Traditional screening methods for prostate cancer face a challenge of focus, and prostate-specific antigen (PSA) tests are overdue a shakeup. Here, Soroush Rais-Bahrami, Professor and Chair of the Department of Urology at Wake Forest University School of Medicine, discusses the benefits of the next generation of blood-based tests for prostate cancer.
PSA testing remains the most common first-line test for prostate cancer. What are its strengths, and what are the main challenges clinicians face when interpreting results?
PSA remains a valuable screening tool and has played a major role in the earlier detection of localized prostate cancer over the past few decades. However, its greatest limitation is that it is prostate-specific, not prostate cancer-specific. Elevated PSA levels may reflect benign conditions such as benign prostatic hyperplasia (BPH) or prostatitis as readily as they may indicate malignancy.
This lack of specificity creates a clinical dilemma because the next step – typically advanced imaging and/or prostate biopsy – can be invasive, costly, and burdensome for patients. The challenge is determining which patients with an elevated PSA truly warrant further investigation. PSA concentration alone often does not provide enough information to make that decision with confidence, underscoring the need for more accurate diagnostic tools.
How can the shape or structure of PSA provide a clearer picture of prostate cancer risk? And why is it important to look beyond PSA levels alone?
Not all PSA molecules are the same. As prostate cells become cancerous, they alter the structure of the PSA protein, including whether it circulates in the bloodstream in a free or protein-bound form. Examining these structural differences, rather than measuring only the total PSA concentration, provides more biologically meaningful information.
A concentration-based test tells you that PSA is elevated relative to age-adjusted reference levels, but a structure-based approach may help explain why. That distinction is important when assessing whether an elevated PSA is more likely to reflect prostate cancer or a benign condition.
Can you explain how the blood test you use to analyze PSA structure works, and how it differs from a traditional PSA test?
The IsoPSA test takes a fundamentally different approach from standard PSA testing. Rather than measuring only the amount of PSA in the blood, it analyzes the structural isoforms of PSA proteins. As prostate cells become cancerous, the structure of the PSA they produce changes in subtle but measurable ways. IsoPSA is designed to detect these structural differences, providing information that a concentration-based PSA test cannot. It evaluates the same protein through a different lens, helping clinicians better distinguish between benign conditions and clinically significant prostate cancer.
How can this type of testing help reduce unnecessary biopsies while still identifying men who may have clinically significant prostate cancer?
Up to 75 percent of men who undergo prostate biopsy following an elevated PSA are not found to have clinically significant prostate cancer. With approximately 1 million prostate biopsies performed each year in the United States, that represents a substantial number of invasive procedures – along with the associated physical, emotional, and financial burden – that may be unnecessary.
PSA remains the gold standard for prostate cancer screening and an excellent first-line test. However, newer tests such as IsoPSA can improve risk stratification by helping identify which patients are more likely to benefit from MRI and/or biopsy, and which can be safely monitored instead. The goal is not to replace PSA, but to make more informed decisions about who truly needs further evaluation while reducing unnecessary procedures.
Where do newer blood-based tests fit alongside other diagnostic tools such as MRI, biopsy, and pathology assessment?
These newer biomarker tests are best used before more invasive investigations. A test such as IsoPSA is not intended to replace MRI or biopsy but to help determine which patients are most likely to benefit from those next steps. For patients with an elevated PSA, having a clearer assessment of cancer risk before proceeding to imaging or biopsy supports more informed clinical decision-making and facilitates more meaningful discussions about the risks and benefits of further evaluation.
What are the biggest gaps or bottlenecks in prostate cancer diagnostics today, and where is there most room for improvement?
There is significant opportunity to expand the use of biomarker testing in prostate cancer risk assessment, but challenges remain around access and consistent adoption across clinical practice. Although these tests are available, many eligible patients do not receive them because of limited clinician awareness, variable practice patterns, and cost.
Wider availability of simple, affordable blood- or urine-based biomarkers that improve the specificity of an elevated PSA result could help identify patients who are most likely to benefit from further evaluation. This has the potential to improve the timely detection of clinically significant prostate cancer while reducing unnecessary biopsies and the associated burden on patients and the health care system.
How do you expect prostate cancer screening and diagnosis to change over the next decade, and what role will laboratory medicine play in improving patient outcomes?
The future of prostate cancer screening lies in more precise, personalized diagnostics. PSA will likely remain the foundation of initial screening, but it will increasingly be complemented by tests that provide more detailed risk information earlier in the diagnostic pathway.
Advances in biomarker testing, AI-assisted image interpretation, and genetic risk assessment are all expected to improve risk stratification and support more informed clinical decision-making. Laboratory medicine will play a central role in this shift – not only for prostate cancer but across many areas of disease detection. Ultimately, the goal is to move beyond simply measuring the presence of a biomarker to understanding what it reveals about the underlying biology, enabling more accurate and individualized patient care.
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