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Lymph Node Metastases in Rectal Cancer After Preoperative Radiochemotherapy: Impact of Intramesorectal Distribution and Residual Micrometastatic Involvement

Sprenger, Thilo MD*; Rothe, Hilka MD; Becker, Heinz MD*; Beissbarth, Tim PhD; Homayounfar, Kia MD*; Gauss, Korbinian*; Kitz, Julia MD§; Wolff, Hendrik MD; Scheel, Andreas H. MD§; Ghadimi, Michael MD*; Rödel, Claus MD; Conradi, Lena-Christin MD*; Liersch, Torsten MD*

American Journal of Surgical Pathology: August 2013 - Volume 37 - Issue 8 - p 1283–1289
doi: 10.1097/PAS.0b013e3182886ced
Original Articles

Introduction: After neoadjuvant chemoradiation (CRT), the pathologic determined lymph node (LN) status is the most important prognostic factor in rectal cancer patients. Here we assessed the prognostic impact of residual LN micrometastases (<0.2 cm) and the intramesorectal distribution of LN metastases.

Patients and Methods: Surgical specimens from 81 patients with cUICC II/III rectal cancer undergoing neoadjuvant CRT and total mesorectal excision within the German Rectal Cancer Trial CAO/ARO/AIO-04 were prospectively evaluated. The entire mesorectal compartment was paraffin embedded and screened microscopically. The number and distribution of mesorectal LN macrometastases and micrometastases were correlated with disease-free (DFS) and cancer-specific overall survival (CSS).

Results: A total of 2412 LNs were detected (mean 29.8±13.7). Twenty-five patients had residual LN metastases (ypN+). The incidence of metastases in the peritumoral mesorectum was higher (7.7%) than that proximal to the tumor (1.5%), whereas no metastases were identified below the tumor level. Patients with both proximal and peritumoral involvement showed a significantly reduced CSS (hazard ratio=5.4; P<0.05). Fourteen patients with ypN+ status (56%) had micrometastases, 9 patients (36%) had only micrometastatic involvement. Patients with nodal macrometastases had a reduced DFS (P<0.01) and CSS (P<0.005) as compared with ypN0 patients, whereas residual micrometastases had no influence on survival.

Conclusions: Despite the high incidence of residual LN micrometastases they did not seem to have a prognostic impact in this series. Micrometastases might indicate responsive tumors to CRT with a more favorable biology. The intramesorectal distribution of LN metastases had a prognostic impact and should be validated in further studies.

Departments of *General and Visceral Surgery

Medical Statistics

§Pathology

Radiation Oncology and Radiotherapy, University Medical Center Göttingen

Department of Pathology, Medical Care Unit Göttingen, Göttingen

Department of Radiotherapy and Oncology, University of Frankfurt, Frankfurt/Main, Germany

L.-C.C and T.L. share senior authorship.

Conflicts of Interest and Source of Funding: Supported by the Deutsche Forschungsgemeinschaft (KFO 179). The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article.

Correspondence: Thilo Sprenger, MD, Department of General and Visceral Surgery, University Medical Center Göttingen, 37099 Göttingen, Germany (e-mail: tsprenger@chirurgie-goettingen.de).

© 2013 by Lippincott Williams & Wilkins.