Abstract

Introduction Controversy exists as to the survival benefit of liver resection in patients with colorectal liver metastases (CRLM) whose disease has progressed despite neoadjuvant chemotherapy. This study looked at outcomes after liver resection for CRLM, in relation to response to neoadjuvant chemotherapy and in those patients whose disease progressed, specifically asked whether the pattern of disease progression influenced survival. Method Clinical, pathologic, and complete follow-up (median 35.3 months) data were prospectively collected from 582 consecutive patients who had neoadjuvant chemotherapy prior to resection of CRLM with curative intent at a single centre (March 1998–March 2013). Patients were divided into four groups according to their response to chemotherapy: complete response (CR) (n = 32), partial response (PR) (n = 447), stable disease (SD) (n = 62) and progressive disease (PD) (n = 41). Patients with PD were subdivided into those whose metastases increased in size (PDs) (n = 19) and those whose metastases increased in both size and number (PDsn) (n = 22). Cumulative disease-free survival (DFS) and cancer-specific survival (CSS) were calculated using Kaplan Meier analysis. Results At the time of liver surgery, patients with PD had a higher median [interquartile range (IQR)] CEA in ug/L [20.5 (4.1–57.8)] compared to patients with CR [2.0 (1.1–10.0)], PR [4.0 (1.9–13.0)] or SD [4.0 (1.2–13.5), p = 0.001]. Patients with PD also had a significantly higher median (IQR) number of CRLM [3 (1–6), p = 0.001] and size of metastases [55 (20–80)mm, p = 0.001], compared to patients with CR [1 (0–1) and 1 (0–4) mm], PR [2 (1–4) and 25 (20–40) mm] or SD [2 (1–3) and 30 (20–40) mm]. No differences were observed regarding patient demographics, the extent of hepatic resection, Clavien-Dindo Grade 3/4 complications, in-hospital mortality or clear resection margin rates. Cumulative 5 year DFS and CSS was significantly higher in the CR patients (50.1% and 53.2%), compared to PR (42.1% and 44.3%), SD (37.1% and 39.4%) or PD (21.0% and 23.8%, p = 0.001 and 0.017 respectively). However, in the patients with PD, the PDs patients had significantly better DFS and CSS (37.5% and 39.1%) compared to the PDsn patients (10.4% and 12.4%, p = 0.046 and 0.045 respectively), such that their DFS and CSS was comparable to those patients with SD. Conclusion Progression on neoadjuvant chemotherapy per se for patients with CRLM should not be considered a contraindication for potentially curative hepatectomy. These data suggest that the type of disease progression is important and that patients whose metastases increase in size only will still derive significant survival benefit. Disclosure of interest None Declared.

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