Genomic and Clinical Predictors of Conversion in Initially Unresectable Colorectal Cancer Liver Metastases.

[BACKGROUND] Colorectal cancer liver metastases (CRLM) present significant treatment challenges, requiring multimodal conversion therapies. Identifying factors that influence treatment outcomes is crucial for improving clinical management.

[PATIENTS AND METHODS] This retrospective cohort study included 286 patients with synchronous CRLM who underwent conversion therapies on the basis of sequencing results. Patients were categorized into successful conversion therapy group (SCTG) and failed conversion therapy group (FCTG). Clinical factors and genomic mutations were analyzed for associations with therapy outcomes and survival.

[RESULTS] Among the patients, 106 (37.1%) achieved successful conversion (SCTG), while 180 (62.9%) failed (FCTG). Compared with SCTG, patients in the FCTG had significantly larger metastatic lesions, higher preoperative mesenteric lymph node positivity, and elevated carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) levels. Six genes (FAT, BRAF, SERPINA3, GRIN2A, ERBB2, and ALK) showed the highest mutation frequency differences in FCTG, correlating with worse outcomes. Any of these mutations was associated with shorter overall survival compared with wild-type patients. A nomogram model using tumor mutation status, CEA, CA19-9, lesion diameter ≥ 5 cm, and positive lymph nodes at diagnosis predicted conversion efficacy (area under the curve = 89.6, 95% confidence interval 22.6-92.4). An extended conversion-related clinical risk score scoring system incorporating these factors effectively stratified poor prognosis populations, serving as a prognostic tool for patients with unresectable CRLM.

[CONCLUSIONS] Genomic profiling improves precision management of CRLM, facilitating tailored conversion strategies and better prognostic prediction. Future studies should validate these findings in prospective cohorts to refine personalized treatment for patients with initially unresectable CRLM.