Prognostic Factors and Survival after Resection of Colorectal Liver Metastasis in the Era of Preoperative Chemotherapy: An 11-Year Single-Centre Study

Abstract

Introduction: A variety of factors have been identified in the literature which influence survival following resection of colorectal liver metastases (CRLM). Much of this literature is historical, and its relevance to contemporary practice is not known. The aim of this study was to identify those factors which influence survival during the era of preoperative chemotherapy in patients undergoing resection of CRLM in a UK centre. Methods: All patients having liver resection for CRLM during an 11-year period up to 2011 were identified from a prospectively maintained database. Prognostic factors analysed included tumour size (≥5 or <5 cm), lymph node status of the primary tumour, margin positivity (R1; <1 mm), neo-adjuvant chemotherapy (for liver), tumour differentiation, number of liver metastases (≥4), preoperative carcinoembryonic antigen (CEA; ≥200 ng/ml) and whether metastases were synchronous (i.e. diagnosed within 12 months of colorectal resection) or metachronous to the primary tumour. Overall survival (OS) was compared using Kaplan-Meier plots and a log rank test for significance. Multivariate analysis was performed using a Cox regression model. Statistical analysis was performed in SPSS v19, and p < 0.05 was considered to be significant. Results: 432 patients underwent resection of CRLM during this period (67% male; mean age 64.5 years), and of these, 54 (13.5%) had re-resections. The overall 5-year survival in this series was 43% with an actuarial 10-year survival of 40%. A preoperative CEA ≥200 ng/ml was present in 10% of patients and was associated with a poorer 5-year OS (24 vs. 45%; p < 0.001). A positive resection margin <1 mm was present in 16% of patients, and this had a negative impact on 5-year OS (15 vs. 47%; p < 0.001). Tumour differentiation, number, biliary or vascular invasion, size, relationship to primary disease, nodal status of the primary disease or the use of neo-adjuvant chemotherapy had no impact on OS. Multivariate analysis identified only the presence of a positive resection margin (OR 1.75; p < 0.05) and a preoperative CEA ≥200 ng/ml (OR 1.88; p < 0.01) as independent predictors of poor OS. Conclusion: Despite the wide variety of prognostic factors reported in the literature, this study was only able to identify a preoperative CEA ≥200 ng/ml and the presence of tumour within 1 mm of the resection margin as being of value in predicting survival. These variables are likely to identify patients who may benefit from intensive follow-up to enable early aggressive treatment of recurrent disease.

Pre-hepatectomy carcinoembryonic antigen (CEA) levels among patients undergoing resection of colorectal liver metastases: do CEA levels still have prognostic implications?

“…These data were consistent with previous reports that included patients from a similar time span, which demonstrated the prognostic relevance a wide range of CEA cut-off values. [4][5][6][14][15][16][17][18] In contrast, in the current study, in the later time period of 2008-2015 pre-hepatectomy CEA levels had no prognostic significance, until a much higher-cutoff value was utilized. Of interest, in the later period, the HRs associated with OS increased sharply when the CEA level exceeded 70 ng/mL.…”

“…The following factors were included in multivariate analysis: (i) variables that were significant on univariate analysis (P < 0.10) (Supplemental Table 1) (ii) clinically relevant characteristics such as bilobar disease, and location of CRC. [4][5][6][14][15][16][17][18] The prognostic significance of pre-hepatectomy CEA level was determined by assessing the HRs associated with various CEA cut-off levels ranging from 5 to 200 ng/mL. 4,6,[14][15][16][17][18] HRs and P values for each individual CEA cutoff level were calculated after adjusting for other relevant clinicopathological variables on multivariate analysis.…”

“…4,[14][15][16][17][18] In fact, CEA levels have been incorporated into the Fong clinical risk score, as well as in several prognostic nomograms utilized to estimate long-term prognosis of patients with CRLM. 5,6,11 While the prehepatectomy CEA level is influenced by primary CRC status and CRLM tumor burden, several studies have reported that prehepatectomy CEA levels remained independently predictive of prognosis even after adjusting for clinicopathological variables.…”

“…5,6,11 While the prehepatectomy CEA level is influenced by primary CRC status and CRLM tumor burden, several studies have reported that prehepatectomy CEA levels remained independently predictive of prognosis even after adjusting for clinicopathological variables. [4][5][6][14][15][16][17][18] Pre-hepatectomy CEA levels can, however, also be influenced by receipt and response to chemotherapy, 11,12,23,24 and detailed data on the impact of CEA on prognosis in the era of modern chemotherapy are lacking. 4-6,14 -16 Therefore, the objective of the current study was to reappraise the prognostic implications of CEA levels in a contemporary clinical environment characterized by the use of modern chemotherapy regimens.…”

“…>5, 10, >30, >60, >100 and >200 ng/mL) as being independently predictive of prognosis. 4,6,[14][15][16][17][18] The introduction of novel multi-drug combination chemotherapeutic regimens, including oxaliplatin, irinotecan, and biologic agents has made curative-intent hepatectomy among initially unresectable CRLM patients feasible. [19][20][21] Advances in systemic therapy have also changed the treatment strategy for resectable CRLM.…”