Neoadjuvante Therapie des resektablen Ösophaguskarzinoms

Zusammenfassung

Hintergrund: Die chirurgische Therapie des lokalisierten Ösophaguskarzinoms stellt nach wie vor das einzige kurative Therapieverfahren dar. Häufig sind bei Patienten mit lokal fortgeschrittenen Tumoren bereits intraabdominelle paraaortale Lymphknotenmetastasen nachweisbar und/oder es besteht eine beträchtliche Komorbidität, so dass nur wenige operiert werden können. Diese Tatsache hat dazu geführt, perioperative Therapiemodalitäten zu prüfen, wobei ein allgemein akzeptierter multimodaler Therapiestandard derzeit für kein Tumorstadium existiert. Methodik: Mittels einer computerunterstützten (MEDLINE, ASCO Proceedings) sowie manuellen Suche wurden randomisierte klinische Studien und Metaanalysen, welche eine präoperative Therapie plus anschließender Operation bei Patienten mit resektablen Ösophaguskarzinom untersuchten, identifiziert. Ergebnisse: Dreiundzwanzig randomisierte kontrollierte Studien und fünf Metaanalysen wurden identifiziert. Probleme in der Interpretation vor allem älterer Studien ergeben sich unter anderem durch das Fehlen moderner bildgebender Untersuchungsmethoden, wodurch keine exakte Festlegung des Tumorstadiums möglich war, durch die Inklusion von Patienten mit unterschiedlichen Tumorstadien (potenziell resektabel/lokal fortgeschritten) sowie unterschiedliche histologische Entitäten (Plattenepithelkarzinom/Adenokarzinom), durch den Einsatz unterschiedlicher Operationstechniken und durch das Vorliegen kleiner Patientenzahlen. Es gab keine Unterschiede bezüglich der Mortalität für folgende perioperative Therapiemodalitäten: präoperative Radiotherapie versus postoperative Radiotherapie, prä- und postoperative Radiotherapie versus postoperative Radiotherapie (prä- und postoperative Radiotherapie zeigte eine höhere Sterblichkeitsrate), präoperative Radiotherapie versus Operation, präoperative Chemotherapie versus Operation, prä- und postoperative Chemotherapie versus Operation. Bezüglich der 3-Jahres-Mortalität ergaben sich für folgende Therapiemodalitäten statistisch signifikante Unterschiede: präoperative Radiochemotherapie versus Operation (präoperative Therapie überlegen), präoperative Chemotherapie versus präoperative Radiotherapie (präoperative Radiotherapie überlegen). Schlussfolgerung: Aus der vorliegenden Literatur kann keine eindeutige Standardempfehlung zur multimodalen Therapie bei resektablen Ösophaguskarzinomen abgeleitet werden. Somit kann heutzutage eine neoadjuvante Therapie dieser Erkrankung ausschließlich an Zentren mit maximaler chirurgischer Expertise und im Rahmen interdisziplinär erarbeiteter Studienprotokolle gerechtfertigt werden.

Abstract

Background: Surgical excision remains the only therapeutic approach with curative potential in patients with localized esophageal cancer. Due to the presence of lymph node metastases upon diagnosis in a large percentage of patients with locally advanced tumors and/or the presence of considerable co-morbidity, only a limited number of patients are amenable to surgery. These facts have prompted us to evaluate approaches including perioperative therapy modalities. Methods: By means of a computer-supported search (MEDLINE, ASCO Proceedings) as well as a manual literature search, randomized clinical trials and meta-analyses evaluating preoperative therapy plus surgery in patients with resectable esophageal cancer were identified. Results: Twenty-three randomized clinical studies and five meta-analyses were identified. Interpretation - especially of the older studies - however, is hampered by the lack of a stringent application of modern examination techniques allowing for exact specification of tumor stage (resectable/locally advanced) as well as the inclusion of patients with different histological entities (squamous cell/adenocarcinoma), different surgical techniques and the low number of patients. There were no significant differences for the following perioperative therapy modalities regarding tumor-related mortality: preoperative radiotherapy versus postoperative radiotherapy, preoperative and postoperative radiotherapy versus postoperative radiotherapy (higher mortality in preoperative and postoperative radiotherapy arm), preoperative radiotherapy versus surgery, preoperative chemotherapy versus surgery, preoperative and postoperative chemotherapy versus surgery. In terms of 3-year mortality, statistically significant differences could be found for the following therapy modalities: preoperative radiochemotherapy versus surgery (preoperative therapy superior), preoperative chemotherapy versus preoperative radiotherapy (preoperative radiotherapy superior). Conclusion: Judging from these data, no clear recommendation for a standard multimodality approach outside clinical studies can be given for patients with resectable esophageal cancer. Neoadjuvant therapy, therefore, can only be recommended in centers with a maximum surgical expertise and in the context of multidisciplinary study protocols.

Schlüsselwörter

Ösophaguskarzinom - präoperative Therapie - neoadjuvante Therapie - Chemotherapie - Radiotherapie - Radiochemotherapie

Key words

Esophageal cancer - preoperative therapy - neoadjuvant therapy - chemotherapy - radiotherapy - radiochemotherapy

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