#0545

Heterogeneity of [68Ga] Ga‑PSMA‑11 PET/CT in the assessment of therapy response in metastatic renal cell carcinoma treated with immune checkpoint inhibitors plus tyrosine kinase inhibitors

S. Chen¹, X. Wu¹, X. Xue¹, N. Xu¹

¹The First Affiliated Hospital of Fujian Medical University, Fuzhou, China

Introduction:

This study aimed to assess the predictive significance of 68Ga-labeled prostate-specific membrane antigen-11 positron emission tomography/computerized tomography ([68Ga] Ga-PSMA-11 PET/CT) for evaluating treatment response in patients with metastatic renal cell carcinoma (mRCC) undergoing treatment with tyrosine kinase inhibitors (TKIs) in combination with immune checkpoint inhibitors (ICIs).

Material and methods:

This retrospective study included 108 patients with mRCC who underwent [68Ga] Ga-PSMA-11 PET/CT and were treated with TKIs plus ICIs between January 2019 and March 2023. Evaluation of therapeutic response to treatment with TKIs plus ICIs was based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 guidelines. Logistic regression analysis was used to determine independent predictors of response to TKIs plus ICIs. Kaplan-Meier analyses and receiver operating characteristics curve (ROC) analyses were performed to evaluate the performance of the independent predictors. RNA sequencing, bioinformatics analyses, immunohistochemistry (IHC), and immunofluorescence (IF) staining were performed to reveal the tumor microenvironment.

Results:

Among the 108 patients with mRCC, twelve (11.11%) experienced a complete response (CR), 24 (22.22%) experienced a partial response (PR), 45 (41.67%) experienced stable disease (SD), and 27 (25.00%) experienced progressive disease (PD). On [68Ga] Ga-PSMA-11 PET/CT, the area under the curve of a cumulative standardized uptake value (SUV)-volume histogram (AUC-CSH) (P <0.001) and SUVmax (P=0.001) were independent predictors of response to treatment with TKIs plus ICIs in patients with mRCC. The AUC-CSH for predicting treatment response was 0.812 (95% CI:0.678–0.908), and the SUVmax was 0.757 (95% CI:0.625–0.872). Lower PSMA heterogeneity and higher [68Ga] Ga-PSMA-11 SUVmax both correlated with increased progression-free survival (PFS). Further analyses of the tumor environment revealed that regions with PSMA heterogeneity were enriched with M2 macrophages and cancer-associated fibroblast (CAFs) cells, whereas low PSMA heterogeneity clusters were enriched in CD8+ T cells, and M1 macrophages. Patients with low PSMA heterogeneity had significantly higher levels of immune checkpoint expression than patients with high PSMA heterogeneity, and their Tumor Immune Dysfunction and Exclusion scores were significantly lower than those of patients with high PSMA heterogeneity.