Review
. 2011 Aug;38(4).
doi: 10.1053/j.seminoncol.2011.05.005.

Challenges in the management of stage II colon cancer

Efrat Dotan 1 Steven J Cohen  
Affiliations
  • PMID: 21810510
  •     97 References
  •     31 citations

Abstract

Approximately one third of patients diagnosed with early-stage colon cancer will present with lymph node involvement (stage III) and about one quarter with transmural bowel wall invasion but negative lymph nodes (stage II). Adjuvant chemotherapy targets micrometastatic disease to improve disease-free (DFS) and overall survival (OS). While beneficial for stage III patients, the role of adjuvant chemotherapy is unestablished in stage II disease. This likely relates to the improved outcome of these patients, and the difficulties in developing studies with sufficient power to document benefit in this patient population. However, recent investigation also suggests that molecular differences may exist between stage II and III cancers and within stage II patients. Validated pathologic prognostic markers are useful at identifying stage II patients at high risk for recurrence for whom the benefit from adjuvant chemotherapy may be greater. Such high-risk features include higher T stage (T4 v T3), suboptimal lymph node retrieval, presence of lymphovascular invasion, bowel obstruction, or bowel perforation, and poorly differentiated histology. However, for the majority of patients who do not carry any of these adverse features and are classified as "average-risk" stage II patients, the benefit of adjuvant chemotherapy remains unproven. Emerging understanding of the underlying biology of stage II colon cancer has identified molecular markers that may change this paradigm and improve our risk assessment and treatment choices for stage II disease. Assessment of microsatellite stability (MSI), which serves as a marker for DNA mismatch repair (MMR) system function, has emerged as a useful tool for risk stratification of patients with stage II colon cancer. Patients with high frequency of MSI have been shown to have increased OS and limited benefit from 5-fluorouracil (5-FU)-based chemotherapy. Additional research is necessary to clearly define the most appropriate way to use this marker and others in routine clinical practice.

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Int J Mol Sci, 2016 May 03; 17(5). PMID: 27136531    Free PMC article.
The Management and Prognostic Prediction of Adenocarcinoma of Appendix.
Xin Xie, Zhangjian Zhou, +4 authors, Hao Zhang.
Sci Rep, 2016 Dec 17; 6. PMID: 27982068    Free PMC article.
Molecular subtypes in cancers of the gastrointestinal tract.
Maarten F Bijlsma, Anguraj Sadanandam, Patrick Tan, Louis Vermeulen.
Nat Rev Gastroenterol Hepatol, 2017 Apr 13; 14(6). PMID: 28400627
Highly Cited. Review.
Prognostic value of loss of heterozygosity and sub-cellular localization of SMAD4 varies with tumor stage in colorectal cancer.
Xu Jia, Chandrakumar Shanmugam, +7 authors, Upender Manne.
Oncotarget, 2017 Apr 21; 8(12). PMID: 28423626    Free PMC article.
Ezrin expression combined with MSI status in prognostication of stage II colorectal cancer.
Khadija Slik, Samu Kurki, +3 authors, Jari Sundström.
PLoS One, 2017 Sep 28; 12(9). PMID: 28953975    Free PMC article.
Evolving notions on immune response in colorectal cancer and their implications for biomarker development.
Fabio Grizzi, Gianluca Basso, +6 authors, Luigi Laghi.
Inflamm Res, 2018 Jan 13; 67(5). PMID: 29322204
Review.
Establishment of a 12-gene expression signature to predict colon cancer prognosis.
Dalong Sun, Jing Chen, +5 authors, Ling Dong.
PeerJ, 2018 Jun 20; 6. PMID: 29915691    Free PMC article.
Gene pair based prognostic signature for colorectal colon cancer.
Peng Shu, Jianping Wu, +2 authors, Xingguo Zhang.
Medicine (Baltimore), 2018 Oct 20; 97(42). PMID: 30334969    Free PMC article.
RBP7 is a clinically prognostic biomarker and linked to tumor invasion and EMT in colon cancer.
Manal Elmasry, Lydia Brandl, +3 authors, David Horst.
J Cancer, 2019 Oct 11; 10(20). PMID: 31598160    Free PMC article.
The Use of Circulating Tumor DNA to Monitor and Predict Response to Treatment in Colorectal Cancer.
Mifanwy Reece, Hariti Saluja, +4 authors, Erin L Symonds.
Front Genet, 2019 Dec 12; 10. PMID: 31824558    Free PMC article.
Review.
A network view of microRNA and gene interactions in different pathological stages of colon cancer.
Jia Wen, Benika Hall, Xinghua Shi.
BMC Med Genomics, 2020 Jan 01; 12(Suppl 7). PMID: 31888617    Free PMC article.
Treatment of splenic flexure colon cancer: a comparison of three different surgical procedures: Experience of a high volume cancer center.
Daniela Rega, Ugo Pace, +5 authors, Paolo Delrio.
Sci Rep, 2019 Jul 31; 9(1). PMID: 31358904    Free PMC article.
Establishment and validation of a novel nomogram incorporating clinicopathological parameters into the TNM staging system to predict prognosis for stage II colorectal cancer.
Shaobo Mo, Zheng Zhou, +5 authors, Junjie Peng.
Cancer Cell Int, 2020 Jul 14; 20. PMID: 32655317    Free PMC article.
Somatic POLE exonuclease domain mutations elicit enhanced intratumoral immune responses in stage II colorectal cancer.
Shaobo Mo, Xiaoji Ma, +7 authors, Junjie Peng.
J Immunother Cancer, 2020 Aug 30; 8(2). PMID: 32859741    Free PMC article.
Adjuvant chemotherapy in stage II-III operated colon cancer patients from a nontrial cohort in a low colon cancer prevalence country with predominant use of modified CAPOX.
Anant Ramaswamy, Rushabh Kothari, +10 authors, Vikas Ostwal.
South Asian J Cancer, 2019 Sep 07; 8(3). PMID: 31489288    Free PMC article.
Lymphocytic infiltration in stage II microsatellite stable colorectal tumors: A retrospective prognosis biomarker analysis.
Rebeca Sanz-Pamplona, Marilena Melas, +20 authors, Victor Moreno.
PLoS Med, 2020 Sep 25; 17(9). PMID: 32970670    Free PMC article.
Revised Exon Structure of l-DOPA Decarboxylase (DDC) Reveals Novel Splice Variants Associated with Colorectal Cancer Progression.
Pinelopi I Artemaki, Maria Papatsirou, +5 authors, Christos K Kontos.
Int J Mol Sci, 2020 Nov 19; 21(22). PMID: 33202911    Free PMC article.
MicroRNAs and inflammation in the pathogenesis and progression of colon cancer.
Hirokazu Okayama, Aaron J Schetter, Curtis C Harris.
Dig Dis, 2012 Dec 12; 30 Suppl 2. PMID: 23207927    Free PMC article.
Review.
DeepCC: a novel deep learning-based framework for cancer molecular subtype classification.
Feng Gao, Wei Wang, +5 authors, Xin Wang.
Oncogenesis, 2019 Aug 20; 8(9). PMID: 31420533    Free PMC article.