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Hyslop T , Weinberg DS , Schulz S , Barkun A , Waldman SA
Occult tumor burden predicts disease recurrence in lymph node-negative colorectal cancer
Clin Cancer Res. 2011 May 15;17(10) :3293-303
PMID: 21307149    PMCID: PMC3096730    URL: https://www.ncbi.nlm.nih.gov/pubmed/21307149
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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 (Mol(Low)), 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 (Mol(Int)) and 30 [33.3% (23.7-44.1)] developed recurrent disease. Furthermore, 25 (9%) patients exhibited high tumor burden (Mol(High)) and 17 [68.0% (46.5-85.1)] developed recurrent disease (P < 0.001). Occult tumor burden was an independent marker of prognosis. Mol(Int) and Mol(High) patients exhibited a graded risk of earlier time to recurrence [Mol(Int), adjusted HR 25.52 (11.08-143.18); P < 0.001; Mol(High), 65.38 (39.01-676.94); P < 0.001] and reduced disease-free survival [Mol(Int), 9.77 (6.26-87.26); P < 0.001; Mol(High), 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.
Hyslop, Terry Weinberg, David S Schulz, Stephanie Barkun, Alan Waldman, Scott A eng R21 CA112147/CA/NCI NIH HHS/ R01 CA075123-02/CA/NCI NIH HHS/ CA75123/CA/NCI NIH HHS/ R01 CA095026-02/CA/NCI NIH HHS/ R01 CA095026-04S1/CA/NCI NIH HHS/ R01 CA075123-04/CA/NCI NIH HHS/ R01 CA075123-07/CA/NCI NIH HHS/ R01 CA095026-03/CA/NCI NIH HHS/ R01 CA095026-01A2/CA/NCI NIH HHS/ R01 CA095026-04/CA/NCI NIH HHS/ R01 CA095026/CA/NCI NIH HHS/ CA95026/CA/NCI NIH HHS/ RC1 CA146033-02/CA/NCI NIH HHS/ R01 CA075123-06/CA/NCI NIH HHS/ R01 CA095026-06/CA/NCI NIH HHS/ R01 CA095026-05S1/CA/NCI NIH HHS/ R01 CA075123-03A1/CA/NCI NIH HHS/ R01 CA075123-05/CA/NCI NIH HHS/ R01 CA095026-05/CA/NCI NIH HHS/ R01 CA075123/CA/NCI NIH HHS/ R33 CA112147/CA/NCI NIH HHS/ RC1 CA146033/CA/NCI NIH HHS/ RC1 CA146033-01/CA/NCI NIH HHS/ CA112147/CA/NCI NIH HHS/ Multicenter Study Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Validation Study Clin Cancer Res. 2011 May 15;17(10):3293-303. doi: 10.1158/1078-0432.CCR-10-3113. Epub 2011 Feb 9.