Kolonkarzinom: Aktueller Stand der multimodalen Therapie

 

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Zusammenfassung

Im UICC-I-Stadium kann bei T1-Karzinomen mit einem geringen Risikoprofil für eine Lymphknotenmetastasierung bei selektionierten Patienten auf eine chirurgisch onkologische Resektion verzichtet werden, wenn der Befund komplett endoskopisch entfernt wurde. Im Stadium UICC II ist eine routinemäßige adjuvante CT nicht indiziert, lediglich bei Patienten mit einem Hochrisiko­pro­fil (T4-Tumor, weniger als 12 histopathologisch untersuchte Lymphknoten, Notfall-OP, intraoperative Tumorperforation) sollte auch in diesem Tumorstadium eine adjuvante CT mit 5-FU / FS durchgeführt werden. Standardtherapie im Sta­dium UICC III ist eine adjuvante CT nach dem FOLFOX4-Protokoll. Irinotecan und Antikörpertherapien erbringen in diesem Tumorstadium keine zusätzliche Verbesserung der Überlebensdaten. Aufgrund möglicher Nebenwirkungen der CT sollten Patienten, die älter als 70 Jahre sind, bevorzugt ein infusionales 5-FU / FS-Protokoll oder oral Capecitabine erhalten. Im Stadium IV mit resektablen Lebermetastasen steht die chirurgische Entfernung des Primärtumors und der Metastasen im Vordergrund. Der Vorteil einer neoadjuvanten, perioperativen oder adjuvanten CT ist bei resek­tablen Lebermetastasen augenblicklich nicht hinreichend belegt. Hierüber sollte individuell in ­einem Tumorboard entschieden werden. Bei primär nicht resektablen Lebermetastasen ist die Durchführung einer neoadjuvanten Chemotherapie indiziert. Hierzu bietet sich ein FOLFOX-Protokoll, kombiniert z. B. mit dem monoklonalen Antikörper Cetuximab, an. Ziel ist in dieser Situation die Verkleinerung der Metastasen und anschließende Resektion der Metastasen im Gesunden (R0). Patienten mit einer Mikrosatelliteninstabi­lität im Stadium UICC II haben eine vorteihafte Prognose und profitieren nicht von einer adjuvanten CT mit 5-FU / Folinsäure. Sollte bei diesen Patienten dennoch eine CT erwogen werden, empfiehlt sich die Bestimmung der MSI im Tumorgewebe und bei ­positivem Befund eine Kombinations-CT, z. B. mit FOLFOX. Die weitere Bedeutung der MSI für andere Tumorstadien ist augenblicklich nicht hinreichend evaluiert. Vor einer Therapie mit dem monoklonalen Antikörper Cetuximab oder Panitumumab muss der KRAS-Status bestimmt werden, da eine solche Therapie nur bei einem KRAS-Wildtyp im Tumorgewebe wirksam ist. 

Abstract

In UICC stage I a selected group of patients with T1 tumours and a low risk profile regarding simultaneous lymph node metastases can be treated by endoscopic resection alone, if the tumour is thereby completely removed. In UICC stage II an adjuvant chemotherapy (CT) should not be routinely performed. However, in high risk UICC stage II patients (T4 tumour, less than 12 examined lymph nodes, emergency surgery, intraoperative tumour perforation), an adjuvant CT with infusional 5-FU / FA should be recommended. The state of the art in UICC stage III is an adjuvant CT with FOLFOX. In this tumour stage no beneficial effect of CT involving irinotecan or monoclonal antibodies has been documented. Due to CT-induced side effects an infusional 5-FU / FA protocol or oral capecitabine should be given in patients older than 70 years. In stage UICC IV with resectable liver metastases, surgical resection of the primary tumour and the metastases should be implemented. Since no conclusive data are currently available regarding the beneficial effect of neoadjuvant, perioperative or adjuvant CT in this setting, the therapeutic strategy should be individually discussed between surgeons and oncologists (tumour board). In cases of non-resectable liver metastases a neoadjuvant CT should be performed, preferentially with a FOLFOX protocol in combination with targeted therapies, i. e., the monoclonal antibody cetuximab, aimed at tumour regression with radical metastasectomy as the secondary intent (R0). Patients with UICC stage II colon cancer and microsatellite instability (MSI) apparently experience a better prognosis but do not profit from an adjuvant CT with 5-FU / FA alone. If a CT is under consideration for these patients, the MSI status should be determined on tumour tissue. In cases of a positive result a combination CT, i. e., with FOLFOX, should be given. The relevance of the MSI status in other tumour stages is as yet unknown. Before targeted therapies, i. e., cetuximab or panitumumab, are initiated, the KRAS status needs to be determined, since therapies with antibodies against the epithelial growth factor receptor (EGFR) are only effective in tumours bearing the KRAS wild-type. 

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