@article{20e3d97b9d99411eb61250888367de7b,
title = "Prostate-specific Membrane Antigen and Fluciclovine Transporter Genes are Associated with Variable Clinical Features and Molecular Subtypes of Primary Prostate Cancer",
abstract = "18F-Fluciclovine-based positron emission tomography (PET) imaging is recommended in the USA for biochemical recurrence (BCR) after prostate cancer treatment. However, prostate-specific membrane antigen (PSMA)-based PET imaging is more common worldwide, supported by international guidelines, and is now approved by the Food and Drug Administration in the USA for initial staging of primary prostate cancer. Little is known about the molecular profiles of lesions detected by PSMA-targeted PET/computed tomography (CT) versus 18F-fluciclovine PET/CT. We examined the expression of PSMA (FOLH1) and the fluciclovine transporter genes LAT1–4 and ASCT1/2 in a combined cohort of more than 18 000 radical prostatectomy specimens and their associations with clinical outcomes. Expression of PSMA and all but one fluciclovine transporter gene was higher in prostate cancer than in benign tissue. PSMA expression was associated with Gleason score (GS) ≥8 and lymph node involvement (LNI), and had a positive linear correlation with Decipher risk score. By contrast, expression of the fluciclovine transporters LAT2, LAT3, and ASCT2 was negatively associated with GS ≥ 8, LNI, and high Decipher score. The top decile of PSMA expression was associated with poorest metastasis-free survival (MFS), while the bottom deciles of LAT3 and ASCT2 expression were associated with poorest MFS. Patient summary: We measured the expression of genes that encode the targets for two different radiotracers in PET (positron emission tomography) scans of the prostate. We found that PSMA gene expression (PSMA-based tracer) is associated with worse clinical outcomes, while expression of ASCT2, LAT2, and LAT3 genes (fluciclovine tracer) is associated with better outcomes.",
keywords = "Fluciclovine transporter, Gene expression, Nuclear imaging, Prostate cancer, Prostate-specific membrane antigen",
author = "Chu, {Carissa E.} and Mohammed Alshalalfa and Martin Sj{\"o}str{\"o}m and Zhao, {Shuang G.} and Yang Liu and Jonathan Chou and Annika Herlemann and Brandon Mahal and Kishan, {Amar U.} and Spratt, {Daniel E.} and Matthew Cooperberg and Eric Small and Anthony Wong and Sima Porten and Hope, {Thomas A.} and Ross, {Ashley E.} and Elai Davicioni and Paul Nguyen and Karnes, {R. Jeffrey} and Carroll, {Peter R.} and Edward Schaeffer and Feng, {Felix Y.}",
note = "Funding Information: Financial disclosures: Carissa E. Chu certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: R. Jeffrey Karnes has received personal and institutional royalties from Decipher Biosciences. Yang Liu and Elai Davicioni are employees of Decipher Biosciences. Amar Kishan has received personal fees from Varian Medical Systems, ViewRay, Janssen Biotech, and Intelligent Automation, and research funding from ASTRO-PCF and ViewRay. Felix Y. Feng is a consultant for Astellas, Bayer, BlueEarth Diagnostics, Celgene, Clovis, EMD Serono, Genentech, Janssen, Myovant, Ryovant, and Sanofi; is co-founder of PFS Genomics; and is a scientific advisory board member for SerImmune. Ashley E. Ross has received personal fees from Blue Earth Diagnostics, Janssen Biotech, Bayer, Abbvie, and Tempus. Daniel E. Spratt has received personal fees from Janssen, AstraZeneca, and BlueEarth. The remaining authors have nothing to disclose. Funding Information: Funding/Support and role of the sponsor: Carissa E. Chu is supported by NIH-UCSF-CTSI grant number TL1 TR001871 . Martin Sj{\"o}str{\"o}m is supported by the Swedish Research Council (Vetenskapsr{\aa}det; grant number 2018-00382 ) and the Swedish Society of Medicine (Svenska L{\"a}kares{\"a}llskapet). Jonathan Chou is supported by an A.P. Giannini Foundation Postdoctoral Fellowship , a Rosenberg Fellowship in Genitourinary Oncology , and a training grant from the National Cancer Institute ( T32 CA108462 ). Felix Y. Feng is supported by a Prostate Cancer Foundation Challenge Award , the Benioff-Goldberg Fund for Translational Research , and NIH grants 1R01CA230516 and P50CA186786 . The sponsors played no direct role in the study. Publisher Copyright: {\textcopyright} 2021 European Association of Urology",
year = "2021",
month = jun,
doi = "10.1016/j.eururo.2021.03.017",
language = "English (US)",
volume = "79",
pages = "717--721",
journal = "European urology",
issn = "0302-2838",
publisher = "Elsevier",
number = "6",
}