(UroToday.com) The 2022 ASTRO annual meeting featured an improving prostate cancer survival session, including a presentation by Zaeem Lone discussing transcriptomic features of cribriform and intraductal carcinoma of the prostate. Prostate cancer risk stratification has largely relied upon Gleason grade and PSA level. However, recent recommendations from the International Society of Urologic Pathologists has suggested modifying the Gleason grade system to include reporting of cribriform and intraductal carcinoma. Indeed, morphologic features such as cribriform and intraductal carcinoma are associated with unfavorable oncologic outcomes in prostate cancer patients. Few studies have investigated whether commonly utilized genomic classifiers such as Decipher are associated with cribriform and/or intraductal carcinoma. The objective of this study presented at ASTRO 2022 was to identify any correlations between Decipher genomic risk score and cribriform and intraductal carcinoma status while also assessing prostate cancer transcriptomic features of these pathologic features.
A retrospective review of prostate cancer patients who had Decipher testing at a single high-volume center between 2009-2020 was performed. A fellowship trained genitourinary pathologist reviewed specimens for the presence of cribriform and intraductal carcinoma features and annotated three groups: absent cribriform and intraductal carcinoma (cribriform -/intraductal carcinoma -), cribriform positive only (cribriform +/intraductal carcinoma -), and cribriform and intraductal carcinoma positive (cribriform +/intraductal carcinoma +). Categorical clinical, genomic, and pathologic variables were assessed using the Pearson Chi-Square test, quantitative with the Kruskal-Wallis test. Molecular subtyping using the PAM50 classifier was performed. Gene set enrichment analysis was performed to identify differentially expressed pathways between patients that were cribriform -/ intraductal carcinoma - compared to cribriform +/ intraductal carcinoma +.
There were 463 patients included in this study. Patients that were cribriform +/intraductal carcinoma + had the highest median Decipher scores (cribriform +/intraductal carcinoma +: 0.79 vs. cribriform +/intraductal carcinoma -: 0.71 vs. cribriform -/intraductal carcinoma -: 0.56, p < 0.001). Patients who were cribriform +/intraductal carcinoma also had the highest rates of Grade Group > 3 disease on final pathology (cribriform +/intraductal carcinoma +: 79% vs. cribriform +/intraductal carcinoma -: 52% vs. cribriform -/intraductal carcinoma -: 52%, p < 0.001):
Gene network level transcriptomic analysis revealed upregulation of MYC pathway genes (Normalized Enrichment Score: 1.65, p = 0.046) and E2F targets (Normalized Enrichment Score: 1.69, p = 0.031), respectively:
Molecular subtyping revealed that cribriform +/intraductal carcinoma + tumors were associated with luminal proliferating type B classification (cribriform +/intraductal carcinoma +: 53% vs. cribriform +/intraductal carcinoma -: 48% vs. cribriform -/intraductal carcinoma -: 29%, p < 0.001).
Zaeem Lone concluded this presentation discussing transcriptomic features of cribriform and intraductal carcinoma of the prostate with the following concluding points:
- This study reports an association between Decipher score and cribriform/intraductal morphology in prostate cancer
- A limitation of this study is that work was done on radical prostatectomy specimens, and observing these findings in biopsy samples would strengthen the findings
- Cribriform +/intraductal carcinoma + tumors had higher average Decipher scores and upregulated adverse gene programs (e.g., MYC, pRB1)
- Cribriform +/intraductal carcinoma + was associated with the luminal proliferating B subtype, which has been shown to have the worst oncologic outcomes but most sensitive to ADT
Presented by: Zaeem Lone, MD, Cleveland Clinic Lerner College of Medicine, Cleveland, OH
Co-Authors: T. Benidir2, M. Rainey1, M. Nair1, E. Davicioni3, E. Gibb4, S. Williamson2, J. K. Nguyen5, S. Gupta6, M. C. Ornstein7, J. P. Ciezki8, K. L. Stephans8, R. D. Tendulkar8, C. Weight9, E. A. Klein9, and O. Y. Mian2,10; 1Cleveland Clinic Lerner College of Medicine, Cleveland, OH, 2Cleveland Clinic, Cleveland, OH, 3Veracyte Inc., San Diego, CA, 4Veracyte Inc, Vancouver, BC, Canada, 5Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, OH, 6Cleveland Clinic Taussig Cancer Center, Cleveland, OH, 7Dept of Solid Tumor Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, 8Dept of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, 9Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH, 10Cleveland Clinic Foundation, Cleveland Clinic, Cleveland, OH
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2022 American Society of Radiation Oncology (ASTRO) Annual Hybrid Meeting, San Antonio, TX, Sat, Oct 22 – Wed, Oct 26, 2022.