Nachweis hepatischer Mikrometastasen

Zusammenfassung

Das kolorektale Karzinom gehört zu den drei häufigsten humanen Malignomen und zeigt eine altersabhängige Zunahme der Inzidenz. Das Überleben beim kolorektalen Karzinom wird durch das Auftreten von Lokalrezidiven sowie hämatogenen und lymphogenen Metastasen bestimmt. Die primäre Resektion von Lebermetastasen gelingt bei ∼ 20 – 25 % aller Patienten mit hepatischen Metastasen und geht mit einer 50 % Rezidivrate innerhalb von 23 Monaten einher. Die 5-Jahresüberlebensrate im Stadium UICC IV beträgt ohne Therapie nur 5 %, das mittlere Überleben 6 – 9 Monate. Dank der positiven Entwicklung der Chemotherapie und der zielgerichteten Therapien („targeted therapy”) während der letzten Dekade konnte das mittlere Überleben auf deutlich über 2 Jahre angehoben werden. Der Einsatz von Polychemotherapien in Kombination mit anti-angiogenetisch sowie anti-proliferativ wirkenden Biologicals führte außerdem zu einer signifikanten Zunahme der sekundären Resektabilität von Lebermetastasen. Trotz R0-Resektion von Lebermetastasen bleiben nur ca. 30 % der Patienten langfristig rezidivfrei. Zur optimalen Patientenselektion werden prognostische Scores, wie der Fong-Score, herangezogen. Limitiert wird die Resektabilität durch eine hohe Rezidivrate für welche vor allem ortsansässige Mikrometastasen (MM) und disseminierte Tumorzellen (DTC) verantwortlich gemacht werden. Das Ausmaß der disseminierten Tumorzellbelastung korrelierte hierbei signifikant mit dem Überleben und der Rezidivrate nach Resektion. Diese Mikrometastasen werden in aktuell laufenden adjuvanten Therapiestudien (z. B. MT 201) unter Einsatz von anti-EpCam Antikörpern angegriffen. Der DTC Nachweis könnte die bisher angewandten Scores sinnvoll ergänzen und in Zukunft im Rahmen von Studien die Indikation für eine adjuvante Antikörper-basierte (z. B. anti-EpCam) Therapie darstellen.

Abstract

Colorectal cancer is one of the three most frequent malignancies in humans. Survival is mainly determined by local recurrence, lymphatic and hematogenous dissemination. Primary liver resection for metastases is possible in ~20-25% of patients with hepatic metastases and results in a 50% recurrence rate within 23 months. The five-year survival without treatment in patients with UICC stage IV is only 5%, the mean survival 6-9 months. As a result of promising developments in chemotherapy and targeted therapies in the last decade, the mean survival rate has significantly improved to over more than two years. Furthermore, the use of polychemotherapy in combination with anti-angiogenic and anti-proliferative biologicals has resulted in a significant increase of secondary resectability of liver metastases. Despite of a R0-resection (i.e. resection with clear margins) of liver metastases, only 30% of patients remain free of recurrence in the long-term. Prognostic scores are used for optimal patient selection, e.g. the Fong-Score. Resection is often limited by a high number of recurrences: intrahepatic micrometastases and disseminated tumor cells (DTC) are suspected as the cause of their development. In this connection the load of disseminated tumor cells correlates significantly with the survival and recurrence rate after resection. These micrometastases are targets in current adjuvant treatment studies (e.g. MT 201) by using anti-EpCam antibodies. The detection of DTC can supplement the previously used scores and represents the indication for an adjuvant antibody-based treatment (e.g. anti-EpCam) in the context of clinical trials.

Schlüsselwörter

kolorektales Karzinom - Lebermetastasenchirurgie - Mikrometastasen - disseminierte Tumorzellen

Keywords

colorectal cancer - surgery for liver metastases - micrometastases - disseminated tumor cells

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