TY - JOUR
T1 - CtDNA-guided de-escalation of adjuvant chemotherapy in stage III colon cancer
T2 - early model-based evaluation of cost-effectiveness
AU - Wang, Haoyue
AU - Kramer, Astrid
AU - Greuter, Marjolein J E
AU - Rubio-Alarcón, Carmen
AU - Lissenberg-Witte, Birgit
AU - Meijer, Gerrit A
AU - Kok, Niels F M
AU - van den Broek, Daan
AU - Vink, Geraldine R
AU - Roodhart, Jeanine M L
AU - Sausen, Mark
AU - Fijneman, Remond J A
AU - Coupé, Veerle M H
N1 - Publisher Copyright:
© The Author(s), 2025. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).
PY - 2025/11/6
Y1 - 2025/11/6
N2 - BACKGROUND: All stage III colon cancer (CC) patients are recommended adjuvant chemotherapy (ACT) after surgery, while over half are already cured by surgery alone. The prognostic biomarker circulating tumor DNA (ctDNA) could potentially guide the decision on whom to withhold ACT.OBJECTIVE: We assessed the cost-effectiveness of ctDNA-guided ACT de-escalation in stage III CC.DESIGN: A decision model "PATTERN-stageIII" simulates CC from diagnosis till death in surgically treated stage III patients.METHODS: We evaluated administering ACT in all patients (i.e., All ACT strategy), and three ACT de-escalation strategies by omitting ACT in patients who are (Strategy 1) both pT1-3N1 and ctDNA-negative, (Strategy 2) pT1-3N1, have no vascular invasion, and are ctDNA-negative, and (Strategy 3) pT1-2N1 and ctDNA-negative. For each strategy, costs, quality-adjusted life years (QALYs), and net monetary benefit were estimated. Sensitivity analyses assessed changes in ACT effectiveness and ctDNA-related parameters.RESULTS: In de-escalation strategies 1, 2, and 3, respectively, 52%, 61%, and 88% of patients were predicted to receive ACT, thereby losing 0.322, 0.237, and 0.034 QALYs per person. The "All ACT strategy" was preferred in terms of cost-effectiveness. Sensitivity analyses demonstrated scenarios where ctDNA-guided de-escalation strategies were cost-effective compared to "All ACT," including improved ACT treatment effect in ctDNA-positive patients, higher ctDNA positivity rates, enhanced ctDNA prognostic value, and/or reduced ctDNA testing costs.CONCLUSION: ctDNA-guided strategies for ACT de-escalation are currently not cost-effective compared to an "All ACT strategy." One explanation is the non-negligible recurrence risk in ctDNA-negative patients. ctDNA-guided strategies could potentially become cost-effective if more than two ctDNA-related parameters improve simultaneously.
AB - BACKGROUND: All stage III colon cancer (CC) patients are recommended adjuvant chemotherapy (ACT) after surgery, while over half are already cured by surgery alone. The prognostic biomarker circulating tumor DNA (ctDNA) could potentially guide the decision on whom to withhold ACT.OBJECTIVE: We assessed the cost-effectiveness of ctDNA-guided ACT de-escalation in stage III CC.DESIGN: A decision model "PATTERN-stageIII" simulates CC from diagnosis till death in surgically treated stage III patients.METHODS: We evaluated administering ACT in all patients (i.e., All ACT strategy), and three ACT de-escalation strategies by omitting ACT in patients who are (Strategy 1) both pT1-3N1 and ctDNA-negative, (Strategy 2) pT1-3N1, have no vascular invasion, and are ctDNA-negative, and (Strategy 3) pT1-2N1 and ctDNA-negative. For each strategy, costs, quality-adjusted life years (QALYs), and net monetary benefit were estimated. Sensitivity analyses assessed changes in ACT effectiveness and ctDNA-related parameters.RESULTS: In de-escalation strategies 1, 2, and 3, respectively, 52%, 61%, and 88% of patients were predicted to receive ACT, thereby losing 0.322, 0.237, and 0.034 QALYs per person. The "All ACT strategy" was preferred in terms of cost-effectiveness. Sensitivity analyses demonstrated scenarios where ctDNA-guided de-escalation strategies were cost-effective compared to "All ACT," including improved ACT treatment effect in ctDNA-positive patients, higher ctDNA positivity rates, enhanced ctDNA prognostic value, and/or reduced ctDNA testing costs.CONCLUSION: ctDNA-guided strategies for ACT de-escalation are currently not cost-effective compared to an "All ACT strategy." One explanation is the non-negligible recurrence risk in ctDNA-negative patients. ctDNA-guided strategies could potentially become cost-effective if more than two ctDNA-related parameters improve simultaneously.
KW - colon cancer
KW - cost-effectiveness
KW - ctDNA
U2 - 10.1177/17588359251384238
DO - 10.1177/17588359251384238
M3 - Article
C2 - 41209620
SN - 1758-8340
VL - 17
SP - 1
EP - 18
JO - Therapeutic Advances in Medical Oncology
JF - Therapeutic Advances in Medical Oncology
ER -