Hepatic and extrahepatic colorectal metastases: discordant pathologic responses to systemic therapy in patients undergoing simultaneous resection of multiple tumor sites

Abstract

Purpose: Systemic therapy is the standard treatment for patients with hepatic and extrahepatic colorectal metastases. It is assumed to have the same effectiveness on all disease foci, independent of the involved organ. To compare the response rates of hepatic and extrahepatic metastases to systemic therapy. Methods: All consecutive patients undergoing resection for colorectal metastases were considered. Patients undergoing simultaneous resection of hepatic and extrahepatic metastases after preoperative chemotherapy were analyzed. Specimens of hepatic and extrahepatic metastases were reviewed. Pathological response to chemotherapy was classified according to tumor regression grade (TRG). Results: We analyzed 45 patients undergoing resection of 134 hepatic and 72 extrahepatic metastases. Extrahepatic disease was peritoneal in 21 patients, pulmonary in 15, lymph nodal in 14, and adrenal in one (multiple organs in five patients). All patients had oxaliplatin- and/or irinotecan-based preoperative chemotherapy; 60% had associated targeted therapies. Lung and lymph node metastases had lower response rates to chemotherapy than liver metastases (TRG 4–5 in 95% and 100% vs. 67%, P=0.008 and P=0.006, respectively). Peritoneal metastases had a higher pathological response rate than liver metastases (TRG 1–3 66% vs. 33%, P<0.001) and non-hepatic non-peritoneal metastases (vs. 3%, P<0.001). Multivariate analysis identified metastases site, metastasis size and targeted therapies as predictors of pathological response to systemic therapy. Conclusion: Response to chemotherapy of distant metastases from colorectal cancer varies in different organs. Systemic treatment is highly effective for peritoneal metastases, more so than liver metastases, while it has a very poor impact on lung and lymph node metastases.