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Circumferential Margin Involvement Is the Crucial Prognostic Factor after Multimodality Treatment in Patients with Locally Advanced Rectal Carcinoma

Authors' Affiliations: Departments of ¹ Surgery and ² Radiotherapy, Catharina Hospital; ³ Department of Pathology, PAMM Laboratories, Eindhoven, the Netherlands; ⁴ Department of Pathology, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands; and ⁵ Department of Surgery, Medical Centre Rijnmond-South, Rotterdam, the Netherlands

Requests for reprints: Iris D. Nagtegaal, Department of Pathology 437 PA, Radboud University, P.O. Box 9101, Nijmegen, the Netherlands. Phone: 31-243614314; E-mail: i.nagtegaal{at}pathol.umcn.nl.

Purpose: After preoperative (radio)chemotherapy, histologic determinants for prognostification have changed. It is unclear which variables, including assessment of tumor regression, are the best indicators for local recurrence and survival.

Experimental Design: A series of 201 patients with locally advanced rectal cancer (cT3/T4, M0) presenting with an involved or at least threatened circumferential margin (CRM) on preoperative imaging (<2 mm) were evaluated using standard histopathologic variables and four different histologic regression systems. All patients received neoadjuvant radiochemotherapy or radiotherapy. The prognostic value of all factors was tested with univariate survival analysis of time to local recurrence and overall survival.

Results: Local recurrence occurred in only 8% of the patients with a free CRM compared with 43% in case of CRM involvement (P < 0.0001). None of the four regression systems were associated with prognosis, not even when corrected for CRM status. However, we did observe a higher degree of tumor regression after radiochemotherapy compared with radiotherapy (P < 0.001). Absence of tumor regression was associated with increasing invasion depth and a positive CRM (P = 0.02 and 0.03, respectively).

Conclusions: Assessment of CRM involvement is the most important pathologic variable after radiochemotherapy. Although tumor regression increases the chance on a free CRM, in cases with positive resection margins prognosis is poor irrespective of the degree of therapy-induced regression.

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				M. J. E. M. Gosens, R. C. Dresen, H. J. T. Rutten, G. A. P. Nieuwenhuijzen, J. A. W. M. van der Laak, H. Martijn, I. Tan-Go, I. D. Nagtegaal, A. J. C. van den Brule, and J. H. J. M. van Krieken Preoperative radiochemotherapy is successful also in patients with locally advanced rectal cancer who have intrinsically high apoptotic tumours Ann. Onc., July 29, 2008; (2008) mdn428v1. [Abstract] [Full Text] [PDF]