Although deemed potentially curative, surgical resection of hepatocellular carcinoma is associated with >
70% risk of postoperative relapse. Recurrence is uniquely multifactorial in hepatocellular carcinoma, potentially stemming from metachronous reoccurrence of the original tumor or de novo cancerization. ctDNA may improve personalized risk stratification after resection, a setting where adjuvant immunotherapy has failed to provide survival benefit. See related article by Hu et al., p. 1047.