Minimale Resterkrankung beim Magenkarzinom – eine Übersicht

Zusammenfassung

Die Prognose des Magenkarzinoms, insbesondere im fortgeschrittenen Stadium, ist trotz der bedeutenden Entwicklungen der letzten Jahre noch immer als schlecht anzusehen. Die Tatsache, dass auch potenziell kurativ behandelte Patienten ohne nachweisbaren Tumorrest in einem erheblichen Teil der Fälle Metastasen entwickeln und adjuvante Therapien dieses Risiko senken können, weist darauf hin, dass bei diesen Patienten Mikrometastasen und isolierte Tumorzellen („minimal residual disease”, MRD) vorliegen, die mit konventionellen Methoden nicht erfassbar sind und zum Ausgangspunkt für Rezidive werden können. Ein Nachweis der MRD in verschiedenen anatomischen Kompartimenten könnte demnach Bedeutung für eine stärkere Individualisierung der Therapie erlangen. Die Untersuchungsmethodik und die Ergebnisbeurteilung sind jedoch bis heute nicht standardisiert und die vorliegenden Studien daher meist nicht vergleichbar, sodass die MRD-Diagnostik zumindest im europäischen und angloamerikanischen Raum bisher für keines der 4 Kompartimente Lymphknoten, Peritonealflüssigkeit, peripheres Blut und Knochenmark Eingang in die klinische Routine gefunden hat. Die besten Daten für den MRD-Nachweis beim Magenkarzinom liegen für die Peritoneallavage vor. Diese Untersuchung ist an einigen japanischen Zentren bereits etabliert und wird für therapeutische Entscheidungen genutzt (z. B. Indikation zur intraperitonealen Chemotherapie). Der MRD-Nachweis in Lymphknoten wird im Zusammenhang mit dem Sentinel-Lymphknoten-Konzept weiter evaluiert werden und hier vor allem bei Patienten mit frühen Tumorstadien, die normalerweise nicht in multimodalen Konzepten behandelt werden, möglicherweise therapeutische Relevanz erlangen. Für Tumorzellen im peripheren Blut und im Knochenmark zeichnet sich ab, dass diese nur unter bestimmten Voraussetzungen zur Metastasenbildung fähig sind. Zukünftige Untersuchungen werden sich daher neben dem reinen Nachweis von Tumorzellen vor allem auf deren molekulare Charakterisierung und auf die Definition von molekularen Prädiktoren für das Metastasierungspotenzial dieser Zellen konzentrieren. Neben Anwendungen in der Diagnostik und der Prognosebeurteilung könnten sich daraus direkte Auswirkungen auf die Entwicklung zielgerichteter Therapien ergeben.

Abstract

Despite recent developments in therapy for gastric cancer, the prognosis of this disease remains poor in advanced stages. In many cases even curatively treated patients without any residual tumour develop metachronous metastases. As in other solid tumours, adjuvant therapies can reduce the metastatic risk, which implies that some of these patients harbour isolated tumour cells or micrometastases (minimal residual disease, MRD) that are undetectable by radiological imaging and conventional histopathology but can still be the cause of tumour recurrence. Therefore, reliable methods for diagnosing MRD would be desirable for individually tailoring therapy for these patients. Unfortunately, testing methods for MRD and interpretation of their results are not standardised and studies published on this topic are difficult to interpret due to methodological differences and small sample sizes. As of now, testing for MRD has not become relevant in clinical routine for any of the anatomic compartments lymph nodes, peritoneal lavage fluid, peripheral blood, and bone marrow in the Western hemisphere. Most reliable data on MRD in gastric cancer patients have been reported for peritoneal lavage fluid. In some centres in Japan, this test is routinely being used for making therapeutic decisions, e. g., on the use of intraperitoneal chemotherapy. MRD in resected lymph nodes will be further evaluated in the context of the sentinel lymph node concept and possibly be employed for designing individualised therapy for patients in early disease stages who are not routinely candidates for multimodal treatment. As for tumour cells in peripheral blood and in bone marrow, studies suggest that these cells are only able to form metastases in the presence of certain molecular factors. Therefore, rather than simply confirming the existence of isolated tumour cells in blood or bone marrow, future studies should concentrate on defining their molecular characteristics and the conditions required for their metastatic potential. This may gain relevance in diagnostics and prognostic evaluation of individual patients as well as in the development of targeted therapies directly interfering with the metastatic process.

Schlüsselwörter

minimale Resterkrankung - Magenkarzinom - Mikrometastasen - isolierte Tumorzellen

Key words

minimal residual disease - gastric carcinoma - micrometastasis - isolated tumor cells

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