Early changes of PSMA PET expression after initiation of androgen receptor signaling inhibitors in CRPC: an international multicenter retrospective study

Abstract

Background

An increase of PSMA expression under androgen receptor signaling inhibitors (ARSi) measured on PSMA PET was reported: However, results were inconsistently reproduced clinically and the frequency and timing of the PSMA expression modulation by ARSi remains unknown.

Methods

In this multicenter retrospective study, we aimed at assessing in patients with CRPC the influence of ARSi early after initiation (≤ 30 days) on PSMA expression at the whole-body (WB) level by using WB PSMA PET quantitative parameters. (m)CRPC patients from 5 international sites who underwent a PSMA PET prior to (PET1) and early (< 30 days) after (PET2) ARSi initiation were included. WB-PSMA PET quantitative parameters (PSMA-positive WB-tumor volume (TV), WB-SUV_max, WB-SUV_mean) and PSA changes between PET1 and PET2 (PSA1/PSA2) were evaluated. Changes of WB-TV / WB-SUVmax/mean between PET1 and PET2 were considered significant if ≥ 30% of increase or decrease.

Results

Fifty-six patients who initiated ARSi treatment were included. 30/56 (53.6%) were treated with an ARSi for the first time, 26/56 (41.1%) were previously treated with another ARSi agent and 29/56 (51.9%) received prior chemotherapy. 10/56 (17.9%) had a significantly increasing PSA of ≥ 25% between PET1 and PET2. 15/56 (27%), 14/56 (25%) and 1/56 (1.8%) patients had a significantly increasing WB-TV, WB-SUV_max or WB SUV_mean of ≥ 30% between PET1 and PET2, respectively. The patients with significant WB-TV increase (n = 15) and with significant WB SUV_max increase (n = 14) did not differ significantly from the ones with stable or decreased WB-TV (n = 41) or WB-SUV_max (n = 42) in their clinical characteristics or their PSA responses.

Conclusions

In this analysis of patients with early PSMA PET follow-up after ARSi initiation, we observed a PSMA-upregulation by WB-PET imaging in 25% of the patients. Further studies are needed to better understand the potential synergistic and / or additive effects of AR- and PSMA-targeted approaches.

Clinical trial number

Not applicable.