CDX2 Biomarker Testing and Adjuvant Therapy for Stage II Colon Cancer: A Cost-Effectiveness Analysis

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Abstract

Purpose

Adjuvant chemotherapy is not recommended for patients with average-risk stage II colon cancer (T3N0). However, lacking CDX2 biomarker expression predicts responsiveness to adjuvant chemotherapy. We determined the cost-effectiveness of testing for the absence of CDX2 biomarker followed by adjuvant chemotherapy for average-risk stage II colon cancer patients lacking CDX2 expression.

Method

We developed a state-transition model to simulate a hypothetical cohort of 65-year-old average-risk stage II (T3N0) colon cancer patients under two strategies: (1) test for CDX2 biomarker expression followed by adjuvant chemotherapy (leucovorin and fluorouracil, LV5FU) for patients lacking CDX2 expression, and (2) no adjuvant chemotherapy for any patient. CDX2-negative patients (i.e., those without biomarker expression, representing 10% of all patients) face a higher rate of developing recurrence (hazard ratio [HR] = 2.73) compared to CDX2-positive patients (0.0042 per month; calibrated). However, adjuvant chemotherapy only benefits patients who lack CDX2 expression (HR = 0.79). Most patients who develop recurrence will advance to distant metastasis and face an additional risk of dying from colon cancer. We derived the parameters that describe disease progression and adjuvant chemotherapy effectiveness from a recently published analysis, the costs of cancer care from SEER-Medicare and the utility losses associated with cancer care from published literature. In sensitivity analyses, we considered different costs of the test, prevalence of lack of CDX2 expression and effectiveness of adjuvant chemotherapy. Outcomes were quality-adjusted life-years (QALYs), lifetime cost, and incremental cost-effectiveness ratio (ICER).

Result

For the base-case analysis, we considered a test cost of $500 USD. Testing for the absence of CDX2 expression followed by adjuvant chemotherapy for those without biomarker expression compared with no adjuvant chemotherapy had an ICER of $14,000 USD/QALY (5.6 vs. 5.2 QALYs, and $75,100 USD vs. $68,600 USD lifetime costs). The CDX2 testing strategy remains cost-effective under a range of assumptions, and reaches an ICER of $15,100 USD/QALY assuming a cost of test of $1,000 USD, and an ICER of $19,000 assuming 20% of patients lack CDX2 biomarker expression.

Conclusion

We found that identifying a small subgroup of average risk stage II colon cancer patients that lack CDX2 biomarker expression for targeted chemotherapy is effective and potentially cost effective.