Prostate-specific Membrane Antigen and Fluciclovine Transporter Genes are Associated with Variable Clinical Features and Molecular Subtypes of Primary Prostate Cancer

Carissa E Chu; Mohammed Alshalalfa; Martin Sjöström; Shuang G Zhao; Yang Liu; Jonathan Chou; Annika Herlemann; Brandon Mahal; Amar U Kishan; Daniel E Spratt; Matthew Cooperberg; Eric Small; Anthony Wong; Sima Porten; Thomas A Hope; Ashley E Ross; Elai Davicioni; Paul Nguyen; R Jeffrey Karnes; Peter R Carroll; Edward Schaeffer; Felix Y Feng

doi:10.1016/j.eururo.2021.03.017

Prostate-specific Membrane Antigen and Fluciclovine Transporter Genes are Associated with Variable Clinical Features and Molecular Subtypes of Primary Prostate Cancer

Eur Urol. 2021 Jun;79(6):717-721. doi: 10.1016/j.eururo.2021.03.017. Epub 2021 Apr 8.

Authors

Carissa E Chu¹, Mohammed Alshalalfa², Martin Sjöström³, Shuang G Zhao⁴, Yang Liu⁵, Jonathan Chou⁶, Annika Herlemann⁷, Brandon Mahal⁸, Amar U Kishan⁹, Daniel E Spratt⁴, Matthew Cooperberg¹⁰, Eric Small¹¹, Anthony Wong², Sima Porten¹², Thomas A Hope¹³, Ashley E Ross¹⁴, Elai Davicioni⁵, Paul Nguyen¹⁵, R Jeffrey Karnes¹⁶, Peter R Carroll¹², Edward Schaeffer¹⁷, Felix Y Feng¹⁸

Affiliations

¹ Department of Urology, University of California-San Francisco, San Francisco, CA, USA.
² Department of Radiation Oncology, University of California-San Francisco, San Francisco, CA, USA.
³ Department of Radiation Oncology, University of California-San Francisco, San Francisco, CA, USA; UCSF Helen Diller Comprehensive Cancer Center, San Francisco, CA, USA.
⁴ Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA.
⁵ Decipher Biosciences, La Jolla, CA, USA.
⁶ UCSF Helen Diller Comprehensive Cancer Center, San Francisco, CA, USA; Division of Hematology/Oncology, Department of Medicine, University of California-San Francisco, San Francisco, CA, USA.
⁷ Department of Urology, Ludwig-Maximilians University, Munich, Germany.
⁸ Department of Radiation Oncology, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL, USA.
⁹ Department of Radiation Oncology, University of California-Los Angeles, Los Angeles, CA, USA.
¹⁰ Department of Urology, University of California-San Francisco, San Francisco, CA, USA; Department of Radiation Oncology, University of California-San Francisco, San Francisco, CA, USA.
¹¹ UCSF Helen Diller Comprehensive Cancer Center, San Francisco, CA, USA; Decipher Biosciences, La Jolla, CA, USA.
¹² Department of Urology, University of California-San Francisco, San Francisco, CA, USA; UCSF Helen Diller Comprehensive Cancer Center, San Francisco, CA, USA.
¹³ Department of Urology, University of California-San Francisco, San Francisco, CA, USA; UCSF Helen Diller Comprehensive Cancer Center, San Francisco, CA, USA; Department of Radiology and Biomedical Imaging, University of California-San Francisco, San Francisco, CA, USA.
¹⁴ Department of Urology, Northwestern University, Chicago, IL, USA.
¹⁵ Department of Radiation Oncology, Dana Farber Cancer Institute, Brigham and Women's Hospital, Boston, MA, USA.
¹⁶ Department of Urology, Mayo Clinic, Rochester, MN, USA.
¹⁷ Department of Urology, Northwestern University, Chicago, IL, USA. Electronic address: e-schaeffer@northwestern.edu.
¹⁸ Department of Urology, University of California-San Francisco, San Francisco, CA, USA; Department of Radiation Oncology, University of California-San Francisco, San Francisco, CA, USA; UCSF Helen Diller Comprehensive Cancer Center, San Francisco, CA, USA. Electronic address: felix.feng@ucsf.edu.

PMID: 33840559
DOI: 10.1016/j.eururo.2021.03.017

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Humans
Male
Positron Emission Tomography Computed Tomography*
Prostate
Prostate-Specific Antigen
Prostatectomy
Prostatic Neoplasms* / diagnostic imaging
Prostatic Neoplasms* / genetics
Prostatic Neoplasms* / surgery

Substances

Prostate-Specific Antigen

Abstract

Publication types

MeSH terms

Substances

Grants and funding