Estimating Treatment Effect of Adjuvant Chemotherapy in Elderly Patients With Stage III Colon Cancer Using Bayesian Networks

PURPOSE: While adjuvant therapy with capecitabine and oxaliplatin (CAPOX) has been proven to be effective in stage III colon cancer, capecitabine monotherapy (CapMono) might be equally effective in elderly patients. Unfortunately, the elderly are under-represented in clinical trials and patients included may not be representative of the routine care population. Observational data might alleviate this problem but is sensitive to biases such as confounding by indication. Here, we build causal models using Bayesian Networks (BNs), identify confounders, and estimate the effect of adjuvant chemotherapy using survival analyses. METHODS: Patients 70 years and older were selected from the Netherlands Cancer Registry (N = 982). We developed several BNs using constraint-based, score-based, and hybrid algorithms while precluding noncausal relations. In addition, we created models using a limited set of recurrence and survival nodes. Potential confounders were identified through the resulting graphs. Several Cox models were fitted correcting for confounders and for propensity scores. RESULTS: When comparing adjuvant treatment with surgery only, pathological lymph node classification, physical status, and age were identified as potential confounders. Adjuvant treatment was significantly associated with survival in all Cox models, with hazard ratios between 0.39 and 0.45; CIs overlapped. BNs investigating CAPOX versus CapMono did not find any association between the treatment choice and survival and thus no confounders. Analyses using Cox models did not identify significant association either. CONCLUSION: We were able to successfully leverage BN structure learning algorithms in conjunction with clinical knowledge to create causal models. While confounders differed depending on the algorithm and included nodes, results were not contradictory. We found a strong effect of adjuvant therapy on survival in our cohort. Additional oxaliplatin did not have a marked effect and should be avoided in elderly patients.