1. Colon Cancer Stages I-III
Deepak Chander
August 22nd, 2018

2. Epidemiology 140,250 new cases in 2017
Represent 8.1% of new cancer diagnoses. 4th most common
Median age of diagnosis is 67
More common in African Americans
SEER Cancer Stat Facts: Colon Cancer. National Cancer Institute. Bethesda, MD, 

3. Staging
AJCC. Colon and Rectum Cancer Staging. 7th Edition.

4. Surgery Surgery is the mainstay of treatment of all local colon cancer
Neoadjuvant chemotherapy can be considered for tumors invading local organs or tissue
For inoperable patients single agent neoadjuvant chemotherapy can be considered
NCCN Guidelines Colon Cancer Version COL- 2

5. Management by TNM Staging
NCCN Guidelines Colon Cancer Version COL- 3

6. Stage I
Recurrence rate of Stage I colon cancer is estimated to be 5-10%
> 90% survival at 5 years
T2 stage, lymphovascular invasion, low rectal lesions, poorly differentiated cancers and male sex associated with higher risk or recurrence
To date no adjuvant chemotherapy has been shown to be beneficial in Stage I Colon Cancer
To date no surveillance schedule has been shown to be beneficial in Stage I Colon Cancer
J Korean Soc Coloproctol Feb; 28(1): 49–55. N Engl J Med 1990; 322:

7. Stage I
Chan AT, Ogino S, Fuchs CS. Aspirin Use and Survival After Diagnosis of Colorectal Cancer. JAMA.2009;302(6):649–658. doi: /jama
Morales-Oyarvide V, Meyerhardt JA, Ng K. Vitamin D and Physical Activity in Patients with Colorectal Cancer: Epidemiological Evidence and Therapeutic Implications. Cancer journal (Sudbury, Mass). 2016;22(3): doi: /PPO

8. Stage II 5 year DFS in Stage II Colon Cancer is estimated to ~ 81%
Features suggestive of high risk of recurrence are lymphovascular invasion, perineural invasion, obstruction, <12 lymph nodes examined, perforation, close, indeterminate or positive margins
MSI-unstable (MMR preserved) is good prognostic marker and a marker of poor response to adjuvant flouropyrimidine
Multi-gene assays (ColonPrint and Oncotype) do predict risk of recurrence, but do not predict benefit of adjuvant chemotherapy

9. Stage II
80% of recurrence occurs in the first 3 years and 95% occurs in the first 5 years
The CEAWatch trial compared CEA monitoring to imaging and found an increased rate of detection of recurrences able to be treated with curative intent

10. Stage III 5 year DFS with surgery alone for Stage III Cancer ~60%
1st trial to show benefit of adjuvant chemotherapy was in the 1990’s
5-FU/levamasol superior to surgery alone
6 months of treatment was shown to be equivalent to 12 months
Infusional 5-FU shown to be equivilant to weekly bolus 5-FU
Capecitabine shown to be non-inferior (?slightly better) than 5-FU

11. Stage III MOSAIC and NSABP-C-07 trials compared 5-FU/LV to FOLFOX
3 DFS in FOLFOX was 78% versus 71% in 5-FU/LV
Most, if not all, of the benefit was isolated to Stage III patients
Subset analysis showed no benefit and trend to harm in patients > 70 yo with the addition of Oxaliplatin
N Engl J Med 2004; 350:

12. Stage III
Capecitabine + Oxaliplatin was shown to have superior disease free survival (~70%) than 5-FU/Leucovorin alone (66%)
No trial to date has compared CapeOx versus FOLFOX
The dose of Oxaliplatin in CapeOx is higher than in FOLFOX
J Clin Oncol. 2011 Apr 10;29(11):

13. Stage III
Meta-analysis of previous trial data showed a decrease of 14% for every 4 week delay in start of adjuvant chemotherapy
National Cancer Data Base analysis found that a delay of >8 weeks after surgery was found to be associated with worse survival
Data is controversial because patient who were more likely to have delays were more likely to be older and have medical co-morbidities and more likely to have surgical complications
No trial to date has shown benefit of Avastin (bevacizumab) or EGFR agents (Cetuximab, Panitumimab) in the Adjuvant setting.

14. Stage III
IDEA Meta-analysis presented at ASCO 2017 looked at 3 versus 6 months of adjuvant treatment

15. Stage III
In T1-3, N1 patients 3 months of FOLFOX was equivalent to 6 months of FOLFOX
In T1-3, N1 patients 3 months of CapeOX was equivalent (trend to better) to 6 months of CapeOx
In T4, N2 patients 3 months of FOLFOX was inferior to 6 months of FOLFOX
In T4, N2 patients 3 months of CapeOX was equivalent to 6 months of CapeOx

16. Summary Stage I disease – no adjuvant chemo, no imaging surveillance
Stage II, low risk and MSI Unstable (20%) – No adjuvant chemo, surveillance per NCCN
Stage II, low risk and MSI Stable – Can consider single agent adjuvant chemo, surveillance per NCCN
Stage II, high risk – Doublet Adjuvant chemotherapy
Stage III disease – Doublet Adjuvant chemotherapy
MSI-Unstable predicts harm to FU in low risk patients
Multi-gene assays are not recommended to guide adjuvant chemotherapy
Majority of benefit to adjuvant chemo is from 5-FU, majority of toxicity is from Oxaliplatin

17. Summary Addition of Oxaliplatin may be harmful in patients > 75
In patients with low risk (T1-3, N1) Stage III disease 3 months of doublet adjuvant chemotherapy is equivalent to 6 months
In high risk (T4, N2) this is not the case
Bevacizumab, Cetuximab and Panitumimab are not indicated in the adjuvant setting

18. The End