In an attempt to improve prostate cancer outcomes, the STAMPEDE trial utilizes a gene expression test to predict chemotherapy benefits. Here, we speak with Phil Febbo, Chief Scientific Officer at Veracyte, about what this research means for prostate cancer screening and patient outcomes.
What is the STAMPEDE trial?
STAMPEDE is a randomized, prospective, Phase 3 trial designed to identify the most effective treatment strategies for men with newly diagnosed advanced prostate cancer. Funded by Cancer Research UK and led by researchers at University College London, the trial uses an innovative multi-arm, multi-stage design that allows several treatment comparisons to be evaluated within the same study framework. Since its launch in 2005, STAMPEDE has enrolled approximately 12,000 participants.
This analysis contributes to the growing body of research aimed at improving personalized patient care.
What is the most important takeaway from the STAMPEDE trial for pathologists and oncologists?
Results from the study published in Cell demonstrated that molecular profiling can identify biologic differences among tumors that traditional clinical and pathological factors may not capture.
In this large Phase 3 analysis, patients with higher genomic risk scores had significantly different outcomes compared with those who had lower scores, underscoring how genomic classifiers can distinguish tumor aggressiveness and biological behavior. These findings extend the diagnostic value of genomic testing – already used to stratify localized disease – into the metastatic setting, where variability in tumor biology remains a major challenge.
For pathologists, this highlights the importance of integrating molecular data with histopathologic evaluation to provide a more comprehensive understanding of disease biology. For oncologists, it reinforces that genomic classifiers can serve as valuable diagnostic and prognostic tools to help characterize disease risk and support more informed, individualized management decisions.
What does the Decipher score add beyond Gleason grade or disease volume?
Historically, clinical factors such as Gleason score have been used to assess the risk of disease progression in patients with prostate cancer. However, prostate cancer is highly heterogeneous, and considerable variation exists within established risk categories. Genomic profiling provides additional biological insight by evaluating gene expression patterns that can further stratify disease risk beyond standard clinical or pathological features.
Previous research, including multiple multivariate analyses, has shown that genomic classifiers offer independent prognostic and predictive value not captured by traditional measures. The current study provides Level 1B evidence supporting the ability of such classifiers to predict which patients with metastatic prostate cancer are likely to benefit from chemotherapy.
Current clinical practice generally favors docetaxel for patients with high-volume disease, but this analysis found that higher genomic classifier scores correlated with treatment benefit regardless of disease volume. Notably, approximately 40 percent of patients with low-volume disease had higher genomic risk scores and could derive significant benefit from the addition of docetaxel, underscoring the potential of molecular tools to refine treatment selection.
The study showed stronger benefit in patients with both high Decipher scores and PTEN loss. How might this shape future biomarker testing?
While genomic classifiers are designed to capture the overall prognostic biology of prostate cancer, it is well established that specific cell signaling pathways play central roles in disease development and progression. Collaborative research using large genomic datasets has validated a gene expression signature reflecting PTEN activity – or loss of activity, given that PTEN function is frequently lost in aggressive prostate cancers.
Loss of PTEN is associated with poor prognosis and may also identify patients who could benefit from emerging targeted therapies, such as PI3K pathway inhibitors under investigation for advanced disease. Because genomic classifiers, PTEN status, and other adverse molecular features can be measured from the same transcriptomic platform, integrating these findings into a unified diagnostic report could provide clinicians with a more comprehensive molecular profile to support individualized treatment planning.
Ongoing research efforts using large transcriptomic databases continue to refine such molecular signatures, supporting the development of next-generation diagnostic tools in prostate cancer.
How can transcriptomic testing complement traditional pathology methods?
Transcriptomic testing adds an important molecular dimension to the classification and management of prostate cancer. In metastatic disease, traditional pathology provides limited guidance for treatment decisions compared with imaging studies that define disease burden.
Evidence from multiple studies using multivariate analyses shows that molecular information derived from transcriptomic classifiers complements standard clinical and pathological assessment, providing additional prognostic and predictive insight. Integrating these molecular findings with morphological evaluation can further strengthen the pathologist’s role as an interpreter of complex data and an essential contributor to the multidisciplinary care team.
How might genomic classifiers be used more widely in other cancers?
Genomic classifiers are increasingly becoming an integral part of cancer care. With the rise of precision and personalized medicine, it is now more important than ever to understand the molecular biology of each individual tumor. These tools provide critical prognostic and predictive information that complements traditional clinical and pathological assessments, helping clinicians better guide patient management.
Across oncology, genomic testing is being applied to a growing number of cancer types to support diagnosis, refine risk stratification, and inform treatment decisions. Emerging research is also exploring the use of molecular approaches – such as transcriptomic and minimal residual disease (MRD) testing – to improve early detection of recurrence and monitor treatment response.
Together, these advances highlight the expanding role of molecular diagnostics in enabling more precise, data-driven care across the cancer continuum.
What steps should labs take now to prepare for integrating genomic testing into workflows?
Clinicians are increasingly submitting cancer tissue for molecular analysis, yet in many settings, these tests are still ordered manually and reported as static PDF files that are not fully integrated into electronic health record (EHR) systems. This limits efficiency and can delay access to results. As the importance of molecular testing continues to grow, more EHR platforms are beginning to support integrated ordering and reporting processes, aligning molecular diagnostics with other essential aspects of patient care.
To improve workflow integration, laboratories can play a key role by ensuring the timely submission and processing of tissue samples, which supports faster turnaround times and more efficient communication with clinicians. Streamlined electronic ordering systems, automated data checks, and clear documentation processes can further enhance the accuracy, speed, and accessibility of molecular test results.
What’s next for this research?
Beyond PTEN, many other molecular pathways are relevant to prostate cancer biology. Future research is expected to expand the use of genomic signatures to provide deeper insight into tumor behavior and disease progression. Integrating information about tumor biology and prognosis will continue to refine diagnostic precision and support more informed, individualized patient management.
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