The great prostate debate: innovations in prostate cancer screening

While blood tests measuring prostate-specific antigen (PSA) levels have been a primary screening tool, their limitations in specificity have led to challenges such as overdiagnosis and overtreatment. Cleveland Diagnostics is pioneering an alternative approach with the IsoPSA test, focusing on assessing the structure of the PSA protein rather than its concentration. This innovative method, utilising a 2-phase physicochemical system, aims to provide a more specific and sensitive means of identifying individuals at the highest risk for prostate cancer, offering valuable insights beyond conventional PSA testing. The pursuit of resource-efficient testing approaches holds the potential to support early prostate cancer detection while minimising the physical and mental toll associated with overtreatment.


Early diagnosis is vital to improving outcomes in any cancer, and a growing number of novel screening options have emerged to address this need. Patients now have more avenues available to understand their cancer risk, from genetic assessments for hereditary forms of cancer to advanced imaging tests.

Among American men, prostate cancer is the second leading cause of cancer death and the second most common cancer overall, affecting one in every eight men during his lifetime. Discovery of prostate cancer at its earliest stages is vital to ensuring a better prognosis. Prostate cancers detected at the local stages, when the disease is limited to the prostate and its immediately surrounding regions, have a nearly 100 percent five-year survival rate. Conversely, patients with stage IV prostate cancers, which involve metastasis to lymph nodes or more distant regions of the body, have an average five-year survival rate of only 28 percent.

The state of prostate cancer screening

While the benefits of early prostate cancer detection are clear, the utility of current screening approaches is less conclusive which, for a period of time, led many providers to debate the value of screening. Blood tests measuring the level of prostate-specific antigen (PSA) emerged as a first-line screening method for prostate cancer in the early 1990s, directing men with a high PSA result to pursue biopsy for definitive diagnosis. However, assessments of the relative risks and benefits of PSA testing led public health agencies to limit their test recommendations for the general male population.

Guidelines from the U.S. Preventive Services Task Force (USPTF), the American Urological Association and the National Comprehensive Cancer Network now recommend that periodic testing of PSA levels be approached as an individual decision for men aged 55 to 69 due to the associated potential benefits and harms. Although PSA tests are highly sensitive to changes in levels of the biomarker, they lack the appropriate specificity needed to make a conclusive determination of a patient’s current likelihood of having prostate cancer. Many factors beyond prostate cancer can cause elevations in PSA, including age, certain health conditions and medical procedures, and even sexual activity.

Of all men with an elevated PSA level of 4-10 ng/mL, only 30-45 percent will ultimately be diagnosed with prostate cancer as the result of a biopsy. The poor specificity of PSA screening has exacerbated issues of overdiagnosis and overtreatment of low-grade cancers that would not have had clinically significant consequences during a patient’s lifetime. This leaves many patients subject to the uncertainty of their PSA result and the cost, stress, pain, and potentially severe complications related to unnecessary prostate biopsies. In short, there is a clear need for a sensitive and more accurate prostate cancer screening, surveillance and monitoring methods, and PSA testing has failed to deliver.

Searching for specificity

The shortcomings of traditional PSA testing have ignited a search for prostate cancer screening, monitoring or surveillance options that are equally sensitive but provide more reliable insights into a patient’s likelihood of having cancer. Importantly, early screening tests must also be widely accessible to patients. Advances in DNA and RNA-focused molecular diagnostic methods have made blood-based multi-cancer early detection (MCED) tests a reality, but not for all patients. These and similar approaches require complex and expensive sequencing technology, rendering them cost-prohibitive and inaccessible to many patients.

The answer to providing sensitive yet specific, accessible testing for prostate cancer may lie in assessing the structure of the PSA protein, rather than its mere concentration, of PSA in a patient’s blood. Our work at Cleveland Diagnostics aims to harness the valuable information held in cancer-related changes to protein structure and behaviour. Our IsoPSA test leverages a simple 2-phase physicochemical system to detect and separate cancer-specific protein structural isoforms. This approach provides an equally efficient but more specific way to identify patients at the greatest risk for prostate cancer. Rather than elucidating a simple change in PSA levels, these tests help providers and patients understand the potential cause of the change and act accordingly.

A less uncertain future

Over the last three decades, we’ve experienced the rise of PSA testing as a promising prostate cancer screening tool, the realisation of this method’s shortcomings, and the search for a better alternative. The value of early cancer detection is clearer than ever, but it’s also clear that a test should be specific and actionable, empowering diagnostic and treatment decisions rather than cultivating fear and uncertainty. By exploring accessible, resource-efficient testing approaches that provide deeper insights than PSA levels alone, we can continue to support early prostate cancer detection while reducing the physical and mental toll of unnecessary biopsies and overtreatment.

About the author 

bioBob Rochelle

Chief Commercial Officer

Bob Rochelle is a proven expert in launch, strategy, and marketing for novel healthcare products. His more than 30 years of experience ranges from start-ups such as Exact Sciences and Good Start Genetics to established multinationals such as Abbott Laboratories. He has launched, both domestically and internationally, successful pharmaceuticals, medical devices, and sophisticated DNA-based diagnostics, including the lab that became Genzyme Genetics as well as the stool-DNA test for colorectal cancer that became Cologuard®. Bob earned his Bachelor of Science degree in Biology and Psychology from Trinity College and his MBA from the Amos Tuck School of Business at Dartmouth College.

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