A critical appraisal of circumferential resection margins in esophageal carcinoma

Abstract

Background: In esophageal cancer, circumferential resection margins (CRMs) are considered to be of relevant prognostic value, but a reliable definition of tumor-free CRM is still unclear. The aim of this study was to appraise the clinical prognostic value of microscopic CRM involvement and to determine the optimal limit of CRM.

Methods: To define the optimal tumor-free CRM we included 98 consecutive patients who underwent extended esophagectomy with microscopic tumor-free resection margins (R0) between 1997 and 2006. CRMs were measured in tenths of millimeters with inked lateral margins. Outcome of patients with CRM involvement was compared with a statistically comparable control group of 21 patients with microscopic positive resection margins (R1).

Results: A cutoff point of CRM at < or = 1.0 mm and > 1.0 mm appeared to be an adequate marker for survival and prognosis (both P < 0.001). The outcome in patients with CRMs < or = 1.0 and > 0 mm was equal to that in patients with CRM of 0 mm (P = 0.43). CRM involvement was an independent prognostic factor for both recurrent disease (P = 0.001) and survival (P < 0.001). Survival of patients with positive CRMs (< or = 1 mm) did not significantly differ from patients with an R1 resection (P = 0.12).

Conclusion: Involvement of the circumferential resection margins is an independent prognostic factor for recurrent disease and survival in esophageal cancer. The optimal limit for a positive CRM is < or = 1 mm and for a free CRM is >1.0 mm. Patients with unfavorable CRM should be approached as patients with R1 resection with corresponding outcome.

Fig. 1

a Cross-sections of a specimen through the tumor with 0.5-cm-wide slices. b Cross-section with macroscopically minimal distance between the tumor and the nearest inked margin

Fig. 2

Microscopic example of CRM measurement, from most lateral tumor cells to the inked outer margins; an enlargement of the margin is shown in the inset

Fig. 3

Schematic representation of four possible microscopic circumferential resection margins (CRM) measurements in different esophageal cross-sections: a tumor with free CRM, measurement performed in tenths of millimeters; b small tumor with narrow free CRM, damage to the esophageal wall caused by surgical manipulation; c large tumor, directly growing into the CRM; d tumor with satellite (spray) growth into the CRM with few malignant cells

Fig. 4

Cancer-specific survival by CRM in three categories: CRMs with tumor ingrowth (0 mm) had similar outcome to CRMs ≤1 mm and >0 mm (P = 0.43); both had significantly worse outcome compared with CRM >1 mm (P < 0.001 and P = 0.004, respectively)

Fig. 5

Equal cancer-specific survival of positive CRMs and R1 resections. Kaplan–Meier survival curve of patients with positive resection margins (R1) of the control group (n = 21) and patients of the study group with positive CRM ≤1 mm (CRM+) (n = 51, 52%) and free CRM >1 mm (CRM−) (n = 47, 48%). There was no significant difference in survival between CRM+ and R1 (P = 0.12); significant differences were found between CRM− with CRM+ and R1 (both P < 0.001)