Inverse Correlation Between Expression of Prostate-Specific Membrane Antigen and Risk of Metastatic Progression of Renal Cell Cancer Post Surgery

In a study presented at the 25^th Annual Meeting of the Society of Urologic Oncology, greater expression of prostate-specific membrane antigen (PSMA) in patients with non-metastatic clear cell renal cell carcinoma (ccRCC) is correlated with enhanced progression-free survival (PFS), highlighting its potential role as a prognostic marker.

Paz Lotan, MD, and colleagues indicated that PSMA is released in the renal proximal tubule and by endothelial cells within the blood vessels of some tumors, including those of renal cell carcinoma (RCC).

Researchers employed automated quantitative immunohistochemistry to assess PSMA expression variability and the prognostic association in localized RCC.

To ascertain PSMA expression, researchers used tissue microarrays (TMAs) from patients with ccRCC, with samples from eight areas of each tumor and three samples from adjacent benign kidney tissue.

The study cohort was divided into two groups, including patients whose cancer progressed to metastatic disease and those whose cancer did not. The groups were all matched based on age, gender, and overall health status, as well as tumor stage, grade, and size.

PSMA expression was investigated for its correlation with blood vessel density (CD31⁺ cells/mm²) and a previously established tumor-associated blood vessel growth index (CD105⁺/CD31⁺ ratio). To demonstrate variations in tissue samples, researchers utilized Kernel density plots.

Results revealed that 506 tissue samples were utilized to create TMAs from 46 matched ccRCC patients in two cohorts. Twenty six patients advanced to metastatic progression with an average follow-up of seven years (IQR 5-11), while 20 patients had no progression, with an average follow-up of 11 years (IQR 8-15). In general, the average size of a tumor was nine cm.

Moreover, PSMA expression varied exceedingly throughout the RCC tumors. PSMA expression was also greater in benign renal tissue than in RCC, including among tumors that did not progress.

“PSMA was positively correlated with normal endothelial cell density (Spearman, r=.32; P=.001) and negatively correlated with neovascularity (r=-.29; P<.001). After multivariable analysis, higher PSMA expression was associated with improved progression-free survival (hazard ratio [HR] 0.46, P<.001),” the study authors said.

The researchers concluded that PSMA expression demonstrates heterogeneity to some degree across tumor samples, reflecting endothelial cells and vascularity, which is inversely associated with tumor-associated neovascularity.

Additionally, in non-metastatic ccRCC, average tumor PSMA expression could serve as a positive prognostic marker for RCC, necessitating additional research.

Reference

Lotan P., Stevens J, Cho S. PSMA Expression is Inversely Associated with Metastatic Progression Following Surgery in Clinically Localized Renal Cell Carcinoma. Poster #55. Presented at the 25th Annual Meeting of the Society of Urologic Oncology; December 4-6, 2024; Dallas, Texas.