How to Define a Positive Circumferential Resection Margin in T3 Adenocarcinoma of the Esophagus

Abstract

A positive circumferential resection margin (CRM) is associated with poor survival after esophagectomy for cancer. The Royal College of Pathologists (RCP) defines a CRM when tumor is found <1 mm of the lateral margin whereas the College of American Pathologists (CAP) defines CRM when tumor cells are located at the lateral margin. This study evaluates the clinical prognostic significance of CRM on overall survival (OS) and disease-free survival (DFS) in patients who underwent esophagectomy for T3 esophageal adenocarcinoma. Analysis included 132 patients. CRM was found in 26 cases (19.7%) corresponding to CAP criteria versus 89 cases (67.4%) corresponding to RCP criteria. Median OS using RCP criteria was 16.4 (95%CI, 8.5-24.2) months for CRM patients versus 21.0 (95%CI 16.3-25.6) months in CRM patients (P=0.144). With CAP criteria, median OS in CRM and CRM patients was 9.4 (95%CI, 7.6-11.2) months versus 21.6 (95%CI, 18.9-24.3) months, respectively (P=0.000). Median DFS using RCP criteria was 18.0 (95%CI, 11.5-24.6) months for CRM patients versus 11.0 (95%CI, 8.1-14.0) months for CRM patients (P=0.257). Applying the CAP criteria, median DFS in CRM and CRM patients was 16.3 (95%CI, 10.6-22.0) months versus 7.0 (95%CI, 6.3-7.8) months, respectively (P=0.000). Effects of a CRM according to CAP criteria remained significant after multivariate testing [OS: hazard ratio (HR), 2.43; 95%CI, 1.52-3.90; DFS: HR, 2.09; 95%CI, 1.32-3.30]. Only with the CAP criteria, CRM is an independent prognostic factor for survival and recurrence in patients with T3 adenocarcinoma of the esophagus. The circumferential margin should only be considered positive (ie, R1) if the tumor is found at the inked lateral margin of resection in accordance with the CAP criteria.

Does the Margin Matter in Esophageal Cancer

“…Interestingly, another study was only able to demonstrate a negative effect on overall survival in ESCC for CRM positive patients when judged by CAP 199 criteria (HR 5.26; 95% CI 2.37-11.32; p < 0.001) and not RCP criteria (HR 1.3; 95% CI 0.62-2.98; p = 0.50) in multivariate analysis [18]. Similar results were found in 3 other studies were CAP criteria yielded a significant prognostic influence on overall survival while RCP criteria did not [12,13,19]. Notably, some studies were not able to show an effect of the CRM status on overall survival [15,[20][21][22][23].…”

“…In the first study of CRM involvement by Sagar et al [25], significantly (p < 0.01) more patients with a positive CRM (55%) developed a local recurrence as compared to those without involvement of the CRM (13%) [25]. These results were later proven by other studies, which also identified a prognostic role of a positive CRM on recurrences [3,13,14,17,18,22,26]. Chao et al [26] found a significant influence of an involved CRM not only on loco-regional but also on distant recurrences, while an involvement to the CRM of less than 1 mm was associated with early loco-regional recurrences.…”

“…In another study, involvement of the CRM was only associated to recurrences, being outside the lymphatic drainage of the esophagus and the gastroesophageal junction [17]. Interestingly, Verhage et al [13] were able to demonstrate a prognostic effect only when using CAP criteria in multivariate analysis (HR 2.086; 95% CI 1.320-3.296; p = 0.002). CRM involvement was the strongest predictor of recurrence in their analysis comprising only pT3 adenocarcinomas [13].…”

“…Interestingly, Verhage et al [13] were able to demonstrate a prognostic effect only when using CAP criteria in multivariate analysis (HR 2.086; 95% CI 1.320-3.296; p = 0.002). CRM involvement was the strongest predictor of recurrence in their analysis comprising only pT3 adenocarcinomas [13]. The results of the latter study were supported by Hulshoff et al [14] who identified margin involvement according to CAP criteria to be associated with local recurrence in surgically treated patients (p = 0.004) as well as in patients who also received neoadjuvant therapy prior to surgery (p = 0.001).…”

Impact of incremental circumferential resection margin distance on overall survival and recurrence in oesophageal adenocarcinoma

“…The College of American Pathologists (CAP) defines a positive CRM as tumour at the cut margin (TAM), which has been advocated in some studies4, 5, 6, 7, 8, 9, whereas the Royal College of Pathologists (RCP) defines a positive CRM as tumour within 1 mm, preferred in other studies10, 11, 12, 13. Some studies have found the CRM to be independently prognostically significant4 7, 9 10, 13, 14, 15, 16, and others have not5 6, 11 12, 17, 18, 19. A positive margin may increase the likelihood of locoregional and systemic tumour recurrence9 20, although it is unclear whether the latter is simply a reflection of a larger, more advanced tumour.…”