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Rapid modulation of PSMA expression by androgen deprivation: Serial (68)Ga-PSMA-11 PET in men with hormone-sensitive and castrate-resistant prostate cancer commencing androgen blockade

Abstract

Prostate-specific membrane antigen (PSMA) may be targeted for both diagnostic and therapeutic purposes in the management of prostate cancer (PCa). In preclinical models, androgen blockade (AB) increases expression of PSMA in both hormone-sensitive and castrate-resistant xenotypes. The aim of this study was to evaluate the effect of AB treatment on (68)Ga-PSMA-11 PET imaging in hormone-naive (luteinizing hormone-releasing hormone [LHRH] +/- bicalutamide) and in castrate-resistant men (enzalutamide or abiraterone) with metastatic PCa. Methods: Serial (68)Ga-PSMA-11 PET was prospectively performed at baseline and on days 9, 18, and 28 in 8 men with measurable metastatic hormone-sensitive PCa commencing LHRH +/- bicalutamide (cohort 1) and 7 men with castrate-resistant PCa commencing either enzalutamide or abiraterone (cohort 2). Gleason score, age, time since diagnosis, and prior treatments were documented. Testosterone and prostate-specific antigen (PSA) were measured at baseline and all imaging time points. PET/CT was quantitatively analyzed for SUVmax, SUVmean, and total tumor volume. Results: In cohort 1, a median 30% (interquartile range [IQR], 5-61) reduction in SUVmax was recorded by day 9 after AB. A reduction from baseline SUVmax occurred in 86.5% (6/7) men by day 9 (P < 0.04), with an associated PSA response in 100% men (P < 0.03). Total tumor volume reduced in all men by 74.5% (IQR, 27-97) (P < 0.02). After day 9, PSMA response heterogeneity was noted, with persistently high or increasing SUVmax in 37.5% (3/8) and marked reduction in 62.5% (5/8). In cohort 2, a median 45% (IQR, 12.7-66) increase in intensity of PSMA SUV was recorded by day 9 after AB. All men demonstrated an increase in SUVmax and SUVmean on PSMA PET compared with baseline (P < 0.04). This increase at day 9 plateaued by day 28. PSA responses were more delayed in cohort 2 (-15% [IQR, 70-138]), with 2 of 7 men demonstrating PSA progression. Conclusion: There is rapid dichotomous response on (68)Ga-PSMA PET imaging to AB-dependent on the presence of a hormone-sensitive or castrate-resistant PCa phenotype. This has important implications for interpretation of PSMA PET, and in the timing and sequencing of PSMA-targeted therapy.

Type Journal
ISBN 1535-5667 (Electronic) 0161-5505 (Linking)
Authors Emmett, L.; Yin, C.; Crumbaker, M.; Hruby, G.; Kneebone, A.; Epstein, R.; Nguyen, Q.; Hickey, A.; Ihsheish, N.; O'Neill, G.; Horvath, L.; Chalasani, V.; Stricker, P.; Joshua, A. M.
Responsible Garvan Author Dr Anthony Joshua
Publisher Name JOURNAL OF NUCLEAR MEDICINE
Published Date 2019-07-31
Published Volume 60
Published Issue 7
Published Pages 950-954
Status Published in-print
DOI 10.2967/jnumed.118.223099
URL link to publisher's version https://www.ncbi.nlm.nih.gov/pubmed/30552200