Association Between an Intersectionality-Based Risk Score and Cancer Mortality: A Retrospective Cohort Study

Background Cancer mortality disparities persist, and existing prognostic tools have not captured overlapping vulnerabilities, limiting their ability to characterize disparities in mortality and rising digestive cancer incidence among young adults. Our study aims to develop and determine whether a new Intersectionality Score is associated with all-cause cancer mortality, compare its prognostic performance with the Charlson Index and TNM staging, and assess digestive cancer incidence among young adults across intersectionality risk groups. Methods A retrospective cohort study of 5,793 adults with cancer treated at Essentia Health in the upper Midwest (2014–2024) used electronic health records to examine outcomes among patients who initiated chemotherapy or radiation. The outcome was all-cause mortality at last follow-up. The secondary outcome was digestive cancer incidence among young adults (18–49 years). The exposure was the Intersectionality Score, a 12-point index of overlapping social, clinical variables analyzed as continuous and categorical variables. Descriptive statistics, DeLong’s test, and linear, logistic, and Poisson regression models were performed using Stata/SE 18.5, with two-sided P ≤ .05. Results Among 5,793 cancer patients (mean [SD] age, 66.9 [12.4] years; 38.6% female), 50.4% were deceased at last follow-up, and 16.7% had a diagnosis of digestive cancer. Intersectionality Score demonstrated improved prognostic discrimination (AUC 0.630) in cancer mortality prediction compared to CCI (0.605) and TNM staging (0.554) and was significantly associated with mortality: moderate-risk patients had higher odds of death (OR, 1.71; 95% CI, 1.37–2.14) than low-risk patients. Among young adults, digestive cancer incidence was higher in 2017–2019 (IRR, 1.47; 95% CI, 1.31–1.64) and 2020–2022 (IRR, 1.44; 95% CI, 1.29–1.61) versus 2014–2016. Moderate-risk patients had a higher incidence in 2020–2022 (IRR, 1.19) and 2023–2024 (IRR, 1.32). Conclusion The intersectionality risk score was associated with all-cause mortality and demonstrated improved prognostic discrimination over the Charlson Index and TNM staging. Digestive cancer incidence increased among young adults classified as moderate risk. Our cumulative intersectionality score may improve mortality risk stratification and help detect shifting patterns in early-onset digestive cancers among patients with overlapping vulnerabilities, with potential relevance for rural and resource-constrained settings globally.