Primary tumour location affects survival after resection of colorectal liver metastases: A two-institutional cohort study with international validation, systematic meta-analysis and a clinical risk score

Abstract

Background Colorectal cancer (CRC) represents a major cause for cancer death and every third patient develops liver metastases (CRLM). Several factors including number and size of metastases and primary tumour lymph-node status have been linked to survival. The primary tumour location along the colo-rectum continuum (sidedness) was analysed in first-line chemotherapy trials, where right-sided CRCs showed decreased survival. This association has not yet been clearly established in patients undergoing resection for CRLM. Methods Clinicopathological differences in CRLM resections according to sidedness in two Austrian centres (2003–2016) are described and survival is compared through Kaplan-Meier and multivariable analysis. A risk-score is presented with time-dependent receiver operating curve analysis and international validation in two major hepatobiliary centres. Furthermore, a systematic meta-analysis of studies on primary tumour location and survival after CRLM resection was performed. Results 259 patients underwent hepatectomy. Right-sided CRC patients (n = 59) more often had positive primary tumour lymph-nodes (76.3%/61.3%;p = 0.043) and RAS-mutations (60%/34.9%;p = 0.036). The median overall and disease-free survival was 33.5 and 9.1 months in right-sided versus 55.5 (p = 0.051) and 12.1 months (p = 0.078) in left-sided patients. In multivariable analysis nodal-status (HR 1.52), right-sidedness (HR 1.53), extrahepatic disease (HR 1.71) and bilobar hepatic involvement (HR 1.41) were significantly associated with overall survival. Sidedness was not independently associated with disease-free survival (HR 1.33; p = 0.099). A clinical risk score including right-sidedness, nodal-positivity and extrahepatic involvement significantly predicted overall (p = 0.005) and disease-free survival (p = 0.027), which was confirmed by international validation in 527 patients (p = 0.001 and p = 0.011). Meta-analysis including 10 studies (n = 4312) showed a significant association of right-sidedness with overall survival after resection (HR 1.55;p<0.001). There was no significant association with disease-free survival (HR 1.22;p = 0.077), except when rectal-cancers were excluded (HR 1.39;p = 0.006). Conclusions Patients with liver metastases from right-sided CRC experience worse survival after hepatic resection. Sidedness is a simple yet effective factor to predict outcome.

Impact of primary tumour location on colorectal liver metastases: A systematic review

“…For example, a number of studies have demonstrated inferior oncological outcome in patients undergoing surgical resection of CRCLM with right-sided versus left-sided colonic primary tumours[ 8 - 10 ]. This has not been a consistent observation, and others have shown no clear association[ 11 , 12 ]. The aim of the present systematic review is to provide a summary of the available evidence on the impact of PTL on oncological outcomes in patients with CRCLM.…”

“…Study population in these studies ranged from 24 to 3125 patients. Studies comprised two cohort prospective studies[ 15 , 16 ] (evidence level 2+) and 39 retrospective studies (evidence level 2+ - 2++)[ 8 - 12 , 17 - 50 ], this included 6 papers with pooled analysis (evidence level 2+-2++)[ 10 , 12 , 15 , 16 , 18 , 49 ]. There were no randomised controlled trials.…”

Survival after Combined Hepatic Metastasectomy and Chemotherapy in Patients with Concurrent Hepatic and Extrahepatic Colorectal Metastases: a SEER Database Analysis

“…Our study showed that patients had outcomes that were more favorable when their primary tumors were grade I, located at the rectum, or when they had an EHD located at the lungs. Similarly, a study observed more reduced survival rates following liver resection in patients with liver metastases from right-sided colon cancer [18]. In contrast, Aoki et al found no signi cant differences in overall survival between different sites of the primary tumor [16].…”

Survival After Combined Hepatic Metastasectomy and Chemotherapy in Patients with Concurrent Hepatic and Extrahepatic Colorectal Metastases: A SEER Database Analysis.

“…Our study showed that patients had outcomes that are more favorable when their primary tumors were grade I, located at the rectum, or when they had an EHD located at the lungs. Similarly, a study observed more reduced survival rates following liver resection in patients with liver metastases from right-sided colon cancer [18]. On the contrary, Aoki et al found no signi cant differences in overall survival between different sites of the primary tumor [16].…”