The 2023 ASTRO annual meeting included a session on novel prognostication techniques for prostate cancer, featuring a presentation by Dr. Angela Jia discussing a cross-comparison individual patient level analysis of three gene expression signatures in localized prostate in over 50,000 men.
Risk stratification guides the management of localized prostate cancer. Multiple commercial gene expression biomarkers have been developed to improve estimates of prognosis, however, the 22-gene Decipher genomic classifier is the only test with level 1 evidence supporting its use per NCCN guidelines:
Additionally, Dr. Jia notes that the Decipher genomic classifier has been assessed in 12 phase 3 randomized clinical trials, whereas Oncotype and Prolaris have been assessed in 0:
It is unknown whether these other commercial signatures are sufficiently correlated to negate the differences in evidence supporting these commercial tests. At the ASTRO 2023 annual meeting, Dr. Jia and colleagues performed a cross-comparison of these signatures in a large cohort of patients diagnosed with localized prostate cancer.
Patients diagnosed with localized prostate cancer who underwent whole transcriptome gene expression microarray analysis on their primary tumor biopsy specimen were included. The 22-gene Decipher genomic classifier score was calculated by Veracyte using a commercially locked model. Individual genes in each of the Oncotype and Prolaris gene signatures were identified, and the gene weights in each signature were retrained for prediction of metastasis in a multi-institutional cohort of 1,574 men with long-term outcome data. This was performed to improve correlation performance of Oncotype and Prolaris given only the 22-gene Decipher genomic classifier was trained for prediction of metastasis:
For each of the three signatures, both continuous and categorical scores were calculated. Linear regression and spearman correlations were calculated both on univariable and multivariable analyses adjusting for age, grade group, PSA, and T-stage. A total of 50,881 patients were included (15,379 (30.2%) NCCN low-risk, 14,773 (29.0%) favorable intermediate-risk, 15,544 (30.5%) unfavorable intermediate-risk, and 5,185 (10.2%) high/very high-risk) with a median age of 68 years (IQR 62-73), and a median PSA of 6.2 ng/mL (IQR 4.7-8.7). On linear regression, the Oncotype model had poor goodness-of-fit to the 22-gene Decipher genomic classifier with an R2 of 0.36:
Similarly, the Prolaris model to the 22-gene Decipher genomic classifier had an R2 of 0.32:
Results were similar on multivariable analysis adjusting for age, PSA, clinical stage, and grade group. Spearman correlation between the continuous Oncotype model scores and the 22-gene Decipher genomic classifier was moderate at 0.59, as was the correlation between Prolaris model and the 22-gene Decipher genomic classifier of 0.55. Prolaris is a measure of proliferation, but in 22-gene Decipher genomic classifier high-risk patients, the majority (64.1%) of patients had low-average proliferation and only 35.9% had high proliferation, potentially explaining the lack of strong correlation. Finally, ~60% of the information from the Decipher GC is unique and not explained by known variables:
Dr. Jia concluded her presentation discussing a cross-comparison individual patient level analysis of three gene expression signatures in localized prostate in over 50,000 men with the following take-home points:
- There is minimal to moderate correlation between the 22-gene Decipher genomic classifier and Oncotype or Prolaris gene expression signatures tested
- The 22-gene Decipher genomic classifier, Oncotype, and Prolaris should not be viewed as interchangeable, and utilization should be based on the level of evidence supporting each gene expression biomarker
Presented by: Angela Jia, MD, PhD, Case Western Reserve University/University Hospitals Cleveland Medical Center, Cleveland, OH
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the 2023 American Society of Radiation Oncology (ASTRO) Annual Meeting, San Diego, CA, Sun, Oct 1 – Wed, Oct 4, 2023.