Skip to main content
Top
Published in: Annals of Surgical Oncology 12/2021

01-11-2021 | Esophagus Resection | Gastrointestinal Oncology

The “Real R0”: A Resection Margin Smaller Than 0.1 cm is Associated with a Poor Prognosis After Oncologic Esophagectomy

Authors: Penelope St-Amour, MD, Michael Winiker, MD, Christine Sempoux, MD, PhD, François Fasquelle, MD, Nicolas Demartines, MD, FACS, FRCS, FCCS (Hon), Markus Schäfer, MD, FACS, Styliani Mantziari, MD, MSc, PD

Published in: Annals of Surgical Oncology | Issue 12/2021

Login to get access

Abstract

Background

Although resection margin (R) status is a widely used prognostic factor after esophagectomy, the definition of positive margins (R1) is not universal. The Royal College of Pathologists considers R1 resection to be a distance less than 0.1 cm, whereas the College of American Pathologists considers it to be a distance of 0.0 cm. This study assessed the predictive value of R status after oncologic esophagectomy, comparing survival and recurrence among patients with R0 resection (> 0.1-cm clearance), R0+ resection (≤ 0.1-cm clearance), and R1 resection (0.0-cm clearance).

Methods

The study enrolled all eligible patients undergoing curative oncologic esophagectomy between 2012 and 2018. Clinicopathologic features, survival, and recurrence were compared for R0, R0+, and R1 patients. Categorical variables were compared with the chi-square or Fisher’s test, and continuous variables were compared with the analysis of variance (ANOVA) test, whereas the Kaplan-Meier method and Cox regression were used for survival analysis.

Results

Among the 160 patients included in this study, 113 resections (70.6%) were R0, 34 (21.3%) were R0+, and 13 (8.1%) were R1. The R0 patients had a better overall survival (OS) and disease-free survival (DFS) than the R0+ and R1 patients. The R0+ resection offered a lower long-term recurrence risk than the R1 resection, and the R status was independently associated with DFS, but not OS, in the multivariate analysis. Both the R0+ and R1 patients had significantly more adverse histologic features (lymphovascular and perineural invasion) than the R0 patients and experienced more distant and locoregional recurrence.

Conclusions

Although R status is an independent predictor of DFS after oncologic esophagectomy, the < 0.1-cm definition for R1 resection seems more appropriate than the 0.0-cm definition as an indicator of poor tumor biology, long-term recurrence, and survival.
Appendix
Available only for authorised users
Literature
1.
go back to reference Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68:394–424.CrossRef Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68:394–424.CrossRef
2.
go back to reference Arnold M, Laversanne M, Brown LM, Devesa SS, Bray F. Predicting the future burden of esophageal cancer by histological subtype: international trends in incidence up to 2030. Am J Gastroenterol. 2017;112:1247–55.CrossRef Arnold M, Laversanne M, Brown LM, Devesa SS, Bray F. Predicting the future burden of esophageal cancer by histological subtype: international trends in incidence up to 2030. Am J Gastroenterol. 2017;112:1247–55.CrossRef
3.
go back to reference van Hagen P, Hulshof MCCM, van Lanschot JJB, et al. Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med. 2012;366:2074–84.CrossRef van Hagen P, Hulshof MCCM, van Lanschot JJB, et al. Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med. 2012;366:2074–84.CrossRef
4.
go back to reference Al-Batran SE, Homann N, Pauligk C, et al. Perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): a randomised, phase 2/3 trial. Lancet. 2019;393:1948–57.CrossRef Al-Batran SE, Homann N, Pauligk C, et al. Perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): a randomised, phase 2/3 trial. Lancet. 2019;393:1948–57.CrossRef
5.
go back to reference Cunningham D, Allum WH, Stenning SP, et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006;355:11–20.CrossRef Cunningham D, Allum WH, Stenning SP, et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006;355:11–20.CrossRef
6.
go back to reference Ychou M, Boige V, Pignon JP, et al. Perioperative chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma: an FNCLCC and FFCD multicenter phase III trial. J Clin Oncol. 2011;29:1715–21.CrossRef Ychou M, Boige V, Pignon JP, et al. Perioperative chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma: an FNCLCC and FFCD multicenter phase III trial. J Clin Oncol. 2011;29:1715–21.CrossRef
7.
go back to reference Evans R, Bundred JR, Kaur P, Hodson J, Griffiths EA. Meta-analysis of the influence of a positive circumferential resection margin in oesophageal cancer. BJS Open. 2019;3:595–605.CrossRef Evans R, Bundred JR, Kaur P, Hodson J, Griffiths EA. Meta-analysis of the influence of a positive circumferential resection margin in oesophageal cancer. BJS Open. 2019;3:595–605.CrossRef
8.
go back to reference Wu J, Chen QX, Teng LS, Krasna MJ. Prognostic significance of positive circumferential resection margin in esophageal cancer: a systematic review and meta-analysis. Ann Thorac Surg. 2014;97:446–53.CrossRef Wu J, Chen QX, Teng LS, Krasna MJ. Prognostic significance of positive circumferential resection margin in esophageal cancer: a systematic review and meta-analysis. Ann Thorac Surg. 2014;97:446–53.CrossRef
9.
go back to reference Karstens KF, Izbicki JR, Reeh M. Does the margin matter in esophageal cancer. Dig Surg. 2018;35:196–203.CrossRef Karstens KF, Izbicki JR, Reeh M. Does the margin matter in esophageal cancer. Dig Surg. 2018;35:196–203.CrossRef
12.
go back to reference Schlick CJR, Khorfan R, Odell DD, Merkow RP, Bentrem DJ. Margin positivity in resectable esophageal cancer: are there modifiable risk factors? Ann Surg Oncol. 2020;27:1496–507.CrossRef Schlick CJR, Khorfan R, Odell DD, Merkow RP, Bentrem DJ. Margin positivity in resectable esophageal cancer: are there modifiable risk factors? Ann Surg Oncol. 2020;27:1496–507.CrossRef
13.
go back to reference Klevebro F, Alexandersson von Dobeln G, Wang N, et al. A randomized clinical trial of neoadjuvant chemotherapy versus neoadjuvant chemoradiotherapy for cancer of the oesophagus or gastro-oesophageal junction. Ann Oncol. 2016;27:660–7.CrossRef Klevebro F, Alexandersson von Dobeln G, Wang N, et al. A randomized clinical trial of neoadjuvant chemotherapy versus neoadjuvant chemoradiotherapy for cancer of the oesophagus or gastro-oesophageal junction. Ann Oncol. 2016;27:660–7.CrossRef
14.
go back to reference Markar SR, Gronnier C, Duhamel A, et al. Significance of microscopically incomplete resection margin after esophagectomy for esophageal cancer. Ann Surg. 2016;263:712–8.CrossRef Markar SR, Gronnier C, Duhamel A, et al. Significance of microscopically incomplete resection margin after esophagectomy for esophageal cancer. Ann Surg. 2016;263:712–8.CrossRef
15.
go back to reference Lordick F, Mariette C, Haustermans K, Obermannova R, Arnold D, Committee EG. Oesophageal cancer: ESMO clinical practice guidelines for diagnosis, treatment, and follow-up. Ann Oncol. 2016;27(Suppl 5):v50–7.CrossRef Lordick F, Mariette C, Haustermans K, Obermannova R, Arnold D, Committee EG. Oesophageal cancer: ESMO clinical practice guidelines for diagnosis, treatment, and follow-up. Ann Oncol. 2016;27(Suppl 5):v50–7.CrossRef
16.
go back to reference Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004;240:205–13.CrossRef Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004;240:205–13.CrossRef
17.
go back to reference Mantziari S, Allemann P, Winiker M, Demartines N, Schafer M. Locoregional tumor extension and preoperative smoking are significant risk factors for early recurrence after esophagectomy for cancer. World J Surg. 2018;42:2209–17.CrossRef Mantziari S, Allemann P, Winiker M, Demartines N, Schafer M. Locoregional tumor extension and preoperative smoking are significant risk factors for early recurrence after esophagectomy for cancer. World J Surg. 2018;42:2209–17.CrossRef
18.
go back to reference Rice TW, Blackstone EH, Rusch VW. 7th edition of the AJCC cancer staging manual: esophagus and esophagogastric junction. Ann Surg Oncol. 2010;17:1721–4.CrossRef Rice TW, Blackstone EH, Rusch VW. 7th edition of the AJCC cancer staging manual: esophagus and esophagogastric junction. Ann Surg Oncol. 2010;17:1721–4.CrossRef
19.
go back to reference Rice TW, Gress DM, Patil DT, Hofstetter WL, Kelsen DP, Blackstone EH. Cancer of the esophagus and esophagogastric junction: major changes in the American joint committee on cancer eighth edition cancer staging manual. CA Cancer J Clin. 2017;67:304–17.CrossRef Rice TW, Gress DM, Patil DT, Hofstetter WL, Kelsen DP, Blackstone EH. Cancer of the esophagus and esophagogastric junction: major changes in the American joint committee on cancer eighth edition cancer staging manual. CA Cancer J Clin. 2017;67:304–17.CrossRef
20.
go back to reference Mandard AM, Dalibard F, Mandard JC, et al. Pathologic assessment of tumor regression after preoperative chemoradiotherapy of esophageal carcinoma: clinicopathologic correlations. Cancer. 1994;73:2680–6.CrossRef Mandard AM, Dalibard F, Mandard JC, et al. Pathologic assessment of tumor regression after preoperative chemoradiotherapy of esophageal carcinoma: clinicopathologic correlations. Cancer. 1994;73:2680–6.CrossRef
21.
go back to reference Chan DS, Reid TD, Howell I, Lewis WG. Systematic review and meta-analysis of the influence of circumferential resection margin involvement on survival in patients with operable oesophageal cancer. Br J Surg. 2013;100:456–64.CrossRef Chan DS, Reid TD, Howell I, Lewis WG. Systematic review and meta-analysis of the influence of circumferential resection margin involvement on survival in patients with operable oesophageal cancer. Br J Surg. 2013;100:456–64.CrossRef
22.
go back to reference Knight WRC, Zylstra J, Wulaningsih W, et al. Impact of incremental circumferential resection margin distance on overall survival and recurrence in oesophageal adenocarcinoma. BJS Open. 2018;2:229–37.CrossRef Knight WRC, Zylstra J, Wulaningsih W, et al. Impact of incremental circumferential resection margin distance on overall survival and recurrence in oesophageal adenocarcinoma. BJS Open. 2018;2:229–37.CrossRef
23.
go back to reference Verhage RJ, Zandvoort HJ, ten Kate FJ, van Hillegersberg R. How to define a positive circumferential resection margin in T3 adenocarcinoma of the esophagus. Am J Surg Pathol. 2011;35:919–26.CrossRef Verhage RJ, Zandvoort HJ, ten Kate FJ, van Hillegersberg R. How to define a positive circumferential resection margin in T3 adenocarcinoma of the esophagus. Am J Surg Pathol. 2011;35:919–26.CrossRef
24.
go back to reference von Dobeln GA, Klevebro F, Jacobsen AB, et al. Neoadjuvant chemotherapy versus neoadjuvant chemoradiotherapy for cancer of the esophagus or gastroesophageal junction: long-term results of a randomized clinical trial. Dis Esophagus. 2019;32(2). von Dobeln GA, Klevebro F, Jacobsen AB, et al. Neoadjuvant chemotherapy versus neoadjuvant chemoradiotherapy for cancer of the esophagus or gastroesophageal junction: long-term results of a randomized clinical trial. Dis Esophagus. 2019;32(2).
25.
go back to reference Depypere L, Moons J, Lerut T, et al. Prognostic value of the circumferential resection margin and its definitions in esophageal cancer patients after neoadjuvant chemoradiotherapy. Dis Esophagus. 2018;31. Depypere L, Moons J, Lerut T, et al. Prognostic value of the circumferential resection margin and its definitions in esophageal cancer patients after neoadjuvant chemoradiotherapy. Dis Esophagus. 2018;31.
26.
go back to reference O’Neill JR, Stephens NA, Save V, et al. Defining a positive circumferential resection margin in oesophageal cancer and its implications for adjuvant treatment. Br J Surg. 2013;100:1055–63.CrossRef O’Neill JR, Stephens NA, Save V, et al. Defining a positive circumferential resection margin in oesophageal cancer and its implications for adjuvant treatment. Br J Surg. 2013;100:1055–63.CrossRef
27.
go back to reference Ghadban T, Reeh M, Koenig AM, et al. Prognostic significant or not? The positive circumferential resection margin in esophageal cancer: impact on local recurrence and overall survival in patients without neoadjuvant treatment. Ann Surg. 2017;266:988–94.CrossRef Ghadban T, Reeh M, Koenig AM, et al. Prognostic significant or not? The positive circumferential resection margin in esophageal cancer: impact on local recurrence and overall survival in patients without neoadjuvant treatment. Ann Surg. 2017;266:988–94.CrossRef
28.
go back to reference Quinn LM, Hollis AC, Hodson J, et al. Prognostic significance of circumferential resection margin involvement in patients receiving potentially curative treatment for oesophageal cancer. Eur J Surg Oncol. 2018;44:1268–77.CrossRef Quinn LM, Hollis AC, Hodson J, et al. Prognostic significance of circumferential resection margin involvement in patients receiving potentially curative treatment for oesophageal cancer. Eur J Surg Oncol. 2018;44:1268–77.CrossRef
29.
go back to reference Sagar PM, Johnston D, McMahon MJ, Dixon MF, Quirke P. Significance of circumferential resection margin involvement after oesophagectomy for cancer. Br J Surg. 1993;80:1386–8.CrossRef Sagar PM, Johnston D, McMahon MJ, Dixon MF, Quirke P. Significance of circumferential resection margin involvement after oesophagectomy for cancer. Br J Surg. 1993;80:1386–8.CrossRef
30.
go back to reference Cabau M, Luc G, Terrebonne E, et al. Lymph node invasion might have more prognostic impact than R status in advanced esophageal adenocarcinoma. Am J Surg. 2013;205:711–7.CrossRef Cabau M, Luc G, Terrebonne E, et al. Lymph node invasion might have more prognostic impact than R status in advanced esophageal adenocarcinoma. Am J Surg. 2013;205:711–7.CrossRef
31.
go back to reference Hulshoff JB, Faiz Z, Karrenbeld A, et al. Prognostic value of the circumferential resection margin in esophageal cancer patients after neoadjuvant chemoradiotherapy. Ann Surg Oncol. 2015;22(Suppl 3):S1301–9.CrossRef Hulshoff JB, Faiz Z, Karrenbeld A, et al. Prognostic value of the circumferential resection margin in esophageal cancer patients after neoadjuvant chemoradiotherapy. Ann Surg Oncol. 2015;22(Suppl 3):S1301–9.CrossRef
32.
go back to reference Nagtegaal ID, Marijnen CA, Kranenbarg EK, et al. Circumferential margin involvement is still an important predictor of local recurrence in rectal carcinoma: not one millimeter but two millimeters is the limit. Am J Surg Pathol. 2002;26:350–7.CrossRef Nagtegaal ID, Marijnen CA, Kranenbarg EK, et al. Circumferential margin involvement is still an important predictor of local recurrence in rectal carcinoma: not one millimeter but two millimeters is the limit. Am J Surg Pathol. 2002;26:350–7.CrossRef
33.
go back to reference Agger EA, Jorgren FH, Lydrup MA, Buchwald PL. Risk of local recurrence of rectal cancer and circumferential resection margin: population-based cohort study. Br J Surg. 2020;107:580–5.CrossRef Agger EA, Jorgren FH, Lydrup MA, Buchwald PL. Risk of local recurrence of rectal cancer and circumferential resection margin: population-based cohort study. Br J Surg. 2020;107:580–5.CrossRef
Metadata
Title
The “Real R0”: A Resection Margin Smaller Than 0.1 cm is Associated with a Poor Prognosis After Oncologic Esophagectomy
Authors
Penelope St-Amour, MD
Michael Winiker, MD
Christine Sempoux, MD, PhD
François Fasquelle, MD
Nicolas Demartines, MD, FACS, FRCS, FCCS (Hon)
Markus Schäfer, MD, FACS
Styliani Mantziari, MD, MSc, PD
Publication date
01-11-2021
Publisher
Springer International Publishing
Published in
Annals of Surgical Oncology / Issue 12/2021
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-021-10121-y

Other articles of this Issue 12/2021

Annals of Surgical Oncology 12/2021 Go to the issue