Introduction

There is a well-established association between inflammation and malignant tumors. Furthermore, in hepatocellular carcinoma (HCC), liver functional is a critical determinant of prognosis. Accordingly, the C-reactive protein-to-albumin ratio (CAR), which integrates C-reactive protein—a biomarker of systemic inflammation—and albumin—an indicator of liver functional—has been proposed as a potentially valuable prognostic marker in HCC.

Aims & Methods

This study aims to assess the prognostic value of CAR in predicting outcomes in patients with unresectable HCC treated with Atezolizumab/Bevacizumab (Atezo/Bev) combination therapy.A total of 289 patients who received Atezo /Bev across multiple centers between September 2020 and December 2024 were included in this analysis.The baseline characteristics of the cohort were as follows: median age 74.0 years ( IQR, 67.0–79.0), male/female gender distribution 224/65, performance status (PS 0/1/≥2）185/95/9, etiology (hepatitis B/hepatitis C/alcoholic/non-B, non-C) 58/92/37/102, CRP 0.27 mg/dL (0.10–0.91), albumin 3.8 g/dL (3.4–4.2), CAR 0.068 (0.026–0.239), Child-Pugh score (5/6/≥7 points) 165/82/42, Barcelona Clinic Liver Cancer (BCLC) stage (≤A/B/≥C) 24/84/181, alpha-fetoprotein (AFP) level 27.5 ng/mL (5.2–606.6), and median observation period 14.8 months (6.9–26.4). The distribution of patients according to the line of Atezo/Bev was 233/56 for primary/secondary or later systemic therapy lines, respectively.

Results

The median cumulative progression-free survival (PFS) was 6.8 months (95% confidence interval [CI], 5.4–9.8), and the median cumulative overall survival (OS) was 26.5 months (95% CI, 21.4–29.9). Time-dependent receiver operating characteristic (ROC) analysis identified an optimal cutoff for predicting median OS at 0.0056. The radiological responses, according to RECIST version 1.1, were as follows: partial response 5.7%, stable disease 24.7%, progressive disease 45.9%, respectively. The objective response rate (ORR) and disease control rate were 30.5% and 76.3%. Notably, significant differences in radiological responses (p=0.002) and ORR (p = 0.011) were observed based on CAR values. Multivariate analysis, incorporating age, gender, PS, etiology, BCLC stage, Child-Pugh classification, systemic therapy line, AFP, neutrophil-to-lymphocyte ratio (NLR), and CAR, revealed that age (≥75 years) (hazard ratio [HR], 1.361; 95% confidence interval [CI], 1.028–1.802; p=0.031), BCLC stage (≥C) (HR, 1.439; 95% CI, 1.017–2.037; p=0.040), and CAR (≥0.056) (HR, 1.471; 95% CI, 1.105–1.957; p=0.008) were independently associated with PFS. Additionally, in multivariate analysis adjusted for the same covariates, age (≥75 years) (HR, 1.458; 95% CI, 1.004–2.117; p=0.048), Child-Pugh classification (≥7) (HR, 2.329; 95% CI, 1.445–3.754; p<0.001), AFP (≥100ng/ml) (HR, 1.587; 95% CI, 1.087–2.319; p=0.017), and CAR (≥0.056) (HR, 2.042; 95% CI, 1.386–3.008; p<0.001) were independently associated with OS. In the time-dependent ROC analysis, the area under the ROC curve (AUROC) at 6, 12, 18, 24, 30, and 36 months for NLR was 0.690, 0.683, 0.651, 0.573, 0.493, and 0.474, respectively, and 0.757, 0.687, 0.699, 0.695, 0.663, and 0.597 for CAR, with CAR showing a significantly better AUROC after 24 months.

Conclusion

CAR serves as a valuable predictive biomarker for survival in patients undergoing Atezo/Bev for unresectable HCC.

References

Toshifumi Tada, Takashi Kumada , Atsushi Hiraoka et al. C‑reactive protein to albumin ratio predicts survival in patients with unresectable hepatocellular carcinoma treated with Lenvatinib. Scientific Reports. 2022 May 19;12(1):8421.