Leading expert in cancer prevention and epidemiology, Dr. Jack Cuzick, MD, PhD, explains how the Prolaris gene expression test provides a more accurate prediction of prostate cancer progression and mortality than traditional methods like Gleason score and PSA levels. This 31-gene panel, which analyzes cell cycle progression, helps identify patients with low-risk disease who can safely avoid aggressive treatments like radical prostatectomy and opt for active surveillance instead, thereby preventing significant treatment side effects. The test's prognostic power was validated in a major clinical study of over 3,000 men on active surveillance, underscoring the critical shift towards personalized, molecular profiling in prostate cancer care to reduce overtreatment.
Advanced Prostate Cancer Prognosis: Gene Expression Markers for Predicting Metastasis
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- Prolaris Gene Test for Prostate Cancer Prognosis
- Clinical Trial Validation in 3000+ Men
- Ki-67 Tumor Marker for Aggressive Cancer
- Predicting Prostate Cancer Death Risk
- Beyond Gleason Score and PSA Levels
- Active Surveillance Treatment Option
- Reducing Unnecessary Prostate Cancer Treatment
Prolaris Gene Test for Prostate Cancer Prognosis
The Prolaris test is a significant advancement in prostate cancer tumor marker analysis, developed by Myriad Genetics. Dr. Jack Cuzick, MD, PhD, describes it as a gene expression profile that measures 31 genes involved in cell cycle progression. This molecular diagnostic provides a more precise and individualized prognosis for men diagnosed with localized prostate cancer.
This genetic test offers a quantitative assessment of how quickly cancer cells are proliferating. The result helps clinicians and patients make more informed decisions about treatment intensity. By moving beyond histological appearance, Prolaris adds a crucial layer of molecular data to prostate cancer risk stratification.
Clinical Trial Validation in 3000+ Men
The prognostic power of the Prolaris test was demonstrated in a large-scale research study involving over 3,000 men. Dr. Jack Cuzick, MD, explains that this was not a interventional trial but a major analysis of patients managed with active surveillance for their localized prostate cancer. These patients were treated in the UK more than a decade ago, providing a long-term follow-up window.
Researchers collected the original biopsy specimens from these men to perform extensive tumor biomarker analysis. This retrospective study design allowed for a robust validation of how molecular markers performed in predicting real-world clinical outcomes over many years.
Ki-67 Tumor Marker for Aggressive Cancer
Prior to the development of gene expression panels, Ki-67 was a important molecular marker studied in prostate cancer. Dr. Jack Cuzick, MD, PhD, confirmed through this research that Ki-67 is indeed an indicator of higher risk for aggressive prostate cancer. This protein marker, present in growing and dividing cells, provides a snapshot of tumor proliferation activity.
However, Dr. Cuzick's work revealed that the predictive value of Ki-67 was "very much overwhelmed and essentially replaced" by the more comprehensive gene expression profile. While useful, a single marker like Ki-67 lacks the nuanced prognostic power of a multi-gene signature.
Predicting Prostate Cancer Death Risk
The primary clinical value of the Prolaris test is its superior ability to predict subsequent death from prostate cancer. Dr. Jack Cuzick, MD, states that this gene expression tumor marker predicts mortality "better than anything we have actually found so far." This makes it an invaluable tool for identifying which patients truly need aggressive intervention.
For patients with a low Prolaris score, the test provides reassurance that their cancer is likely to progress slowly. This knowledge directly addresses the anxiety that often leads to overtreatment, offering a data-driven rationale for a more conservative management approach.
Beyond Gleason Score and PSA Levels
Traditional prostate cancer prognostic tools like Gleason grade and PSA levels have significant limitations that the Prolaris test helps overcome. Dr. Jack Cuzick, MD, PhD, emphasizes that the gene expression marker is "a stronger prediction marker than Gleason grade" and "more predictive of prostate cancer progression than PSA levels."
While Gleason score assesses cancer cell appearance under a microscope and PSA measures a protein in the blood, Prolaris directly analyzes the tumor's genetic activity. This molecular approach provides a more fundamental understanding of the cancer's biological behavior and potential for metastasis.
Active Surveillance Treatment Option
For patients with a low Prolaris score, active surveillance becomes a viable and often preferable prostate cancer therapy option. Dr. Jack Cuzick, MD, explains that men who learn they have a low risk of cancer progression are "more than happy" to consider conservative management. This approach involves regular monitoring rather than immediate radical treatment.
Active surveillance protocols typically include periodic PSA tests, digital rectal exams, and repeat biopsies. The Prolaris test provides the molecular justification needed to confidently recommend this management strategy, potentially sparing patients from life-altering treatment side effects.
Reducing Unnecessary Prostate Cancer Treatment
The implementation of advanced tumor markers like Prolaris addresses the critical problem of overtreatment in prostate cancer. During his discussion with Dr. Anton Titov, MD, Dr. Jack Cuzick, MD, PhD, highlighted that prostate cancer mortality is approximately 20%, meaning only one in five patients will die from the disease. Yet, the vast majority currently receive radical treatment.
Dr. Cuzick concludes that "there is much scope for reducing treatment in prostate cancer." Molecular profiling ensures that treatment intensity matches the biological aggressiveness of the cancer, preserving quality of life for patients with indolent disease while appropriately targeting aggressive therapies to those who need them most.
Full Transcript
Dr. Anton Titov, MD: What tumor markers have you seen in clinical trials for prostate cancer? Which prostate cancer tumor markers might indicate that local prostate cancer will become metastatic cancer? Tumor markers for prostate cancer might show that cancer is likely to spread slower or faster. Perhaps other prostate cancer markers can indicate that the cancer will stay dormant.
Dr. Jack Cuzick, MD: Our biggest research was a clinical trial of over 3,000 men. This was a clinical trial of men with localized prostate cancer. They were treated by active surveillance and were not given radical treatment of prostate cancer initially.
These patients were treated for prostate cancer more than 10 years ago in the UK. We have gone back and collected all of the original biopsy specimens for these men. I have done a whole range of tumor biomarker research on these biopsy specimens.
We are able to confirm that Ki-67 is an important molecular marker for prostate cancer. Ki-67 tumor marker indicates higher risk of aggressive prostate cancer. But Ki-67 tumor marker was very much overwhelmed and essentially replaced by a gene expression profile tumor marker.
This new gene expression tumor marker was developed by Myriad Genetics. This tumor marker of prostate cancer is called “Prolaris”. This is a mixture of 31 genes that participate in cell cycle progression.
This tumor marker seems to be more predictive of subsequent death from prostate cancer. It predicts death from prostate cancer better than anything we have actually found so far. It is a stronger prediction marker than Gleason grade.
Prolaris gene expression tumor marker is stronger than the histological features of prostate cancer. It is more predictive of prostate cancer progression than PSA levels. “Prolaris” marker is a big step forward in prostate cancer prognosis prediction.
Because there are many men, particularly in the United States, that are being treated by radical prostate cancer treatment. You could do a Prolaris diagnostic test. You could then find that patients had a low level of cancer progression risk.
They would be more than happy to learn about better prognosis of prostate cancer. Their prostate cancer can be treated more conservatively. Active surveillance could be a prostate cancer therapy option in these patients.
Again, this genetic diagnostic test for prostate cancer underscores how important is the individual approach to every patient with cancer. It is important to do a molecular profile of the tumor. Patients should know the gene expression patterns of their tumor.
You have to ensure that unnecessary cancer treatment does not happen.
Dr. Anton Titov, MD: There are many side effects associated with the aggressive treatment of prostate cancer.
Dr. Jack Cuzick, MD: Absolutely true! The mortality rate in prostate cancer is about 20%. So only one in five patients diagnosed with prostate cancer will die from it. Yet the vast majority of patients with prostate cancer get radical treatment. So there is much scope for reducing treatment in prostate cancer.