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

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.

High Dual Expression of the Biomarkers CD44v6/α2β1 and CD44v6/PD-L1 Indicate Early Recurrence after Colorectal Hepatic Metastasectomy

“…In contrast, genomic [20][21][22], transcriptomic [23] and proteomic [24] profiling identified molecular differences between primary tumor, liver and lung metastases that might have potential therapeutic implications for specific metastatic sites. Moreover, distant metastases in different organs revealed discordant responses to standard chemotherapy [25], all together, supporting the concept of inter-and intratumor heterogeneity, which is one of the key factors in tumor progression, therapeutic resistance, and poor patient outcome.…”

Is precision medicine for colorectal liver metastases still a utopia? New perspectives by modern biomarkers, radiomics, and artificial intelligence

“…Fourth, in patients with liver and lung metastases, the pulmonary disease has shown a limited prognostic relevance[ 31 ]. Such data should be paired with those provided by Viganò et al [ 32 ], who demonstrated that the pathological response of colorectal metastases to systemic therapy changes according to the involved organ, being low in the lung and lymph nodes metastases, intermediate in the hepatic ones, and high in the peritoneal ones. The inhomogeneous prognostic relevance and chemosensitivity of the different tumor sites open new perspectives in treatment strategies and oncological research.…”