Contrast-enhanced US Evaluation of Residual Hepatocellular Carcinoma Following Lenvatinib Combined with Anti-PD-1 Antibody Downstaging Therapy.

Abstract

Background Accurate assessment of residual viable hepatocellular carcinoma (HCC) after downstaging therapy is essential for optimizing clinical decision-making in patients with unresectable HCC. Purpose To evaluate the diagnostic performance of contrast-enhanced US (CEUS) in the detection of residual viable tumors in participants with HCC following lenvatinib and anti-programmed cell death protein-1 (PD-1) antibody therapy and to compare it with that of contrast-enhanced MRI (CEMRI). Materials and Methods From March 2024 to March 2025, this prospective study included participants with unresectable HCC who underwent CEUS and CEMRI following lenvatinib and anti-PD-1 antibody therapy, a form of downstaging therapy aimed at converting unresectable HCC to resectable status. Interobserver agreements between CEUS and CEMRI were assessed using the κ coefficient or intraclass correlation coefficients. Diagnostic performance was evaluated using reference standards, including histopathologic findings (38%), 4-8-month follow-up CEMRI (53%), and PET imaging results (9%). A noninferiority design was used to compare sensitivity, specificity, and area under the receiver operating characteristic curve (AUC). Results Sixty-seven participants (median age, 56 years [IQR, 50-66 years]; 57 male) with 95 HCC lesions were included. CEUS and CEMRI demonstrated good agreement in the detection of residual viable tumors (reader 1, κ = 0.78 [95% CI: 0.62, 0.90]; reader 2, κ = 0.73 [95% CI: 0.57, 0.87]). CEUS sensitivity and AUC were noninferior to those of CEMRI (<i>P</i> < .001 and <i>P</i> = .02, respectively), with differences of 5% (95% CI: -2, 12) and 0.01 (95% CI: -0.07, 0.09), respectively. Specificity decreased by 3% (95% CI: -18, 12) and failed noninferiority (<i>P</i> = .24). Subgroup analysis based on pathologic findings (21 viable and 15 nonviable tumors) showed that CEUS had similar sensitivity (difference, 9% [95% CI: 0, 24]; <i>P</i> = .24), specificity (difference, -7% [95% CI: -31, 17]; <i>P</i> = .75), and AUC (difference, 0.01 [95% CI: -0.13, 0.16]; <i>P</i> = .91) compared with that of CEMRI. Conclusion This preliminary study demonstrated that CEUS (consensus interpretation) achieved sensitivity and AUC noninferior to CEMRI (one reader) in the detection of residual viable HCC following lenvatinib and anti-PD-1 antibody therapy. Chinese Clinical Trial Registry no. ChiCTR2400094263 © RSNA, 2025 <i>Supplemental material is available for this article.</i>