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Previous Volume 339:223-228 July 23, 1998 Number 4 Next

	Full Text PDF Editorial by Lindblom, A. Letters Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited PubMed Citation

ABSTRACT

Background Standard treatment of colorectal cancer includes adjuvant chemotherapy for patients with stage III disease (defined by the presence of lymph-node metastases), but not for patients with stage II tumors (who have no lymph-node metastases). However, 20 percent of patients with stage II tumors die of recurrent disease. We investigated whether the detection of micrometastases can be used to identify patients with stage II disease who are at high risk for recurrence.

Methods We analyzed 192 lymph nodes from 26 consecutive patients with stage II colorectal cancer, using a carcinoembryonic antigen–specific nested reverse-transcriptase polymerase chain reaction. Five-year follow-up information was obtained on all patients. Observed and adjusted survival rates were assessed in the patients with and the patients without micrometastases.

Results Micrometastases were detected in one or more lymph nodes from 14 of 26 patients (54 percent). The adjusted five-year survival rate (for which only cancer-related deaths were considered) was 50 percent in this group, whereas in the 12 patients without micrometastases, the survival rate was 91 percent (P=0.02 by the log-rank test). The observed five-year survival rates were 36 percent and 75 percent, respectively (P=0.03). The groups were similar with respect to age, sex, tumor side (location in relation to the flexura lienalis), degree of tumor differentiation (grade), and diameter of the primary tumor.

Conclusions Molecular detection of micrometastases is a prognostic tool in stage II colorectal cancer.

Source Information

From the Department of Surgery (G.-J.L., C.J.H.V., R.A.E.M.T.), the Department of Pathology (A.-M.C.-J., J.H.J.M.K., C.J.C.), and the Department of Medical Statistics (J.H.), Leiden University Medical Center, Leiden, the Netherlands.

Address reprint requests to Dr. Tollenaar at the Department of Surgery K6R, Leiden University Medical Center, P.O. Box 9600, 2300 RC, Leiden, the Netherlands.

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N Engl J Med 1998; 339:1642-1644, Nov 26, 1998. Correspondence

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• Okami, J., Dohno, K., Sakon, M., Iwao, K., Yamada, T., Yamamoto, H., Fujiwara, Y., Nagano, H., Umeshita, K., Matsuura, N., Nakamori, S., Monden, M. (2000). Genetic Detection for Micrometastasis in Lymph Node of Biliary Tract Carcinoma. Clin. Cancer Res. 6: 2326-2332 [Abstract] [Full Text]  
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• Sanchez-Cespedes, M., Esteller, M., Hibi, K., Cope, F. O., Westra, W. H., Piantadosi, S., Herman, J. G., Jen, J., Sidransky, D. (1999). Molecular Detection of Neoplastic Cells in Lymph Nodes of Metastatic Colorectal Cancer Patients Predicts Recurrence. Clin. Cancer Res. 5: 2450-2454 [Abstract] [Full Text]  
• Ghossein, R. A., Bhattacharya, S., Rosai, J. (1999). Molecular Detection of Micrometastases and Circulating Tumor Cells in Solid Tumors. Clin. Cancer Res. 5: 1950-1960 [Abstract] [Full Text]  
• Pantel, K., Cote, R. J., Fodstad, O. (1999). Detection and Clinical Importance of Micrometastatic Disease. JNCI J Natl Cancer Inst 91: 1113-1124 [Abstract] [Full Text]  
• Weitz, J., Kienle, P., Magener, A., Koch, M., Schrodel, A., Willeke, F., Autschbach, F., Lacroix, J., Lehnert, T., Herfarth, C., Doeberitz, M. v. K. (1999). Detection of Disseminated Colorectal Cancer Cells in Lymph Nodes, Blood and Bone Marrow. Clin. Cancer Res. 5: 1830-1836 [Abstract] [Full Text]  
• Merrie, A. E.H., Yun, K., McCall, J. L., Ghossein, R. A., Bostick, P. J., Hoon, D. S.B., Cote, R. J., Liefers, G.-J., Cleton-Jansen, A.-M., Tollenaar, R. A.E.M. (1998). Detection of Carcinoembryonic Antigen Messenger RNA in Lymph Nodes from Patients with Colorectal Cancer. NEJM 339: 1642-1644 [Full Text]  
• Lindblom, A. (1998). Improved Tumor Staging in Colorectal Cancer. NEJM 339: 264-265 [Full Text]