Hepatic and Extrahepatic Colorectal Metastases Have Discordant Responses to Systemic Therapy. Pathology Data from Patients Undergoing Simultaneous Resection of Multiple Tumor Sites

SIMPLE SUMMARY: The standard treatment of patients with hepatic and extrahepatic metastases from colorectal cancer is systemic chemotherapy. We assume that this therapy has the same effectiveness on all disease foci, independent of the involved organ. The effectiveness of chemotherapy is assessed by the pathological response rate: the higher the response rate, the higher the effectiveness of chemotherapy. In the present manuscript, we analyzed patients undergoing resection of hepatic and extrahepatic metastases from colorectal cancer after preoperative chemotherapy. We observed unexpected heterogeneity of the response to chemotherapy of distant metastases from colorectal cancer according to the involved organ. Peritoneal metastases had the highest pathological response rate, which was much higher than the hepatic metastases, while lung and lymph node metastases had extremely poor response rates. Such inhomogeneous effectiveness of systemic treatment in different organs open new perspectives in the treatment of colorectal cancer with distant metastases and oncological research. ABSTRACT: Background: 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. The present study aims to compare the response rates of hepatic and extrahepatic metastases to systemic therapy. Methods: All consecutive patients undergoing simultaneous resection of hepatic and extrahepatic metastases from colorectal cancer after oxaliplatin- and/or irinotecan-based preoperative chemotherapy were analyzed. All specimens 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. Lung and lymph node metastases had lower response rates to chemotherapy than liver metastases (TRG 4–5 95% and 100% vs. 67%, p = 0.008, and p = 0.006). 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 (3%, p < 0.001). Metastases site was an independent predictor of pathological response to systemic therapy. Conclusions: 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.