Transcriptomic Profiling of Primary Prostate Cancers and Nonlocalized Disease on Prostate-Specific Membrane Antigen...

To characterize the relationship between Decipher genomic classifier scores and prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT)-based metastatic spread.

We identified patients from four institutions who underwent PSMA PET/CT scans pretreatment for primary staging or postradical prostatectomy (RP) for suspected recurrence and had Decipher transcriptomic data available from biopsy or RP specimens. PSMA PET/CT-based patterns of spread were classified as localized (miT + N0M0) or nonlocalized (miN1M0 or miM1a-c). We calculated the association between Decipher scores and the risk of nonlocalized disease on PSMA PET/CT using multivariable logistic regression for pretreatment patients and multivariable Cox regression for post-RP patients. We also compared select transcriptomic signatures between patients with localized and nonlocalized diseases.

Five hundred eighty-six patients were included (pretreatment: n = 329; post-RP: n = 257). Higher Decipher scores were associated with nonlocalized disease on PSMA PET/CT both pretreatment (odds ratio, 1.18 [95% CI, 1.03 to 1.36] per 0.1 increase in Decipher score, P = .02) and post-RP (hazard ratio, 1.15 [95% CI, 1.05 to 1.27] per 0.1 increase in Decipher score, P = .003). In the pretreatment setting, nonlocalized disease was associated with higher rates of TP53 mutations and lower rates of PAM50 luminal A subtype compared with localized disease. In the post-RP setting, overexpression of signatures related to metabolism, DNA repair, and androgen receptor signaling were associated with higher rates of nonlocalized disease.

Higher Decipher scores were associated with nonlocalized disease identified on PSMA PET/CT both pretreatment and post-RP. There were several transcriptomic differences between localized and nonlocalized diseases in both settings.