Mediating Effect of Postsurgical Chemotherapy on Presence of Dementia and Survival among Patients 65 and Older with Stage III Colon Cancer

Introduction: Both colon cancer and dementia are prevalent among the elderly and have a high risk of cooccurrence. Previous studies found that patients with dementia were treated less aggressively. In this study, we hypothesized that presence of preexisting dementia was associated with worse survival for stage III colon cancer patients, and that postoperative chemotherapy was on the causal pathway. Methods: We defined preexisting dementia in Surveillance Epidemiology and End Results Medicare data through either a formal diagnosis or a prescription for dementia drugs or both before the diagnosis of cancer. We applied multivariable Cox regression to estimate the effect of preexisting dementia on survival, adjusting for demographic factors, tumor characteristics, and receipt of chemotherapy. We assessed mediating effects in the context of the counterfactual framework using the accelerated failure time model. Results: There were 4,573 patients diagnosed with stage III colon cancer between 2007 and 2009 identified. A preexisting diagnosis of dementia significantly increased the risk of death by 45% (HR = 1.45, 95% CI: 1.29-1.63). Patients with either a formal diagnosis of dementia or a related prescription had significantly lower cause-specific survival than their cognitively healthy counterparts. Receipt of chemotherapy was a significant mediator on the causal pathway. The effect of presence of dementia was mediated by receipt of chemotherapy by 13% for preexisting dementia. Conclusions: Preexisting dementia is significantly associated with worse survival for stage III colon cancer patients, and its deleterious effect is partially explained by decreased likelihood of postoperative chemotherapy receipt. Impact: This is the first study that provides estimate of the mediating effect of diminished chemotherapy in patients with stage III colon cancer and dementia, simultaneously demonstrating the cancer-specific survival benefit of chemotherapy in the presence of dementia. Cancer Epidemiol Biomarkers Prev; 26(10); 155863. (C) 2017 AACR.