A prostate cancer diagnosis is a harrowing experience, one that immediately plunges you into a world of complex statistics, difficult choices, and profound anxiety.
For decades, the conversation between clinicians and patients has centered on numbers such as PSA levels and Gleason scores. While these factors are essential, they can raise more questions than they answer.
Navigating the sheer number of options, from active surveillance to definitive treatment, can be extremely confusing and very anxiety-provoking.
Uncertainty arises from a significant limitation in the traditional approach. Luckily, modern research shows that a deeper layer of information has always existed, hidden within the tumor itself.
A test called a Decipher Genomic Classifier is shedding light on the heterogeneity of prostate cancer, offering a clearer picture by analyzing the unique biology of an individual's cancer.
This post summarizes seven essential facts about how this technology is changing the conversation between doctors and patients, empowering them to make more informed decisions based not only on statistics, but also on biology.
1. PSA and Gleason scores are only half the story
What makes prostate cancer so incredibly difficult to manage is its unpredictability, or what scientists call "heterogeneity." Not all prostate cancers behave the same way due to the vast amount of diversity that exists between tumors.
For years, doctors have relied on clinical and pathological features, such as your prostate-specific antigen (PSA), Gleason score, and the number of positive biopsy cores, to predict how aggressive a cancer might be. But these tools have a blind spot that is the source of so much patient anxiety.
Dr. Pooya Banapour, a urologic oncologist, uses a powerful analogy: there are "two sides to every story." The clinical and pathological features are on one side. Genomics, the study of the tumor's genes, is on the other side.
He explained that traditional features are "Limited in terms of capturing the whole picture of prostate cancer." This lack of the whole picture is why two men with the same PSA and Gleason score can have extremely different outcomes.
The traditional numbers alone can't always tell them apart, leaving both doctor and patient in a state of uncertainty.
2. Your Tumor Has a Unique “Biological Fingerprint”
Genomics reflects the unique biology of the tumor, also known as its molecular signature or, as Dr. Banapour calls it, its "prostate cancer fingerprint." This molecular signature is what a genomic test, such as Decipher, analyzes. It looks past the pathology and PSA level to understand how the tumor is programmed to behave at a genetic level.
The Decipher test measures the activity level of 22 RNA genes within the prostate tumor tissue. Scientists identified them by using artificial intelligence to compare the tumors of thousands of men whose cancer metastasized against those whose cancer didn't, isolating the "biological fingerprint" of aggressive disease.
The test examines what critical genes are actually turned on and turned off. These genes are involved in the very processes that drive a cancer's ability to grow and spread, including:
Androgen signaling
Cell cycle progression
Immune response and modulation
Angiogenesis
Metabolism
Cellular adhesion and motility
Cell structure and organization
Decipher provides a direct look at the cancer's aggressive potential, independent of the PSA or Gleason score.
3. A single score can help refine your next step
This incredibly complex science translates these 22 gene signatures into a straightforward single, continuous score ranging from 0 to 1.0.
Based on a complex algorithm, this score determines the classification of the tumor's genomic risk as Low, Intermediate, or High, with cutoff points of 0.45 and 0.60 for the Decipher Prostate Biopsy and Decipher Prostate Radical Prostatectomy tests.
For Decipher Prostate Metastatic, the report provides a risk classification of either "Lower Risk" or "Higher Risk," with a cutoff of 0.85.
A higher score indicates a more aggressive tumor biology with a greater potential to metastasize. This one number can steer decision-making and clear away ambiguity.
For example, consider a man with NCCN low-risk disease who might be leaning toward active surveillance. If his Decipher score comes back high, it indicates that the biological activity of his tumor is not truly low-risk.
For low-risk men with a high Decipher score, NCCN recommends more intensive active surveillance (AS) given the higher likelihood of progression. For favorable intermediate-risk men, a low score can support AS, whereas a high score may favor definitive therapy.
4. Genomics helps you choose the next step
One of the biggest challenges in oncology is striking a balance between effective treatment and maintaining quality of life. Here is where Decipher can guide both the intensification of treatment for aggressive cancer and the deintensification of treatment for less aggressive cancer.
A powerful example comes from a re-analysis of the landmark NRG/RTOG 9601 clinical trial. The original trial showed that for men with a rising PSA after surgery, adding two years of hormone therapy to radiation improved survival.
Researchers tested stored prostatectomy tumor samples from the RTOG 9601 trial with the Decipher Genomic Classifier test. They checked whether the survival benefit of adding hormone therapy to salvage radiation changed across different scores.
However, when researchers applied the Decipher test to the archived tissue samples, they discovered that mainly only men with high-risk Decipher scores derived benefit from the addition of hormone therapy.
The crucial takeaway was that patients with low-risk scores derived no clinical benefit from the addition of hormone therapy. For these men, genomic testing could have spared them from life-altering treatment that wasn't helping them.
5. Three versions for three points
Decipher Genomic Classifier for prostate cancer is a suite of three distinct tests, each tailored to answer a different critical question at a key point in the cancer journey.
All three tests use the same robust 22-gene assay to interrogate the cancer. However, the final report is custom-tuned to answer the most critical question you are facing at that specific moment in your journey.
Decipher Prostate Biopsy: Used for newly diagnosed men to answer: "Should I choose active surveillance or immediate definitive treatment, such as surgery or radiation?"
Decipher Prostate Radical Prostatectomy: Used after prostatectomy to clarify the need for observation versus adjuvant radiation when PSA is undetectable, and when PSA is persistent or rising, to guide early salvage radiation and whether to add short-term hormone therapy.
Decipher Prostate Metastatic is for use in metastatic castration-sensitive prostate cancer (mCSPC) and provides a risk assessment designed to inform prognosis and support shared decision-making around treatment intensification. It is not yet a therapy-selection (predictive) test.
6. It's the only test of its kind in a key guideline
In the world of oncology, NCCN guidelines are highly respected. Decipher isn't just in the guidelines, but is the only test of its kind to make the cut.
It is the most scientifically validated genomic test for prostate cancer, evaluated in over 90 scientific publications and more than 25 prospective, randomized National Cancer Institute clinical trials, involving over 200,000 patients.
According to the NCCN Prostate Cancer guidelines, Version 1.2025, the Decipher 22-gene classifier is the only gene expression test included in the "Advanced Tools" table for risk stratification of localized prostate cancer.
The NCCN panel assigned it the highest Simon Level 1B evidence rating in the biopsy and post-radical prostatectomy settings.
Other tissue-based genomic tests, such as Prolaris (31-gene assay) and Oncotype DX (17-gene assay), do not meet this high threshold of Level 1 evidence.
This unique standing signifies that a consensus of leading cancer experts recognizes the test's data as robust and clinically actionable.
7. Prognostic versus predictive - what we know
The evidence from robust clinical trials shows that Decipher is a powerful prognostic tool, accurately predicting the future course and aggressiveness of the disease.
While the post-hoc analysis of NRG/RTOG 9601 suggests that it has predictive power, the question for many is whether it's a truly predictive tool, one that can predict which patients will respond to a specific therapy.
The American Urological Association (AUA) and the European Association of Urology (EAU) advise against the routine use of tissue-based genomic tests to determine therapy, pending the results of prospective trials that utilize genomic biomarkers.
Conclusion
While a prostate cancer diagnosis will always be a formidable challenge, tools like genomic classifiers are fundamentally changing how clinicians manage prostate cancer.
We are moving away from a one-size-fits-all approach based on broad statistics and toward a personalized one based on each cancer's unique biological drivers.
By providing a clearer, more individualized picture of risk, these tests empower doctors and patients to make better, more informed decisions together.
While this technology provides a much clearer picture of a cancer's individual biology, the next frontier isn't just about choosing the proper treatment, but about predicting and stopping aggressive disease before it even begins.
In the next newsletter, I'll provide a step-by-step guide to reading your Decipher Prostate Biopsy report and explain the meaning of each page.
Until then, I wish you good health.
And much love,
Keith
The decipher test along with certain other genetic tests are invaluable tools to help manage treatment choices for prostate cancer.
My post salvage prostatectomy Decipher score was 0.95 Gleason 9 (4+5) Stage T3N1. Post surgery PSA nadir was 0.40.
I originally was diagnosed with low risk Gleason 6 prostate cancer in 2020. I asked my RO/MO for genetic testing on the biopsy sample and he told me that he didn’t see the point. I opted for focal LDR brachytherapy with the belief that I’d put cancer behind me once and for all. That was wishful thinking. Had a decipher test been performed and shown a high score. I would’ve opted for RALP the first time before the cancer spread outside the prostate.
After salvage RALP, I had 31 sessions of I MRT, which included treatment to the lymph node basin and a boost to the left obturnator lymph node that couldn’t be reached safely during surgery.
I did 11 months of ADT, which included ORGOVYX and abiraterone. The goal was 18 months, but we had to stop early due to unmanageable side effects.
Hi
Is ARTERA AI also used for future predictions and prognosis giving effective info such as DECIPHER does?