Clinical evolution after surgery of hepatic metastases of colorectal cancer according to genomic profile.
Authors: Morón García Blanca , Alva Bianchi Manuel , Muñoz Martín Andrés J. , Calvo Ferrándiz Aitana , Ortega Morán Laura , Torres Pérez-Solero Gabriela , Blanco-Codesido Montserrat , Tirado Anula Victoria , de Toro Carmena María , de Toro Carmena María , Soto Alsar Javier , Gutiérrez Alonso Natalia , Bringas Beranek Marianela , Garcia-Alfonso Pilar 
Published: January 2022

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Background: Hepatic metastatic disease from colorectal cancer (CRC) is a significant clinical problem, as the liver is the dominant metastatic site for patients with CRC and 25% of patients will have liver affection at diagnosis. Due to improvement in systemic therapy and locoregional treatments in the last decade, survival has increased significantly. In this regard, it is key to be able to establish several prognostic factors that significantly influence survival. Methods: We carried out a retrospective analysis of 554 patients with mCRC treated at the Gregorio Marañon Hospital (Madrid, Spain) between January 2010 and 2021. We analyzed the clinical and molecular characteristics of patients undergoing liver metastasis surgery as first metastasis surgery together with relapse patterns to progression. Results: Out of our cohort of 554 patients with mCRC we identified 169 patients that underwent liver metastasis surgery as 1st surgery, achieving a media of survival of 56.38 months [95% CI, 44.21-73.78 months]. Regarding the clinical characteristics of the population, the majority were men (63,91%) and had a PS 0-1 (90,5%); and 46 patients (27,2%) were more than 70 years old. In relation to the location of the primary tumour, 46 patients (27,2%) had it n the right colon and 120 in the left colon (71,0%). And 43 patients (25,4%) had extrahepatic disease at the time of surgery. Regarding the biomakers, we indentified the following mutations: 68 mutated KRAS (40,2%), 5 mutated NRAS (2,9%), 9 mutated BRAF (5,3%), 13 mutated PI3K (7,6%), 1 HER2 amplification (0,5%) and 4 with IMS phenotype (2,3%). After the metastasis surgery, progression was mainly hepatic (50,3%), followed by pulmonary (24,8%), peritoneal (11,8%), lymph node (12%), bones (4,7%) and cerebral (1,1%), without having significant differences in relapse patterns at the statistics when analyzed by genomic profile. When analyzing progression-free survival (PFS) and overall survival (OS) according to the genomic profile, in the BRAF mutated vs BRAF WT population, no statistically significant differences were found, obtaining therefore an evident benefit. Furthermore, we found significant differences in OS for patients with right vs left primary tumour as well as for patients with extrahepatic involvement at the time of surgery. Conclusions: Patients undergoing sequential metastatic surgery have a long survival, so it is important to analyse patterns of relapse and clinical course. There is no evidence of significant differences in the progression patterns according to the mutational status of the mCRC; but selected patients with BRAF mutations may obtain benefit in PFS and OS with locoregional approaches to their liver disease.