Patients’ baseline characteristics
Overall, 505 patients were included in this study (Figure 1). The clinicopathological features of all cohorts are presented in Table 1. In the entire cohort, the median age was 61 years, the majority (80%) were men, approximately half had hepatitis B virus (HBV, 45.0%), one-fourth had hepatitis C virus (HCV, 24.6%), and 20.2% had a history of alcohol use. Approximately 32.3% of patients had liver cirrhosis, with the majority (96.8%) having CP class A. Several patients (45.2%) had tumors ≥5 cm in size, and 10.2% had multiple tumors.
Among the 505 patients, 35 (7.0%) patients had cHCC-CC, 419 (82.9%) had HCC, and 51 (10.1%) had CC (Table 1). Significant intergroup differences were observed regarding factors such as sex, alcohol use, tumor size ≥ 5 cm, AFP level ≥ 200 ng/mL, operative margin > 1 cm, major hepatectomy, microvascular invasion, macrovascular invasion, AJCC stage I–II, recurrence, recurrence per 100 person-years, mortality, mortality per 100 person-years, and median follow-up time.
The cHCC-CC group had the highest proportion of patients with hypertension, smoking, alcohol use, CP class A, tumor size ≥ 5 cm, microvascular invasion, lymph node metastasis, AJCC stage I–II, recurrence per 100 person-years, and mortality per 100 person-years. By contrast, the HCC group had more patients with old age, male, cirrhosis, Edmondson–Steiner grades I-II, tumor number, AFP level ≥ 200 ng/mL, ICG%, operative margin >1 cm, macrovascular invasion, and antiviral therapy. Moreover, the CC group was noted to more likely have diabetes mellitus, HBV, HCV, CP class A, major hepatectomy, and distal metastasis, as presented in Table 1.
Significant differences were observed between cHCC-CC and HCC groups in terms of age, diabetes mellitus status, tumor size ≥ 5 cm, lymph node metastasis, mortality, mortality per 100 person-years, and median follow-up time. Furthermore, significant differences were observed between cHCC-CC and CC groups in terms of diabetes mellitus, alcohol use, cirrhosis, AFP level ≥ 200 ng/mL, operative margin > 1 cm, major hepatectomy, microvascular invasion, and macrovascular invasion. In addition, significant differences were noted between HCC and CC groups in terms of sex, hypertension, cirrhosis, Edmondson–Steiner Grades I–II, tumor size ≥ 5 cm, AFP level ≥ 200 ng/mL, operative margin > 1 cm, major hepatectomy, microvascular invasion, macrovascular invasion, lymph node metastasis, AJCC stage I–II, recurrence, recurrence per 100 person-years, mortality, mortality per 100 person-years, and median follow-up time.
Overall survival in the entire cohort and different groups
Of the 505 patients, 149 (29.5%) died, and the median follow-up duration was 38 months (range: 1–94 months; Table 1). The mortality rate was 94.1 per 100 person-years. Cumulative OS at 1, 3, 5, and 7 years was 89.0%, 72.2%, 63.1%, and 61.9%, respectively (Figure 2A). OS was significantly better in the HCC group than in the cHCC-CC group [hazard ratio (HR): 1.77; 95% CI: 1.01–3.09, p = 0.045, Figure 2B]. OS was significantly better in the HCC group than in the CC group (HR: 2.84; 95% CI: 1.85–4.34, p < 0.0001, Figure 2B). Moreover, OS was not significantly better in the cHCC-CC group than in the CC group (HR: 1.60; 95% CI: 0.84–3.05, p = 0.152, Figure 2B). The median OS for cHCC-CC, HCC, and CC groups was 50.1 months (95% CI: 38.7–61.2), 62.3 months (CI: 42.1–72.9), and 36.2 months (CI: 15.4–56.5), respectively. The mortality was 104.1, 86.7, and 113.8 per 100 person-years in cHCC-CC, HCC, and CC groups, respectively. The cumulative OS rates at 1, 3, 5, and 7 years in cHCC-CC, HCC, and CC groups were 88.5%, 62.2%, 44.0%, and 44.0%; 91.2%, 76.1%, 68.0%, and 66.6%; and 72.0%, 48.1%, 34.5%, and 34.5%, respectively (Figure 2B).
Recurrence in the entire cohort and different groups
Of the 505 patients, 135 (26.7%) had recurrence (Table 1). The recurrence rate was 33.7 per 100 person-years. The disease-free survival rates were not significantly different among cHCC-CC, HCC, and CC groups (all p >s 0.05, Figure 2C). The median time to recurrence for cHCC-CC, HCC, and CC were 26.2 months (95% CI: 9.85–56.4), 10.9 months (CI: 7.15–12.8), and 6.8 months (CI: 1.47–10.5), respectively. The cumulative DFS rates at 1, 3, 5, and 7 years in cHCC-CC, HCC, and CC groups were 88.6%, 72.2%, 57.7%, and 57.7%; 82.7%, 70.8%, 61.6%, and 60.4%; and 91.7%, 80.9%, 75.1%, and 75.1%, respectively (Figure 2C).
Overall survival in different groups after PSM
PSM was performed using sex, age, cirrhosis status, CP class, tumor size, tumor number, and AJCC stage, and no significant differences were noted regarding crucial features (Tables 2 and 3).
Comparing cHCC-CC and HCC groups after PSM (Table 2), there were 35 patients each in cHCC-CC and HCC groups. OS was not significantly different between cHCC-CC and HCC groups (p = 0.632, Figure 3A). Cumulative OS rates at 1, 3, 5, and 7 years in cHCC-CC and HCC groups were 80.0%, 71.1%, 58.2%, and 50.4% and 88.5%, 62.2%, 44%, and 44.0%, respectively (Figure 3A).
Comparing cHCC-CC and CC groups after PSM (Tables 2), there were 35 and 35 patients in cHCC-CC and CC groups, respectively. OS was not significantly different between cHCC-CC and CC groups (p = 0.057, Figure 3B). Cumulative OS rates at 1, 3, 5, and 7 years in cHCC-CC and CC groups were 88.5%, 62.2%, 44.0%, and 44.0% and 71.4%, 47.5%, 20.8%, and 20.8%, respectively (Figure 3B).
Comparing HCC and CC groups after PSM (Table 3), there were 43 and 51 patients in HCC and CC groups, respectively. OS was significantly better in the HCC group than in the CC group (HR: 3.29, 95% CI: 1.62–6.64, p < 0.0001, Figure 3C). Cumulative OS rates at 1, 3, 5, and 7 years in HCC and CC groups were 88.3%, 83.5%, 72.6%, and 66.6% and 72.0%, 48.1%, 34.5%, and 34.5%, respectively (Figure 3C).
Recurrence in different groups after PSM
Upon comparing cHCC-CC and HCC groups after PSM (Table 2), no significant intergroup difference was observed regarding the recurrence rate (p = 0.831, Figure 4A). Cumulative DFS at 1, 3, 5, and 7 years in cHCC-CC and HCC groups were 88.6%, 72.2%, 57.7%, and 57.7% and 84.2%, 65.8%, 61.4%, and 61.4%, respectively (Figure 4A).
When cHCC-CC and CC groups were compared after PSM (Table 2), no significant intergroup difference was noted regarding the recurrence rate (p = 0.213, Figure 4B). Cumulative DFS at 1, 3, 5, and 7 years in cHCC-CC and CC groups were 88.6%, 72.2%, 57.7%, and 57.7% and 94.1%, 84.2%, 84.2%, and 84.2%, respectively (Figure 4B).
Upon comparing HCC and CC groups after PSM (Table 2), no significant intergroup difference was observed regarding OS (p = 0.056, Figure 4C). Cumulative DFS at 1, 3, 5, and 7 years in HCC and CC groups were 80.9%, 65.4%, 59.3%, and 59.3% and 91.7%, 84.9%, 84.9%, and 84.9%, respectively (Figure 4C).