Highlights
- •Adjuvant chemotherapy is not recommended for patients with average-risk stage II (T3N0) colon cancer. Nevertheless, a subgroup of these patients who are CDX2-negative might benefit from adjuvant chemotherapy.
- •Testing patients with stage II colon cancer’ tumor for CDX2 and administering adjuvant treatment to the subgroup found to be CDX2-negative is a cost-effective and high-value management strategy across a broad range of plausible assumptions.
- •We provide compelling evidence in support of conducting prospective studies to formally demonstrate the benefit of adjuvant chemotherapy in patients with stage II CDX2-negative colon cancer.
Abstract
Objectives
Adjuvant chemotherapy is not recommended for patients with average-risk stage II (T3N0)
colon cancer. Nevertheless, a subgroup of these patients who are CDX2-negative might
benefit from adjuvant chemotherapy. We evaluated the cost-effectiveness of testing
for the absence of CDX2 expression followed by adjuvant chemotherapy (fluorouracil
combined with oxaliplatin [FOLFOX]) for patients with stage II colon cancer.
Methods
We developed a decision model to simulate a hypothetical cohort of 65-year-old patients
with average-risk stage II colon cancer with 7.2% of these patients being CDX2-negative
under 2 different interventions: (1) test for the absence of CDX2 expression followed
by adjuvant chemotherapy for CDX2-negative patients and (2) no CDX2 testing and no
adjuvant chemotherapy for any patient. We derived disease progression parameters,
adjuvant chemotherapy effectiveness and utilities from published analyses, and cancer
care costs from the Surveillance, Epidemiology, and End Results (SEER)-Medicare data.
Sensitivity analyses were conducted.
Results
Testing for CDX2 followed by FOLFOX for CDX2-negative patients had an incremental
cost-effectiveness ratio of $5500/quality-adjusted life-years (QALYs) compared with
no CDX2 testing and no FOLFOX (6.874 vs 6.838 discounted QALYs and $89 991 vs $89 797
discounted US dollar lifetime costs). In sensitivity analyses, considering a cost-effectiveness
threshold of $100 000/QALY, testing for CDX2 followed by FOLFOX on CDX2-negative patients
remains cost-effective for hazard ratios of <0.975 of the effectiveness of FOLFOX
in CDX2-negative patients in reducing the rate of developing a metastatic recurrence.
Conclusions
Testing tumors of patients with stage II colon cancer for CDX2 and administration
of adjuvant treatment to the subgroup found CDX2-negative is a cost-effective and
high-value management strategy across a broad range of plausible assumptions.
Keywords
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References
- Counterpoint: adjuvant therapy in stage II colon cancer: pain not justified by the gain.J Natl Compr Canc Netw. 2012; 10: 1379-1386
- Adjuvant chemotherapy for stage II colon cancer with poor prognostic features.J Clin Oncol. 2011; 29: 3381-3388
- Ongoing challenge of stage II colon cancer.J Clin Oncol. 2011; 29: 3346-3348
- NCCN guidelines for patients: colon cancer. National Comprehensive Cancer Network.(Accessed May 30, 2021)
- American Society of Clinical Oncology recommendations on adjuvant chemotherapy for stage II colon cancer.J Clin Oncol. 2004; 22: 3408-3419
- CDX2 as a prognostic biomarker in Stage II and Stage III colon cancer.N Engl J Med. 2016; 374: 211-222
- CDX2, a highly sensitive and specific marker of adenocarcinomas of intestinal origin: an immunohistochemical survey of 476 primary and metastatic carcinomas.Am J Surg Pathol. 2003; 27: 303-310
- Boolean implication networks derived from large scale, whole genome microarray datasets.Genome Biol. 2008; 9: R157
- Prognostic impact of CDX2 in stage II colon cancer: results from two nationwide cohorts.Br J Cancer. 2018; 119: 1367-1373
- Gastrointestinal cancer: CDX2: prognostic marker for high-risk colon cancer.Nat Rev Clin Oncol. 2016; 13: 134-135
- Guide to the methods of technology appraisal 2013. National Institute for Clinical Excellence.(Accessed May 30, 2021)
- Markov models in medical decision making: a practical guide.Med Decis Making. 1993; 13: 322-338
- The Markov process in medical prognosis.Med Decis Making. 1983; 3: 419-458
- Procedure and submission guidelines for the CADTH common drug review. Canadian Agency for Drugs and Technologies in Health.(Accessed May 30, 2021)
- Neumann P.J. Sanders G.D. Russell L.B. Siegel J.E. Ganiats T.G. Cost-effectiveness in health and medicine. 2nd ed. Oxford University Press, Incorporated, New York, NY2017
- ICER’s reference case for economic evaluations: principles and rationale. Institute for Clinical and Economic Reviews (ICER).https://icer.org/wp-content/uploads/2020/10/ICER_Reference_Case_013120.pdfDate accessed: April 23, 2019
- Is there a European view on health economic evaluations? Results from a synopsis of methodological guidelines used in the EUnetHTA Partner Countries.Pharmacoeconomics. 2016; 34: 59-76
- Nonidentifiability in model calibration and implications for medical decision making.Med Decis Making. 2018; 38: 810-821
- Bayesian methods for calibrating health policy models: a tutorial.Pharmacoeconomics. 2017; 35: 613-624
- Estimating and projecting trends in HIV/AIDS generalized epidemics using incremental mixture importance sampling.Biometrics. 2010; 66: 1162-1173
- Computing normalizing constants for finite mixture models via incremental mixture importance sampling (IMIS).J Comput Graph Stat. 2006; 15: 712-734
- Adjuvant chemotherapy versus observation in patients with colorectal cancer: a randomised study.Lancet. 2007; 370: 2020-2029
- Utility valuations for outcome states of colorectal cancer.Am J Gastroenterol. 1999; 94: 1650-1657
- Medicare physician fee schedule.Healthc Paym Syst. 2010; : 33-77
- 2018 ASP drug pricing files. Centers for Medicare & Medicaid Services.(Accessed May 30, 2021)
- First- and second-line bevacizumab in addition to chemotherapy for metastatic colorectal cancer: a United States-based cost-effectiveness analysis.J Clin Oncol. 2015; 33: 1112-1118
- Association of CDX2 expression with survival in early colorectal cancer: a systematic review and meta-analysis.Clin Colorectal Cancer. 2018; 17: 97-103
- Secular trends in colon and rectal cancer relative survival.J Natl Cancer Inst. 2013; 105: 1806-1813
- Colon cancer survival rates with the new American Joint Committee on Cancer sixth edition staging.J Natl Cancer Inst. 2004; 96: 1420-1425
- Estimating population-based recurrence rates of colorectal cancer over time in the United States.Cancer Epidemiol Biomarkers Prev. 2020; 29: 2710-2718
- Human mortality database (USA). Max Planck Institute for Demographic Research (Germany), University of California Berkeley.www.mortality.orgDate accessed: February 5, 2021
- Cost of care for elderly cancer patients in the United States.J Natl Cancer Inst. 2008; 100: 630-641
- Stool DNA testing to screen for colorectal cancer in the Medicare population: a cost-effectiveness analysis.Ann Intern Med. 2010; 153: 368-377
- Loss of CDX2 expression is associated with poor prognosis in colorectal cancer patients.World J Gastroenterol. 2015; 21: 1457-1467
- Relationship of CDX2 loss with molecular features and prognosis in colorectal cancer.Clin Cancer Res. 2009; 15: 4665-4673
- Reduced CDX2 expression predicts poor overall survival in patients with colorectal cancer.Am Surg. 2013; 79: 353-360
- Quantitative analysis of CDX2 protein expression improves its clinical utility as a prognostic biomarker in stage II and III colon cancer.Eur J Cancer. 2021; 144: 91-100
- Duration of adjuvant chemotherapy for stage III colon cancer.N Engl J Med. 2018; 378: 1177-1188
- Body surface area, creatinine excretion rate, and total body water: reference data for adults in the United States.Kidney Med. 2021; 3: 312-313
- Anthropometric reference data for children and adults: United States, 2015-2018.Vital Health Stat 3. 2021; : 1-44
- Adjusting health expenditures for inflation: a review of measures for health services research in the United States.Health Serv Res. 2018; 53: 175-196
- Personal consumption expenditures price index. Bureau of Economic Analysis.https://www.bea.gov/data/personal-consumption-expenditures-price-indexDate accessed: April 25, 2019
- A multidimensional array representation of state-transition model dynamics.Med Decis Making. 2020; 40: 242-248
- Model parameter estimation and uncertainty analysis: A report of the ISPOR-SMDM Modeling Good Research Practices Task Force Working Group-6.Med Decis Making. 2012; 32: 722-732
- The threshold approach to clinical decision making.N Engl J Med. 1980; 302: 1109-1117
- Reflecting uncertainty in cost-effectiveness analysis.in: Neumann P.J. Sanders G.D. Russell L.B. Siegel J.E. Ganiats T.G. Cost-Effectiveness in Health and Medicine. 2nd ed. Oxford University Press, New York, NY2017: 289-318
- A trial-based assessment of the cost-utility of bevacizumab and chemotherapy versus chemotherapy alone for advanced non-small cell lung cancer.Value Health. 2011; 14: 836-845
- “Time Traveling Is Just Too Dangerous” but some methods are worth revisiting: the advantages of expected loss curves over cost-effectiveness acceptability curves and frontier.Value Health. 2019; 22: 611-618
- Expected value of perfect information: an empirical example of reducing decision uncertainty by conducting additional research.Value Health. 2008; 11: 1070-1080
- The value of value of information: best informing research design and prioritization using current methods.Pharmacoeconomics. 2010; 28: 699-709
- Establishing the cost-effectiveness of new pharmaceuticals under conditions of uncertainty -- when is there sufficient evidence?.Value Health. 2005; 8: 431-446
- Using value of information analysis to prioritise health research: some lessons from recent UK experience.Pharmacoeconomics. 2006; 24: 1055-1068
- An overview of R in health decision sciences.Med Decis Making. 2017; 37: 735-746
- A Tutorial on time-dependent cohort state-transition models in R using a cost-effectiveness analysis example.arXiv:210813552v1 [Internet]. 2021; : 1-41
- A need for change! A coding framework for improving transparency in decision modeling.Pharmacoeconomics. 2019; 37: 1329-1339
- R: a language and environment for statistical computing. R Foundation for Statistical Computing.(Accessed May 30, 2021)
- IMIS: incremental mixture importance sampling. R Package Documentation.(Accessed May 30, 2021)
- dampack: Decision-Analytic Modeling Package. R package version 1.0.1. 2021.(Accessed July 30, 2021)
- A multigene prognostic assay for selection of adjuvant chemotherapy in patients with T3, stage II colon cancer: impact on quality-adjusted life expectancy and costs.Value Health. 2012; 15: 1014-1021
- Comparative economics of a 12-gene assay for predicting risk of recurrence in stage II colon cancer.Pharmacoeconomics. 2014; 32: 1231-1243
- Molecular biomarkers and precision medicine in colorectal cancer: a systematic review of health economic analyses.Oncotarget. 2019; 10: 3408-3423
- Costs and effectiveness of genomic testing in the management of colorectal cancer.Oncology (Williston Park). 2015; 29: 175-183
- Upfront genotyping of DPYD ∗ 2A to individualize fluoropyrimidine therapy: a safety and cost analysis.J Clin Oncol. 2016; 34: 227-234
Article info
Publication history
Published online: November 02, 2021
Accepted:
July 7,
2021
Identification
Copyright
© 2021 International Society for Pharmacoeconomics and Outcomes Research, Inc. Published by Elsevier Inc.
