Transcriptomic Heterogeneity in High-risk Prostate Cancer and Implications for Extraprostatic Disease at Presentation on Prostate-specific Membrane Antigen Positron Emission Tomography

Clayton P Smith; James A Proudfoot; Paul C Boutros; Robert E Reiter; Luca Valle; Matthew B Rettig; Nicholas G Nickols; Felix Y Feng; Paul L Nguyen; Himanshu Nagar; Daniel E Spratt; Gert Attard; Adam Weiner; Joanne B Weidhaas; Jeremie Calais; T Martin Ma; Elai Davicioni; Michael Xiang; Amar U Kishan

doi:10.1016/j.euo.2023.02.009

Transcriptomic Heterogeneity in High-risk Prostate Cancer and Implications for Extraprostatic Disease at Presentation on Prostate-specific Membrane Antigen Positron Emission Tomography

Eur Urol Oncol. 2023 Apr;6(2):224-227. doi: 10.1016/j.euo.2023.02.009. Epub 2023 Mar 2.

Authors

Clayton P Smith¹, James A Proudfoot², Paul C Boutros³, Robert E Reiter⁴, Luca Valle¹, Matthew B Rettig⁵, Nicholas G Nickols¹, Felix Y Feng⁶, Paul L Nguyen⁷, Himanshu Nagar⁸, Daniel E Spratt⁹, Gert Attard¹⁰, Adam Weiner⁴, Joanne B Weidhaas¹, Jeremie Calais¹¹, T Martin Ma¹, Elai Davicioni², Michael Xiang¹, Amar U Kishan¹²

Affiliations

¹ Department of Radiation Oncology, University of California-Los Angeles, Los Angeles, CA, USA.
² Veracyte, Inc, South San Francisco, CA, USA.
³ Department of Human Genetics, University of California-Los Angeles, Los Angeles, CA, USA; Department of Urology, University of California-Los Angeles, Los Angeles, CA, USA.
⁴ Department of Urology, University of California-Los Angeles, Los Angeles, CA, USA.
⁵ Department of Urology, University of California-Los Angeles, Los Angeles, CA, USA; Division of Hematology/Oncology, Department of Medicine, University of California-Los Angeles, Los Angeles, CA, USA.
⁶ Department of Radiation Oncology, University of California-San Francisco, San Francisco, CA, USA.
⁷ Department of Radiation Oncology, Brigham and Women's Hospital/Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
⁸ Department of Radiation Oncology, Weill Cornell Medicine, New York, NY, USA.
⁹ Department of Radiation Oncology, University Hospitals Seidman Cancer Center, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
¹⁰ University College London Cancer Institute, London, UK.
¹¹ Ahmanson Translational Theranostics Division, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, USA.
¹² Department of Radiation Oncology, University of California-Los Angeles, Los Angeles, CA, USA; Department of Urology, University of California-Los Angeles, Los Angeles, CA, USA. Electronic address: aukishan@mednet.ucla.edu.

PMID: 36870853
DOI: 10.1016/j.euo.2023.02.009

Abstract

Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) has greater specificity and sensitivity for detection of extraprostatic prostate cancer (PCa) at presentation than conventional imaging. Although the long-term clinical significance of acting on these findings is unknown, it has been shown that the risk of upstaging is prognostic for long-term outcomes in men with high-risk (HR) or very high-risk (VHR) PCa. We evaluated the association between the risk of upstaging on PSMA PET and the Decipher genomic classifier score, a known prognostic biomarker in localized PCa that is being evaluated for its predictive ability to direct systemic therapy intensification. In a cohort of 4625 patients with HR or VHR PCa, the risk of upstaging on PSMA PET was significantly correlated with the Decipher score (p < 0.001). These results should be seen as hypothesis-generating and warrant further studies on the causal pathways linking PSMA findings, Decipher scores, extraprostatic disease, and long-term clinical outcomes. PATIENT SUMMARY: We found significant correlation between the risk of having prostate cancer outside the prostate gland on a sensitive scan (based on prostate-specific membrane antigen [PSMA]) at initial staging and the Decipher genetic score. The results warrant further studies on the causal pathways between PSMA scan findings, Decipher scores, disease outside the prostate, and long-term outcomes.

Keywords: Computed tomography; Decipher score; High-risk prostate cancer; Positron emission tomography; Prostate-specific membrane antigen.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Gallium Radioisotopes
Humans
Male
Positron Emission Tomography Computed Tomography / methods
Positron-Emission Tomography
Prostate* / diagnostic imaging
Prostatic Neoplasms* / diagnostic imaging
Prostatic Neoplasms* / genetics
Transcriptome

Substances

Gallium Radioisotopes