A pilot study of prostate‐specific membrane antigen (PSMA) dynamics in men undergoing treatment for advanced prostate cancer

Abstract

Background Prostate‐specific membrane antigen (PSMA) is a rational target for noninvasive detection of recurrent prostate cancer (PCa) and for therapy of metastatic castration‐resistant prostate cancer (mCRPC) with PSMA‐targeted agents. Here we conducted serial measurements of PSMA expression on circulating tumor cells (CTCs) to evaluate patterns of longitudinal PSMA dynamics over the course of multiple sequential therapies. Methods A retrospective investigation of men with mCRPC undergoing evaluation at medical oncology clinics at our institution assessed the dynamics of PSMA expression in the context of different systemic treatments administered sequentially. Eligibility included patients who began systemic therapies with androgen receptor (AR)‐directed agents or taxane agents for whom peripheral blood samples were tested for CTC mRNA of AR splice variant‐7 (AR‐V7), prostate‐specific antigen (PSA), and PSMA (with >2 CTC + results) in a CLIA‐accredited laboratory. Results From August 2015 to November 2017, we identified 96 eligible men. Fifteen had greater than or equal to 2 sequential therapies and evaluable CTC samples, greater than or equal to 1 expressing PSMA (PSMA+). Among the 15 patients included in this analysis, a total of 54 PSMA status evaluations were performed in the context of 48 therapies during a median follow‐up of 18 months. At baseline, PSMA signal was detected (“positive”) in 11 of 15 (73.3%) patients, while for 4 of 15 (26.7%) patients PSMA signal was undetectable (“negative”). In all but two patients, the baseline collection corresponded with a change in treatment. On the second assessment, PSMA increases were detected in all 4/4 (100%) PSMA‐negative patients and 8 of 11 (72.7%) PSMA‐positive patients. PSMA significantly decreased in a patient treated with 177Lu‐PSMA‐617. Serum PSA declines were seen in 7 of 8 (88%) of the treatment periods where PSMA decreased. Conclusions PSMA expression in CTCs is a dynamic marker. PSMA transcript declines appear to be associated with concurrent decreases in serum PSA. Sequential CTC sampling could provide a noninvasive response assessment to systemic treatment for mCRPC.

Response assessment using [68Ga]Ga‐PSMA ligand PET in patients undergoing systemic therapy for metastatic castration‐resistant prostate cancer

“…This is in agreement with preclinical studies, which have demonstrated that PSMA uptake in the tumor reliably reflects the number of living tumor cells . Another study evaluating the role of PSMA dynamics in men undergoing treatment for advanced PC showed that the PSMA expression in circulating tumor cells shows promising results as a dynamic marker for therapy response . Nevertheless, the data available for PSMA 11‐PET in mCRPC patients are still scarce.…”

“…16 Another study evaluating the role of PSMA dynamics in men undergoing treatment for advanced PC showed that the PSMA expression in circulating tumor cells shows promising results as a dynamic marker for therapy response. 17 Nevertheless, the data available for PSMA 11-PET in mCRPC patients are still scarce. In this study, we aimed to compare the value of PSMA 11-PET parameters to that of standard imaging with focus on their predictive and monitoring abilities in mCRPC patients receiving systemic therapy.…”

Prognostic Significance of Gene Expression and DNA Methylation Markers in Circulating Tumor Cells and Paired Plasma Derived Exosomes in Metastatic Castration Resistant Prostate Cancer

“…The presence of AR-V7 in CTCs was shown to predict resistance to new generation anti-AR-targeted treatments (abiraterone and enzalutamide) but not to taxane-based chemotherapy in mCRPC [ 29 , 30 , 31 ]. The development of molecular assays for the detection of AR-V7 with high analytical sensitivity, specificity and accuracy is very important for the application of this biomarker in clinical practice [ 19 , 32 , 33 ].…”

Circulating Tumor Cells Expressing the Prostate Specific Membrane Antigen (PSMA) Indicate Worse Outcome in Primary, Non-Metastatic Triple-Negative Breast Cancer

“…One of our key findings was the significant correlation of PSMA+ CTCs with early relapse and reduced OS. Interestingly, using the same method for the detection of PSMA+ CTCs, PSMA transcript declines appeared to be associated with concurrent decreases in serum PSA, thus, sequential CTC sampling was proposed to provide a non-invasive response assessment to systemic treatment for metastatic castration-resistant PCA (57).…”