This breakthrough, published in the Journal of Hepatology, provides new tools for personalized therapeutic decision-making.
The study was coordinated by Dr. Alba Díaz from the Pathology Department at Clínic and Dr. Alejandro Forner from the Hepatology Department. Both are part of the Hepatic Oncology Unit at Clínic and the Hepatic Oncology (BCLC) group at IDIBAPS and CIBEREHD, led by Dr. Maria Reig.
Hepatocellular carcinoma accounts for 90% of liver tumors
Hepatocellular carcinoma (HCC) is the most common type of liver cancer, primarily affecting people with chronic liver diseases, and is one of the leading causes of cancer-related mortality worldwide. Despite advancements in treatment, long-term success is limited by high recurrence rates.
Assessing recurrence risk is crucial for defining optimal treatment in early stages and considering options such as liver transplantation or investigational adjuvant therapies.
To date, no molecular pattern has been available that, combined with conventional pathological examination of the removed tumor, can predict the magnitude of relapse risk and its aggressiveness. This predictive ability is essential for providing prognostic information to patients and families and for designing clinical trials focused on preventing tumor recurrence after seemingly curative treatment.
Predicting Aggressive Recurrence
The study analyzed 218 patients with early-stage HCC, with no vascular invasion or metastasis and preserved liver function. Researchers evaluated various tumor characteristics, including microvascular invasion (when tumor cells invade small blood vessels) and microscopic satellite nodules—small tumor foci around the main tumor.
Recurrence occurred in 60% of patients, and in one-third of these cases, it was aggressive, preventing curative treatment with surgery or liver transplantation.
Microvascular invasion and satellite nodules (mVI/S) emerged as independent predictors of aggressive recurrence and lower survival rates. Their presence significantly increases the risk of aggressive relapse and mortality.
On the other hand, the macrotrabecular-massive pattern and the presence of vessels encapsulating nests of tumor cells were associated with more advanced tumor characteristics, implying a higher risk of recurrence and, consequently, a worse prognosis. However, this pattern was not found to be an independent predictor of survival.
Dr. María Reig, Head of the Hepatic Oncology Unit at Hospital Clínic and the Hepatic Oncology Group (BCLC) at IDIBAPS and CIBEREHD, emphasizes that "these results highlight the importance of a thorough histological assessment in the treatment planning of HCC. The presence of these anatomopathological profiles should be considered a relevant criterion to identify which patients could benefit from more intensive options, such as upfront liver transplantation before recurrence occurs."
New Strategies to Prevent Recurrence
This breakthrough also paves the way for future research and the design of new clinical trials exploring complementary therapies for liver cancer patients at high risk of recurrence after treatment. “One initial option would be to consider liver transplantation due to the risk of relapse. If this is not feasible, the risk profile would allow patients to be enrolled in clinical trials to evaluate potential treatments, such as immunotherapy, which could reduce the risk of recurrence and improve long-term survival,” explain the study coordinators.
Additionally, research must continue to identify the molecular mechanisms and genetic abnormalities that drive tumor development. These could be detected through a biopsy of the tumor before surgery or via liquid biopsy using peripheral blood.
Study reference:
Fuster-Anglada C, Mauro E, Ferrer-Fàbrega J, Caballol B, Sanduzzi-Zamparelli M, Bruix J, Fuster J, Reig M, Díaz A, Forner A. Histological predictors of aggressive recurrence of hepatocellular carcinoma after liver resection. J Hepatol. 2024 Jun 24:S0168-8278(24)02324-9. doi: 10.1016/j.jhep.2024.06.018.
