Pretreatment [⁶⁸Ga]-PSMA-11 PET/CT to Predict the Response to Treatment With Immune Checkpoint Inhibitors Plus Tyrosine Kinase Inhibitors in Patients With Metastatic Renal Cell Carcinoma.

[OBJECTIVE] This study aimed to investigate the feasibility of pretreatment ⁶⁸Ga-labeled prostate-specific membrane antigen-11 ([⁶⁸Ga]-PSMA-11) PET/CT for predicting treatment response in patients with metastatic renal cell carcinoma (mRCC) undergoing first-line therapy with tyrosine kinase inhibitors (TKIs) in combination with immune checkpoint inhibitors (ICIs).

[MATERIALS AND METHODS] This retrospective study included 108 patients (age, 69.4 ± 6.2 years; 38 males) with mRCC who underwent pretreatment [⁶⁸Ga]-PSMA-11 PET/CT and were treated with TKIs plus ICIs between January 2019 and March 2023. Evaluation of the therapeutic response to treatment with TKIs plus ICIs was based on the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Univariable and multivariable logistic regression analyses were performed to identify the independent predictors of response, defined as complete response (CR) or partial response (PR), to combinations of TKIs and ICIs. Receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive performance.

[RESULTS] Of the 108 patients with mRCC, 12 (11.1%), 24 (22.2%), 45 (41.7%), and 27 (25.0%) achieved CR, PR, stable disease, and progressive disease, respectively. The area under the curve of the cumulative standardized uptake value (SUV)-volume histogram (AUC-CSH) (adjusted odds ratio [aOR], 8.358; = 0.002) and maximum SUV (SUVmax; aOR, 1.092; = 0.024) from pretreatment [⁶⁸Ga]-PSMA-11 PET/CT scans and the programmed death-ligand 1 (PD-L1) status (aOR, 6.248; = 0.026) were identified as independent predictors of treatment response. A predictive model combining AUC-CSH, SUVmax, and PD-L1 status achieved an area under ROC curve (AUROC) value of 0.880 (95% confidence interval: 0.804-0.935), which was significantly higher than the AUROC values of AUC-CSH alone (0.812 [0.726-0.881], = 0.020), SUVmax alone (0.757 [0.665-0.834], = 0.031), and PD-L1 status alone (0.637 [0.532-0.733], < 0.001).

[CONCLUSION] AUC-CSH and SUVmax from pretreatment [⁶⁸Ga]-PSMA-11 PET/CT scans were independent predictors of the response to treatment with TKIs plus ICIs in mRCC. When combined with PD-L1 status, they may enhance patient stratification and facilitate clinical decision-making before treatment initiation.