(ChemotherapyAdvisor) – Patients with untreated stage II colon cancer and node negative disease with a guanylyl cyclase C (GCC) high-risk lymph node ratio (LNR) have significantly poorer outcomes than those with low-risk status, particularly among patients traditionally considered to be low risk, according to a study presented during the ASCO 2012 Gastrointestinal Cancers Symposium.

Daniel J. Sargent, PhD, Mayo Clinic Cancer Center, Rochester, MN, and colleagues conducted a pooled individual patient data analysis to confirm the prognostic value of GCC lymph node classification for disease recurrence.

The study included 310 patients with stage II colon cancer diagnosed from 1991–2006 enrolled in two studies. GCC mRNA was quantified by RT-aPCR using formalin-fixed lymph nodes from these patients, who were classified by GCC ratio: high risk (LNR ≥0.1) or low risk (LNR <0.1). LNR was defined as the number of GCC positive lymph nodes divided by the number of information lymph nodes.

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Stratified log-rank tests and multivariate Cox models assessed the association between clinical outcomes—time to recurrence (TTR), overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS)—and GCC lymph node status.

In study 1 (n=241), the five-year recurrence rate was 15.8% and, in study 2 (n=69), 24.9%. Patients classified as GCC LNR high risk had a significantly higher risk of TTR, OS, DSS, and DFS, all of which remained after adjusting for age, T stage, grade, number of lymph nodes examined, and presence of lymphvascular invasion.

In a secondary analysis of patients with stage II colon cancer considered to be at low risk (T3, ≥12 lymph nodes examined, and negative survival margins), “a strong relationship between GCC LNR and each end point remained,” the investigators noted. For TTR, the hazard ratio was 4.34 (95% CI 2.07-9.13; P<0.001).