Das Plattenepithelkarzinom des Ösophagus – Stellenwert der Chirurgie im therapeutischen Konzept

Zusammenfassung

Zusammenfassend sind Plattenepithelkarzinome des Ösophagus seitens ihrer Ätiopathogenese, Tumorbiologie, Komorbidität und ihres operativen Risikos sowie der Prognose eine komplett unterschiedliche Entität verglichen mit den Adenokarzinomen. Beim oberflächlichen Plattenepithelkarzinom besteht bereits ab der Mukosainfiltrationstiefe m3 das Risiko einer relevanten Lymphknotenmetastasierung und somit die Indikation zur onkologischen Resektion. Beim lokal fortgeschrittenen Plattenepithelkarzinom ist die neoadjuvante Radiochemotherapie internationaler Standard. Eine Früh-Response-Determinierung sollte angestrebt werden. Nonresponder müssen frühzeitig erkannt und einer Salvage-Operation mit vertretbarem operativen Risiko zugeführt werden. Die definitive Radiochemotherapie ist aufgrund ihrer hohen kompletten Response eine Option insbesondere für hochsitzende Plattenepithelkarzinome und für Patienten mit hohem operativen Risiko, wenngleich die lokale Tumorkontrolle nach operativer Therapie signifikant besser ist. Aufgrund des Erfolgs der definitiven Radiochemotherapie stellt sich zunehmend die Frage, ob zukünftig eine chirurgische Resektion nach neoadjuvanter Radiochemotherapie weiterhin erforderlich ist, oder ob durch die alleinige Radiochemotherapie ähnliche Ergebnisse des rezidivfreien Überlebens und des Gesamtüberlebens erreicht werden können. Die chirurgische Therapie sollte immer in einem Expertenzentrum mit niedriger Morbidität und Mortalität durchgeführt werden. Im Fokus zukünftiger Forschung stehen Prädiktoren der histopathologischen Response, um möglicherweise gezielter die chirurgische Morbidität bei Patienten mit kompletter pathologischer Response nach multimodaler Therapie zu vermeiden.

Abstract

Squamous cell carcinomas of the oesophagus are a completely different entity from adenocarcinomas in regard to their aetiopathology, tumour biology, co-morbidity, operative risk, and prognosis. For superficial squamous cell carcinomas, the risk of a relevant lymph node metastatisation already exists from the mucosal infiltration level m3 onward, and thus oncological resection is indicated. Neoadjuvant radiochemotherapy is the international standard for locally advanced squamous cell carcinoma. The early-response should be determined. Non-responders must be identified early, and a salvage operation with a justifiable operative risk should be carried out. Due to its high complete response rate, definitive radiochemotherapy is an option especially for squamous cell carcinomas of the upper third of the oesophagus and for patients with a high operative risk, even though local tumour control is significantly better after surgical therapy. Due to the success of definitive radiochemotherapy, the question is being asked increasingly, whether surgical resection after neoadjuvant radiochemotherapy will still be necessary in the future or whether radiochemotherapy alone can attain similar results for relapse-free survival and total survival. Surgical therapy should always be carried out in a specialised high volume centre with low morbidity and mortality. Future research will focus on predictors of the histopathological response, in order to possibly more accurately avoid surgical morbidity in patients with complete pathological responses after multimodal therapy.

Schlüsselwörter

Plattenepithelkarzinom des Ösophagus - Stellenwert der Chirurgie - therapeutisches Konzept

Key words

squamous cell carcinoma of the oesophagus - impact of surgery - therapeutic concept

Literatur

• 1 Brown L M, Devesa S S, Chow W H. Incidence of adenocarcinoma of the esophagus among white Americans by sex, stage, and age.  J Natl Cancer Inst. 2008;  100 1184-1187
• 2 Blot W J, Devesa S S, Kneller R W. et al . Rising incidence of adenocarcinoma of the esophagus and gastric cardia.  JAMA. 1991;  256 1287-1289
• 3 Devesa S S, Blot W J, Fraumeni J F. Changing patterns in the incidence of esophageal and gastric carcinoma in the United States.  Cancer. 1998;  83 2049-2053
• 4 Brown L M, Devesa S S. Epidemiologic trends in esophageal and gastric cancer in the United States.  Surg Oncol Clin N Am. 2002;  11 235-256
• 5 Corley D A, Buffler P A. Oesophageal and gastric cardia adenocarcinomas: analysis of regional variation using the cancer incidence in five continents database.  Int J Epidemiology. 2001;  30 1415-1425
• 6 Chang S S, Lu C L, Chao J Y. et al . Unchanging trend of adenocarcinoma of the esophagus and gastric cardia in Taiwan: a 15-year experience in a single center.  Dig Dis Sci. 2002;  47 735-740
• 7 Hongo Jr M. Review article: Barrett’s oesophagus and carcinoma in Japan.  Aliment Pharmacol Ther. 2004;  20 (Suppl 8) 50-54
• 8 Law S, Wong J. Changing disease burden and management issues for esophageal cancer in the Asia-Pacific region.  J Gastroenterol Hepatol. 2002;  17 374-381
• 9 Shibata S, Matsuda T, Ajiki W. et al . Trend in incidence of adenocarcinoma of the esophagus in Japan, 1993 – 2001.  Jpn J Clin Oncol. 2008;  38 464-468
• 10 Fock K M, Talley N J, Fass R. et al . Asia-Pacific consensus on the management of gastroesophageal reflux disease: update.  J Gastroenterol Hepatol. 2008;  23 8-22
• 11 Wong W M, Lam S K, Hui W M. et al . Long-term perspective follow-up of endoscopic oesophagitis in southern Chinese – prevalence and spectrum of the disease.  Aliment Pharmacol Ther. 2002;  16 2037-2042
• 12 Hongo M, Nagasaki Y, Shoji T. Epidemiology of esophageal cancer: Orient to Occident. Effects of chronology, geography and ethnicity.  J Gastroenterol Hepatol. 2009;  24 729-735
• 13 The Coordinating Group for Research on the Etiology of Esophageal Cancer of North China . The epidemiology of esophageal cancer in North China and preliminary results in the investigation of its etiological factors.  Scientia Sinica. 1991;  18 131-148
• 14 Ribeiro Jr U, Posner M C, Safatale-Ribeiro A V. et al . Risk factors for squamous cell carcinoma of the oesophagus.  Br J Surg. 1996;  83 1174-1185
• 15 Siewert J R, Ott K. Are squamous and adenocarcinomas of the esophagus the same disease?.  Semin Radiat Oncol. 2006;  17 38-44
• 16 Takubo K, Aida J, Sawabe M. et al . Early squamous cell carcinoma of the oesophagus: the Japanese viewpoint.  Histopathology. 2007;  51 733-742
• 17 Endo M, Yoshino K, Kawano T. et al . Clinicopathologic analysis of lymph node metastasis in surgically resected superficial cancer of the thoracic esophagus.  Dis Esophagus. 2000;  13 125-129
• 18 Eguchi T, Nakanishi Y, Shimoda T. et al . Histopathological criteria for additional treatment after endoscopic mucosal resection for esophageal cancer: analysis of 464 surgically resected cases.  Mod Pathol. 2006;  19 475-480
• 19 Matsubara T, Ueda M, Abe T. et al . Unique distribution patterns of metastatic lymph nodes in patients with superficial carcinoma of the thoracic oesophagus.  Br J Surg. 1999;  86 669-673
• 20 Narahara H, Iishi H, Tatsuta M. et al . Effectiveness of endoscopic mucosal resection with submucosal saline injection technique for superficial squamous carcinomas of the esophagus.  Gastrointest Endosc. 2000;  52 730-734
• 21 Shimizu Y, Tsukagoshi H, Fujita M. et al . Metachronous squamous cell carcinoma of the esophagus arising after endoscopic mucosal resection.  Gastrointest Endosc. 2001;  54 190-194
• 22 Shimizu Y, Tsukagoshi H, Fujita M. et al . Long-term outcome after endoscopic mucosal resection in patients with esophageal squamous cell carcinoma invading the muscularis mucosae and deeper.  Gastrointest Endosc. 2002;  56 387-390
• 23 Pech O, Gossner L, May A. et al . Endoscopic resection of superficial esophageal squamous-cell carcinomas: western experience.  Am J Gastroenterol. 2004;  99 1126-1232
• 24 Pech O, May A, Gossner L. et al . Curative endoscopic therapy in patients with early esophageal squamous-cell carcinoma or high-grade intraepithelial neoplasia.  Endoscopy. 2008;  39 30-35
• 25 Katada C, Muto M, Manabe T. et al . Local recurrence of squamous cell carcinoma of the esophagus after EMR.  Gastrointest Endosc. 2005;  61 219-225
• 26 Fujishiro M, Yahagi N, Kakushima N. et al . Endoscopic submucosal dissection of esophageal squamous cell neoplasms.  Clin Gastroenterol Hepatol. 2006;  4 688-694
• 27 Oyama T, Miyata Y, Shimatani S. et al . Lymph node metastasis of m3 and sm1 esophageal cancer.  I Cho (Stomach Intestine). 2002;  37 71-74
• 28 Gockel I, Domeyer M, Sgourakis G G. et al . Prediction model of lymph node metastasis in superficial esophageal adenocarcinoma and squamous cell cancer including D 2 – 40 immunostaining.  J Surg Oncol. 2009;  100 191-198
• 29 Gockel I, Sgourakis G, Lyros O. et al . Risk of lymph node metastasis in submucosal esophageal cancer: A review of surgically resected patients.  submitted.
• 30 Bollschweiler E, Baldus S E, Schröder W. et al . High rate of lymph-node metastasis in submucosal esophageal squamous-cell carcinomas and adenocarcinomas.  Endoscopy. 2006;  38 149-156
• 31 Stein H J, Feith M, Bruecher B L. et al . Early esophageal cancer: pattern of lymphatic spread and prognostic factors for long-term survival after surgical resection.  Ann Surg. 2005;  242 566-573
• 32 Stahl M, Oliveira J (on behalf of the ESMO Guidelines Working Group). Esophageal cancer: ESMO Clinical recommendations for diagnosis, treatment and follow-up.  Ann Oncol. 2008;  19 (Suppl 2) ii21-ii22
• 33 Gockel I, Kneist W, Junginger T. Incurable esophageal cancer: patterns of tumor spread and therapeutic consequences.  World J Surg. 2006;  30 183-190
• 34 Kelsen D P, Ginsberg R, Pajak T F. et al . Chemotherapy followed by surgery compared with surgery alone for localized esophageal cancer.  N Engl J Med. 1998;  339 1979-1984
• 35 Urschel J D, 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;  186 538-543
• 36 Fiorica F, Di Bona D, Schepis F. et al . Preoperative chemoradiotherapy for oesophageal cancer: a systematic review and meta-analysis.  Gut. 2004;  53 925-930
• 37 Malthaner R A, Wong R, Rumble R B. et al . ,.  BMC Med. 2004;  2 35-51
• 38 Stuschke M, Sarbia M. Neoadjuvante Radiochemotherapie und Responseprädiktion.  Onkologe. 2004;  10 1179-1190
• 39 Greer S E, Goodney P P, Sutton J E. et al . Neoadjuvant chemoradiotherapy for esophageal carcinoma: A meta-analysis.  Surgery. 2005;  137 172-177
• 40 Gebski V, Burmeister B, Smithers B M. et al . Survival benefits from neoadjuvant chemoradiotherapy or chemotherapy in oesophageal carcinoma: a meta-analysis.  Lancet Oncol. 2007;  8 226-234
• 41 Burmeister B H, Smithers B M, Gebski V. et al . Surgery alone versus chemoradiotherapy followed by surgery for resectable cancer of the oesophagus. A randomised controlled phase III trial.  Lancet Oncol. 2005;  6 659-668
• 42 Tepper J, Krasna M J, Niedzwiecki D. 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 1086-1092
• 43 Jouve J, Michel P, Mariette C. et al . ,.  J Clin Oncol. 2008;  26 (Suppl) 220 (Abstr. 4555)
• 44 Stahl M. Combined preoperative radiochemotherapy in squamous cell carcinoma: The view of the medical oncologist.  Chirurg. 2009;  Epub ahead of print
• 45 Weber W A, Ott K, Becker K. et al . Prediction of response to preoperative chemotherapy in adenocarcinomas of the esophagogastric junction by metabolic imaging.  J Clin Oncol. 2001;  19 3058-3065
• 46 Ott K, Weber W A, Lordick F. et al . Metabolic imaging predicts response, survival, and recurrence in adenocarcinoma of the esophagogastric junction.  J Clin Oncol. 2006;  24 4692-4698
• 47 Lordick F, Ott K, Krause B J. 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;  8 797-805
• 48 Wieder H, Brücher B L, Zimmermann F. et al . Time course of tumor metabolic activity during chemoradiotherapy of esophageal squamous cell carcinoma and response to treatment.  J Clin Oncol. 2004;  22 900-908
• 49 Gillham C M, Lucey J A, Keogan M. et al . 18FDG uptake during induction chemoradiation for oesophageal cancer fails to predict histomorphological tumour response.  Br J Cancer. 2006;  95 1174-1179
• 50 Brücher B L, Weber W, Bauer M. et al . Neoadjuvant therapy of esophageal squamous cell carcinoma: Response evaluation by positron emission tomography.  Ann Surg. 2001;  233 300-309
• 51 Brücher B LDM, Swisher S G, Königsrainer A. et al . Response to preoperative therapy in upper gastrointestinal cancers.  Ann Surg Oncol. 2009;  16 878-886
• 52 Stahl M, Stuschke M, Lehmann N. et al . Chemoradiation with and without surgery in patients with locally advanced squamous cell carcinoma of the esophagus.  J Clin Oncol. 2005;  23 2311-2317
• 53 Stahl M, Wilke H, Lehmann N. et al . Long-term results of a phase III study investigating chemoradiation with and without surgery in locally advanced squamous cell carcinoma (LA-SCC) of the esophagus.  J Clin Oncol. 2008;  26 (Suppl) 220 (Abstr. 4530)
• 54 Bedenne L, Michel P, Bouché O. et al . Chemoradiation followed by surgery compared with chemoradiation alone in squamous cell cancer of the esophagus: FFCD 9102.  J Clin Oncol. 2007;  25 1160-1186
• 55 Stahl M. Clinical recommendations. Esophageal cancer: ESMO Clinical recommendations for diagnosis, treatment and follow-up.  Ann Oncol. 2007;  18 (Suppl 2) ii15-ii16