275P - Prognosis of metastatic castration-resistant prostate cancer in response to chemotherapy and PSMA expression in circulating tumor cells

Background

In 2022, the U.S. Food and Drug Administration (FDA) approved Lutetium-177 Prostate-specific membrane antigen (Lu-177 PSMA). This approval was based on the VISION trial, in which Lu-177 PSMA demonstrated improved progression-free survival (PFS) and overall survival (OS) compared to standard therapy alone. PSMA is more strongly expressed in prostate cancer than in benign prostatic hyperplasia and correlates with Gleason Score and cancer grade. PSMA is involved in tumor growth by activating IP3K-AKT-mTOR signaling through folate metabolism. PSMA expression is suppressed by androgen receptor (AR) bound complexes with testosterone and promoted by unbound AR. In other words, inhibition of AR signaling enhances PSMA expression. These findings suggest that PSMA is involved in the mechanism of resistance to treatment in castration resistant prostate cancer (CRPC). Our previous study also showed that CRPC patients with PSMA expression in the blood circulating tumor cells (CTCs) have a shorter PFS. In this study, we aimed to determine the association between PSMA expression in CTCs and OS after the initiation of taxane-based chemotherapies in metastatic CRPC.

Methods

Forty-eight patients with metastatic CRPC treated with docetaxel followed by cabazitaxel were included in the study. PSMA expression in CTCs was analyzed over time, and the association between PSMA expression and OS was analyzed.

Results

Twenty-seven patients were positive for PSMA expression, and 21 patients were negative for PSMA expression in CTC. The analysis comparing patient backgrounds showed no significant differences with respect to Gleason Score, number of docetaxel treatments, prior ARATs administration, or metastatic site. On the other hand, patients with positive PSMA showed a longer time to acquire castration resistance. The log-rank test result showed shorter OS after initiation of docetaxel treatment in patients with positive PSMA than in those with negative PSMA (median survival at observation, PSMA-positive group: 618 days; PSMA-negative group: 1187 days; P=0.05).

Conclusions

The expression of PSMA in CTCs was associated with OS after initiation of taxane-based chemotherapy in metastatic CRPC.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.