Nominal between-group differences were observed for CCI ≥ 42.4 (43.8% vs. 11.8%; p = 0.024) and anastomotic leak (37.5% vs. 8.8%; p = 0.022), but neither remained statistically significant after Benjamini–Hochberg correction (both q = 0.156). Rates of any complication and Clavien–Dindo grade ≥III morbidity were similar between groups. Thirty-day mortality was 18.8% versus 2.9% (p = 0.091). Conclusions: No independent association between mFI-5 ≥ 2 and index-hospitalization cumulative morbidity was demonstrated after adjustment, and the crude association did not persist in the death-excluded analysis. The attenuation of the CCI difference after exclusion of deaths indicates that fatal events contributed to the observed crude association. In this cohort, mFI-5 ≥ 2 predominantly reflected cardiometabolic and pulmonary comorbidity burden rather than functional impairment. These findings do not support mFI-5 ≥ 2 as a stand-alone risk-stratification tool and require validation in larger prospective cohorts.