Characterization of PSMA and 18F-fluciclovine transporter gene expression in localized prostate cancer.

Authors

Carissa Chu

Carissa Chu

University of California, San Francisco, San Francisco, CA

Carissa Chu , Mohammed Alshalalfa , Martin Sjöström , Shuang Zhao , Annika Herlemann , Jonathan Chou , Brandon Arvin Virgil Mahal , Amar Upadhyaya Kishan , Daniel Eidelberg Spratt , Jeffrey Karnes , Eric Jay Small , Anthony C. Wong , Sima P. Porten , Thomas Hope , Elai Davicioni , Paul L. Nguyen , Peter Carroll , Edward M. Schaeffer , Felix Y Feng , Matthew R. Cooperberg

Organizations

University of California, San Francisco, San Francisco, CA, Dana-Farber Cancer Institute, Vancouver, BC, Canada, Lund University, Department of Oncology and Pathology, Lund, Sweden, University of Michigan, Ann Arbor, MI, University of California San Francisco, San Francisco, CA, Harvard Radiation Oncology Program, Boston, MA, Department of Radiation Oncology, University of California, Los Angeles, CA, Memorial Sloan Kettering Cancer Center, New York, NY, Mayo Clinic, Rochester, MN, UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, Dept. of Radiation Oncology, University of California, San Francisco, San Francisco, CA, GenomeDx Biosciences Inc., San Diego, CA, Dana-Farber Cancer Institute, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, University of California-San Francisco, San Francisco, CA, Northwestern University Feinberg School of Medicine, Chicago, IL

Research Funding

U.S. National Institutes of Health
U.S. National Institutes of Health, Other Foundation.

Background: While 18F-fluciclovine PET/CT is approved in the US and recommended by the NCCN, prostate-specific membrane antigen (PSMA) PET/CT is more common in Europe/Australia and recommended by the EAU. Less is known about the biology of lesions detected by either modality. 18F-fluciclovine PET relies on radiotracer uptake by amino acid transporters LAT1-4 and ASCT1-2. PSMA PET is dependent on surface expression of PSMA. We compared relative expression of PSMA and fluciclovine transporter genes in radical prostatectomy (RP) samples to determine their distribution across subtypes and correlation with outcomes. Methods: Gene expression data of 19,102 RP samples were analyzed using the Affymetrix Human Exon 1.0 ST microarray. 1,135 patients had long term follow up. Associations between expression of PSMA and fluciclovine transporter genes (LAT1-4 and ASCT1-2) and pathologic variables, molecular subtypes, and clinical outcomes were conducted. Results: All fluciclovine transporter genes (LAT 1-4, ASCT1-2) were expressed at lower levels than PSMA (p <0.0001). PSMA expression was positively correlated with genomic risk score and pathologic Gleason score (p<0.0001), but LAT2-3 and ASCT2 were inversely correlated with genomic risk in primary tumors (p<0.0001) and less expressed in GS 9-10 tumors (p<0.0001). PSMA expression was associated with worse metastasis-free survival (MFS) (HR 1.45, p=0.001) and lymph node involvement (HR 2.14, p<0.0001). Expression of LAT2, LAT3, ASCT2 expression was associated with better MFS (HR 0.85, 0.63, 0.74, p<0.0001-0.04). After multivariable adjustment, PSMA expression remained independently prognostic of poorer MFS (HR 1.3, p=0.028). Luminal B subtype was notable for PSMA overexpression; Luminal A was enriched in ASCT2 and LAT2 (p<0.0001). PSMA expression did not correlate with ERG fusion prostate cancers, but LAT2, ASCT1, and ASCT2 were overexpressed in ERG fusion negative tumors (p<0.0001). Conclusions: PSMA expression is associated with more aggressive disease and poorer clinical outcomes than fluciclovine transporter genes in localized prostate cancer. Molecular subtypes of prostate cancer vary in PSMA and fluciclovine transporter gene expression.

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Abstract Details

Meeting

2020 Genitourinary Cancers Symposium

Session Type

Poster Session

Session Title

Poster Session A: Prostate Cancer

Track

Prostate Cancer - Advanced,Prostate Cancer - Localized

Sub Track

Imaging

Citation

J Clin Oncol 38, 2020 (suppl 6; abstr 295)

Abstract #

295

Poster Bd #

L1

Abstract Disclosures