Impact on survival of primary tumor resection in patients with colorectal cancer and unresectable metastasis: Pooled analysis of individual patients’ data from four randomized trials.

Abstract

3507 Background: In patients with colorectal cancer (CRC) and unresectable metastasis, the prognostic impact of primary tumor resection still remains a matter of debates. The goal of this study was to estimate, after adjustment for prognostic factors, the effect of primary tumor resection on survival. Methods: Individual patients’ data of the 1155 patients with metastatic CRC included in 4 first-line chemotherapy trials (FFCD 9601, FFCD 2000-05, ACCORD 13 and ML 16987) where retrieved. Patients were eligible for this study if they had synchronous metastasis judged unresectable. Primary endpoint was overall survival (OS), secondary endpoint was progression free survival (PFS). A Cox proportional hazard model stratified on the trial was used to estimate the impact on survival. Results: 810 patients beginning first-line chemotherapy with either fluoropyrimidine alone, oxaliplatin, irinotecan and/or bevacizumab were eligible. Patients with a history of resection (n = 478 (59%)), as compared to those without (n = 332 (41%)), were more likely to have colonic primary (p < 0.0001), lower carcino embryonic antigen (CEA) (p < 0.0001) or alkaline phosphatase (ALP) level (p=0.04) and normal white blood cell count (WBC) (p < 0.0001). In the univariate analysis, stratified on the trial, primary tumor resection was associated with a better OS (Hazard Ratio HR: 0.73 [0.63-0.84]; p < 0.0001) and PFS (HR : 0.73 [0.63-0.84]; p < 0.0001). Multivariate analysis, adjusted for primary tumor location, CEA, ALP and WBC levels, OMS performance status and number of metastatic sites confirmed that primary tumor resection was an independent predictor of better OS (HR : 0.63 [0.53-0.75] ; p < 0.0001), and PFS (HR : 0.82 [0.70-0.95] ; p = 0.0007). Significant interactions were found between resection and CEA level (p=0.02) and resection and primary tumor location (p=0.01) for OS (not for PFS) with a lower impact of resection with higher CEA levels or a colonic primary. Conclusions: This study confirmed the independent prognostic value on survival of primary tumor resection in patients with unresectable metastases of CRC.