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The Prognostic Effect of Micrometastases in Previously Staged Lymph Node Negative (N0) Colorectal Carcinoma: A Meta-analysis

Department of Surgical Oncology, John Wayne Cancer Institute at Saint John’s Health Center, Santa Monica, CA, USA

Correspondence: Address correspondence and reprint requests to: Anton Bilchik, MD, PhD; John Wayne Cancer Institute at Saint John’s Health Center, 2200 Santa Monica Boulevard, Santa Monica, CA 90404, USA; E-mail: bilchika{at}jwci.org

Background: The prognostic relevance of lymphatic micrometastases in colorectal carcinoma is unclear. To determine the prognostic significance of micrometastases in colorectal cancer, a meta-analysis was performed on all studies, which reported 3-year disease-free survival (DFS) and overall survival (OS).

Methods: Published studies selected for meta-analysis contained sufficient data from which to extrapolate estimates of 3-year DFS and/or OS. From 1991–2003, 25 studies re-examined N0 lymph nodes by serial sectioning and immunohistochemical (IHC) staining or reverse transcriptase-polymerase chain reaction (RT-PCR) assay. Eight studies (566 patients) with IHC detected micrometastases and three (173 patients) with RT-PCR micrometastases were used to determine DFS and OS. Weighted estimates of 3-year survival were combined across studies within each group, and the combined survival estimates were compared across groups using a binomial test.

Results: Micrometastases were identified in all IHC studies; upstaging, including N1, N1mi and N0_(i+), was achieved in 32% (179/566 patients). All RT-PCR studies identified micro-metastases; upstaging to N0_(mol+) was achieved in 37% (64/173 patients). There was a statistically significant difference in 3-year OS between RT-PCR positive N0_(mol+) patients (77.8%) and those for whom micrometastases were not detected (96.6%) (P<.001).

Conclusion: The prognostic value of micrometastases detected retrospectively by RT-PCR is significant in AJCC stage II colorectal patients. Studies utilizing RT-PCR performed a more complete nodal analysis when compared to studies using IHC techniques. RT-PCR may also be more specific for the detection of clinically relevant micrometastases compared to IHC detected cytokeratins. Prospective studies are needed to evaluate the potential benefit of systemic chemotherapy in patients with molecular metastases.

Key Words: Colorectal micrometastases • Occult metastatic disease • Meta-analysis • Prognostic markers

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