Resektable Lebermetastasen beim kolorektalen Karzinom: pro neoadjuvante Therapie – contra neoadjuvante Therapie

Zusammenfassung

Bei ungefähr einem Drittel der Patienten mit kolorektalem Karzinom (KRK) stellt die Leber den alleinigen Metastasierungsort dar. Bei ca. 15 % dieser Patienten sind die Metastasen primär resektabel. Die 5-Jahres-Überlebensrate nach Resektion beträgt 25 – 40 %. Die EORTC-Studie von Nordlinger et al. hat den Stellenwert einer neoadjuvanten bzw. perioperativen Chemotherapie bei resektablen Lebermetastasen untersucht und für die Subgruppe der tatsächlich resezierten Patienten eine signifikante Verbesserung des progressionsfreien Überlebens durch die perioperative Therapie gefunden. In der Intent-to-treat-Population waren die Ergebnisse nicht signifikant. Für eine neoadjuvante Therapie bei resektablen Lebermetastasen spricht das Modell der frühen Eradikation möglicher disseminierter Tumorzellen, die präoperative Identifzierung der Tumorbiologie (Ausschluss primär progredienter Patienten), die höhere Dosisdichte, die präoperativ erreicht werden kann, sowie die höhere Wahrscheinlichkeit für eine tatsächlich stattfindende R 0-Resektion. Gegen eine präoperative Therapie bei resektablen Metastasen spricht die Hepatotoxizität der Chemotherapie mit einer – wenn auch moderaten – Erhöhung der perioperativen Morbidität, die Gefahr einer kompletten Remission, die dann das Auffinden der Metastase intraoperativ schwierig macht, und die unklare optimale Dauer einer neoadjuvanten Therapie. Vor allem seitens der Viszeralchirurgie in Deutschland wird die neoadjuvante Therapie bei resektablen Lebermetastasen nicht als Standardbehandlung angesehen. Die zusammenfassende Wertung spricht sich bei fehlender Evidenz der Stärke 1 zur neoadjuvanten Therapie für eine intensive interdisziplinäre Zusammenarbeit von Viszeralchirurgen, Gastroenterologen und internistischen Onkologen bei der Behandlung dieser Patienten aus. Möglicherweise wird die Publikation der Gesamtüberlebensdaten der EORTC-Studie, die für den Herbst 2010 geplant ist, die Evidenzlage ändern.

Abstract

Approximately one third of patients with colorectal cancer (CRC) present with metastases confined to the liver only. In 15 % of these patients the metastases are primarily resectable. After resection of colorectal liver metastases the 5-year survival rate is 25 – 40 %. The EORTC trial of Nordlinger et al. has examined the role of perioperative/neoadjuvant chemotherapy of resectable liver metastases and found in the subgroup of resected patients a significant improvement in disease-free survival through chemotherapy. The results were not significant in the intent-to-treat population. Possible arguments pro neoadjuvant therapy of resectable liver metastases are the early eradication of disseminated tumour cells, the identification of a worse prognosis tumour biology in the individual patient and the higher dose density which can be achieved preoperatively versus postoperatively. Arguments against preoperative chemotherapy are the chemotherapy-induced hepatotoxicity and related increase in perioperative morbidity, the risk of achieving a complete remission of lesions which then cannot be detected intraoperatively and the uncertain optimal duration of chemotherapy. Especially surgical oncologists in Germany do not consider the neoadjuvant treatment of resectable liver metastases as a standard of care. In summary, because of the lack of level 1 evidence, patients with resectable liver metastases of colorectal cancer should be discussed within interdisciplinary tumour boards together with surgeons, gastroenterologists and medical oncologists. Potentially, overall survival data of the EORTC trial which is expected for late 2010 could change the level of evidence.

Schlüsselwörter

kolorektales Karzinom - Lebermetastasen - neoadjuvante Therapie

Key words

colorectal cancer - liver metastases - neoadjuvant therapy

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