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Prognostic Value of Hepatic Margin Status After Resection of Colorectal Liver Metastases After Preoperative Chemotherapy
Hannes P. Neeff*1, Peter Bronsert2, Ulrich T. Hopt1, Frank Makowiec1
1Dept. of Surgery, University of Freiburg, Freiburg, Germany; 2Institute of Pathology, University of Freiburg, Freiburg, Germany
Modern chemotherapy (CTX) clearly increases survival in stage IV colorectal cancer (CRC). In (isolated) liver metatases (CRC-LM) neoadjuvant/perioperative (neo) CTX may increase rates of resectability and also improve postoperative long-term survival although clear data are lacking. Due to the widespread use of (preoperative) CTX in patients with CRC-LM recent studies assessed the prognostic role of the hepatic margin after CTX and resection, with conflicting results reported. We, therefore, evaluated the outcome after resection of CRC-LM in relation to preoperative CTX and the hepatic resection status.
Methods: Since 2000 541 hepatic resections for CRC-LM were performed in our department. Only patients with first hepatic resections and isolated hepatic metastases (without any extraheptic disease) were included in this study (n=332). 129 patients (39%) had neoCTX (Oxaliplation or Irinotecan-based; in 32% of those including targeted therapy). The remaining 203 patients (61%) never had CTX before hepatectomy or CTX longer than 6 months before hepatectomy (in general adjuvant CTX after primary tumor). In the entire group 52% underwent at least hemihepatectomy. The results were gained by analysis of our prospective colorectal/hepatic database.
Results: Mortality after resection was 2.4% (1.6% with and 2.9% without neoCTx). Positive hepatic margins occurred in 32 of 332 resections (9.6%; in 7% after neoCTx, in 11% without neoCTx). Both, patients after neoCTX and patients with positive margins had larger (p<0.02/<0.03) and more CRC-LM (p<0.01/<0.001) than patients without neoCTx/free margins. After hepatectomy overall 5-year-survival (5ySurv; n=324) was 47%. In the entire group survival correlated strongly with the margin status (5ySurv 49% in R-0 and 29% in R+; p<0.001). Survival also correlated with margin status in the subgroups with neoCTX (5ySurv 45% in R-0 vs formally 0% in R+; last patient at risk died after 4.1 years; p<0.01) or without neoCTx (51% in R-0 vs 35% in R+; p<0.001). In multivariate analysis of the entire group hepatic margin status (p<0.001) and size of metastases > 30 mm (p<0.003) were associated with poorer survival. In patients after neoCTX only the resection margin was an independent predictor of survival (p<0.01).
Conclusion: In patients with isolated colorectal liver metastases undergoing resection the hepatic margin status was an independent prognostic factor. This strong effect was also present after neoadjuvant chemotherapy for CRC-LM.
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