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Prognostic Impact of Micrometastases in Colon Cancer: Interim Results of a Prospective Multicenter Trial

Bilchik, Anton J. MD, PhD, FACS*; Hoon, Dave S. B. PhD*; Saha, Sukamal MD, FACS†; Turner, Roderick R. MD*; Wiese, David MD†; DiNome, Maggie MD, FACS*; Koyanagi, Kazuo MD*; McCarter, Martin MD, FACS‡; Shen, Perry MD, FACS§; Iddings, Douglas DO*; Chen, Steven L. MD, MBA*; Gonzalez, Maria BA*; Elashoff, David PhD*; Morton, Donald L. MD, FACS*

doi: 10.1097/SLA.0b013e318155a9c7
Original Articles

Objective: The 25% rate of recurrence after complete resection of stage II colon cancer (CC) 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 29.6% rate of micrometastases (MM) identified by immunohistochemical staining (IHC) of H&E-negative SNs in CC. We hypothesized that these MM have prognostic importance.

Methods: Between March 2001 and August 2006, 152 patients with resectable colorectal cancer were enrolled in the trial. IHC and quantitative RT-PCR (qRT) assay were performed on H&E-negative SNs. Results were correlated with disease-free survival.

Results: The sensitivity of lymphatic mapping was significantly better in CC (75%) than rectal cancer (36%), P < 0.05. Of 92 node-negative CC patients 7 (8%) were upstaged to N1 and 18 (22%) had IHC MM. Four patients negative by H&E and IHC were positive by qRT. At a mean follow-up of 25 months, 15 patients had died from noncancer-related causes, 12 had developed recurrence, 5 had died of CC (2 with macrometastases, 3 with MM), and 7 were alive with disease. The 12 recurrences included 4 patients with SN macrometastases and 6 with SN MM (2 by IHC, 4 by qRT). One of the 2 SN-negative recurrences had other positive lymph nodes by H&E. All patients with CC recurrences had a positive SN by either H&E/IHC or qRT. No CC patient with a negative SN by H&E and qRT has recurred (P = 0.002).

Conclusion: This is the first prospective evaluation of the prognostic impact of MM in colorectal cancer. These results indicate that the detection of MM may be clinically relevant in CC and may improve the selection of patients for adjuvant systemic chemotherapy. Patients with CC who are node negative by cumulative detection methods (H&E/IHC and qRT) are likely to be cured by surgery alone.

Recurrence in node-negative colon cancer may be attributed to missed micrometastases. Focused analysis of the sentinel node improves staging accuracy and may improve the selection of patients for chemotherapy.

From the *Departments of Gastrointestinal Oncology and Molecular Oncology, John Wayne Cancer Institute at Saint John's Health Center, Santa Monica, CA; †Michigan State University McLaren Regional Medical Center, Flint, MI; ‡Department of Surgery, Division of GI Tumors and Endocrine Surgery, University of Colorado at Denver and Health Sciences Center, Denver, CO; and §Department of Surgical Oncology, Wake Forest University Medical Center, Winston-Salem, NC.

Supported by Grant CA090848 from the National Cancer Institute and by funding from the Rod Fasone Memorial Cancer Fund (Indianapolis, IN), the Henry L. Guenther Foundation (Los Angeles, CA), the William Randolph Hearst Foundation (San Francisco, CA), the Davidow Charitable Fund (Los Angeles, CA), and Mrs. Ruth Weil (Los Angeles, CA).

Presented at American Surgical Association, Colorado, April 26th, 2007.

Reprints: Anton J. Bilchik, MD, PhD, FACS, Departments of Gastrointestinal Oncology and Molecular Oncology, John Wayne Cancer Institute, 2200 Santa Monica Boulevard, Santa Monica, CA 90404. E-mail: bilchika@jwci.org.

© 2007 Lippincott Williams & Wilkins, Inc.