Abstract
Traditionally, surgery is considered the best treatment for esophageal cancer in terms of locoregional control and long-term survival, but survival after surgery alone for locally advanced esophageal cancer is not satisfactory. A multidisciplinary approach that includes surgery, radiotherapy, and chemotherapy, alone or in combination, has been developed to improve the prognosis. Multiple clinical trials have addressed the preferred treatment strategy, such as neoadjuvant or adjuvant and chemotherapy, radiotherapy, or chemoradiotherapy, in managing locally advanced esophageal cancer. In this review, we provide an update on treatment strategies for locally advanced esophageal cancers. Recent studies indicate that neoadjuvant chemoradiotherapy or chemotherapy has a survival benefit over surgery alone in this patient group. Neoadjuvant chemoradiotherapy is an accepted standard of care in the United States while neoadjuvant chemotherapy is regarded as standard treatment in Japan and the United Kingdom. The standard treatment differs among countries because two large randomized controlled trials that evaluated the effectiveness of neoadjuvant chemotherapy reported conflicting results and no trial has made a comparison between neoadjuvant chemoradiotherapy and neoadjuvant chemotherapy directly. Future trials in locally advanced esophageal cancer should focus on identifying the optimum strategy and its regimen and aim to minimize treatment toxicities and effects on quality of life.
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Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61(2):69–90.
Matsuda A, Matsuda T, Shibata A, Katanoda K, Sobue T, Nishimoto H, The Japan Cancer Surveillance Research Group. Cancer incidence and incidence rates in Japan in 2007: a study of 21 population-based cancer registries for the monitoring of cancer incidence in Japan (MCIJ) project. Jpn J Clin Oncol. 2013;43(3):328–336.
Allum WH, Stenning SP, Bancewicz J, Clark PI, Langley RE. Longterm results of a randomized trial of surgery with or without preoperative chemotherapy in esophageal cancer. J Clin Oncol. 2009;27(30):5062–7.
Rutegård M, Charonis K, Lu Y, Lagergren P, Lagergren J, Rouvelas I. Population-based esophageal cancer survival after resection without neoadjuvant therapy: an update. Surgery. 2012;152(5):903–10.
Ando N, Iizuka T, Ide H, Ishida K, Shinoda M, Nishimaki T, et al. Surgery plus chemotherapy compared with surgery alone for localized squamous cell carcinoma of the thoracic esophagus: a Japan Clinical Oncology Group Study—JCOG9204. J Clin Oncol. 2003;21:4592–6.
Kunath U, Fischer P. Radical nature and life expectancy in the surgical treatment of esophageal and cardial carcinoma. Dtsch Med Wochenschr. 1984;109:450–3.
Ténière P, Hay JM, Fingerhut A, Fagniez PL. Postoperative radiation therapy does not increase survival after curative resection for squamous cell carcinoma of the middle and lower esophagus as shown by a multicenter controlled trial. French University Association for Surgical Research. Surg Gynecol Obstet. 1991;173:123–30.
Fok M, Sham JS, Choy D, Cheng SW, Wong J. Postoperative radiotherapy for carcinoma of the esophagus: a prospective, randomized controlled study. Surgery. 1993;113:138–47.
Zieren HU, Müller JM, Jacobi CA, Pichlmaier H, Müller RP, Staar S. Adjuvant postoperative radiation therapy after curative resection of squamous cell carcinoma of the thoracic esophagus: a prospective randomized study. World J Surg. 1995;19:444–9.
Xiao ZF, Yang ZY, Liang J, Miao YJ, Wang M, Yin WB, et al. Value of radiotherapy after radical surgery for esophageal carcinoma: a report of 495 patients. Ann Thorac Surg. 2003;75:331–6.
Pouliquen X, Levard H, Hay JM, McGee K, Fingerhut A, Langlois-Zantin O. 5-Fluorouracil and cisplatin therapy after palliative surgical resection of squamous cell carcinoma of the esophagus. A multicenter randomized trial. French Associations for Surgical Research. Ann Surg. 1996;223:127–33.
Ando N, Iizuka T, Kakegawa T, Lsono K, Watanabe H, Lde H, et al. A randomized trial of surgery with and without chemotherapy for localized squamous carcinoma of the thoracic esophagus: the Japan Clinical Oncology Group Study. J Thorac Cardiovasc Surg. 1997;114:205–9.
Macdonald JS, Smalley SR, Benedetti J, Hundahl SA, Estes NC, Stemmermann GN, et al. Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med. 2001;345(10):725–30.
Tachibana M, Yoshimura H, Kinugasa S, Shibakita M, Dhar DK, Ueda S, et al. Postoperative chemotherapy vs chemoradiotherapy for thoracic esophageal cancer: a prospective randomized clinical trial. Eur J Surg Oncol. 2003;29(7):580–7.
Launois B, Delarue D, Campion JP, Kerbaol M. Preoperative radiotherapy for carcinoma of the esophagus. Surg Gynecol Obstet. 1981;153:690–2.
Gignoux M, Roussel A, Paillot B, Gillet M, Schlag P, Favre JP, et al. The value of preoperative radiotherapy in esophageal cancer: results of a study by the EORTC. World J Surg. 1987;11:426–32.
Wang M, Gu XZ, Yin WB, Huang GJ, Wang LJ, Zhang DW. Randomized clinical trial on the combination of preoperative irradiation and surgery in the treatment of esophageal carcinoma: report on 206 patients. Int J Radiat Oncol Biol Phys. 1989;16:325–7.
Arnott SJ, Duncan W, Kerr GR, Walbaum PR, Cameron E, Jack WJ, et al. Low dose preoperative radiotherapy for carcinoma of the oesophagus: results of a randomized clinical trial. Radiother Oncol. 1992;24:108–13.
Nygaard K, Hagen S, Hansen HS, Hatlevoll R, Hultborn R, Jakobsen A, et al. Pre-operative radiotherapy prolongs survival in operable esophageal carcinoma: a randomized, multicenter study of pre-operative radiotherapy and chemotherapy. The second Scandinavian trial in esophageal cancer. World J Surg. 1992;16:1104–9 discussion 1110.
Arnott SJ, Duncan W, Gignoux M, Girling DJ, Hansen HS, Launois B, et al. Preoperative radiotherapy for esophageal carcinoma. Cochrane Database Syst Rev. 2005;4:CD001799.
Schlag PM. Randomized trial of preoperative chemotherapy for squamous cell cancer of the esophagus. The Chirurgische Arbeitsgemeinschaft Fuer Onkologie der Deutschen Gesellschaft Fuer Chirurgie Study Group. Arch Surg. 1992;127:1446–50.
Maipang T, Vasinanukorn P, Petpichetchian C, Chamroonkul S, Geater A, Chansawwaang S, et al. Induction chemotherapy in the treatment of patients with carcinoma of the esophagus. J Surg Oncol. 1994;56:191–7.
Law S, Fok M, Chow S, Chu KM, Wong J. Preoperative chemotherapy versus surgical therapy alone for squamous cell carcinoma of the esophagus: a prospective randomized trial. J Thorac Cardiovasc Surg. 1997;114:210–7.
Boonstra JJ, Kok TC, Wijnhoven BP, van Heijl M, van Berge Henegouwen MI, Ten Kate FJ, et al. Chemotherapy followed by surgery versus surgery alone in patients with oesophageal squamous cell carcinoma: long-term results of a randomized controlled trial. BMC Cancer. 2011;11:181.
Kelsen DP, Winter KA, Gunderson LL, Mortimer J, Estes NC, Haller DG, Radiation Therapy Oncology Group, USA Intergroup, et al. Long-term results of RTOG trial 8911 (USA Intergroup 113): a random assignment trial comparison of chemotherapy followed by surgery compared with surgery alone for esophageal cancer. J Clin Oncol. 2007;25:3719–25.
Ancona E, Ruol A, Santi S, Merigliano S, Sileni VC, Koussis H, et al. Only pathologic complete response to neoadjuvant chemotherapy improves significantly the long term survival of patients with resectable esophageal squamous cell carcinoma: final report of a randomized, controlled trial of preoperative chemotherapy versus surgery alone. Cancer. 2001;91:2165–74.
Ychou M, Boige V, Pignon JP, Conroy T, Bouché O, Lebreton G, 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.
Ando N, Kato H, Igaki H, Shinoda M, Ozawa S, Shimizu H, et al. A randomized trial comparing postoperative adjuvant chemotherapy with cisplatin and 5-fluorouracil versus preoperative chemotherapy for localized advanced squamous cell carcinoma of the thoracic esophagus (JCOG9907). Ann Surg Oncol. 2012;19(1):68–74.
Sjoquist KM, Burmeister BH, Smithers BM, Zalcberg JR, Simes RJ, Barbour A, et al. Survival after neoadjuvant chemotherapy or chemoradiotherapy for resectable oesophageal carcinoma: an updated meta-analysis. Lancet Oncol. 2011;12:681–92.
Walsh TN, Noonan N, Hollywood D, Kelly A, Keeling N, Hennessy TP. A comparison of multimodal therapy and surgery for esophageal adenocarcinoma. N Engl J Med. 1996;335(7):462–7.
Bosset JF, Gignoux M, Triboulet JP, Tiret E, Mantion G, Elias D, et al. Chemoradiotherapy followed by surgery compared with surgery alone in squamous-cell cancer of the esophagus. N Engl J Med. 1997;337:161–7.
Urba SG, Orringer MB, Turrisi A, Iannettoni M, Forastiere A, Strawderman M. Randomized trial of preoperative chemoradiation versus surgery alone in patients with locoregional esophageal carcinoma. J Clin Oncol. 2001;19(2):305–13.
Lee JL, Park SI, Kim SB, Jung HY, Lee GH, Kim JH, et al. A single institutional phase III trial of preoperative chemotherapy with hyperfractionation radiotherapy plus surgery versus surgery alone for resectable esophageal squamous cell carcinoma. Ann Oncol. 2004;15:947–54.
Burmeister BH, Smithers BM, Gebski V, Fitzgerald L, Simes RJ, Devitt P, et al. Surgery alone versus chemoradiotherapy followed by surgery for resectable cancer of the oesophagus: a randomised controlled phase III trial. Lancet Oncol. 2005;6:659–68.
Tepper J, Krasna MJ, Niedzwiecki D, Hollis D, Reed CE, Goldberg R, et al. Phase III trial of trimodality therapy with cisplatin, fluorouracil, radiotherapy, and surgery compared with surgery alone for esophageal cancer: CALGB 9781. J Clin Oncol. 2008;26:1086–92.
Mariette C, Seitz JF, Maillard E. Impact of neoadjuvant chemoradiation in localized esophageal cancer: results of a randomized, controlled phase III trial. FFCD 9901 (abstract 8000). In: Proceedings of the 35th ESMO Congress. Milan, 2010.
van Hagen P, Hulshof MC, van Lanschot JJ, Steyerberg EW, van Berge Henegouwen MI, Wijnhoven BP, et al. Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med. 2012;366(22):2074–84.
Burmeister BH, Thomas JM, Burmeister EA, Walpole ET, Harvey JA, Thomson DB, et al. Is concurrent radiation therapy required in patients receiving preoperative chemotherapy for adenocarcinoma of the oesophagus? A randomised phase II trial. Eur J Cancer. 2011;47(3):354–60.
Stahl M, Walz MK, Stuschke M, Lehmann N, Meyer HJ, Riera-Knorrenschild J, et al. Phase III comparison of preoperative chemotherapy compared with chemoradiotherapy in patients with locally advanced adenocarcinoma of the esophagogastric junction. J Clin Oncol. 2009;27(6):851–6.
Hulscher JB, van Sandick JW, de Boer AG, Wijnhoven BP, Tijssen JG, Fockens P, et al. Extended transthoracic resection compared with limited transhiatal resection for adenocarcinoma of the esophagus. N Engl J Med. 2002;347:1662–9.
Omloo JM, Lagarde SM, Hulscher JB, Reitsma JB, Fockens P, van Dekken H, et al. Extended transthoracic resection compared with limited transhiatal resection for adenocarcinoma of the mid/distal esophagus: five-year survival of a randomized clinical trial. Ann Surg. 2007;246(6):992–1000.
Yekebas EF, Schurr PG, Kaifi JT, Link BC, Kutup A, Mann O, et al. Effectiveness of radical en-bloc-esophagectomy compared to transhiatal esophagectomy in squamous cell cancer of the esophagus is influenced by nodal micrometastases. J Surg Oncol. 2006;93(7):541–9.
Horstmann O, Verreet PR, Becker H, Ohmann C, Röher HD. Transhiatal oesophagectomy compared with transthoracic resection and systematic lymphadenectomy for the treatment of oesophageal cancer. Eur J Surg. 1995;161(8):557–67.
Boshier PR, Anderson O, Hanna GB. Transthoracic versus transhiatal esophagectomy for the treatment of esophagogastric cancer: a meta-analysis. Ann Surg. 2011;254(6):894–906.
Uzunoglu FG, Reeh M, Kutup A, Izbicki JR. Surgery of esophageal cancer. Langenbecks Arch Surg. 2013;398(2):189–93.
Hirao M, Ando N, Tsujinaka T, Udagawa H, Yano M, Yamana H, et al. Influence of preoperative chemotherapy for advanced thoracic oesophageal squamous cell carcinoma on perioperative complications. Br J Surg. 2011;98(12):1735–41.
Cunningham D, Allum WH, Stenning SP, Thompson JN, Van de Velde CJ, Nicolson M, et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006;355(1):11–20.
Van Cutsem E, Moiseyenko VM, Tjulandin S, Majlis A, Constenla M, Boni C, V325 Study Group, et al. Phase III study of docetaxel and cisplatin plus fluorouracil compared with cisplatin and fluorouracil as first-line therapy for advanced gastric cancer: a report of the V325 Study Group. J Clin Oncol. 2006;24(31):4991–7.
Vermorken JB, Remenar E, van Herpen C, Gorlia T, Mesia R, Degardin M, EORTC 24971/TAX 323 Study Group, et al. Cisplatin, fluorouracil, and docetaxel in unresectable head and neck cancer. N Engl J Med. 2007;357(17):1695–704.
Posner MR, Hershock DM, Blajman CR, Mickiewicz E, Winquist E, Gorbounova V, TAX 324 Study Group, et al. Cisplatin and fluorouracil alone or with docetaxel in head and neck cancer. N Engl J Med. 2007;357(17):1705–15.
Yamasaki M, Miyata H, Tanaka K, Shiraishi O, Motoori M, Peng YF, et al. Multicenter phase I/II study of docetaxel, cisplatin and fluorouracil combination chemotherapy in patients with advanced or recurrent squamous cell carcinoma of the esophagus. Oncology. 2011;80(5–6):307–13.
Pasini F, de Manzoni G, Zanoni A, Grandinetti A, Capirci C, Pavarana M, et al. Neoadjuvant therapy with weekly docetaxel and cisplatin, 5-fluorouracil continuous infusion, and concurrent radiotherapy in patients with locally advanced esophageal cancer produced a high percentage of long-lasting pathological complete response: a phase 2 study. Cancer. 2013;119(5):939–45.
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Yamasaki, M., Miyata, H., Miyazaki, Y. et al. Perioperative therapy for esophageal cancer. Gen Thorac Cardiovasc Surg 62, 531–540 (2014). https://doi.org/10.1007/s11748-014-0458-y
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DOI: https://doi.org/10.1007/s11748-014-0458-y