Validating Protein Targets for Imaging of Bladder Cancer Metastases - Expert Commentary

Computed tomography (CT) is the most commonly used technique for imaging lymph node metastases, although it has relatively low sensitivity rates. Accordingly, targeted imaging techniques are needed for enhanced detection. Vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR), and prostate-specific membrane antigen (PSMA) can be used for targeted imaging. Van der Fels et al. aimed to evaluate VEGF, EGFR, and PSMA expression as potential targets for imaging lymph node metastasis in urothelial carcinoma.

The study cohort consisted of 17 patients with urothelial cancer who underwent lymph node dissection and had lymph node metastases compared to 40 patients who did not. VEGF expression was high in primary tumors and lymph node metastases. It was also expressed in negative lymph nodes to a lesser extent. EGFR expression was elevated in most samples, but the intensity score was low in lymph nodes and primary tumors. It was not expressed in negative lymph nodes. Levels of PSMA expression were very low or absent in lymph nodes and primary tumors.

Overall, only VEGF appeared to be suitable for further exploration of its utility as a target for imaging techniques due to the low staining intensity of the other markers. These findings were in line with previous studies that revealed high expression of VEGF across lymph node metastases and primary tumors in bladder cancer. Previous studies have also highlighted the low to moderate expression of EGFR in bladder cancer samples. In contrast, studies have yielded contradictory findings regarding PSMA expression in bladder cancer, with some reports indicating very low staining and others showing strong expression in many patients. The validation of targets that are specifically more highly expressed in metastases will be critical for developing targeted imaging modalities for the sensitive detection of metastatic disease. In addition, understanding the spatial and cell-type specific expression of these proteins is essential as some markers are expressed in a cancer-cell autonomous manner. In contrast, other are primarily expressed by other cell types in the tumor microenvironment including endothelial and immune effector cells.

Written by: Bishoy M. Faltas, MD, Director of Bladder Cancer Research, Englander Institute for Precision Medicine, Weill Cornell Medicine


  1. Van der Fels CAM, Leliveld A, Buikema H, van den Heuvel MC, de Jong IJ. VEGF, EGFR and PSMA as possible imaging targets of lymph node metastases of urothelial carcinoma of the bladder. BMC Urol. 2022;22(1):213. Published 2022 Dec 29. doi:10.1186/s12894-022-01157-7
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