Colorectal cancerChallenges in the Management of Stage II Colon Cancer
Section snippets
Tumor Stage
The American Joint Committee of Cancer (AJCC) 7th edition staging manual classifies stage II tumors as T3 with invasion through the muscularis propria or into pericolic tissue, and T4 with invasion into adherent organs.10 T4 tumors are subclassified into T4a (penetrating visceral peritoneum) and T4b (penetrating other organs/structures). A Surveillance, Epidemiology, and End Results (SEER) database analysis supported the revised staging by demonstrating significant differences in 5-year
Molecular Markers
Increasing understanding of colon cancer biology has identified potential molecular markers to risk-stratify early-stage colon cancer patients. This may be most useful for patients with stage II colon cancer where adjuvant chemotherapy is debated. However, tests using immunohistochemistry or gene expression analysis are costly. In addition, proper validation of markers, techniques, and cutoff values is critical.
Addition of Oxaliplatin
While the role of adjuvant combination chemotherapy is well established in stage III colon cancer, the benefit in stage II patients remains controversial. The Multicenter International Study of Oxaliplatin/5-FU/Leucovorin in the Adjuvant Treatment of Colon Cancer (MOSAIC) study demonstrated improved DFS and OS for stage III patients treated with FOLFOX compared with those treated with 5-FU alone (DFS HR 0.80, P = .003; OS HR 0.84, P = .046 for OS), and established FOLFOX as the current standard
Summary
Adjuvant therapy for stage II colon cancer remains a topic of debate, primarily for “average-risk” patients without clear pathologic risk factors. As our knowledge of underlying biology expands, molecular markers will play a more prominent role in our decision-making. To date, MSI-H status has emerged as the marker most closely linked to improved outcome and limited benefit from adjuvant fluoropyrimidine therapy. Much work still remains to be done to improve our ability to risk-stratify
References (106)
- et al.
Predictors of occult nodal metastasis in colon cancer: results from a prospective multicenter trial
Surgery
(2010) - et al.
The human mutator gene homolog MSH2 and its association with hereditary nonpolyposis colon cancer
Cell
(1993) - et al.
Mutations of a mutS homolog in hereditary nonpolyposis colorectal cancer
Cell
(1993) - et al.
Hypermutability and mismatch repair deficiency in RER+ tumor cells
Cell
(1993) - et al.
Molecular predictive and prognostic markers in colon cancer
Cancer Treat Rev
(2010) - et al.
Mismatch repair proficiency and in vitro response to 5-fluorouracil
Gastroenterology
(1999) - et al.
A systematic review and meta-analysis of the relationship between chromosome 18q genotype, DCC status and colorectal cancer prognosis
Eur J Cancer
(2005) - et al.
Allelic loss on chromosome 18q as a prognostic marker in stage II colorectal cancer
Gastroenterology
(1998) - et al.
DNA markers predicting benefit from adjuvant fluorouracil in patients with colon cancer: a molecular study
Lancet
(2002) - et al.
EORTC Elderly Task Force experts' opinion for the treatment of colon cancer in older patients
Cancer Treat Rev
(2010)
Efficacy of adjuvant fluorouracil and folinic acid in B2 colon cancerInternational Multicentre Pooled Analysis of B2 Colon Cancer Trials (IMPACT B2) Investigators
J Clin Oncol
Controlled trial of fluorouracil and low-dose leucovorin given for 6 months as postoperative adjuvant therapy for colon cancer
J Clin Oncol
Clinical trial to assess the relative efficacy of fluorouracil and leucovorin, fluorouracil and levamisole, and fluorouracil, leucovorin, and levamisole in patients with Dukes' B and C carcinoma of the colon: results from National Surgical Adjuvant Breast and Bowel Project C-04
J Clin Oncol
Improved overall survival with oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment in stage II or III colon cancer in the MOSAIC trial
J Clin Oncol
NCCN clinical practice guidelines in oncology: colon cancer
J Natl Compr Cancer Netw
Phase III study of fluorouracil, leucovorin, and levamisole in high-risk stage II and III colon cancer: final report of Intergroup 0089
J Clin Oncol
Oxaliplatin combined with weekly bolus fluorouracil and leucovorin as surgical adjuvant chemotherapy for stage II and III colon cancer: results from NSABP C-07
J Clin Oncol
Intergroup study of fluorouracil plus levamisole as adjuvant therapy for stage II/Dukes' B2 colon cancer
J Clin Oncol
Adjuvant chemotherapy use for Medicare beneficiaries with stage II colon cancer
J Clin Oncol
AJCC cancer staging staging manual
Revised TN categorization for colon cancer based on national survival outcomes data
J Clin Oncol
Pooled analysis of fluorouracil-based adjuvant therapy for stage II and III colon cancer: who benefits and by how much?
J Clin Oncol
Adjuvant postoperative radiation therapy in the management of adenocarcinoma of the colon
Cancer
Postoperative radiotherapy for locally advanced colon cancer
Ann Surg Oncol
Adjuvant postoperative radiation therapy for colorectal carcinoma above the peritoneal reflectionI. Sigmoid colon
Cancer
Adjuvant postoperative radiation therapy for colorectal carcinoma above the peritoneal reflectionII. Antimesenteric wall ascending and descending colon and cecum
Cancer
Postoperative radiation therapy for high-risk colon carcinoma
J Clin Oncol
Phase III study of adjuvant chemotherapy and radiation therapy compared with chemotherapy alone in the surgical adjuvant treatment of colon cancer: results of intergroup protocol 0130
J Clin Oncol
Colon cancer survival is associated with decreasing ratio of metastatic to examined lymph nodes
J Clin Oncol
Colon cancer survival is associated with increasing number of lymph nodes analyzed: a secondary survey of intergroup trial INT-0089
J Clin Oncol
Number of nodes examined and staging accuracy in colorectal carcinoma
J Clin Oncol
Impact of number of nodes retrieved on outcome in patients with rectal cancer
J Clin Oncol
How many lymph nodes are necessary to stage early and advanced adenocarcinoma of the sigmoid colon and upper rectum?
Virchows Arch
Impact of lymph node retrieval and pathological ultra-staging on the prognosis of stage II colon cancer
J Surg Oncol
Accuracy of determining nodal negativity in colorectal cancer on the basis of the number of nodes retrieved on resection
Ann Surg Oncol
The staging of colorectal cancer: 2004 and beyond
CA Cancer J Clin
Impact of tumor location on nodal evaluation for colon cancer
Dis Colon Rectum
Meeting the 12 lymph node (LN) benchmark in colon cancer
J Surg Oncol
Assessing the impact of a targeted educational initiative on colorectal cancer lymph node retrieval: a Fox Chase Cancer Center Partners' quality initiative [abstract 6524]
J Clin Oncol
Pathologic determinants of survival associated with colorectal cancer with lymph node metastasesA multivariate analysis of 579 patients
Cancer
Prognostic factors in colorectal cancerCollege of American Pathologists Consensus Statement 1999
Arch Pathol Lab Med
The prognostic significance of tumor location and bowel obstruction in Dukes B and C colorectal cancerFindings from the NSABP clinical trials
Ann Surg
Variables correlated with the risk of lymph node metastasis in early rectal cancer
Cancer
Histologic features and clinical significance of venous invasion in colorectal carcinoma with hepatic metastasis
Cancer
Invasion of veins by carcinoma of rectum: method of detection, histological features and significance
Histopathology
Resectable adenocarcinoma of the rectosigmoid and rectumII. The influence of blood vessel invasion
Cancer
Venous and neural invasion as predictors of recurrence in rectal adenocarcinoma
Dis Colon Rectum
Tumor microsatellite instability and clinical outcome in young patients with colorectal cancer
N Engl J Med
Mutation of a mutL homolog in hereditary colon cancer
Science
Mutation in the DNA mismatch repair gene homologue hMLH1 is associated with hereditary non-polyposis colon cancer
Nature
Cited by (86)
Impact of high-risk features for stage II adenocarcinoma of the appendix
2021, Cancer Treatment and Research CommunicationsNode negative colorectal cancer patients: assesment of high-risk features on recurrence
2020, Pathology Research and PracticeCitation Excerpt :Therefore, adjuvant treatment is still controversial in this subgroup of patients and in daily practice, just 16% of the high-risk stage II CRC patients are currently treated with adjuvant chemotherapy [8,15]. More recently, potential molecular features to risk-stratify node negative patients were identified alongside the increased understanding of colon cancer biology [14]. These features are found in the two most important pathways involved in causing CRC, i.e. DNA mismatch repair (MMR) and the Epidermal Grow Factor Receptor (EGFR) signal pathway, involving KRAS and BRAF [16].
Scoulerine promotes cell viability reduction and apoptosis by activating ROS-dependent endoplasmic reticulum stress in colorectal cancer cells
2020, Chemico-Biological InteractionsZNF326 as a potential prognostic and predictive biomarker in stage II colorectal cancer
2024, Journal of Gastrointestinal Oncology