Transcriptomic Analysis of Prostate Cancer Patients: A Study on Nonlocalized Disease Based on Prostate-Specific Membrane Antigen Positron Emission Tomography/Computed Tomography

Academic Background

Prostate cancer is a common male malignancy, and its diagnosis and treatment are crucial to patient prognosis. Transcriptomic analysis is a technique used to understand gene expression levels and has been widely applied in cancer research in recent years. The Decipher genomic classifier is a prognostic biomarker used to estimate the risk of metastasis in prostate cancer patients after radical prostatectomy (RP) or radiation therapy. The current study arose from an interest in the prognostic capabilities of the Decipher test in the era of prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT). Given the high specificity and sensitivity of PSMA PET/CT in detecting nonlocalized disease, researchers aimed to evaluate the relationship between Decipher scores and the detection of nonlocalized disease using this advanced molecular imaging technology.

Study Source

This study was conducted in collaboration by John Nikitas, MD; Kritika Subramanian, MD; Nimrod Barashi Gozal, MD, among others, with participating institutions including Washington University School of Medicine, NewYork-Presbyterian/Weill Cornell Medical Center, UCLA, and Northwestern University Feinberg School of Medicine. The study findings were published in JCO Precision Oncology on July 16, 2024, in the article titled “Transcriptomic Profiling of Primary Prostate Cancers and Nonlocalized Disease on Prostate-Specific Membrane Antigen Positron Emission Tomography/Computed Tomography: A Multicenter Retrospective Study.” DOI link: https://doi.org/10.1200/po.24.00161.

Study Process

1. Patient Cohort

The study included 586 patients, with 329 pre-treatment and 257 post-RP recurrence patients. These patients from four institutions underwent Decipher genomic classifier testing and PSMA PET/CT scanning. PSMA PET/CT scans were used for primary staging before treatment or for recurrence assessment post-RP.

2. Clinical Data Collection

Clinical data were collected from each patient, including age at the time of scan, International Society of Urological Pathology (ISUP) grading, TNM staging, prostate-specific antigen (PSA) levels, and PSMA PET/CT report results. Transcriptomic signature data used for analysis were derived from a prospectively maintained gene expression registry.

3. Data Processing and Analysis

All data were de-identified to protect patient privacy. The study used multivariate logistic regression and multivariate Cox regression models to analyze the association between Decipher scores and PSMA PET/CT results in pre-treatment and post-RP patients. Additionally, transcriptomic signatures were compared to explore the differences between disease states.

Study Results

1. Association Between Decipher Scores and PSMA PET/CT Results

Pre-treatment, each 0.1 increase in the Decipher score significantly increased the likelihood of nonlocalized disease (OR: 1.18, 95% CI: 1.03-1.36, p=0.02). Post-RP, higher Decipher scores were also associated with a higher incidence of nonlocalized disease (HR: 1.15, 95% CI: 1.05-1.27, p=0.003).

2. Differences in Transcriptomic Signatures

Pre-treatment, patients with nonlocalized disease had a higher rate of TP53 mutations and a lower rate of PAM50 luminal A subtype (21% vs 36%). Post-RP, signatures related to metabolism, DNA repair, and androgen receptor signaling were higher. For patients with bone and visceral metastases, a high signature of DNA repair and neuroendocrine was associated with a higher risk of nonlocalized disease.

3. Exploration of Gene Expression Signatures

Multivariable regression analysis found that higher Decipher scores were associated with higher risks of peripheral lymph node and visceral metastases. Furthermore, in both pre-treatment and post-RP patients, different transcriptomic signatures (such as metabolic effects, Hallmarks of Cancer, and AR biology) revealed molecular biological differences between disease states.

Study Conclusion

The study showed that higher Decipher scores were associated with nonlocalized disease detected by PSMA PET/CT, applicable in both pre-treatment and post-RP patient scenarios. Pre-treatment, nonlocalized disease was associated with a higher rate of TP53 mutations and a lower rate of the PAM50 luminal A subtype. Post-RP, signatures related to metabolism, DNA repair, and androgen receptor signaling pathways were associated with higher rates of nonlocalized disease. These data suggest that a high Decipher score may indicate a more aggressive metastatic risk, but further prospective studies are needed to validate the impact of treatment regimen adjustments on patient prognosis.

Study Significance

This study underscores the importance of the Decipher score as a prognostic biomarker in the diagnosis and treatment of prostate cancer. Combined with PSMA PET/CT, it further enhances the identification of nonlocalized disease. Future research can focus on the comprehensive evaluation of Decipher scores and PSMA PET/CT results to guide optimization of clinical treatment strategies, including increasing or decreasing the intensity of treatment, to improve long-term patient outcomes.