The Impact of Surgical Resection in Early Onset Colorectal Cancer Patients With Liver Limited Disease

Background: Recent studies have shown an increased incidence of early-onset CRC (EO-CRC), particularly in advanced stages and with metastatic disease. Our study aimed to evaluate the role of metastasectomies related to the clinical and molecular characteristics of EO-CRC patients with liver metastases compared to average-onset CRC (AO-CRC) patients. Methods: We retrospectively collected data from 1123 stage IV colorectal cancers, including 782 with liver metastases, from 5 different Italian institutions. The main objective of the study was to compare the overall survival of liver metastatic EO-CRC and AO-CRC patients who underwent metastasectomy versus those who were not resected. Results: Liver resected EO-CRCs patients showed a statistically significant lower mOS than liver resected AO-CRCs (44.0 vs. 64.0 months, P < .0001). mPFS was also statistically significant lower in EO-CRCs (13.0 vs. 17.0, P < .0001). Same outcomes were found in RAS mut subgroup (37.0 vs. 52.0 months, P < .0001) and in RAS/BRAF wild-type subgroup (50.0 vs. 81.0 months, P < .0001).EO-CRC patients showed a higher prevalence of TP53 alterations (56.2%) and a lower of APC mutation (29.9%). EO-CRCs presented a higher frequency of ARID1A (4.4%) and CTNNB1 (3.0%) alterations. Conclusion: The results indicate a worse overall prognosis for EO-CRC patients undergoing metastasectomy compared to average-onset patients. This outcome appears to occur independently of the molecular status. These observations could have a considerable impact on clinical practice and research.