A total of 64019 patients were included, including 15746 who received operation, and 48273 who did not receive operation.
For the survival analysis, patients with survival months code 0 (contact lost after diagnosis) and 9999 (unknown length of survival month) and patients with transplantation were excluded, leaving 52338 patients in this part of the study. After PSM, a total of 18872 patients were included into survival analysis. Among them, 9436 patients received operation treatment and 9436 patients received non-operation treatment. The baseline characteristics of patients before PSM and after PSM in the two group were compared (Table 1).
To determine whether patients could gain an additional survival benefit from surgery, the patients were divided into seven groups (group A-G) based on the BCLC stage A and B. Group A included patients with a single tumor size smaller than 5 cm. Group B included patients with a single tumor larger than 5 cm but no more than 7 cm. Group C included patients with a single tumor larger than 7 cm but no more than 9 cm. Group D included patients with a single tumor larger than 9 cm. Group E included patients with 2-3 tumors no more than 3 cm. Group F included patients with 2-3 tumors larger than 3 cm. Group G included patients with multiple tumors (>3 tumors) (Figure 1).
Trends of operation and surgery on HCC
The trends of operation rate increased in localized, regional and distant group (all P<0.001). (Figure 2A). For surgery, the frequencies and trends in localized (P=0.016), regional (P=0.009), distant group (P=0.018) declined with time (Figure 2B). For patients without operation treatment, the non-operation rate in the localized, regional and distant group increased (all P<0.001) (Figure 2C).
Median Overall Survival (mOS) in all patients and the subgroups
After PSM, the mOS of patients in the surgery group (45 months, 95%CI: 42.4,47.6) was longer than that in the non-surgery operation group (32 months, 95%CI; 31.1,32.9, P<0.001), which was longer than that in the non-operation group (12 months, 95%CI: 11.7,12.3), P<0.001) (Figure 3). The mOS of patients in localized group receiving surgery (59 months, 95%CI: 54.8,63.2) was longer than that of patients with non-surgery operation (38 months, 95%CI: 36.1,39.9, P<0.001), which was longer than patients with non-operation (16 months, 95%CI: 15.3,16.7, P<0.001) (Figure 4A). Similar results were presented in regional, distant and unknown stage groups. In reginal group, the mOS of patients with surgery(23 months, 95%CI: 19.9,26.1) was longer than patients with non-surgery operation (22 months, 95%CI: 20.1,23.9, P=0.031), which was longer than patients in the non-operation (7 months, 95%CI: 6.4,7.6, P<0.001) (Figure 4B). In distant group, the mOS of patients with non-surgery operation (11 months, 95%CI: 8.9,13.1) was longer than patients with non-operation (4 months, 95%CI: 3.5,4.5, P<0.001) (Figure 4C). In the subgroups analysis, the patients in the group A who underwent surgery (59 months, 95%CI: 53,65) had better survival than patients with non-surgery operation (36 months, 95%CI: 34.1,37.9, P<0.001), which was longer than patients with non-operation (18 months, 17.1,18.9, P<0.001) (Figure 5A). In group B, patients with surgery (43 months, 95%CI: 36,50) had also better survival than patients with non-surgery operation (21 months, 95%CI: 18,24, P<0.001), which was longer than patients with non-operation (9 months, 95%CI: 8,10, P<0.001) (Figure 5B). In group C, the mOS of patients with surgery (37 months, 95%CI: 29.9,44.1) was longer than patients with non-surgery operation (19 months, 95%CI: 14,24, P<0.001), which was longer than patients with non-operation (6 months, 95%CI: 4.9,7.1, P<0.001) (Figure 5C). In group D, the mOS of patients with surgery (27 months, 95%CI: 23.2,30.8) was longer than patients with non-surgery operation (12 months, 95%CI: 10.4,13.6, P<0.001), which was longer than patients in the non-operation (4 months, 95%CI: 3.7,4.3, P<0.001) (Figure 5D). In group E, the mOS of patients with surgery (74 months, 95%CI: 56.6,91.4) was longer than patients with non-surgery operation (44 months, 95%CI: 36.9,51.1, P<0.001), which was longer than patients with non-operation (23 months, 95%CI: 20.2,25.8, P<0.001) (Figure 5E). In group F, the mOS of patients with surgery (47 months, 95%CI: 39.1,54.9) was longer than patients with non-surgery operation (27 months, 95%CI: 23.6,30.4, P<0.001), which was longer than patients with non-operation (10 months, 95%CI: 8.8,11.2, P<0.001) (Figure 5F). In group G, the mOS of patients with surgery (67 months, 95%CI:43.6,90.4) was longer than patients with non-surgery operation (22 months, 95%CI: 6.8,37.2, P=0.009). (Figure 5G).
Predictors of OS in all patients and the operation group
The multivariable regression analysis of all patients showed that operation was an independent favor factor for OS compared with non-operation (HR:2.412, 95%CI:1.2.329,2.499, P<0.001) for all patients after PSM. For patients with operation, the multivariable regression analysis showed that surgery was an independent favor factor for OS compared with patients with non-surgery operation (HR:1.556, 95%CI:1.471,1.667, P<0.001) (Table 2).