Genetic classifiers have potential, but need more research for men considering AS and other management approaches, VA researchers
By Howard Wolinsky
Patients with very low- or low-risk Gleason 6/Grade Group 1 prostate cancer (PCa) were highly likely to have their risk levels classified as the same or lower with genetic classifier (GC) tests, Veterans Administration researchers reported in a review article in the Annals of Internal Medicine.
Amir Alishahi Tabriz, MD, PhD, MPH, of the Department of Health Outcomes and Behavior, Moffitt Cancer Center, Tampa, Florida, and colleagues said that in 10 observational studies that risk scores remained the same or lowered were 100% to 88.1% for Genomic Prostate Score (GPS) by Oncotype DX, 87.2% to 82.9% for Decipher by Veracyte, and 76.9% for Prolaris by Myriad Genetics.
(Dr. Amir Alishahi Tabriz)
However, one randomized study found that genetic reclassification with GPS was 34.5% of very low-risk patients and 29.4% of low-risk patients moved to a higher risk category.
“Twelve observational studies indicated that treatment decisions after GC testing either remained unchanged or slightly favored active surveillance. In contrast, analyses from a single randomized trial found fewer choices for active surveillance after GPS testing,” the researchers said.
Moffit researchers added: “While genomic classifier (GC) tests may influence risk classifications or treatment decisions for patients with localized prostate cancer (PCa), there is a need for better data on their cost-effectiveness, clinical utility, and their impact on racial and ethnic groups, particularly Black men.”
The gene classifiers “offer a genetic snapshot of tumor aggressiveness, potentially detecting things that clinical tools might miss. Despite the potential of these tests, their use in clinical practice is inconsistent due to conflicting guidelines,” Syed Arsalan Ahmed Naqvi, MD, nd Irbaz Bin Riaz, MD, PhD, of the Division of Hematology and Oncology, Department of Medicine, Mayo Clinic, Phoenix, Arizona said in an editorial accompanying the study.
They said, “Evidence suggests that test results likely influenced clinical practice even though there is no strong evidence that treatment decisions driven by GC-based reclassification improved long-term outcomes.”
The ediorialists said that these classifications and reclassifications are key to the future of personalizing management of localized PCa and remain “a critical unmet need. Decisions about active surveillance (AS), radical prostatectomy, or definitive radiation—with or without androgen deprivation therapy (ADT)—are guided by initial risk stratification into low-, intermediate-, or high-risk groups.”
It’s a high-stakes game.
“Surgery or radiation can result in life-altering toxicities, such as permanent incontinence and impotence, whereas delayed treatment can lead to metastasis, compromising survival.”
The genetic classifier approach started in the early 2000s with breast cancer and in recent years has moved into prostate cancer.
“Building on their success in breast cancer, genomic classifiers (GCs) are now cautiously recommended by clinical guidelines for localized PCa to address key questions. Which low-risk patients can safely undergo AS? Which postprostatectomy patients need adjuvant treatment? Who should receive systemic therapy with ADT alongside radiation? Despite their promise, the role of GCs in PCa treatment decisions remains debated as evidence evolves,” Naqvi and Riaz wrote.
The Tabriz study based on GC-based assays “often confirmed existing risk classifications in low- and very low–risk patients with PCa, frequently resulting in downward reclassification in intermediate-risk patients, whereas data were inconsistent and prone to bias, making it difficult to draw reliable conclusions in high-risk patients,” the Mayo team said.
They stressed “it is not established whether GC-based reclassification to a lower risk category resulting in AS or using GCs to decide adjunct therapies, such as ADT, for intermediate- or high-risk patients improves clinical outcomes.”
They noted that artificial intelligence (AI)-driven multimodal tools “are in early development and lack prospective validation. However, their emerging success may hinder the momentum needed to advance GCs as standalone predictive biomarkers.”
Todd Morgan, MD, chief of urologic oncology at the University of Michigan, who is. doing a study comparing the major GCs, told me: “These types of articles can be helpful summaries of the current state of knowledge.”
Tabriz et al. conclude: “Although GC tests may affect risk reclassification and treatment choice, differences between observational studies and randomized trials, across type of GC test, and patient characteristics complicate understanding of the role of these tests for patient care. Clarity on which patients and what situations would benefit the most is needed to inform optimal use of these novel tests appropriately.”
Check out my monthly companion Substack newsletter Prostate Cores. It covers abstracts on new research on prostate cancer, BPH, and related topics: https://prostateblogmonthly.substack.com/publish/post/154354964
https://howardwolinsky.substack.com/p/welcome-to-prostate-cores-my-new
MRI-invisible lesions: A good sign—like a Gleason 6? Still time to sign up for the webinar—don’t be invisible
By Howard Wolinsky
Did you know that it’s possible for prostate cancer can be confirmed by a pathologist but the lesion can be invisible in an MRI?
Is this a good thing? Many researchers think it is.
Dr. Mark Emberton, Professor of interventional oncology at University College London and Dean of its Faculty of Medical Sciences, will be speaking to the ASPI webinar about MRI-invisible lesions on Saturday, January 25, 2025, from noon – 1:30 p.m. Eastern (5:00pm-6:30pm UK time). Emberton is a pioneer on the use of MRIs in diagnosing, classifying and monitoring prostate cancer.
Don’t be invisible. Register here: https://zoom.us/meeting/register/tJYldu-qqzojGNEzCkgPQuTOWYGhcL80Dhec'
MRI-invisible lesions are considered a good thing comparable to Gleason 6.
Professor Emberton’s clinical research is aimed at improving the diagnostic and risk stratification tools and treatment strategies for prostate cancer (PCa). He specializes in the implementation of new imaging techniques, nanotechnologies, bio-engineering materials and non-invasive treatment approaches, such as high intensity focused ultrasound and photo-dynamic therapy.
His research has been published in over 300 peer-reviewed scientific papers in journals including BMJ, Lancet Oncology and European Urology. He has also contributed to the development of guidelines for the management of PCa and lower urinary tract symptoms, published by the International Society of Geriatric Oncology and the European Association of Urology.
If you have questions, please send them to: contactus@aspatients.org
Harley,
Drop trou, as you say, and lead the march for more funding.
Howard
Yes, yes, and yes! More research in this area, it's the future!