Abstract
Background
In 2013, roughly 18,000 cases of esophageal cancer will be diagnosed in the United States with more than 15,000 people dying from the disease. Worldwide, an estimated 482,300 new esophageal cancer cases were diagnosed with 406,800 deaths in 2008. Squamous cell carcinoma (SCC) and adenocarcinoma (AC) account for >90 % of all esophageal cancer cases.
Methods
The authors will examine the role of radiation therapy, chemotherapy, and surgery in the curative management of esophageal cancer by examining randomized control data, single arm phase II trials, several recently published meta-analyses, as well as retrospective data where there is no clinical trial data available. The role of positron emission tomography (PET) will be reviewed as well.
Results
Current data support the role of neoadjuvant chemoradiotherapy followed by surgical resection for locally advanced esophageal cancer with 3-year overall survival ranging from 30 % to 60 %. The benefit of adjuvant chemoradiation therapy is limited to margin positive and/or node positive patients. There is emerging data questioning the survival benefit of surgical resection after chemoradiotherapy. External beam radiation therapy alone results in very few long-term survivors and is considered palliative at best. Radiation dose-escalation has failed to improve local control or survival. PET scanning is vital in staging and has become a strong predictor of response and survival.
Conclusions
Preoperative or definitive concurrent chemoradiotherapy is the established standard of care for locally advanced cancers of the esophagus. While preoperative chemotherapy is supported by level 1 evidence, the true benefit of induction chemotherapy before chemoradiotherapy has not been established in a prospective randomized control trial. The role of surgery in the management of SCC is still a hotly debated subject, however, it is still recommended for AC. There is no data to support adjuvant chemotherapy after preoperative chemoradiotherapy. The benefit of neoadjuvant chemotherapy seems to be limited AC. Radiation without chemotherapy is palliative and never curative. PET continues to be integrated into treatment decisions and predicts for response and survival after therapy.
Similar content being viewed by others
References
Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin. 2013;63(1):11–30.
Cooper JS et al. Chemoradiotherapy of locally advanced esophageal cancer: long-term follow-up of a prospective randomized trial (RTOG 85–01). Radiation Therapy Oncology Group. JAMA. 1999;281(17):1623–7.
Herskovic A et al. Combined chemotherapy and radiotherapy compared with radiotherapy alone in patients with cancer of the esophagus. N Engl J Med. 1992;326(24):1593–8.
Gebski V et al. Survival benefits from neoadjuvant chemoradiotherapy or chemotherapy in oesophageal carcinoma: a meta-analysis. Lancet Oncol. 2007;8(3):226–34.
Jin HL et al. Neoadjuvant chemoradiotherapy for resectable esophageal carcinoma: a meta-analysis. World J Gastroenterol. 2009;15(47):5983–91.
Urschel JD, Vasan H. A meta-analysis of randomized controlled trials that compared neoadjuvant chemoradiation and surgery to surgery alone for resectable esophageal cancer. Am J Surg. 2003;185(6):538–43.
Fiorica F et al. Preoperative chemoradiotherapy for oesophageal cancer: a systematic review and meta-analysis. Gut. 2004;53(7):925–30.
Sjoquist KM et al. Survival after neoadjuvant chemotherapy or chemoradiotherapy for resectable oesophageal carcinoma: an updated meta-analysis. Lancet Oncol. 2011;12(7):681–92.
Kranzfelder M et al. Meta-analysis of neoadjuvant treatment modalities and definitive non-surgical therapy for oesophageal squamous cell cancer. Br J Surg. 2011;98(6):768–83.
John MJ et al. Radiotherapy alone and chemoradiation for nonmetastatic esophageal carcinoma. A critical review of chemoradiation. Cancer. 1989;63(12):2397–403.
Raman NV, Small Jr W. The role of radiation therapy in the management of esophageal cancer. Cancer Control. 1999;6(1):53–62.
Sykes AJ et al. Radical radiotherapy for carcinoma of the oesophagus: an effective alternative to surgery. Radiother Oncol J Eur Soc Ther Radiol Oncol. 1998;48(1):15–21.
Appelqvist P, Silvo J, Rissanen P. The results of surgery and radiotherapy in the treatment of small carcinomas of the thoracic oesophagus. Ann Clin Res. 1979;11(5):184–8.
Newaishy GA et al. Results of radical radiotherapy of squamous cell carcinoma of the oesophagus. Clin Radiol. 1982;33(3):347–52.
Petrovich Z et al. Management of carcinoma of the esophagus: the role of radiotherapy. Am J Clin Oncol. 1991;14(1):80–6.
Van Houtte P. Radiotherapy of oesophagus cancer. A review of 136 cases treated at the Institut Bordet (author's transl). Acta Gastroenterol Belg. 1977;40(3–4):121–28.
Earlam R, Cunha-Melo JR. Oesophogeal squamous cell carcinoms: II. A critical view of radiotherapy. Br J Surg. 1980;67(7):457–61.
Arnott SJ et al. Preoperative radiotherapy for esophageal carcinoma. Cochrane Database Syst Rev. 2005;4, CD001799.
Kasai M, Mori S, Watanabe T. Follow-up results after resection of thoracic esophageal carcinoma. World J Surg. 1978;2(4):543–51.
Xiao ZF et al. Influence of number of metastatic lymph nodes on survival of curative resected thoracic esophageal cancer patients and value of radiotherapy: report of 549 cases. Int J Radiat Oncol Biol Phys. 2005;62(1):82–90.
Fok M et al. Postoperative radiotherapy for carcinoma of the esophagus: a prospective, randomized controlled study. Surgery. 1993;113(2):138–47.
Teniere P et al. 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(2):123–30.
Araujo CM et al. A randomized trial comparing radiation therapy versus concomitant radiation therapy and chemotherapy in carcinoma of the thoracic esophagus. Cancer. 1991;67(9):2258–61.
Smith TJ et al. Combined chemoradiotherapy vs. radiotherapy alone for early stage squamous cell carcinoma of the esophagus: a study of the Eastern Cooperative Oncology Group. Int J Radiat Oncol Biol Phys. 1998;42(2):269–76.
Rousell A, Haegele P, Paiilot B. Resulls of the EORTC–GTCCG Phase III trial of irridiation vs irridiation and CDDP in inoperable esophageal. Proc Annu Meet Am Soc Clin Oncol. 1994;13:A583.
Minsky BD et al. INT 0123 (Radiation Therapy Oncology Group 94–05) phase III trial of combined-modality therapy for esophageal cancer: high-dose versus standard-dose radiation therapy. J Clin Oncol. 2002;20(5):1167–74.
Wong R, Malthaner R. Combined chemotherapy and radiotherapy (without surgery) compared with radiotherapy alone in localized carcinoma of the esophagus. Cochrane Database Syst Rev. 2006;1, CD002092.
Schreurs LM et al. Impact of 18-fluorodeoxyglucose positron emission tomography on computed tomography defined target volumes in radiation treatment planning of esophageal cancer: reduction in geographic misses with equal inter-observer variability: PET/CT improves esophageal target definition. Dis Esophagus. 2010;23(6):493–501.
Shimizu S et al. Can hybrid FDG-PET/CT detect subclinical lymph node metastasis of esophageal cancer appropriately and contribute to radiation treatment planning? A comparison of image-based and pathological findings. Int J Clin Oncol. 2009;14(5):421–5.
Fernandez D et al. Stability of endoscopic ultrasound-guided fiducial marker placement for esophageal cancer target delineation and image-guided radiation therapy. Pract Radiat Oncol. 2013;3:32–9.
Macdonald JS 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.
Lv J et al. Long-term efficacy of perioperative chemoradiotherapy on esophageal squamous cell carcinoma. World J Gastroenterol WJG. 2010;16(13):1649–54.
Tachibana M et al. Postoperative chemotherapy vs chemoradiotherapy for thoracic esophageal cancer: a prospective randomized clinical trial. Eur J Surg Oncol. 2003;29(7):580–7.
Cunningham D et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006;355(1):11–20.
Ychou M 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(13):1715–21.
Ando N 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(2):205–9.
Ando N 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(24):4592–6.
Pouliquen X et al. 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(2):127–33.
Huang WZ et al. Meta-analysis of postoperative adjuvant chemotherapy for localized esophageal carcinoma. Ai Zheng. 2006;25(10):1303–6.
Burmeister BH 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(9):659–68.
Gaast AV et al. Effect of preoperative concurrent chemoradiotherapy on survival of patients with resectable esophageal or esophagogastric cancer: results from a multinational randomized phase III study. J Clin Oncol. 2010;28:15s.
Mariette C et al. Surgery alone versus chemoradiotherapy followed by surgery for localized esophageal cancer: analysis of a randomized controlled phase III trial FFCD 9901. J Clin Oncol. 2010;28:15S.
Tepper J 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(7):1086–92.
Urba SG et al. Randomized trial of preoperative chemoradiation versus surgery alone in patients with locoregional esophageal carcinoma. J Clin Oncol. 2001;19(2):305–13.
Walsh TN et al. A comparison of multimodal therapy and surgery for esophageal adenocarcinoma. N Engl J Med. 1996;335(7):462–7.
Lee JL 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 Off J Eur Soc Med Oncol/ESMO. 2004;15(6):947–54.
van Hagen P et al. Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med. 2012;366(22):2074–84.
Greer SE et al. Neoadjuvant chemoradiotherapy for esophageal carcinoma: a meta-analysis. Surgery. 2005;137(2):172–7.
Allum WH et al. Long-term results of a randomized trial of surgery with or without preoperative chemotherapy in esophageal cancer. J Clin Oncol. 2009;27(30):5062–7.
Boonstra JJ et al. Chemotherapy followed by surgery versus surgery alone in patients with resectable oesophageal squamous cell carcinoma: long-term results of a randomized controlled trial. BMC Cancer. 2011;11:181.
Group MRCOCW. Surgical resection with or without preoperative chemotherapy in oesophageal cancer: a randomised controlled trial. Lancet. 2002;359(9319):1727–33.
Ancona E 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(11):2165–74.
Kelsen DP 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(24):3719–25.
Law S et al. Preoperative chemotherapy versus surgical therapy alone for squamous cell carcinoma of the esophagus: a prospective randomized trial. J Thorac Cardiovasc Surg. 1997;114(2):210–7.
Maipang T et al. Induction chemotherapy in the treatment of patients with carcinoma of the esophagus. J Surg Oncol. 1994;56(3):191–7.
Nygaard K 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(6):1104–9. discussion 1110.
Roth JA et al. Randomized clinical trial of preoperative and postoperative adjuvant chemotherapy with cisplatin, vindesine, and bleomycin for carcinoma of the esophagus. J Thorac Cardiovasc Surg. 1988;96(2):242–8.
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(12):1446–50.
Block MI et al. Improvement in staging of esophageal cancer with the addition of positron emission tomography. Ann Thorac Surg. 1997;64(3):770–6. discussion 776–7.
Flamen P et al. Utility of positron emission tomography for the staging of patients with potentially operable esophageal carcinoma. J Clin Oncol. 2000;18(18):3202–10.
Flanagan FL et al. Staging of esophageal cancer with 18F-fluorodeoxyglucose positron emission tomography. AJR Am J Roentgenol. 1997;168(2):417–24.
Luketich JD et al. Evaluation of distant metastases in esophageal cancer: 100 consecutive positron emission tomography scans. Ann Thorac Surg. 1999;68(4):1133–6. discussion 1136–7.
Meyers BF et al. The utility of positron emission tomography in staging of potentially operable carcinoma of the thoracic esophagus: results of the American College of Surgeons Oncology Group Z0060 trial. J Thorac Cardiovasc Surg. 2007;133(3):738–45.
Rasanen JV et al. Prospective analysis of accuracy of positron emission tomography, computed tomography, and endoscopic ultrasonography in staging of adenocarcinoma of the esophagus and the esophagogastric junction. Ann Surg Oncol. 2003;10(8):954–60.
van Vliet EP et al. Staging investigations for oesophageal cancer: a meta-analysis. Br J Cancer. 2008;98(3):547–57.
Pan L et al. Prognostic significance of SUV on PET/CT in patients with esophageal cancer: a systematic review and meta-analysis. Eur J Gastroenterol Hepatol. 2009;21(9):1008–15.
Rizk NP et al. Predictive value of initial PET-SUVmax in patients with locally advanced esophageal and gastroesophageal junction adenocarcinoma. J Thorac Oncol. 2009;4(7):875–9.
Bruzzi JF et al. Detection of interval distant metastases: clinical utility of integrated CT–PET imaging in patients with esophageal carcinoma after neoadjuvant therapy. Cancer. 2007;109(1):125–34.
Downey RJ et al. Whole body 18FDG-PET and the response of esophageal cancer to induction therapy: results of a prospective trial. J Clin Oncol. 2003;21(3):428–32.
Lordick F et al. PET to assess early metabolic response and to guide treatment of adenocarcinoma of the oesophagogastric junction: the MUNICON phase II trial. Lancet Oncol. 2007;8(9):797–805.
Wieder HA et al. Time course of tumor metabolic activity during chemoradiotherapy of esophageal squamous cell carcinoma and response to treatment. J Clin Oncol. 2004;22(5):900–8.
Monjazeb AM et al. Outcomes of patients with esophageal cancer staged with [(1)F]fluorodeoxyglucose positron emission tomography (FDG-PET): can postchemoradiotherapy FDG-PET predict the utility of resection? J Clin Oncol. 2010;28(31):4714–21.
McLoughlin JM et al. Are patients with esophageal cancer who become PET negative after neoadjuvant chemoradiation free of cancer? J Am Coll Surg. 2008;206(5):879–86. discussion 886–7.
Lomas H et al. Post Chemoradiation PET SUV is highly predictive of overall survival in esophageal cancer. J Nucl Med Radiat Ther. 2012;3(2):125.
Weber WA et al. Prediction of response to preoperative chemotherapy in adenocarcinomas of the esophagogastric junction by metabolic imaging. J Clin Oncol. 2001;19(12):3058–65.
Zum Buschenfelde CM et al. (18)F-FDG PET-guided salvage neoadjuvant radiochemotherapy of adenocarcinoma of the esophagogastric junction: the MUNICON II trial. J Nucl Med. 2011;52(8):1189–96.
Stahl M 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.
Bedenne L et al. Chemoradiation followed by surgery compared with chemoradiation alone in squamous cancer of the esophagus: FFCD 9102. J Clin Oncol. 2007;25(10):1160–8.
Chiu PW et al. Multicenter prospective randomized trial comparing standard esophagectomy with chemoradiotherapy for treatment of squamous esophageal cancer: early results from the Chinese University Research Group for Esophageal Cancer (CURE). J Gastrointest Surg. 2005;9(6):794–802.
Stahl M et al. Chemoradiation with and without surgery in patients with locally advanced squamous cell carcinoma of the esophagus. J Clin Oncol. 2005;23(10):2310–7.
Coia LR et al. Outcome of patients receiving radiation for cancer of the esophagus: results of the 1992–1994 Patterns of Care Study. J Clin Oncol. 2000;18(3):455–62.
McKenzie S et al. Improved outcomes in the management of esophageal cancer with the addition of surgical resection to chemoradiation therapy. Ann Surg Oncol. 2011;18(2):551–8.
Markar SR et al. Volume–outcome relationship in surgery for esophageal malignancy: systematic review and meta-analysis 2000–2011. J Gastrointest Surg. 2012;16(5):1055–63.
Birkmeyer JD et al. Hospital volume and surgical mortality in the United States. N Engl J Med. 2002;346(15):1128–37.
Derogar M et al. Hospital and surgeon volume in relation to survival after esophageal cancer surgery in a population-based study. J Clin Oncol. 2013;31(5):551–7.
Conflict of Interest
The authors declare that they have no conflict of interest.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Shridhar, R., Imani-Shikhabadi, R., Davis, B. et al. Curative Treatment of Esophageal Cancer; An Evidenced Based Review. J Gastrointest Canc 44, 375–384 (2013). https://doi.org/10.1007/s12029-013-9511-9
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12029-013-9511-9