Genomic Classifier in Prostate Cancer: Intermediate-Risk

Genomic Classifier in Prostate Cancer: High-Risk

Publications
Articles and Abstracts
Genomic classifiers are used for prognostication and risk stratification in prostate cancer. Despite the emerging data, a commonly cited limitation is the retrospective datasets used for analysis. While there has been a litany of data using retrospective datasets to extrapolate the value of commercially available platforms in the pretreatment setting,
Key Points:
Question: Can a genomic biomarker estimate the risk of prostate cancer clinical endpoints in men who received salvage radiation for rising prostate-specific antigen levels after surgery?

Purpose The role of immune-oncologic mechanisms of racial disparities in prostate cancer (PCa) remains understudied. Limited research exists to evaluate the molecular underpinnings of immune differences in African American (AAM) and European American (EAM) prostate tumor microenvironment (TME).

Prostate Cancer (PCa) is the most prevalent cancer in men. Radical Prostatectomy (RP) as a primary definitive treatment may be followed by adjuvant or salvage radiotherapy. However, there are some uncertainties about receiving immediate adjuvant radiation after RP in men with adverse pathological features versus early salvage radiation therapy.

Molecular biomarkers aim to address the established limitations of clinicopathologic factors to accurately risk stratify patients with prostate cancer (PCa). Questions remain as to whether sufficient evidence supports adoption of these biomarkers for clinical use.

Decipher Biopsy is a commercially available gene expression classifier used in risk stratification of newly diagnosed prostate cancer (PCa). Currently, there are no prospective data evaluating its clinical utility.

Tumors with mutations associated with homologous recombination deficiency (HRD) are uncommon in prostate cancer (PCa) and variably responsive to PARP inhibition. To better identify tumors with HRD, we developed a transcriptomic signature for HRD in PCa (HRD-P).

Although the Decipher genomic classifier has been validated as a prognostic tool for several prostate cancer endpoints, little is known about its role in assessing the risk of biopsy reclassification for patients on active surveillance, a key event that often triggers treatment.

The impact of pelvic inflammation on prostate cancer (PCa) biology and aggressive phenotype has never been studied. Our study objective was to evaluate the role of pelvic inflammation on PCa aggressiveness and its association with clinical outcomes in patients following radical prostatectomy (RP).

The role of endogenous testosterone in de novo prostate cancer pathogenesis in humans remains unclear. The effect of testosterone on the tumor genome is not explored. To explore the correlation between perioperative testosterone level on genomic risk score in a cohort of men who underwent radical prostatectomy.

The Decipher genomic classifier (GC) has shown to independently prognosticate outcomes in prostate cancer. The objective of this study was to validate the GC in a randomized phase III trial of dose-escalated salvage radiotherapy (SRT) after radical prostatectomy.

Cribriform (CF) and/or intraductal carcinoma (IDC) are associated with more aggressive prostate cancer (CaP) and worse outcomes.

The transcriptomic features that typify CF/IDC are not well described and the capacity for clinically utilized genomic classifiers to improve risk modeling for CF/IDC remains undefined.

The aim of this study was to develop a model to predict high-genomic-risk prostate cancer (PCa) according to Decipher score, a validated 22 gene prognostic panel. By doing so, one might select the individuals who are likely to benefit from genomic testing and improve pre-op counseling about the need for adjuvant treatments.

Active surveillance is a safe and effective strategy for men with lower-risk prostate cancer who want to avoid local therapy; however, many patients on active surveillance progress to active treatment (eg, prostatectomy or radiation).

Pelvic lymph node metastasis (PLNM) at the time of radical prostatectomy (RP) portends an unfavorable prognosis in prostate cancer patients. Conventional and advanced imaging remains limited in its ability to detect PLNM.

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.

Men with rising prostate-specific antigen (PSA) after radical prostatectomy (RP) may progress despite radiation and androgen-deprivation therapy (ADT). Tissue-based transcriptomic signatures can identify who may benefit from a more aggressive systemic approach.

BERKELEY, CA (UroToday Inc.) - Perioperative narcotic use and patient reported pain are low in both the radical retropubic prostatectomy (RRP) and the robot assisted laparoscopic prostatectomy (RALP) in this Vanderbilt University study.
Physician-Scientist Commentaries
Peer-reviewed Abstract Supplemental Commentaries
Written by Udit Singhal, MD, and Randy A. Vince Jr., MD, MS
Genomic classifiers are used for prognostication and risk stratification in prostate cancer. Despite the emerging data, a commonly cited limitation is the retrospective datasets used for analysis. While there has been a litany of data using retrospective datasets to extrapolate the value of commercially available platforms in the pretreatment setting, the evaluation of these assays using prospectively collected data is still needed.
Physician-Scientist Review Articles
State of the Evidence Review Articles
November 8, 2021
In prostate pre- and post-biopsy decision making, more precision is urgently needed. Whereas expert imaging and biomarker-based risk scores already enable the clinician in this respect, the dilemma remains for those patients that are diagnosed with apparent indolent cancer. Additional diagnostic tools that (de)select patients for active surveillance (AS) would provide a great benefit for the patient.
Conference Coverage
Conference Highlights Written by Physician-Scientist
Presented by Rana McKay, MD
At the 2024 ESMO Annual Congress Dr. Rana McKay delivered the discussant session for CONTACT-02 and the post-hoc analysis of STAMPEDE Docetaxel assessing Decipher® as a potential predictive biomarker for overall survival in metastatic hormone sensitive prostate cancer (mHSPC) patients receiving docetaxel doublet therapy.
Presented by Emily Grist, MBBS, PhD
 The 2024 ESMO Annual Congress was host to a proffered paper session for prostate cancer. Dr. Emily Grist presented the results of an ancillary study of the STAMPEDE Docetaxel trial evaluating the genomic classifier Decipher® mRNA score for predicting a survival benefit with docetaxel doublet therapy intensification for metastatic hormone sensitive prostate cancer (mHSPC) patients.
Presented by John Sheng, MD
The 2024 American Urological Association (AUA) Annual Meeting held in San Antonio, TX was host to a prostate cancer detection and screening moderated poster session. Dr. John Sheng presented the results of a study evaluating Decipher® score for prediction of clinically significant upgrading on final radical prostatectomy pathology.
Presented by David Han, MD
The 2024 AUA was host to a prostate cancer moderated poster session. Dr. David Han presented the results of a study evaluating high Decipher® scores for defining the subgroup most at risk of metastatic progression among patients with lower-grade tumors classified as NCCN high-risk based on elevated prostate-specific antigen (PSA) level alone.
Presented by John Sheng, MD
The 2023 SUO annual meeting included a session on prostate cancer, featuring a presentation by Dr. John Sheng discussing the influence of the Decipher genomic classifier on initial prostate biopsy Gleason Score upgrading on final radical prostatectomy pathology.
Presented by Nimrod S. Barashi, MD
The 2023 SUO included a session on prostate cancer, featuring a presentation by Dr. Nimrod Barashi discussing the association of the Decipher genomic classifier on initial prostate biopsy and progression from active surveillance to treatment. 
Presented by Archan Khandekar, MD
The 2023 SUO annual meeting included a session on prostate cancer, featuring a presentation by Dr. Archan Khandekar discussing grade and volume progression and its association with the Decipher genomic classifier using patients enrolled in a prospective active surveillance protocol.
Presented by Alec Zhu, MD

The 2023 AUA annual meeting, was host to a prostate cancer detection and screening moderated poster session. Dr. Alec Zhu presented the results of an analysis evaluating the use of Decipher® prostate biopsy testing in men with favorable-risk prostate cancer undergoing conservative management in The Surveillance, Epidemiology, and End Results (SEER) registry.

 

Presented by Michael Leapman, MD, MHS
(UroToday.com) The 2023 AUA annual meeting included a session on markers in prostate cancer, featuring a presentation by Dr. Michael Leapman discussing the development of a longitudinal prostate cancer transcriptomic and real-world clinical data linkage. Genomic classifiers have been shown to be prognostic
Presented by Michael Leapman, MD, MHS
(UroToday.com) The 2023 AUA annual meeting included a session on markers in prostate cancer, featuring a presentation by Dr. Michael Leapman discussing the association between the Decipher genomic classifier and prostate cancer outcomes in a large-scale, real-world dataset.
Presented by Daniel Keizman, MD
The 2023 ASCO GU cancers symposium held in San Francisco, CA between February 16th and 18th was host to a prostate cancer poster session where Dr. Daniel Keizman presented his group’s study evaluating the geographic variation of Decipher® genomic classifier in patients with early prostate cancer.
Presented by Alan Dal Pra, MD
The 2022 ASTRO Annual Meeting was host to a session evaluating new insights into post-prostatectomy radiotherapy. Dr. Dal Pra presented his group’s work evaluating the prognostic and predictive performance of a 24-gene post-operative radiation therapy outcomes score (PORTOS) 
Presented by Zaeem Lone, MD
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.  
Presented by Skyler B. Johnson, MD
The 2022 ASTRO annual meeting featured an improving prostate cancer survival session, including a presentation by Dr. Skyler Johnson discussing the impact of tertiary Gleason pattern 5 and high Genomic Classifier Score on predicting lymph node invasion at the time of radical prostatectomy in patients with intermediate-risk disease.  
Presented by Felix Feng, MD

(UroToday.com) The 2022 Advanced Prostate Cancer Consensus Conference (APCCC) Hybrid Meeting included a session on biochemical recurrence, and a presentation by Dr. Felix Feng discussing how treatment can be individualized by using genomic classifiers. Dr. Feng started by highlighting that genomic biomarkers are included in certain treatment 

Presented by Daniel Spratt, MD
Dr. Dan Spratt presented a poster outlining validation of the Decipher biopsy genomic classifier in intermediate-risk prostate cancer. The 22-gene Decipher genomic classifier (GC) is a prognostic biomarker that has been validated in phase III trials in high-risk localized,
Presented by Alan Dal Pra, MD

The 2021 ASTRO Meeting included a session on biomarkers and salvage radiotherapy and discussion by Dr. Alan Dal Pra regarding the performance of a genomic classifier within a phase 3 randomized trial of dose escalated salvage radiotherapy after radical prostatectomy.

Presented by Paul Nguyen, MD

The 2021 ASTRO Meeting included a session on biomarkers and salvage radiotherapy and discussion by Dr. Paul Nguyen regarding the validation of a 22-gene genomic classifier in the NRG Oncology/RTOG 9202, 9413, and 9902 phase III randomized trials.

Presented by Brian Baumann, MD

The 2021 ASTRO Meeting’s included a session on biomarkers and salvage radiotherapy and a discussant presentation of five presentations in this session by Dr. Brian Baumann. With regards to organizing these five presentations into clinical context, Dr. Baumann highlighted the SAKK 09/10 trial, a phase I trial of neoadjuvant stereotactic body radiotherapy, biomarker studies

Presented by Derya Tilki, MD
Athens, Greece (Urotoday.com) In this talk, Dr. Tilki reviewed several prognostic biomarkers in the setting of localized prostate cancer management.  According to the EAU guidelines, the results of prospective multicenter studies are awaited before a recommendation can be made regarding the routine application of currently available prognostic biomarkers. This means more evidence is required before these biomarkers can be used in a standardized manner.