Of the 611 patients, 141 (23.1%) had primary tumors located in right-sided CRC, and 470 (76.9%) had primary tumors located in left-sided CRC. Clinicopathological characteristics of two groups were presented in Table 1. Compared to left-sided group, right-sided group tended to have larger tumor size in CRC (4.2 vs. 3.6 cm, P = 0.011) and less people underwent preoperative chemotherapy before hepatectomy (48.2 vs. 61.1%, P = 0.008). Other baseline parameters such as largest size of liver tumors, number and distribution of liver metastases were comparable between two groups.
After PSM, 127 matched pairs were generated from right-sided and left-sided groups. The standardized mean differences of included PSM factors were decreased (Table 1). Also, Hansen-Bowers test for global imbalance was not significant (P = 0.996) and the Iacus-King-Porro test showed that L1 was reduced in the matched sample, indicating the improvement of the overall balance (L1: before matching 0.929; after 0.899). The reduction of imbalance is pictured by histograms with overlaid kernel density estimates for SMD (Supplementary Figure 1).
The average follow-up interval for all the included patients was 36.9 months (range: 2.2-151.5 months). The median OS for right-sided group and left-sided group were 77 months and 64 months respectively. The 1-, 3- and 5-year OS rates after CRLM resection in right-sided group were 91.0%, 75.0% and 56.3%, respectively, and 94.9%, 84.8%, and 51.1%, respectively, in left-sided group (P = 0.575; Figure 1a). The 1-, 3- and 5-year RFS rates after R0 resection of liver metastases in right-sided group were 27.8%, 10.1%, and 5.1%, respectively, and 40.9%, 22.6%, and 8.8%, respectively, in left-sided group. Left-sided group have a significant better RFS rate than right-sided group (P = 0.028; Figure 1b).
After PSM, the median OS time for patients in right-sided group was 77 months and was 58 months in left-sided group. Cumulative 1-, 3- and 5-year OS rates were 89.2%, 64.2% and 55.9%, respectively, in right-sided group, compared to 95.9%, 75.7% and 47.3%, respectively, in left-sided group (P = 0.453; Figure 1c). The median RFS for patients in right-sided group was 5.8 months and was 10.9 months for patients in left-sided group. Cumulative 1- and 3-year RFS rates were 25.9% and 10.1%, respectively, in the patients from right-sided group, compared to 48.8% and 17.2%, respectively, in patients from left-sided group (P = 0.003; Figure 1d).
Prognosis stratified by CRS score and tumor number
We further explored the prognostic role of CRC location according to CRS scores and liver lesions. Similar OS were found in CRLM patients stratified by CRC location with different CRS scores. Significant worse RFS were found in right-sided group before and after PSM among patients with low CRS scores (P = 0.037, P = 0.011; Figure 2). However, RFS were comparable before and after PSM between right-sided and left-sided group with high CRS scores (P = 0.284, P = 0.117; Figure 3). Among patients with single liver lesion, OS and RFS were comparable before and after PSM between right-sided and left-sided group (P = 0.322, P = 0.338; P = 0.191, P = 0.118; Supplementary Figure 2). Among patients with multiple liver metastases, significant worse RFS were also found in right-sided group before and after PSM (P = 0.022, P = 0.012; Supplementary Figure 3b,3d).
Prognostic Factors for patients after resection of liver metastases
Next, we performed univariate and multivariate analysis to identify prognostic factors in our patients. Factors including lymph node metastases (HR 1.600, 95% confidence interval [CI] 1.155-2.216, P = 0.005), liver lesions > 5cm (HR 1.923, 95% CI 1.298-2.849, P = 0.001) and non-R0 resection (HR 1.998, 95% CI 1.424-2.804, P < 0.001) were found to affect OS (Table 2). For RFS, significant factors in multivariate analysis were tumor location (HR 0.659, 95% CI 0.478-0.910, P = 0.011), lymph node metastases (HR 1.533, 95% CI 1.159-2.029, P = 0.003) and resection combined with ablation (HR 1.793, 95% CI 1.253-2.566, P = 0.001) (Table 2).
Treatment of recurrence
Of the 611 patients, 240 (39.3%) patients had recurrence after liver metastases resection. There were 99 (39.0%) patients with relapsed after PSM. Treatment modality of recurrence in two groups were presented in Table 3. Before PSM, 41 (75.9%) and 119 (64.0%) patients underwent resection/ ablation/ chemotherapy alone and 13 (24.1%) and 67 (36.0%) patients underwent combined therapy in right-sided and right-sided group, respectively. Treatment modality of recurrence in two groups was comparable between two groups before and after PSM.