Expression of Prostate-Specific Membrane Antigen (PSMA) on Biopsies Is an Independent Risk Stratifier of Prostate Cancer Patients at Time of Initial Diagnosis

Abstract

Background: Stratifying prostate cancer (PCa) patients into risk groups at time of initial diagnosis enabling a risk-adapted disease management is still a major clinical challenge. Existing studies evaluating the prognostic potential of PSMA (prostate-specific membrane antigen) for PCa were performed on radical prostatectomy specimens (RPE), i.e., decision making for disease management was already completed at time of sample analysis. Aim of our study was to assess the prognostic value of PSMA expression for PCa patients on biopsies at time of initial diagnosis.Methods: PSMA expression was assessed by immunohistochemistry on 294 prostate biopsies with corresponding RPE, 621 primary tumor foci from 242 RPE, 43 locally advanced or recurrent tumors, 34 lymph node metastases, 78 distant metastases and 52 benign prostatic samples. PSMA expression was correlated with clinico-pathologic features. Primary endpoint was recurrence free survival. Other clinicopathologic features included WHO/ISUP grade groups, PSA serum level, TNM-stage, and R-status. Chi-square test, ANOVA-analyses, Cox-regression, and log-rank tests were performed for statistical analyses.Results: High PSMA expression on both biopsy and RPE significantly associates with a higher risk of disease recurrence following curative surgery. The 5-year-recurrence free survival rates were 88.2, 74.2, 67.7 and 26.8% for patients exhibiting no, low, medium, or high PSMA expression on biopsy, respectively. High PSMA expression on biopsy was significant in multivariate analysis predicting a 4-fold increased risk of disease recurrence independently from established prognostic markers. PSMA significantly increases during PCa progression.Conclusion: PSMA is an independent prognostic marker on biopsies at time of initial diagnosis and can predict disease recurrence following curative therapy for PCa. Our study proposes the application of the routinely used IHC marker PSMA for outcome prediction and decision making in risk-adapted PCa management on biopsies at time of initial diagnosis.

3-Year Freedom from Progression After 68Ga-PSMA PET/CT–Triaged Management in Men with Biochemical Recurrence After Radical Prostatectomy: Results of a Prospective Multicenter Trial

“…The receptor plays a key role in glutamate cleavage and activation of growth pathways (phosphoinositide-3-kinase and protein Kinase B) in the cancer cell. High PSMA expression is known to equate to poor outcomes (24). It is likely that men with PSMA PET-positive disease occupy a biologically poorer prognostic category than those with negative scan results, with higher growth rates and metastatic potential in those demonstrating significant PSMA expression.…”

Preparation of the alpha‐emitting prostate‐specific membrane antigen targeted radioligand [212Pb]Pb‐NG001 for prostate cancer

“…17,35 In the final step, NG001 was synthesized by conjugating the isothiocyanato group of p-SCN-Bn-TCMC to the amino group of a PSMA binding intermediate. NG001 was characterized by 1…”

“…The prostate‐specific membrane antigen (PSMA) is highly expressed in metastatic castrate‐resistant prostate cancer (mCRPC) with limited expression in healthy tissues and correlates with a dismal prognosis . The majority of bone, visceral, and lymph‐node metastases highly express PSMA, making PSMA an ideal target for radioligand therapy (RLT) of mCRPC . A variety of low molecular weight PSMA‐targeting ligands have been synthesized, labelled with radionuclides, and tested in both preclinical and clinical trials .…”

Patients Resistant Against PSMA-Targeting α-Radiation Therapy Often Harbor Mutations in DNA Damage-Repair–Associated Genes

“…Eventually the focus on highly PSMA target-positive cancers, stratified by PSMA-groups found high PSMA-expression either measured by immunohistochemistry (24)(25)(26) or PSMA-PET (27) to correlate with traditional negative prognostic factors such as Gleason score, T-stage, d'Amico-criteria and as an independent predictor of prostate cancer recurrence and progression. A similar correlation between Gleason score, tumor stage and prognosis was found for patients with DRMs (28,29).…”