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.
Bibliographical noteFunding Information:
CJP has served as a paid advisor for Omnitura and has received research funding from Lilly. ESA has served as a paid consultant/advisor for Janssen, Astellas, Bayer, AstraZeneca, Clovis, Merck, Bristol Myers‐Squibb, Sanofi, Dendreon, Essa, and Medivation; he has received research funding from Janssen, Johnson & Johnson, Sanofi, Dendreon, Genentech, Novartis, AstraZeneca, Clovis, Merck, Bayer, Bristol Myers‐Squibb and Tokai; he is a coinventor of a technology that has been licensed to Tokai. JL has served as a paid consultant/advisor for Sun Pharma, Janssen, and Astellas, has been a speaker for Sanofi and Gilead, has received research funding from Sanofi, Mirati, Orion, Astellas, and Constellation, and is a coinventor of a technology that has been licensed to Tokai, A&G, and Qiagen. MGP is a coinventor on a US patent covering 18 F‐DCFPyL and as such is entitled to a portion of any licensing fees and royalties generated by this technology. SPR is a consultant for Progenics Pharmaceuticals, Inc., the licensee of 18 F‐DCFPyL. MGP and SPR receive research funding from Progenics Pharmaceuticals, Inc. Relevant disclosures have been reviewed and approved by Johns Hopkins University in accordance with its conflict of interest policies. Remaining authors declare that there are no conflict of interests.
We thank the study participants and their families. This study was supported by the Prostate Cancer Foundation (PCF), the Department of Defense (DOD) Prostate Cancer Research Program grant (W81XWH‐12–1‐0605), the Patrick C. Walsh Fund, the Johns Hopkins Prostate SPORE grant (P50 CA058236), NIH (P30 CA006973, CA134675, CA184228, EB024495, and CA183031) and NCI (K23 CA197526).
© 2019 Wiley Periodicals, Inc.
- circulating tumor cells
- metastatic prostate cancer
- prostate-specific membrane antigen