Circulating Tumour DNA as a Potential Cost-Effective Biomarker to Reduce Adjuvant Chemotherapy Overtreatment in Stage II Colorectal Cancer

Background and Objective: Substantial adjuvant chemotherapy (AC) overtreatment for stage II colorectal cancer results in a health and financial burden. Circulating tumour DNA (ctDNA) can improve patient selection for AC by detecting micro-metastatic disease. We estimated the health economic potential of ctDNA-guided AC for stage II colorectal cancer. Methods: A cost-utility analysis was performed to compare ctDNA-guided AC to standard of care, where 22.6% of standard of care patients and all ctDNA-positive patients (8.7% of tested patients) received AC and all ctDNA-negative patients (91.3%) did not. A third preference-sensitive ctDNA strategy was included where 6.8% of ctDNA-negative patients would receive AC. A state-transition model was populated using data from a prospective cohort study and clinical registries. Health and economic outcomes were discounted at 5% over a lifetime horizon from a 2019 Australian payer perspective. Extensive scenario and probabilistic analyses quantified model uncertainty. Results: Compared to standard of care, the ctDNA and preference-sensitive ctDNA strategies increased quality-adjusted life-years by 0.20 (95% confidence interval − 0.40 to 0.81) and 0.19 (− 0.40 to 0.78), and resulted in incremental costs of AUD − 4055 (− 16,853 to 8472) and AUD − 2284 (− 14,685 to 10,116), respectively. Circulating tumour DNA remained cost effective at a willingness to pay of AUD 20,000 per quality-adjusted life-year gained throughout most scenario analyses in which the proportion of ctDNA-positive patients cured by AC and compliance to a ctDNA-negative test results were decreased. Conclusions: Circulating tumour-guided AC is a potentially cost-effective strategy towards reducing overtreatment in stage II colorectal cancer. Results from ongoing randomised clinical studies will be important to reduce uncertainty in the estimates.