Clinical significance of serum tumor marker dynamics during preoperative chemotherapy and hepatectomy for colorectal liver metastases.

Abstract

204 Background: Surgical resection of colorectal cancer liver metastasis (CRLM) provides the best chance for long-term survival. Preoperative chemotherapy before liver resection may improve outcomes. Carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) have been reported as prognostic markers; however, the clinical significance of perioperative changes in these tumor markers in CRLM remains unclear. Methods: We retrospectively reviewed patients who underwent initial CRLM resection after preoperative chemotherapy between October 2016 and August 2021 at a single cancer center. Patients with extrahepatic disease were excluded. Serum CEA and CA19-9 levels were assessed before chemotherapy, after chemotherapy, and after surgery. Patients were categorized into 4 groups by CEA/CA19-9: Group 1 (G1), normal before chemotherapy; Group 2 (G2), high before chemotherapy and normalized after chemotherapy; Group 3 (G3), high before/after chemotherapy and normalized after surgery; Group 4 (G4), perioperative persistent elevation. The association between changes in these markers and clinical outcomes was analyzed. Results: A total of 222 patients were enrolled. Median chemotherapy duration was 13.0 weeks (IQR 11.6–15.1). Median largest liver metastasis diameter was 38.0 mm (range 7.0–230.0), and the number of liver metastases was 1–5 in 115 patients (51.8%), 6–9 in 56(25.2%), and ≥10 in 51 (23.0%). Median recurrence free survival (RFS) and overall survival (OS) were 11.1 months (95% CI 9.3-13.3) and 99.9 months (95% CI, 69.4-116.4), respectively. Multivariate analysis revealed that high CA19-9 before chemotherapy (HR 1.61, p=0.02), high CEA and CA19-9 after chemotherapy (CEA: HR 1.96, p<0.01; CA19-9: HR 2.34, p<0.01), and high CEA and CA19-9 after surgery (CEA: HR 4.94, p<0.01; CA19-9: HR 5.05, p<0.01) were identified as independent poor factors for OS. Similarly, high CA19-9 before chemotherapy (HR 1.40, p=0.03), high CEA and CA19-9 after chemotherapy (CEA: HR 2.10, p<0.01; CA19-9: HR 1.91, p<0.01), and high CEA and CA19-9 after surgery (CEA: HR 4.45, p<0.01; CA19-9: HR 6.45, p<0.01) were identified as independent poor factors for RFS. G4 in both cohorts developed recurrence. Survival was stratified by these patterns. Compared with G1, G3 had shorter RFS (CEA: HR 1.90, 95% CI, 1.17–3.08; CA19-9: HR 1.61, 95% CI, 1.04–2.50) and OS (CEA: HR 1.60, 95% CI, 0.85–3.02; CA19-9: HR 2.19, 95% CI, 1.27–3.78) and G4 showed the poorest RFS (CEA: HR 6.56, 95% CI, 3.11–13.81; CA19-9: HR 6.93, 95% CI, 3.32–14.44) and OS (CEA: HR 7.86, 95% CI, 3.21–19.21; CA19-9: HR 9.33, 95% CI, 4.04–21.56). The proportion of patients with extrahepatic recurrence increased stepwise from G1 to G4 (CEA: 27.3%, 33.3%, 48.9%, 90.9%; CA19-9: 33.6%, 38.7%, 63.3%, 100%). Conclusions: Perioperative levels and dynamic changes of CEA and CA19-9 were associated with recurrence and survival in CRLM.