Prognostic significance of early and multiple recurrences after curative resection for hepatocellular carcinoma

Abstract

Background: In hepatocellular carcinoma (HCC), postoperative recurrence remains high. This study aimed to evaluate the recurrence patterns and prognosis of HCC after curative hepatectomy.

Methods: Among 352 patients with primary HCC who underwent initial hepatectomy between January 2002 and December 2022, 151 with recurrence were assessed for the relationship between recurrence pattern and prognosis.

Results: The early recurrence group (within 6 months postoperatively; n = 38) had significantly higher serum alpha-fetoprotein (p = 0.002), des-γ-carboxyprothrombin (DCP; p = 0.004) levels and Barcelona Clinic Liver Cancer (BCLC) stage (p < 0.001), larger tumor size (p < 0.001), higher incidence of multiple tumors (p = 0.002) and lower overall survival (OS) (p < 0.001) than the late recurrence group (> 6 months postoperatively; n = 113). The tumor size (p = 0.013) and BCLC stage (p = 0.001) were independent risk factors for early recurrence within 6 months in multivariate analysis. The multiple recurrence group (intrahepatic multinodular recurrence or distant metastasis; n = 89) had significantly lower prognostic nutritional index (p = 0.026), larger tumor size (p = 0.017), lower incidence of liver cirrhosis (p = 0.03) than the single recurrence group (single nodule recurrence; n = 62). The multiple recurrence group, especially patients with ≥ three intrahepatic nodules and distant metastases, had lower postoperative OS (p < 0.001) and shorter time to recurrence (p < 0.001) than the single recurrence group. When the patients were classified into three groups: late recurrence with one or two tumors (Group A; n = 74), early recurrence or three or more tumors or distant metastasis (Group B; n = 54), and early recurrence with three or more tumors or distant metastasis (Group C; n = 23), OS was significantly lower in Groups B and C than Group A (p < 0.001).

Conclusions: Patients with early recurrence within 6 months after surgery and three or more recurrence nodule or distant metastasis exhibited poor prognosis after initial recurrence, and they should be carefully followed up.

Keywords: Curative hepatectomy; Early recurrence; Hepatocellular carcinoma; Intrahepatic metastases; Metachronous multicentric occurrence; Multiple recurrence.

Fig. 1

Flow diagram of patients with HCC who underwent hepatectomy without previous treatment

Fig. 2

Overall survival (OS) in patients with HCC recurrence after hepatectomy according to recurrence period. a: OS after the time of hepatectomy: early vs late recurrence groups. b: OS after the time of recurrence: early vs late recurrence groups

Fig. 3

Overall survival (OS) in patients with HCC recurrence after hepatectomy, according to recurrence period in subgroup based on BCLC stage and tumor size. a: OS after the time of recurrence in BCLC stage 0 or A: early vs late recurrence groups. b: OS after the time of recurrence in BCLC stage B or C: early vs late recurrence groups. c: Receiver operating characteristic (ROC) curves for early recurrence using tumor size. d: OS after the time of recurrence in tumor < 3.85 cm: early vs late recurrence groups. e: OS after the time of recurrence in tumor ≥ 3.85 cm: early vs late recurrence groups

Fig. 4

Overall survival (OS) and time to recurrence after surgery in patients with HCC recurrence after hepatectomy according to the number of initial recurrent tumors. a: OS after the time of hepatectomy: single vs multiple recurrence groups. b: OS after the time of recurrence: single vs multiple recurrence groups. c: OS after the time of hepatectomy: single vs two vs ≥ three vs distant metastasis. d: OS after the time of recurrence: single vs two vs ≥ three vs distant metastasis. e: Time to recurrence after hepatectomy: single vs multiple recurrence groups. f: Time to recurrence after hepatectomy: single vs two vs ≥ three vs distant metastasis

Fig. 5

Overall survival (OS) in patients with HCC recurrence after hepatectomy according to the combination of recurrence period and the number of initial recurrent tumors. a: OS after the time of hepatectomy. b: OS after the time of recurrence

Fig. 6

Overall survival (OS) after surgery in patients with HCC recurrence after hepatectomy, according to recurrence pattern in subgroup based on post-recurrence treatment. a: OS after local treatment for recurrences: early vs late recurrence groups. b: OS after non-local treatment for recurrences: early vs late recurrence groups. c: OS after local treatment for recurrences: single vs two vs ≥ three vs distant metastasis. d: OS after non-local treatment for recurrences: single vs two vs ≥ three vs distant metastasis. e: OS after local treatment for recurrences according to the combination of recurrence period and number. f: OS after non-local treatment for recurrence according to the combination of recurrence period and number