Imaging-Based Factors Associated with Rapid Growth in Early-Stage Hepatocellular Carcinoma

Academic Background

Hepatocellular carcinoma (HCC) is the most common primary liver cancer globally and the third leading cause of cancer-related mortality, with increasing incidence and mortality rates reported in North America, South America, and Europe. Although the prognosis for advanced-stage HCC remains poor, with a 5-year survival rate of less than 20%, patients diagnosed with HCC at an early stage are potentially eligible for curative treatment. Therefore, accurate diagnosis and risk stratification, particularly the prediction of tumor growth rate, are clinically crucial for the management of early-stage HCC patients.

However, predicting the growth rate of early HCC is challenging due to significant variability among individual lesions, and the results in the literature are inconsistent. Earlier studies suggested that the tumor volume doubling time (TVDT) of HCC is approximately 70 to 120 days, but a recent multicenter study revealed considerable heterogeneity in HCC growth rates, with a median TVDT of 229 days and an interquartile range (IQR) of 89 to 627 days. The study also found that one-third of HCCs exhibited indolent growth (TVDT > 365 days), while one-fourth exhibited rapid growth (TVDT < 90 days).

Predicting tumor growth rates can facilitate the development of individualized treatment plans. Specifically, patients with HCC predicted to have rapid growth may require expedited treatment or shorter follow-up intervals and are at high risk for early recurrence and poor outcomes after curative treatment. Therefore, this study aimed to evaluate the percentage of rapidly growing early-stage HCCs in each Liver Imaging Reporting and Data System (LI-RADS) category and to identify prognostic factors associated with rapid growth.

Source of the Paper

This study was conducted by Hyeon Ji Jang, Sang Hyun Choi, Sungwoo Wee, Se Jin Choi, Jae Ho Byun, Hyung Jin Won, and Yong Moon Shin from the Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea, and Claude B. Sirlin from the Liver Imaging Group, Department of Radiology, University of California–San Diego. The paper was published in December 2024 in the journal Radiology.

Study Design and Methods

Study Design and Sample

This single-center retrospective study was approved by the Institutional Review Board of Asan Medical Center, and the requirement for informed consent was waived due to the retrospective nature of the study. The study included patients who underwent surgical resection for HCC between January 2016 and December 2020 and met the following inclusion criteria: age ≥18 years, cirrhosis or chronic hepatitis B virus infection, pathologically proven early-stage HCC (Barcelona Clinic Liver Cancer stage 0 or A), gadoxetate-enhanced MRI performed within 1 month before surgery, and tumor size ≥5 mm at baseline CT or MRI. Exclusion criteria included local-regional treatment for HCC before surgery without biopsy and suboptimal image quality precluding LI-RADS categorization.

Imaging Examinations

All patients underwent gadoxetate-enhanced MRI within 1 month before surgery and at least one prior multiphasic CT or MRI examination. For patients with multiple prior CT or MRI examinations, the earliest examination was selected as the baseline imaging to facilitate the calculation of TVDT.

Selection of Target HCC and Image Analysis

An experienced hepatic imaging specialist (J.H.B.) assessed the quality of the baseline and preoperative MRI images and flagged the target HCC. Subsequently, two abdominal radiologists (S.J.C. and H.J.J.) independently assigned LI-RADS categories to the baseline CT or MRI images and measured TVDT according to the guidelines.

Statistical Analysis

Descriptive statistics, univariable, and multivariable logistic regression analyses were performed to identify factors associated with rapid growth in HCC. TVDT was calculated based on changes in tumor volume, and growth rates were classified as rapid (TVDT < 3 months), intermediate (TVDT = 3–9 months), or indolent (TVDT > 9 months).

Results

Patient Characteristics

The study included 322 patients (mean age, 61 years; 249 men) with 345 HCC lesions. Among these, 30 were classified as LR-3, 64 as LR-4, 221 as LR-5, and 30 as LR-M.

Growth Rate and LI-RADS Categories

The median TVDT for all HCCs was 131 days (IQR, 87–233 days), with 27.0% of HCCs exhibiting rapid growth. The growth rates differed significantly among LI-RADS categories, with 70.0% of LR-M HCCs showing rapid growth, significantly higher than LR-3 (3.3%), LR-4 (12.5%), and LR-5 (28.5%) categories.

Factors Associated with Rapid Growth

Multivariable logistic regression analysis revealed that serum alpha-fetoprotein (AFP) level >400 ng/mL (adjusted OR = 2.54, p = 0.02), baseline tumor diameter (adjusted OR = 0.65, p = 0.004), and LR-M category (adjusted OR = 9.26, p < 0.001) were independent predictors of rapid growth in HCC.

Conclusion

This study demonstrated that the growth rate of early-stage HCC varies significantly among LI-RADS categories, with 70% of LR-M HCCs exhibiting rapid growth. Serum AFP level, baseline tumor diameter, and LR-M category were independent predictors of rapid growth in HCC. These findings may help in developing individualized treatment plans and follow-up strategies for HCC patients.

Highlights of the Study

1. Key Findings: 70% of LR-M HCCs exhibited rapid growth, significantly higher than other LI-RADS categories.
2. Methodological Innovation: This study is the first to correlate LI-RADS categories with HCC growth rates, providing new imaging-based insights for individualized HCC management.
3. Clinical Significance: The results may help identify high-risk HCC patients, optimize treatment plans and follow-up intervals, and improve patient outcomes.

Additional Valuable Information

The study also found that smaller baseline tumor diameters were associated with rapid growth, suggesting that small tumors may have higher growth potential. Additionally, serum AFP levels >400 ng/mL were significantly associated with rapid growth, further supporting the importance of AFP in HCC risk stratification.

Future Research Directions

Future studies are needed to validate these findings and explore how LI-RADS categories can be integrated into individualized treatment strategies for HCC patients to optimize clinical management.