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Risk Stratification in Stage II Colon Cancer Patients
*Ramzi Amri, Liliana G Bordeianou, David L Berger
Harvard Medical School/Massachusetts General Hospital, Boston, MA

Objective: AJCC Stage II colon cancer patients form a group where the choice to either undergo or forego adjuvant chemotherapy is far from evident and often remains controversial. This study analyzes several pathological characteristics in order to assess their predictive value for outcomes in stage II colon cancer.
Design: Retrospective review of a prospectively maintained, IRB-approved data repository.
Setting: Tertiary care center.
Patients: A series of 313 consecutive stage II patients treated surgically for colon cancer at our center (2004-2011) were included.
Main outcome measures: Mortality, disease-specific mortality and metastasis, including multivariable Cox regression adjusted for stage subdivisions (II-A/II-B/II-C) and potential confounders.
Results: Colon cancer-specific mortality was substage-independently increased in patients with baseline carcinoembryonic antigen (CEA) >5ng/L (HR=2.97;P=0.041), large vessel invasion (HR=3.93; P=0.002) and perineural invasion (HR=3.67; P=0.004). Overall mortality adjusted for substage, age and comorbidity was also significantly higher in patients with high-grade disease (HR=2.73; P<0.001) and perineural invasion (HR=1.82; P<0.001). Metastatic recurrence adjusted for adjuvant chemotherapy status had substage-independent associations with baseline CEA>5ng/L (HR=2.37; P=0.046), large vessel invasion (HR=2.80; P=0.002), perineural invasion (HR=2.57; P=0.010), and extramural vascular invasion (EMVI) (HR=2.83; P=0.002). The number of high-risk features (0,1,2-3,4+) was associated with a clearly incremental increase in disease-specific mortality (P=0.008) and recurrence (P<0.001).
Conclusion: High-grade disease, baseline CEA>5ng/L, large vessel invasion, perineural invasion and EMVI are all independent risk factors for recurrence and disease-specific mortality in Stage II colon cancer patients. The number of factors present form risk strata that should be weighed heavily in decisions regarding adjuvant treatment.
Baseline CEA >5ng/L *
(Incidence: 19.5%)
Yes (%)No (%)HR (95%CI)P
Overall mortality31.116.41.78(0.93-3.40)0.080
Colon cancer mortality14.84.72.97(1.05-8.43)0.041
Metastatic recurrence18.08.62.37(1.02-5.50)0.046
High-grade disease
(Incidence: 16.3%)
Yes (%)No (%)HR (95%CI)P
Overall mortality45.122.72.73(1.63-4.59)<0.001
Colon cancer mortality9.86.21.84(0.65-5.16)0.249
Metastatic recurrence15.711.51.62(0.73-3.56)0.235
Large vessel invasion
(Incidence: 21.7%)
Yes (%)No (%)HR (95%CI)P
Overall mortality32.424.51.43(0.86-2.38)0.169
Colon cancer mortality14.74.53.93(1.66-9.31)0.002
Metastatic recurrence22.19.42.80(1.45-5.41)0.002
Perineural invasion
(Incidence: 16.0%)
Yes (%)No (%)HR (95%CI)P
Overall mortality46.022.41.82(1.08-3.06)<0.001
Colon cancer mortality12.05.72.31(0.87-6.15)0.094
Metastatic recurrence22.010.32.57(1.25-5.29)0.010
Extramural vascular invasion
(Incidence: 22.7%)
Yes (%)No (%)HR (95%CI)P
Overall mortality40.821.92.38(1.50-2.78)<0.001
Colon cancer mortality15.54.13.67(1.52-8.83)0.004
Metastatic recurrence23.98.72.83(1.46-5.47)0.002
Number of high–risk features012-3≥4P
Number of patients:**7054508
Overall mortality (%)10.016.736.050.00.001
Colon cancer mortality (%)2.93.716.025.00.008
Metastatic recurrence (%)7.17.428.062.5<0.001
HR: hazard ratio adjusted for stage II subdivision (stage IIA/IIB/IIC i.e. T3/T4a/T4b).
Overall survival also adjusted for age, Charlson comorbidity score.
Metastatic recurrence also adjusted for adjuvant chemotherapy status.
* Preoperative CEA known in 189/313 patients (60.4%)
** Aggregate score calculated in patients with data on all 5 characteristics (n=182)


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