Local Treatment of Colorectal Liver Metastases in the Presence of Extrahepatic Disease: Survival Outcomes from the Amsterdam Colorectal Liver Met Registry (AmCORE)

Abstract

Background: The simultaneous presence of colorectal liver metastases (CRLMs) and extrahepatic metastases in patients with colorectal cancer (CRC) can be considered a relative contraindication for local treatment with curative intent. This study aims to assess the survival outcomes of patients with CRLMs and extrahepatic metastases after comprehensive local treatment of all metastatic sites.

Methods: Patients with CRLMs who received local treatment of all metastatic sites were extracted from the prospective AmCORE registry database and subdivided into two groups: CRLM only vs. CRLM and extrahepatic metastasis. To address potential confounders, multivariate analysis was performed. The primary endpoint was overall survival (OS).

Results: In total, 881 patients with CRLM only and 60 with CRLM and extrahepatic disease were included, and the median OS was 55.7 months vs. 42.7 months, respectively. Though OS was significantly lower in patients with concomitant extrahepatic metastases (HR 1.477; 95% CI 1.029-2.121; p = 0.033), the survival curve plateaued after 6.2 years. Extrahepatic manifestations were pulmonary (43.3%), peritoneal (16.7%) and non-regional lymph node metastases (10.0%). In patients with pulmonary and non-regional lymph node metastases, OS did not significantly differ from patients with CRLM-only disease; concomitant peritoneal metastases showed an inferior OS (HR 1.976; 95% CI 1.017-3.841, p = 0.041).

Conclusions: In this comparative series, OS was inferior for patients with multi-organ metastatic CRC versus patients with CRLMs alone. Nonetheless, the long-term survival curve plateau seemed to justify local treatment in a subset of patients with multi-organ metastatic CRC, especially for patients with CRLMs and pulmonary or lymph node metastases.

Keywords: colorectal cancer (CRC); colorectal liver metastases (CRLMs); extra hepatic colorectal metastases; irreversible electroporation; local treatment; partial hepatectomy; stereotactic ablative radiotherapy; surgical resection; thermal ablation.

Figure 1

Flowchart of included and excluded patients.

Figure 2

Organ(s) affected by extrahepatic disease. Reported as number of patients (%). Multiple = more than one organ is affected by metastatic disease; other = spleen and adrenal gland. Lymph node metastases were located in the lung hilum (1×), liver hilum (1×), spleen (2×), supra clavicular (1×), para-cardiac (1×), para-aortic (3×), para-iliac (2×), retro peritoneal (1×), and unknown (2×) regions due to no clear description in the available radiology report.

Figure 3

Kaplan–Meier curves of overall survival (OS), p = 0.033. Compared with log-rank test. Red indicates patients with CRLM-only disease. Blue indicates patients with extrahepatic disease at time of first diagnosis CRLM.

Figure 4

Kaplan–Meier curves of overall survival (OS). Compared with log-rank test. OS per patient comparing CRLM only to (a) CRLM with pulmonary metastasis (p = 0.363), to (b) CRLM with peritoneal metastasis (p = 0.041), and to (c) comparing CRLM only and non-regional lymph node metastasis (p = 0.483). Number of events are per patient.

Figure 5

Kaplan–Meier curves of distant progression-free survival (DPFS), p = 0.011. Compared with log-rank test. Red indicates patients with CRLM-only disease. Blue indicates patients with extrahepatic disease at time of first diagnosis of CRLM. Successfully retreated local recurrences were not considered as an event in this analysis.