[Surgical and perioperative therapy of liver metastases]

Multimodal management approaches and innovative surgical techniques have completely transformed treatment and prognosis for patients with liver metastases, bringing considerable improvements. Whether patients with resectable liver metastases should be given neoadjuvant and/or adjuvant chemotherapy is still a matter of controversy. If a R0 resection is possible (either first-line or after pretreatment), then from a surgical point of view this should be carried out without delay. A limited resection (subsegment/segment/non-anatomical resection) is sufficient if the metastases can be removed completely - and has the advantage of retaining more functional liver tissue, thus allowing a 2nd or 3rd resection to be carried out in the event of tumor recurrence. A small disease-free margin (< 1 cm) is enough, and does not worsen the prognosis. Perioperative chemotherapy with FOLFOX4 was shown to reduce the risk of recurrence by approximately 25% (7.3% in absolute terms) in patients with metastases that are resectable (EORTC 40983) - and this in a group of patients who, in terms of their metastasis patterns, with a median of only 1 solitary metastasis, were "ideal" candidates for primary resection. The difference was not significant in intention to treat (ITT) analysis, but was significant in the 'eligible' patients. It is notable, however, that the whole of the overall difference arose as a result of events in the first 10 weeks - thereafter the curves run in parallel. The EORTC and the majority of the experts now, on the basis of the clinically relevant improvement in disease-free survival, recommend adopting pre- and postoperative chemotherapy with FOLFOX4 (3 months before and after surgery) as the new standard. This recommendation is, however, controversial. The question of whether cetuximab or bevacizumab should be given in addition is still open, but clinical trials have started. The evidence concerning adjuvant chemotherapy alone after R0 metastasis resection is less clear. Despite this, and especially among specialist surgeons, adjuvant chemotherapy is however more widely supported than is perioperative chemotherapy - because the risk of presurgical toxicity and thus potential inoperability or tumor progression during chemotherapy is avoided. The new S3 guidelines from 2008 also favor adjuvant treatment - even if data are only available for adjuvant treatment with bolus 5-FU. If adjuvant treatment is given, then combination chemotherapy should be used. Surgeons, for the most part, continue to regard primary resection as the standard.