Evaluation of the prognostic value of guanylyl cyclase C (GCC) lymph node (LN) classification in patients with stage II colon cancer: A pooled analysis.

Authors

null

Daniel J. Sargent

Mayo Clinic, Rochester, MN

Daniel J. Sargent , Qian Shi , Murray B. Resnick , Stephen Lyle , Michael O. Meyers , Atoussa Goldar-Najafi , Thomas E. Clancy , Sharlene Gill , Jean-Francois Haince , Yves Fradet

Organizations

Mayo Clinic, Rochester, MN, Rhode Island Hospital and Brown University, Providence, RI, Department of Cancer Biology, University of Massachusetts Medical School, Worcester, MA, Division of Surgical Oncology and Endocrine Surgery, University of North Carolina School of Medicine, Chapel Hill, NC, Lahey Clinic, Burlington, MA, Brigham and Women's Hospital/Dana-Farber Cancer Institute, Boston, MA, British Columbia Cancer Agency, Vancouver, BC, Canada, DiagnoCure, Quebec City, QC, Canada

Research Funding

No funding sources reported

Background: Identification of a sensitive and specific prognostic marker would aid in the management of patients (pts) with standard histopathology node negative colon cancer (CC). We conducted a pooled individual pt data analysis to confirm the prognostic value of GCC for disease recurrence in untreated stage II CC. Methods: GCC mRNA was quantified by RT-qPCR using formalin-fixed LN from 310 stage II pts diagnosed from 1991-2006 enrolled in two studies (Sargent 2011 [study1] and Haince 2009 [study2]). Patients were classified by GCC LN ratio (LNR) (high risk: LNR ≥ 0.1; low risk: LNR < 0.1), with LNR defined as number of GCC positive LN divided by number of informative LNs. Clinical outcomes included time to recurrence (TTR), overall survival (OS), disease-specific survival (DSS) and disease-free survival (DFS). Stratified log-rank tests and multivariate Cox models assessed the association between clinical outcomes and GCC LN status. Results: The 5-year recurrence rate in study 1 (n=241) was 15.8%, 24.9% in study 2 (n=69). GCC LNR high risk pts had significantly higher risk of TTR, OS, DSS and DFS, which remained after adjusting for age, T stage, grade, number of LNs examined, and presence of lymphovascular invasion (Table). In a secondary analysis of low risk stage II pts (T3, ≥12 LNs examined, and negative surgical margins, n=241), a strong relationship between GCC LNR and each endpoint remained (TTR HR=4.34, 95% CI=2.07 – 9.13, p<0.001). Conclusions: Pts with GCC LNR high risk status have significantly poorer outcomes compared to pts with low risk status, particularly among those traditionally considered to be low risk.



Hazard ratios comparing high- (LNR ≥ 0.1) and low-risk (LNR < 0.1) groups.

Outcome GCC risk group 3-year event-free
rate [95% CI]
Univariate
Multivariate
HR [95% CI] p HR [95% CI] p

TTR High 0.81 [0.74, 0.90] 2.99 [1.65, 5.42] <0.001 2.55 [1.41, 4.61] 0.002
Low 0.91 [0.87, 0.95] - -
OS High 0.85 [0.79, 0.92] 1.83 [1.17, 2.87] 0.008 1.72 [1.06, 2.80] 0.028
Low 0.92 [0.88, 0.96] - -
DSS High 0.81 [0.74, 0.90] 3.07 [1.73, 5.48] <0.001 2.62 [1.47, 4.67] 0.001
Low 0.91 [0.87, 0.95] - -
DFS High 0.75 [0.67, 0.84] 2.23 [1.51, 3.31] <0.001 2.15 [1.42, 3.25] <0.001
Low 0.86 [0.82, 0.91] - -

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Abstract Details

Meeting

2012 Gastrointestinal Cancers Symposium

Session Type

Poster Session

Session Title

General Poster Session C: Cancers of the Colon and Rectum

Track

Cancers of the Colon, Rectum, and Anus

Sub Track

Translational Research

Citation

J Clin Oncol 30, 2012 (suppl 4; abstr 443)

DOI

10.1200/jco.2012.30.4_suppl.443

Abstract #

443

Poster Bd #

B14

Abstract Disclosures