Abstract
Purpose and Design
Esophageal adenocarcinoma (EAC) develops as a consequence of gastroesophageal reflux disease and Barrett’s esophagus (BE). While combination therapy with chemotherapy or concurrent chemoradiotherapy followed by esophagectomy improves survival in more advanced tumors, the optimal treatment strategy for early-stage EAC is undefined. Endoscopic eradication therapy, consisting of endoscopic resection and mucosal ablation, has revolutionized therapy for superficial (T1a) EAC in BE and allows for esophageal preservation in appropriate patients at low risk for lymph node metastasis (LNM). This review critically examines the literature regarding evaluation, treatment, and outcomes in patients with T1 EAC.
Methods
The literature was queried via the PubMed database to include articles published between 1990 and 2017. Search terms were generated from the key statements “Endoscopic eradication therapy results in equivalent overall survival when compared to esophagectomy for clinical T1aN0 EAC” and “Esophagectomy provides better overall survival than endoscopic eradication therapy for cT1b EAC”. Abstracts were reviewed and included according to predefined selection and exclusion criteria, and were then assessed according to the GRADE system.
Results and Conclusions
In patients with T1aN0 EAC, overall survival with endoscopic eradication therapy is equal to esophagectomy. Given the substantial risk of LNM in patients with submucosal (T1b) EAC, esophagectomy remains the standard of care for surgical candidates. In the case of inoperability or low-risk lesions, endoscopic resection may be considered adequate therapy. Chemotherapy and radiation can be offered as primary therapy for non-surgical candidates with lesions not amenable to endoscopic therapy, but does not have a clear role in the adjuvant setting after either endoscopic or surgical resection.
References
Cunningham D, Allum WH, Stenning SP, et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006;355(1):11–20.
Shapiro J, van Lanschot JJ, Hulshof MC, et al. Neoadjuvant chemoradiotherapy plus surgery versus surgery alone for oesophageal or junctional cancer (CROSS): long-term results of a randomised controlled trial. Lancet Oncol. 2015;16(9):1090–98.
Pech O, May A, Manner H, et al. Long-term efficacy and safety of endoscopic resection for patients with mucosal adenocarcinoma of the esophagus. Gastroenterology. 2014;146(3):652–660 e651.
Ancona E, Rampado S, Cassaro M, et al. Prediction of lymph node status in superficial esophageal carcinoma. Ann Surg Oncol. 2008;15(11):3278–88.
Bogoevski D, Bockhorn M, Koenig A, et al. How radical should surgery be for early esophageal cancer? World J Surg. 2011;35(6):1311–20.
Bolton WD, Hofstetter WL, Francis AM, et al. Impact of tumor length on long-term survival of pT1 esophageal adenocarcinoma. J Thorac Cardiovasc Surg. 2009;138(4):831–36.
Dunbar KB, Spechler SJ. The risk of lymph-node metastases in patients with high-grade dysplasia or intramucosal carcinoma in Barrett’s esophagus: a systematic review. Am J Gastroenterol. 2012;107(6):850–62 (quiz 863).
Estrella JS, Hofstetter WL, Correa AM, et al. Duplicated muscularis mucosae invasion has similar risk of lymph node metastasis and recurrence-free survival as intramucosal esophageal adenocarcinoma. Am J Surg Pathol. 2011;35(7):1045–53.
Leers JM, DeMeester SR, Oezcelik A, et al. The prevalence of lymph node metastases in patients with T1 esophageal adenocarcinoma a retrospective review of esophagectomy specimens. Ann Surg. 2011;253(2):271–78.
Lorenz D, Origer J, Pauthner M, et al. Prognostic risk factors of early esophageal adenocarcinomas. Ann Surg. 2014;259(3):469–76.
Rice TW, Blackstone EH, Goldblum JR, et al. Superficial adenocarcinoma of the esophagus. J Thorac Cardiovasc Surg. 2001;122(6):1077–90.
Sepesi B, Watson TJ, Zhou D, et al. Are endoscopic therapies appropriate for superficial submucosal esophageal adenocarcinoma? An analysis of esophagectomy specimens. J Am Coll Surg. 2010;210(4):418–27.
Stein HJ, Feith M, Bruecher BL, Naehrig J, Sarbia M, Siewert JR. Early esophageal cancer: pattern of lymphatic spread and prognostic factors for long-term survival after surgical resection. Ann Surg. 2005;242(4):566–73 (discussion 573–565).
Stein HJ, Feith M, Mueller J, Werner M, Siewert JR. Limited resection for early adenocarcinoma in Barrett’s esophagus. Ann Surg. 2000;232(6):733–42.
Westerterp M, Koppert LB, Buskens CJ, et al. Outcome of surgical treatment for early adenocarcinoma of the esophagus or gastro-esophageal junction. Virchows Arch. 2005;446(5):497–04.
Dhupar R, Rice RD, Correa AM, et al. endoscopic ultrasound estimates for tumor depth at the gastroesophageal junction are inaccurate: implications for the liberal use of endoscopic resection. Ann Thorac Surg. 2015;100(5):1812–16.
McDonough PB, Jones DR, Shen KR, et al. Does FDG-PET add information to EUS and CT in the initial management of esophageal cancer? A prospective single center study. Am J Gastroenterol. 2008;103(3):570–74.
Pouw RE, Heldoorn N, Alvarez Herrero L, et al. Do we still need EUS in the workup of patients with early esophageal neoplasia? A retrospective analysis of 131 cases. Gastrointest Endosc. 2011;73(4):662–68.
Rampado S, Bocus P, Battaglia G, Ruol A, Portale G, Ancona E. Endoscopic ultrasound: accuracy in staging superficial carcinomas of the esophagus. Ann Thorac Surg. 2008;85(1):251–56.
Prasad GA, Wu TT, Wigle DA, et al. Endoscopic and surgical treatment of mucosal (T1a) esophageal adenocarcinoma in Barrett’s esophagus. Gastroenterology. 2009;137(3):815–23.
Schunemann HJ, Oxman AD, Brozek J, et al. Grading quality of evidence and strength of recommendations for diagnostic tests and strategies. BMJ. 2008;336(7653):1106–10.
Zehetner J, DeMeester SR, Hagen JA, et al. Endoscopic resection and ablation versus esophagectomy for high-grade dysplasia and intramucosal adenocarcinoma. J Thorac Cardiovasc Surg. 2011;141(1):39–47.
Barbour AP, Jones M, Brown I, et al. Risk stratification for early esophageal adenocarcinoma: analysis of lymphatic spread and prognostic factors. Ann Surg Oncol. 2010;17(9):2494–02.
Kaneshiro DK, Post JC, Rybicki L, Rice TW, Goldblum JR. Clinical significance of the duplicated muscularis mucosae in Barrett esophagus-related superficial adenocarcinoma. Am J Surg Pathol. 2011;35(5):697–700.
Kauppi J, Gockel I, Rantanen T, et al. Cause of death during long-term follow-up for superficial esophageal adenocarcinoma. Ann Surg Oncol. 2013;20(7):2428–33.
Ngamruengphong S, Wolfsen HC, Wallace MB. Survival of patients with superficial esophageal adenocarcinoma after endoscopic treatment vs surgery. Clin Gastroenterol Hepatol. 2013;11(11):1424–1429 e1422 (quiz e1481).
Nurkin SJ, Nava HR, Yendamuri S, et al. Outcomes of endoscopic resection for high-grade dysplasia and esophageal cancer. Surg Endosc. 2014;28(4):1090–95.
Oh DS, Hagen JA, Chandrasoma PT, et al. Clinical biology and surgical therapy of intramucosal adenocarcinoma of the esophagus. J Am Coll Surg. 2006;203(2):152–61.
Pech O, Bollschweiler E, Manner H, Leers J, Ell C, Holscher AH. Comparison between endoscopic and surgical resection of mucosal esophageal adenocarcinoma in Barrett’s esophagus at two high-volume centers. Ann Surg. 2011;254(1):67–72.
Peyre CG, DeMeester SR, Rizzetto C, et al. Vagal-sparing esophagectomy: the ideal operation for intramucosal adenocarcinoma and barrett with high-grade dysplasia. Ann Surg. 2007;246(4):665–71 (discussion 671–664).
Saha AK, Sutton CD, Sue-Ling H, Dexter SP, Sarela AI. Comparison of oncological outcomes after laparoscopic transhiatal and open esophagectomy for T1 esophageal adenocarcinoma. Surg Endosc. 2009;23(1):119–24.
Wu J, Pan YM, Wang TT, Gao DJ, Hu B. Endotherapy versus surgery for early neoplasia in Barrett’s esophagus: a meta-analysis. Gastrointest Endosc. 2014;79(2):233–241 e232.
Manner H, Wetzka J, May A, et al. Early-stage adenocarcinoma of the esophagus with mid to deep submucosal invasion (pT1b sm2-3): the frequency of lymph-node metastasis depends on macroscopic and histological risk patterns. Dis Esophagus. 2017;30(3):1–11.
Cummings LC, Kou TD, Schluchter MD, Chak A, Cooper GS. Outcomes after endoscopic versus surgical therapy for early esophageal cancers in an older population. Gastrointest Endosc. 2016;84(2):232–240.e1.
Schmidt HM, Mohiuddin K, Bodnar AM, et al. Multidisciplinary treatment of T1a adenocarcinoma in Barrett’s esophagus: contemporary comparison of endoscopic and surgical treatment in physiologically fit patients. Surg Endosc. 2016;30(8):3391–01.
Pech O, Gossner L, May A, et al. Long-term results of photodynamic therapy with 5-aminolevulinic acid for superficial Barrett’s cancer and high-grade intraepithelial neoplasia. Gastrointest Endosc. 2005;62(1):24–30.
Sgourakis G, Gockel I, Lang H. Endoscopic and surgical resection of T1a/T1b esophageal neoplasms: a systematic review. World J Gastroenterol. 2013;19(9):1424–37.
Pech O, Behrens A, May A, et al. Long-term results and risk factor analysis for recurrence after curative endoscopic therapy in 349 patients with high-grade intraepithelial neoplasia and mucosal adenocarcinoma in Barrett’s oesophagus. Gut. 2008;57(9):1200–06.
Shaheen NJ, Falk GW, Iyer PG, Gerson LB, American College of Gastroenterology. ACG clinical guideline: diagnosis and management of Barrett’s esophagus. Am J Gastroenterol. 2016;111(1):30–50 (quiz 51).
Ramay FH, Cui Q, Greenwald BD. Outcomes after liquid nitrogen spray cryotherapy in Barrett’s esophagus-associated high-grade dysplasia and intramucosal adenocarcinoma: 5-year follow-up. Gastrointest Endosc. 2017;86(4):626–32.
Tsai FC, Ghorbani S, Greenwald BD, et al. Safety and efficacy of endoscopic spray cryotherapy for esophageal cancer. Dis Esophagus. 2017;30(11):1–7.
Neuhaus H, Terheggen G, Rutz EM, Vieth M, Schumacher B. Endoscopic submucosal dissection plus radiofrequency ablation of neoplastic Barrett’s esophagus. Endoscopy. 2012;44(12):1105–13.
Probst A, Aust D, Markl B, Anthuber M, Messmann H. Early esophageal cancer in Europe: endoscopic treatment by endoscopic submucosal dissection. Endoscopy. 2015;47(2):113–21.
Chevaux JB, Piessevaux H, Jouret-Mourin A, Yeung R, Danse E, Deprez PH. Clinical outcome in patients treated with endoscopic submucosal dissection for superficial Barrett’s neoplasia. Endoscopy. 2015;47(2):103–12.
Hobel S, Dautel P, Baumbach R, et al. Single center experience of endoscopic submucosal dissection (ESD) in early Barrett’s adenocarcinoma. Surg Endosc. 2015;29(6):1591–97.
Barret M, Cao DT, Beuvon F, et al. Endoscopic submucosal dissection for early Barrett’s neoplasia. United European Gastroenterol J. 2016;4(2):207–15.
Yang D, Coman RM, Kahaleh M, et al. Endoscopic submucosal dissection for Barrett’s early neoplasia: a multicenter study in the United States. Gastrointest Endosc. 2017;86(4):600–07.
Coman RM, Gotoda T, Forsmark CE, Draganov PV. Prospective evaluation of the clinical utility of endoscopic submucosal dissection (ESD) in patients with Barrett’s esophagus: a Western center experience. Endosc Int Open. 2016;4(6):E715–721.
Terheggen G, Horn EM, Vieth M, et al. A randomised trial of endoscopic submucosal dissection versus endoscopic mucosal resection for early Barrett’s neoplasia. Gut. 2017;66(5):783–93.
Cao Y, Liao C, Tan A, Gao Y, Mo Z, Gao F. Meta-analysis of endoscopic submucosal dissection versus endoscopic mucosal resection for tumors of the gastrointestinal tract. Endoscopy. 2009;41(9):751–57.
Badreddine RJ, Prasad GA, Lewis JT, et al. Depth of submucosal invasion does not predict lymph node metastasis and survival of patients with esophageal carcinoma. Clin Gastroenterol Hepatol. 2010;8(3):248–53.
Sihag S, Kosinski AS, Gaissert HA, Wright CD, Schipper PH. Minimally invasive versus open esophagectomy for esophageal cancer: a comparison of early surgical outcomes from the society of thoracic surgeons national database. Ann Thorac Surg. 2016;101(4):1281–89.
Manner H, Pech O, Heldmann Y, et al. Efficacy, safety, and long-term results of endoscopic treatment for early stage adenocarcinoma of the esophagus with low-risk sm1 invasion. Clin Gastroenterol Hepatol. 2013;11(6):630–35 (quiz e645).
Tian J, Prasad GA, Lutzke LS, Lewis JT, Wang KK. Outcomes of T1b esophageal adenocarcinoma patients. Gastrointest Endosc. 2011;74(6):1201–06.
The Paris endoscopic classification of superficial neoplastic lesions: esophagus, stomach, and colon: November 30 to December 1, 2002. Gastrointest Endosc. 2003;58(6 Suppl):S3–43.
Gaur P, Sepesi B, Hofstetter WL, et al. A clinical nomogram predicting pathologic lymph node involvement in esophageal cancer patients. Ann Surg. 2010;252(4):611–17.
Gertler R, Stein HJ, Schuster T, Rondak IC, Hofler H, Feith M. Prevalence and topography of lymph node metastases in early esophageal and gastric cancer. Ann Surg. 2014;259(1):96–01.
Lee L, Ronellenfitsch U, Hofstetter WL, et al. Predicting lymph node metastases in early esophageal adenocarcinoma using a simple scoring system. J Am Coll Surg. 2013;217(2):191–99.
The National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology-Esophageal and Esophagogastric Junction Cancers. 2017; Version 1.2017.
Funding
Research reported in this publication was supported by the University of Maryland under Award No. T32DK067872 (FR). The content is solely the responsibility of the authors and does not necessarily reflect the views of the National Institutes of Health.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
DISCLOSURE
Fariha H. Ramay, Ashley A. Vareedayah, Kavel Visrodia, Prasad G. Iyer, Kenneth K. Wang, Swathi Eluri, Nicholas J. Shaheen, Rishindra Reddy, Linda W. Martin, Bruce D. Greenwald, and Melanie A. Edwards have no conflicts of interest to disclose.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Ramay, F.H., Vareedayah, A.A., Visrodia, K. et al. What Constitutes Optimal Management of T1N0 Esophageal Adenocarcinoma?. Ann Surg Oncol 26, 714–731 (2019). https://doi.org/10.1245/s10434-018-07118-5
Received:
Published:
Issue Date:
DOI: https://doi.org/10.1245/s10434-018-07118-5