Investigating confounders of the association between survival and adjuvant radiation therapy after breast conserving surgery in a sample of elderly breast Cancer patients in Appalachia

To explain the association between adjuvant radiation therapy after breast conserving surgery (BCS RT) and overall survival (OS) by quantifying bias due to confounding in a sample of elderly breast cancer beneficiaries in a multi-state region of Appalachia. We used Medicare claims linked registry data for fee-for-service beneficiaries with AJCC stage I-III, treated with BCS, and diagnosed from 2006 to 2008 in Appalachian counties of Kentucky, Ohio, North Carolina, and Pennsylvania. Confounders of BCS RT included age, rurality, regional SES, access to radiation facilities, marital status, Charlson comorbidity, Medicaid dual status, institutionalization, tumor characteristics, and surgical facility characteristics. Adjusted percent change in expected survival by BCS RT was examined using Accelerated Failure Time (AFT) models. Confounding bias was assessed by comparing effects between adjusted and partially adjusted associations using a fully specified structural model. The final sample had 2675 beneficiaries with mean age of 75, with 81% 5-year survival from diagnosis. Unadjusted percentage increase in expected survival was 2.75 times greater in the RT group vs. non-RT group, with 5-year survival of 85% vs 60%; fully adjusted percentage increase was 1.70 times greater, with 5-year rates of 83% vs 71%. Quantification of incremental confounding showed age accounted for 71% of the effect reduction, followed by tumor features (12%), comorbidity (10%), dual status(10%), and institutionalization (8%). Adjusting for age and tumor features only resulted in only 4% bias from fully adjusted percent change (70% change vs 66%). Quantification of confounding aids in determining covariates to adjust for and in interpreting raw associations. Substantial confounding was present (60% of total association), with age accounting for the largest share (71%); adjusting for age plus tumor features corrected for most of the confounding (4% bias). The direct effect of BCS RT on OS accounted for 40% of the total association.