Prognostic Value of Molecular Detection of Lymph Node Metastases After Curative Resection of Stage II Colon Cancer: A Systematic Pooled Data Analysis

Guanylyl cyclase C (GCC) is a colon-specific marker that may aid in the detection of otherwise occult metastases in lymph nodes. This pooled analysis of 3 independent cohort studies demonstrates that a high GCC lymph node ratio is significantly associated with inferior outcomes in stage II colon cancers otherwise, deemed to be low risk by routine histologic examination. Background: We aimed to clarify the prognostic value of guanylyl cyclase C (GCC) lymph node ratio (LNR) status as a predictor of recurrence in untreated stage IIA colon cancer on the basis of pooled individual data from previous studies. Methods: Patients were classified according to predefined GCC LNR risk groups (low, LNR <= 0.1; intermediate, 0.1 < LNR <= 0.2; high, LNR > 0.2). Outcomes included time to recurrence, disease-free survival, and overall survival. Stratified log-rank tests and multivariate Cox models assessed the association between outcomes and GCC lymph node status. Results: The final data set contained 553 patients with stage IIA colon cancer with a median of 18 lymph nodes examined after resection; 65 patients (11.8%) had recurrence. Overall, 109 patients (19.7%) were classified high risk on the basis of GCC LNR. In multivariate analysis, high GCC LNR value (> 0.2) was a significant predictor of cancer recurrence (hazard ratio [HR], 3.18; 95% confidence interval [Cl], 1.77-5.71; P <.001) and lower disease-free survival (HR, 2.40; 95% Cl, 1.60-3.62; P <.001) and overall survival (HR, 2.12; 95% Cl, 1.35-3.33; P =.001). Conclusion: Patients considered at high risk on the basis of their GCC LNR status have significantly inferior outcomes compared to those with low GCC LNR values, particularly among those traditionally considered to be at low risk for recurrence.