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

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.

European urology oncology. 2023 Mar 02 [Epub ahead of print]

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

Department of Radiation Oncology, University of California-Los Angeles, Los Angeles, CA, USA., Veracyte, Inc, South San Francisco, CA, USA., 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., Department of Urology, University of California-Los Angeles, Los Angeles, CA, USA., 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., Department of Radiation Oncology, University of California-San Francisco, San Francisco, CA, USA., Department of Radiation Oncology, Brigham and Women's Hospital/Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA., Department of Radiation Oncology, Weill Cornell Medicine, New York, NY, USA., Department of Radiation Oncology, University Hospitals Seidman Cancer Center, Case Western Reserve University School of Medicine, Cleveland, OH, USA., University College London Cancer Institute, London, UK., Ahmanson Translational Theranostics Division, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, USA., 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: .