Early evaluation of the effectiveness and cost-effectiveness of ctDNA-guided selection for adjuvant chemotherapy in stage II colon cancer

• Published in: Therapeutic advances in medical oncology 2024-01, Vol.16, p.17588359241266164
• Main Authors: Kramer, Astrid, Greuter, Marjolein J E, Schraa, Suzanna J, Vink, Geraldine R, Phallen, Jillian, Velculescu, Victor E, Meijer, Gerrit A, van den Broek, Daan, Koopman, Miriam, Roodhart, Jeanine M L, Fijneman, Remond J A, Retèl, Valesca P, Coupé, Veerle M H
• Format: Article
• Language: English
• Subjects: Original Research
• ISSN: 1758-8340; 1758-8359
• DOI: 10.1177/17588359241266164

Current patient selection for adjuvant chemotherapy (ACT) after curative surgery for stage II colon cancer (CC) is suboptimal, causing overtreatment of high-risk patients and undertreatment of low-risk patients. Postoperative circulating tumor DNA (ctDNA) could improve patient selection for ACT. We conducted an early model-based evaluation of the (cost-)effectiveness of ctDNA-guided selection for ACT in stage II CC in the Netherlands to assess the conditions for cost-effective implementation. A validated Markov model, simulating 1000 stage II CC patients from diagnosis to death, was supplemented with ctDNA data. Five ACT selection strategies were evaluated: the current guideline (pT4, pMMR), ctDNA-only, and three strategies that combined ctDNA status with pT4 and pMMR status in different ways. For each strategy, the costs, life years, quality-adjusted life years (QALYs), recurrences, and CC deaths were estimated. Sensitivity analyses were performed to assess the impact of the costs of ctDNA testing, strategy adherence, ctDNA as a predictive biomarker, and ctDNA test performance. Model predictions showed that compared to current guidelines, the ctDNA-only strategy was less effective (+2.2% recurrences, -0.016 QALYs), while the combination strategies were more effective (-3.6% recurrences, +0.038 QALYs). The combination strategies were not cost-effective, since the incremental cost-effectiveness ratio was €67,413 per QALY, exceeding the willingness-to-pay threshold of €50,000 per QALY. Sensitivity analyses showed that the combination strategies would be cost-effective if the ctDNA test costs were lower than €1500, or if ctDNA status was predictive of treatment response, or if the ctDNA test performance improved substantially. Adding ctDNA to current high-risk clinicopathological features (pT4 and pMMR) can improve patient selection for ACT and can also potentially be cost-effective. Future studies should investigate the predictive value of post-surgery ctDNA status to accurately evaluate the cost-effectiveness of ctDNA testing for ACT decisions in stage II CC.