Objective: To appraise the health economic evidence for adjuvant chemotherapy (AC) strategies in stage II and III colorectal cancer (CRC) and to identify the limitations of available evidence that might inform further research.

Method: A systematic review of published economic evaluations was undertaken. Four databases were searched and full-text publications in English were screened for inclusion. The Consolidated Health Economic Evaluation Reporting Standards (CHEERS) Checklist was used to assess the quality of included evaluations, and a narrative synthesis was performed to summarise the evidence.

Results: Thirty-nine studies were identified, stratified by cancer stage and AC strategies. Reporting quality was high, with evaluations reporting 89% of relevant CHEERS checklist items on average. The majority (90%) were full economic evaluations, with 56% being cost-utility analyses (CUA). AC was found to be cost-effective compared to no AC for both stage II and III CRC. Oral and oxaliplatin-based AC was cost-effective for stage III. Three months of CAPOX was cost-effective compared to 6-months in high-risk stage II and stage III CRC. Preliminary evidence suggests that biomarker approaches to AC selection in stage II, such as the use of circulating tumor DNA, are also cost-effective. Notably, assessment of quality-adjusted life years (QALYs) were reliant on a small number of non-contemporary health-utility (HUV) studies as few AC trials collected utility data. Only 31% of studies considered societal costs.

Conclusions: Published economic evaluations consistently support the use of AC in stage II and III colorectal cancer. Biomarker-driven approaches to patient selection have great potential to be cost-effective, but more robust clinical and economic evidence is warranted. Patient surveys embedded into clinical trials that collect utility data and societal costs would allow more accurate estimation of QALYs that account for contemporary patient experiences with the interventions under investigation including disutility from toxicities and reduce underestimation of costs.