Colon cancer represents one of the most common and lethal forms of malignancy in the
human population, accounting for approximately 10% of global cancer diagnoses and
>570 000 annual deaths worldwide.
1
Among patients diagnosed with colon cancer, approximately one-third (35%) are diagnosed
with a tumor that is locally advanced (i.e., infiltrating beyond the full thickness
of the muscular layer of the intestinal wall) but not yet overtly metastatic, a condition
defined as stage II by the American Joint Committee on Cancer staging manual.
2
,3
Most patients with stage II colon cancer are cured by surgical resection of the primary
tumor, but a substantial percentage (10%-15%) are poised to relapse and eventually
die of the disease.
2
A common strategy implemented in medical oncology to improve the survival of patients
with a locally advanced malignancy is to treat them with adjuvant chemotherapy (i.e.,
chemotherapy administered after surgical resection of all detectable tumor tissue)
to prevent relapse from undetectable cancer cells. Adjuvant chemotherapy, however,
can cause toxicity and is best reserved for patients who are both at high risk of
relapse and affected by chemosensitive tumors. In the specific case of stage II colon
cancer, several prognostic factors have been identified as capable of stratifying
patients into “high-risk” versus “low-risk” categories with regard to the likelihood
of relapse,
4
,5
but none have proven useful to identify patients who would indisputably benefit from
adjuvant chemotherapy,
6
leaving clinicians uncertain with regard to the best treatment strategy.
10
,
11
,
7
,
8
,
9
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Value in HealthAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.CA Cancer J Clin. 2021; 71: 209-249
- Colon cancer survival rates with the new American Joint Committee on Cancer sixth edition staging.J Natl Cancer Inst. 2004; 96: 1420-1425
- AJCC Cancer Staging Manual.8th ed. Springer, New York, NY2017
- American Joint Committee on Cancer Prognostic Factors Consensus conference: colorectal working group.Cancer. 2000; 88: 1739-1757
- Adjuvant chemotherapy for stage II colon cancer.Cancers (Basel). 2020; 12: 2584
- Adjuvant chemotherapy for stage II colon cancer with poor prognostic features.J Clin Oncol. 2011; 29: 3381-3388
- Should adjuvant chemotherapy become standard treatment for patients with stage II colon cancer? For the proposal [published correction appears in Lancet Oncol. 2006;7(7):533].Lancet Oncol. 2006; 7: 515-516
- Ongoing challenge of stage II colon cancer.J Clin Oncol. 2011; 29: 3346-3348
- Chemotherapy: is adjuvant chemotherapy an option for stage II colon cancer?.Nat Rev Clin Oncol. 2011; 8: 574-576
- Dilemma of stage II colon cancer and decision making for adjuvant chemotherapy.J Am Coll Surg. 2014; 219: 1056-1069
- Adjuvant chemotherapy for stage II colon cancer: a clinical dilemma.J Oncol Pract. 2017; 13: 233-241
- Loss of CDX2 expression is associated with poor prognosis in colorectal cancer patients.World J Gastroenterol. 2015; 21: 1457-1467
- CDX2 as a prognostic biomarker in stage II and stage III colon cancer.N Engl J Med. 2016; 374: 211-222
- CDX2 prognostic value in stage II/III resected colon cancer is related to CMS classification.Ann Oncol. 2017; 28: 1032-1035
- Prognostic significance of CDX2 immunoexpression in poorly differentiated clusters of colorectal carcinoma.Virchows Arch. 2017; 471: 731-741
- Lack of caudal-type homeobox transcription factor 2 expression as a prognostic biomarker in metastatic colorectal cancer.Clin Colorectal Cancer. 2017; 16: 124-128
- Prognostic impact of CDX2 in stage II colon cancer: results from two nationwide cohorts.Br J Cancer. 2018; 119: 1367-1373
- CDX2 in colorectal cancer is an independent prognostic factor and regulated by promoter methylation and histone deacetylation in tumors of the serrated pathway.Clin Epigenetics. 2018; 10: 120
- Association of CDX2 expression with survival in early colorectal cancer: a systematic review and meta-analysis.Clin Colorectal Cancer. 2018; 17: 97-103
- 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
- Prognostic, predictive, and pharmacogenomic assessments of CDX2 refine stratification of colorectal cancer.Mol Oncol. 2018; 12: 1639-1655
- 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
- The homeobox intestinal differentiation factor CDX2 is selectively expressed in gastrointestinal adenocarcinomas.Mod Pathol. 2004; 17: 1392-1399
- CDX-2, a new marker for adenocarcinoma of gastrointestinal origin.Adv Anat Pathol. 2004; 11: 101-105
- Demonstration of CDX2 is highly antibody dependant.Appl Immunohistochem Mol Morphol. 2013; 21: 64-72
- Markers of adenocarcinoma characteristic of the site of origin: development of a diagnostic algorithm.Clin Cancer Res. 2005; 11: 3766-3772
- Practical applications in immunohistochemistry: carcinomas of unknown primary site.Arch Pathol Lab Med. 2016; 140: 508-523
Alarid-Escudero F, Schrag D, Kuntz KM. CDX2 biomarker testing and adjuvant therapy for stage II colon cancer: an exploratory cost-effectiveness analysis. Value Health. In press.
- Updating cost-effectiveness--the curious resilience of the $50,000-per-QALY threshold.N Engl J Med. 2014; 371: 796-797
- What does the value of modern medicine say about the $50,000 per quality-adjusted life-year decision rule?.Med Care. 2008; 46: 349-356
- Adjuvant chemotherapy versus observation in patients with colorectal cancer: a randomised study.Lancet. 2007; 370: 2020-2029
- Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer.N Engl J Med. 2004; 350: 2343-2351
Article info
Publication history
Published online: November 02, 2021
Accepted:
September 1,
2021
Identification
Copyright
© 2021 International Society for Pharmacoeconomics and Outcomes Research, Inc. Published by Elsevier Inc.
