Risk Factors for Late Recurrence After Resection for Hepatocellular Carcinoma


Key Points

  • Risk factors for late recurrence included male sex, cirrhosis, and several aggressive tumor characteristics of the initial HCC.
  • Factors associated with improved survival included regular surveillance for postoperative recurrence and receipt of subsequent potentially curative treatment.

In a Chinese retrospective study reported in JAMA Surgery, Xu et al found that risk of late recurrence (> 2 years) of hepatocellular carcinoma (HCC) after curative liver resection was associated with male sex, presence of cirrhosis, and aggressive characteristics of the initial HCC.

The study involved 734 patients from 6 sites in China who were alive and free of recurrence 2 years after curative resection performed between January 2001 and December 2015. Patients had a mean age of 51 years, and 88.8% were male. 

Risk Factors for Recurrence and Other Factors Affecting Outcome

At a median follow-up of 78.0 months (interquartile range = 52.8–112.5 months), late recurrence was identified in 303 patients (41.3%). On multivariate analysis, male sex (hazard ratio [HR] = 1.37, P = .04), cirrhosis (HR = 1.42, P = .008), multiple tumors (HR = 1.56, P = .006), satellite nodules (1.59, P = .004), tumor size > 5 cm (HR = 1.49, P = .009), macroscopic vascular invasion (HR = 4.63, P < .001), and microscopic vascular invasion (HR = 1.69, P = .001) were independent risk factors for late recurrence.

Among patients with late recurrence, 273 (90.1%) had only intrahepatic recurrence, 30 (9.9%) had both intrahepatic and extrahepatic recurrence, and none had only extrahepatic recurrence. Potentially curative treatments were subsequently given to 165 patients (54.5%), including reresection, transplantation, and local ablation.

On multivariate analysis, independent predictors of better or worse overall survival in patients with late recurrence were regular surveillance for postoperative recurrence (HR = 0.47, P = .001), cirrhosis (HR = 1.38, P = .02), portal hypertension (HR = 2.42, P < .001), Child-Pugh grade B or C (HR = 1.38, P < .001), Barcelona Clinic Liver Cancer stage B (HR = 1.30, P = .04) and stage C (HR = 2.04, P < .001), and subsequent potentially curative treatment (HR = 0.44, P < .001).

The investigators concluded, “Late recurrence after HCC resection was associated with sex, cirrhosis, and several aggressive tumor characteristics of the initial HCC. The patterns of late recurrence suggested surveillance for recurrence after 2 years of surgery should be targeted to the liver. Postoperative surveillance improved the chance of potentially curative treatments, with improved survival outcomes in patients with late recurrence.”

The study was funded by grants from the National Natural Science Foundation of China and Shanghai Pujiang Program.

Tian Yang, MD, and Feng Shen, MD, PhD, of the Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, are the corresponding authors for the JAMA Surgery article.

Disclosure: See study authors’ full disclosures at

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