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

Luca Vigano,Pio Corleone,Lorenzo Viggiani,Shadya Sara Darwish,Guido Torzilli,Daniele Del Fabbro,Simone Famularo,Luca Di Tommaso,Nicolò Turri,Lorenza Rimassa

doi:10.3390/cancers13030464

Abstract

Simple SummaryThe 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.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.

Highlights

Systemic therapy has a major impact on the prognosis of patients with stage IV colorectal cancer [1,2,3]
Twentythree patients were excluded for the following reasons: eight patients with hepatic and pulmonary metastases underwent a staged resection of the two organs; seven patients had hepatic disease progression while on preoperative chemotherapy; four patients did not receive preoperative chemotherapy; two patients had a complete response to chemotherapy and were operated upon for disease reappearance without further chemotherapy; two patients had no confirmation of extrahepatic disease at final pathology
Radiological response to chemotherapy of hepatic and extrahepatic metastases was classified according to RECIST criteria version 1.1 [40]

Summary

Introduction

Systemic therapy has a major impact on the prognosis of patients with stage IV colorectal cancer [1,2,3]. Systemic therapy prolongs progression-free survival after surgery and may lead to five-year survival rates approaching 50% [7,8,9,10]. Patients with both hepatic and extrahepatic metastases have lower survival expectancy than patients with liver-only disease, but systemic therapy improves their prognosis as well [1]. 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

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