American Surgical Association
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Prognostic Impact of Micrometastases In Colon Cancer: Interim Results of A Prospective Multicenter Trial
Anton J Bilchik1, David Hoon1, Kazuo Koyanagi1, Maggie DiNome2, Sukamal Saha3, Martin McCarter4, Perry Shen5, Roderick Turner1, David Elashoff1, Donald Morton1
1John Wayne Cancer Institute, Santa Monica, CA;2St. Johns Health Center, Santa Monica, CA;3McLaren Regional Center, Flint, MI;4University of Colorodo, Denver, CO;5Wake Forest University Medical Center, Winston-Salem, NC

OBJECTIVE(S): The 25% rate of recurrence after complete resection of stage II colon cancer suggests the presence of occult nodal metastases not identified by hematoxylin and eosin staining (H&E). Interim data from our ongoing prospective multicenter trial of sentinel node (SN) biopsy indicate a 24% rate of micrometastases (MM) identified by immunohistochemical staining (IHC) of H&E-negative SNs. We hypothesized that these MM have prognostic importance.
METHODS: The incidence of MM identified by H&E, IHC and/or quantitative RT-PCR (qRT) was examined in 144 evaluable patients enrolled in the trial between March 2001 and August 2006. IHC and qRT were performed on H&E-negative nodes. Results were correlated with disease-free survival.
RESULTS: At a mean follow-up of 21 months, 15 patients had expired from non-cancer-related causes, 10 had developed recurrence, 5 had died of colon cancer (2 with macrometastases, 3 with MM), and 5 were alive with disease. The 10 recurrences included 2 patients with SN macrometastases and 3 with SN MM (2 by IHC, 1 by IHC/qRT). Of 125 patients with H&E-negative SNs, 29 had IHC MM and 12 had qRT MM. The rate of recurrence was 1.2% (1/85) when SNs were negative by IHC and qRT, compared to 15.3% (9/59) when SNs were positive by H&E or IHC/qRT (p < .001).
CONCLUSIONS: This is the first prospective evaluation of the prognostic impact of MM in colon cancer. Results indicate that ultrastaging based on IHC/qRT may improve selection of patients for adjuvant systemic chemotherapy, based on nodal evidence of MM .

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