CCR Translation for This Article from Occult Tumor Burden Predicts Disease Recurrence in Lymph Node–Negative Colorectal Cancer
ARTICLE ABSTRACT
Purpose: Lymph node involvement by histopathology informs colorectal cancer prognosis, whereas recurrence in 25% of node-negative patients suggests the presence of occult metastasis. GUCY2C (guanylyl cyclase C) is a marker of colorectal cancer cells that identifies occult nodal metastases associated with recurrence risk. Here, we defined the association of occult tumor burden, quantified by GUCY2C reverse transcriptase-PCR (RT-PCR), with outcomes in colorectal cancer.Experimental Design: Lymph nodes (range: 2–159) from 291 prospectively enrolled node-negative colorectal cancer patients were analyzed by histopathology and GUCY2C quantitative RT-PCR. Participants were followed for a median of 24 months (range: 2–63). Time to recurrence and disease-free survival served as primary and secondary outcomes, respectively. Association of outcomes with prognostic markers, including molecular tumor burden, was estimated by recursive partitioning and Cox models.Results: In this cohort, 176 (60%) patients exhibited low tumor burden (MolLow), and all but four remained free of disease [recurrence rate 2.3% (95% CI, 0.1–4.5%)]. Also, 90 (31%) patients exhibited intermediate tumor burden (MolInt) and 30 [33.3% (23.7–44.1)] developed recurrent disease. Furthermore, 25 (9%) patients exhibited high tumor burden (MolHigh) and 17 [68.0% (46.5–85.1)] developed recurrent disease (P < 0.001). Occult tumor burden was an independent marker of prognosis. MolInt and MolHigh patients exhibited a graded risk of earlier time to recurrence [MolInt, adjusted HR 25.52 (11.08–143.18); P < 0.001; MolHigh, 65.38 (39.01–676.94); P < 0.001] and reduced disease-free survival [MolInt, 9.77 (6.26–87.26); P < 0.001; MolHigh, 22.97 (21.59–316.16); P < 0.001].Conclusion: Molecular tumor burden in lymph nodes is independently associated with time to recurrence and disease-free survival in patients with node-negative colorectal cancer. Clin Cancer Res; 17(10); 3293–303. ©2011 AACR.
