TP53 Alteration and Its Effect on Pathologic Response Are Associated with Survival after Resection of Colorectal Liver Metastases

The aims of this study were to assess the effect of known gene alterations (RAS, TP53, APC, SMAD4, BRAF, and FBXW7) on pathologic response (PR) and their combined association with survival in patients with colorectal liver metastases (CLM). From a prospectively maintained database, we collected data on 458 patients who underwent curative-intent hepatectomy after receiving the first-line preoperative chemotherapy between 2004 and 2020. Major PR was defined as tumor viability of less than 50% in all tumors. Multivariate logistic regression revealed that oxaliplatin-containing regimen (OR: 2.54, 95% CI: 1.58-4.07, P < 0.001), bevacizumab-containing regimen (OR: 2.15, 95%CI: 1.36-3.39, P = 0.001), and TP53 alteration (OR: 0.42, 95%CI: 0.27-0.66, P < 0.001) were independently associated with major PR. Multivariate Cox regression also revealed that patients with TP53 wild-type and major PR (HR: 0.49, 95%CI: 0.31-0.77, P = 0.002) and those with TP53 alteration and major PR (HR: 0.70, 95%CI: 0.49-1.00, P = 0.048) had significantly better overall survival compared to those with minor PR. Further studies targeting the association of TP53 with PR and survival can help clarify the role of TP53 in CLM.