[⁶⁸Ga]Ga-PSMA-11 PET/CT improves tumor detection and impacts management in patients with hepatocellular carcinoma (HCC)

Abstract

Rationale: Hepatocellular carcinoma (HCC) is the sixth most prevalent cancer and the third most frequent cause of cancer-related death. A growing number of local and systemic therapies are available, and accurate staging is critical for management decisions. We assessed the impact of neovasculature imaging by ⁶⁸Ga-Ga-PSMA-11 PET/CT on disease staging, prognostic groups and management of patients with HCC compared to staging with computed tomography (CT). Methods: Forty patients who received imaging with ⁶⁸Ga-Ga-PSMA-11 PET/CT for HCC staging between September 2018 and September 2019 were retrospectively included. Management pre- and post-PET scan was assessed by standardized surveys. Presence of HCC was evaluated by three blinded readers on a per-patient and per-region basis for PET/CT (PET criteria) and multi-phase contrast-enhanced CT (CT criteria) in separate sessions. Lesions were validated by follow-up imaging or histopathology, and progression-free survival (PFS) was recorded. Endpoints were detection rate and positive predictive value (PPV) for ⁶⁸Ga-Ga-PSMA-11 PET vs. CT, inter-reader reproducibility, and changes in stage, prognostic groups and management plans. Results: Median age was 65 years (range, 37-81), median Child-Pugh score was 5 (range, 5-9). Most patients were treatment naïve (27 of 40, 67.5%). The sensitivity of PET vs. CT to identify liver lesions for patients with lesion validation was 31/32 (97%) for both modalities, while it was 6/6 (100%) vs. 4/6 (67%) for extra-hepatic lesions. PET and CT each had a PPV of 100% at the liver level. PET vs. CT stage was congruent in 30/40 (75%) patients; upstaging was seen in 8/40 patients (20%), while 2/40 (5%) had downstaging by PET. Intended management changed in 19/40 patients (47.5%); 9/19 of these patients were found to have detectable distant metastases (47.4%) and assigned stage 4 disease, the majority of whom were shifted to systemic therapy (8 of 9, 89%). Two patients underwent ¹⁷⁷Lu-Lu-PSMA-617 radioligand therapy. Median PFS was 5.2 months for the entire cohort; 5.3 months for PET M0, and 4.7 months for PET M1 patients, respectively. Conclusion: ⁶⁸Ga-Ga-PSMA-11 PET demonstrated higher accuracy than CT in the detection of HCC metastases and was associated with management change in about half of the patient cohort.