Results in males with mCRPC have significantly improved thanks to PSMA-targeted radioligand treatment. For a study, researchers sought to determine the best course of treatment and the individuals most likely to benefit. A liquid biopsy technology to detect and quantify PSMA expression and heterogeneity might be useful.

A retrospective study of the males with mCRPC (n=118) who received abiraterone (abi) or enzalutamide (enza) as part of the multicenter PROPHECY experiment was done. Using a reliable immunofluorescent technique, CTCs were used to measure the expression and heterogeneity of the PSMA protein both before and after treatment. Using Cox modeling, associations between the number of PSMA+ CTCs and both overall survival (OS) and radiographic progression-free survival (rPFS) were investigated. They discussed variations in expression predominance through time and their relationships to neuroendocrine and AR-V7 traits.

At baseline, 97 men had evaluable samples for CTC PSMA detection, with 78 men (80%) having at least 1 CTC. Of these guys, 21% (16/78) had ≥2 PSMA+ CTCs+ (the ideal cut-off), 55% (43/78) had PSMA expression on CTCs, and 19% had perfect PSMA homogeneity (100% expression). About 88% (50/57) of the males had at least ≥1 detectable CTC at the time of advancement on abi/enza; 68% (34/58) of these CTCs were PSMA+ CTCs, and 12% had 100% PSMA+ CTCs. In comparison to pre-treatment expression, the bulk of PSMA+CTC (>50%) was expressed throughout the progression on abi/enza (n=29, 34% vs. 17%). The median OS was 26, 21, and 11 months for CTC 0 (the reference group), PSMA-CTC, and PSMA+CTC, respectively. PSMA+ CTC were shown to be unfavorably predictive in univariate studies for both OS (hazard ratio (HR)=3.4; 95% CI=1.6-7.0) and rPFS (HR=2.8, 95% CI=1.4-5.8). The HRs for OS and rPFS PSMA+ CTC+ after adjusting for previous treatment, Halabi risk score, and CTC were 3.0 (95% CI=1.1-7.8) and 2.3 (95% CI=0.9-5.8), respectively. It didn’t matter whether the phenotype was CTC NEPC or AR-V7; they saw variability in PSMA expression.

Before and after advancement on abi/enza medication, they measured the PSMA CTC heterogeneity in mCRPC males and discovered a rise in PSMA CTC detection. Since PSMA CTC enumeration and CTC were negatively prognostic, the test may be helpful in identifying individuals who will responded well to PSMA-targeted therapy.

Reference: annalsofoncology.org/article/S0923-7534(22)03348-8/fulltext