Considerations on Integrating Prostate-Specific Membrane Antigen Positron Emission Tomography Imaging Into Clinical Prostate Cancer Trials by National Clinical Trials Network Cooperative Groups

PURPOSE As prostate-specific membrane antigen (PSMA) positron emission tomography (PET) becomes increasingly available in the United States, the greater sensitivity of the technology in comparison to conventional imaging poses challenges for clinical trials. The NCI Clinical Imaging Steering Committee (CISC) PSMA PET Working Group was convened to coordinate the identification of these challenges in various clinical scenarios and to develop consensus recommendations on how best to integrate PSMA PET into ongoing and upcoming National Clinical Trials Network (NCTN) trials. METHODS NCI CISC and NCI Genitourinary Steering Committee members and leadership nominated clinicians, biostatisticians, patient advocates, and other imaging experts for inclusion in the PSMA PET Working Group. From April to July 2021, the working group met independently and in conjunction with the CISC to frame challenges, including stage migration, response assessment, trial logistics, and statistical challenges, and to discuss proposed solutions. An anonymous, open-ended survey was distributed to members to collect feedback on challenges faced. Representatives from each NCTN group were invited to present an overview of affected trials. From these discussions, the consensus document was developed and circulated for the inclusion of multiple rounds of feedback from both the Working Group and CISC. RESULTS The current consensus document outlines the key challenges for clinical prostate cancer trials resulting from the increasing availability of PSMA PET. We discuss implications for patient selection and definition of end points and provide guidance and potential solutions for different clinical scenarios, particularly with regard to best practices in defining eligibility criteria and outcome measures. RECOMMENDATIONS This article provides guidance regarding clinical trial design and conduct, and the interpretation of trial results.

Expression of Prostate Specific Membrane Antigen (PSMA) in Breast Cancer

Background Prostate specific membrane antigen (PSMA) is a promising protein for breast cancer patients. It has not only been detected in prostate cancer but is also expressed by tumor cells and the endothelial cells of tumor vessels in breast cancer patients. PSMA plays a role in tumor progression and tumor angiogenesis. For this reason, a number of diagnostic and therapeutic methods to target PSMA have been developed. Method This paper provides a general structured overview of PSMA and its oncogenic potential, with a special focus on its role in breast cancer. This narrative review is based on a selective literature search carried out in PubMed and the library of Freiburg University Clinical Center. The following key words were used for the search: “PSMA”, “PSMA and breast cancer”, “PSMA PET/CT”, “PSMA tumor progression”. Relevant articles were explicitly read through, processed, and summarized. Conclusion PSMA could be a new diagnostic and therapeutic alternative, particularly for triple-negative breast cancer. It appears to be a potential predictive and prognostic marker.

Prostate-specific membrane antigen (PSMA) targeted singlet oxygen delivery via endoperoxide tethered ligands

A PSMA targeting ligand is functionalized with endoperoxides which thermally release singlet oxygen. The results show that this modular design results in significantly more cell death in PSMA-expressing prostate cancer cells.

18F-PSMA-1007 PET in Biochemical Recurrent Prostate Cancer: An Updated Meta-Analysis

Background. Prostate-specific membrane antigen- (PSMA-) targeted agents labeled with fluorine-18 (18F) have recently become available to evaluate patients with biochemical recurrent prostate cancer (BRPCa) by using positron emission tomography/computed tomography (PET/CT) or positron emission tomography/magnetic resonance imaging (PET/MRI). We performed a systematic review and meta-analysis about the detection rate (DR) of 18F-PSMA-1007 PET/CT or PET/MRI in BRPCa patients. Methods. A comprehensive computer literature search of PubMed/MEDLINE, EMBASE, and Cochrane Library databases for studies published through 17 May 2021 was carried out using the following search algorithm: “PSMA” AND “1007”. Only studies providing data on the DR of 18F-PSMA-1007 PET/CT or PET/MRI in BRPCa were included. A random-effects model was used to calculate the pooled DR on a per scan basis. Results. Fifteen articles (853 patients) were selected and included in the systematic review, and ten were included in the quantitative analysis. Most of the studies reported a good DR of 18F-PSMA-1007 PET/CT or PET/MRI in BRPCa including also patients with low prostate-specific membrane antigen (PSA) values. The DR of 18F-PSMA-1007 PET/CT or PET/MRI was dependent on PSA serum values. The pooled DR was 81.3% (95% confidence interval: 74.6–88%) with statistical heterogeneity. A significant reporting bias (publication bias) was not detected. Conclusions. 18F-PSMA-1007 PET/CT or PET/MRI showed a good DR in BRPCa patients in line with other PSMA-targeted agents. The DR of 18F-PSMA-1007 PET/CT or PET/MRI is influenced by serum PSA values. These findings should be confirmed by prospective multicentric trials.