Recurrent Hepatocellular Carcinoma: Patterns, Detection, Staging and Treatment

Abstract

Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related deaths worldwide with the incidence of recurrence being as high as 88% even among patients who have undergone curative-intent treatment. Despite improvements in overall survival, recurrence remains a challenge necessitating accurate reappraisal of patient and disease status. To that end, accurate staging of recurrent HCC is a necessity to provide better care for these patients. Risk factors for poor survival after HCC recurrence have been identified and include characteristics of the primary disease, such as tumor multifocality, large size (≥5 cm), macroscopic vascular or microscopic lymphovascular invasion, preoperative a-fetoprotein (AFP) levels, R0 resection, and the presence of impaired liver function. Close surveillance with imaging is warranted following curative-intent therapy, with magnetic resonance imaging (MRI) being the preferred approach to identify small, early recurrent HCCs. Treatment decisions at the time of recurrence involve ruling out extrahepatic disease and identifying candidates for potentially curative-intent repeat treatment options. Patients with recurrent disease are, however, very diverse in terms of tumor morphology and biologic behavior, as well as residual hepatic functional reserve. Patients with preserved liver function may benefit from repeat liver resection or ablation. Patients with recurrence within the Milan criteria may even be candidates for salvage liver transplantation, while multimodality treatment with combination of liver-directed therapies appears to enhance oncologic outcomes for individuals with advanced recurrent disease. A “one-size-fits-all” approach in staging recurrent HCC does not exist. Rather, individualized and evidence-based decision-making is necessary in order to optimize outcomes for patients with recurrent HCC.

Recurrence and tumor-related death after resection of hepatocellular carcinoma in patients with metabolic syndrome

“…Different thresholds have been used in the literature to define early and late recurrences, with 2 years being the most widely adopted. 27 , 28 The time-dependent approach of the present study suggests that categorizing recurrences using specific thresholds is somewhat limited. Indeed, earlier and later recurrences are not mutually exclusive, because patients with significant risk factors for early recurrences might still develop relapse later in time.…”

Neuropilins as potential biomarkers in hepatocellular carcinoma: a systematic review of basic and clinical implications

“…Invasion and migration processes are well-described events that characterizes the aggressiveness of solid tumors and are highly associated with tumor progression and recurrence. 50 The NRPs' main effects in human pathologies are generally related to the modulation of signaling pathways that drive angiogenesis and cancer cell migration. 10 Numerous studies evaluated the NRPs' role in these cellular processes in preclinical models 12,26,[35][36][37]39,40,42,43,[51][52][53][54] and human patients (Figure 2).…”

Machine learning-based radiomic analysis and growth visualization for ablation site recurrence diagnosis in follow-up CT

“…Risk factors for ASR include insufficient ablative margins, tumor location, and tumor morphology [ 9 – 12 ]. Accurate and timely diagnosis of ASR is crucial to ensure the option of (minimally invasive) re-treatments with curative intent leading to the best long-term outcomes [ 13 ]. However, diagnosing ASR on follow-up computed tomography (CT) scans remains difficult, even for experienced radiologists due to the similarity between post-ablative necrosis/perilesional inflammation and true ASR [ 14 – 16 ].…”