What can serum vascular endothelial growth factor do for 68Ga-PSMA image for patients with clear cell renal cell carcinoma?

Introduction: To validate the application serum vascular endothelial growth factor (serum VEGF) in the selection and prognosis of patients with clear cell renal cell carcinoma (ccRCC) using 68Ga-PSMA.

Methods: This was a retrospective study of patients who received a ⁶⁸Ga-PSMA PET/CT scan for diagnosing and stage of ccRCC between January 2021 and October 2023. Analysis was based on radiological parameters and angiogenesis indicators, including visual score of PSMA, maximum standard uptake value (SUVmax), volume rate (VR) of SUV≥50% SUVmax, and serum VEGF. Evaluated the correlation of serum VEGF and PSMA, the efficacy of serum VEGF in selecting high PSMA uptake lesion in diagnosing ccRCC and evaluated the role of PSMA uptake characteristics in predicting patient risk was evaluated by analyzing the changes in VEGF levels pre- and post-operation.

Results: A total of 44 patients with pathologically confirmed ccRCC who evaluated serum VEGF levels before PSMA imaging and operation were included in this study. The serum VEGF was 86.7±34.4 pg/mL, average SUVmax was 15.3±8.97, TBR (tumor to liver) was 3.25±1.89, VR was 0.32±0.28, the median of PSMA ICH stain was 2 and median visual score was 2. The serum VEGF showed poor correlation with PSMA ICH stain (r=-0.054, P=0.816) and VR (r=0.065, P=0.748), moderate correlation with SUVmax (r=0.338, P=0.025) and TBR (r=0.310, P=0.041), and strong correlation with visual score (r=0.405, P=0.008). Based on the visual score of PSMA image, patients were divided in two groups, low group (0-1) and high group (2-3). The serum VEGF was significant different in two groups (P=0.029). serum VEGF was a good predictor of PSMA PET visual score with an AUC value of 0.707 (95% CI, 0.497-0.917, P=0.043), and stratified by the critical value of serum VEGF, 67.71 pg/mL, the corresponding sensitivity and specificity for predicting PSMA visual scores (0-1 vs. 2-3), were 85% and 78%, respectively. Patients had high pre-operation serum VEGF might show high PSMA uptake. 19 patients measured serum VEGF post-operation and the median of follow-up was 81 days (IQR: 36-181 days). All patients imaging examination and clinical signs were normal during follow-up time, however serum VEGF of 9 patients increased during the follow-up time. Compared the pre-operative PSMA uptake characteristics between VEGF increased and decreased group, SUVmax was no statistically difference (P=0.464), the VR showed significantly difference (P=0.049), patients with increased VEGF had lower VR. ROC curve analysis found that using VR to predict postoperative VEGF changes, with an AUC value of 0.750 (95% CI, 0.472-1.000, P=0.143), the corresponding sensitivity and specificity were 50% and 100%, respectively. Patients with preoperative VR≤0.42 were more likely to have increased VEGF postoperative. Serum VEGF was associated with patient prognosis, and results suggested that patients with low VR (high intratumoral heterogeneity) may have poor prognosis.

Conclusions: Our study showed that serum VEGF reflected 68Ga-PSMA-11 PET/CT uptake characteristics for ccRCC. Pre-operative serum VEGF levels can provide assistance in screening patients suitable for PSMA imaging. Base on the change of serum VEGF, the Intratumoral heterogeneity index VR had potential value in predict of tumor prognosis risk.

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