Professor Pockley and other researchers at the John van Geest Cancer Research Center recently developed a blood test to detect prostate cancer. News-Medical spoke to Professor Pockley for more information!
What provoked your research on prostate cancer detection? Why is there an urgent need for a more accurate test to detect prostate cancer?
The John van Geest Cancer Research Center at Nottingham Trent University works closely with several prostate cancer support groups and a common theme has been the process of providing tissue for analysis (prostate biopsy) and the difficulty of making a definitive diagnosis.
Current tests for prostate cancer are not 100% accurate and so there is an opportunity to underdiagnose prostate cancer. It is essential that men with low risk prostate abnormalities are not diagnosed with prostate cancer, as those with low risk / grade of the disease do not require active treatment.
In addition, unnecessary labeling of men with prostate cancer can assign these men to lifelong surveillance and have significant psychological, quality of life, financial and social consequences.
So we started a program to see if we could reliably detect prostate cancer based on a simple blood test.
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Why is prostate cancer the most common cancer in men?
Overall, prostate cancer is the second most common cancer in men, the most commonly diagnosed cancer in the UK and the fourth most common cancer overall. In the UK, about 1 in 8 men will develop prostate cancer in their lifetime.
Prostate cancer mainly affects men over 50, with the risk increasing with age and a family history of prostate cancer. The risk is even higher for African-Caribbean black men who are 3 times more likely to get the disease – 1 in 4 African-Caribbean black men will develop prostate cancer in their lifetime. These men are also more likely to develop prostate cancer and die from the disease at a younger age (about 5 years younger than white British men). ‘
What current methods are available for prostate cancer detection and what are their limitations with regard to PSA levels?
The most commonly used diagnostic test currently available measures the blood level of a protein called Prostate Specific Antigen (Abbreviated PSA).
Increased amounts of PSA may mean the patient has cancer, but 15% of people with prostate cancer have normal levels of the protein, and many healthy people can have high amounts of PSA. This blood test is therefore not widely accepted as a reliable diagnostic tool.
There are other methods of detecting prostate cancer, but they are not always accurate. A small piece of the prostate can be taken for analysis, but the results of this invasive procedure are often inaccurate. Although interest in the potential diagnostic capabilities of MRI scanning is developing, MRI cannot currently be used as the sole diagnosis, as a positive MRI may be incorrect in about 25% (1 in 4) of cases and a negative MRI in about 20 cases may be incorrect. % (1 in 5) of cases.
Scans can therefore help to recognize a tumor, but they are not accurate enough to be conclusive on their own. New tests are therefore urgently needed.
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Why is it important not only to detect the presence of prostate cancer, but also to identify the stage it is in?
The clinical challenge in the diagnosis of prostate cancer lies in distinguishing men with low- or small-volume prostate cancer with an average risk that is unlikely to progress (both require ‘active surveillance’) from men with medium disease that is likely to progress or increase. a high-risk disease (both of which require treatment).
Some prostate cancer grows too slowly to cause problems or affect your lifespan. Because of this, many men with prostate cancer will never need any treatment. However, some prostate cancer grows quickly and spreads more quickly. This is likely to cause more problems and needs treatment to keep it from spreading.
Recent findings from a ten-year study of 415,000 British men (The Cluster Randomized Trial of PSA Testing for Prostate Cancer (CAP) Randomized Clinical Trial) have not supported any population-based PSA tests and suggest that asymptomatic men should not be routine. tested to avoid unnecessary anxiety and treatment. It is therefore essential that new approaches are developed to allow for a more definitive, early detection of prostate cancer.
Can you describe your research that led to the discovery of your new blood test? How have you incorporated computational models into your research?
The John van Geest Cancer Research Center at Nottingham Trent University has expertise in monitoring immune responses and we thought we could use this approach to detect the presence of cancer. We know that there is a two-way relationship between cancer and the immune system and that the immune system has the potential to recognize cancer, so we stated that the presence of cancer produces changes in the biology / appearance of white blood cells (immune cells). ) that can be detected in the blood.
However, ‘standard’ statistical tests could not detect differences in the profiles of white blood (immune) cells in the blood of patients with prostate cancer and men without prostate cancer.
We have therefore switched to more complex calculation models. Our model uses data from blood tests and artificial intelligence-based computers (machine learning) to more accurately detect the presence of prostate cancer.
The tool has two elements, the first detects whether a man has prostate cancer. If prostate cancer is diagnosed, the second element detects the clinical risk of the disease (low, medium, high) and allows the clinician to decide whether the patient does not require further examination / treatment (‘watch and wait’) or whether further investigation and treatment are required
How does this test work?
This test works by analyzing the biology of immune cells known as natural killer (NK) cells in the blood. NK cells are the first line of attack against cancer and are therefore likely to be affected by the presence of cancer.
The data from the analysis is then analyzed using the computational model that predicts whether cancer is present and, if so, its severity.
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How could the new test you developed help reduce invasive biopsies? Do you believe this could also limit the psychological impact of these biopsies on men?
The studies focused on asymptomatic men with PSA levels below 20 ng / ml, as men with PSA levels above 20 ng / ml are more likely to develop prostate cancer and therefore less likely to pose a clinical diagnostic dilemma.
In contrast, men with a PSA below 20 ng / ml are a major problem, because while only 30-40% of these men will have prostate cancer, all are currently undergoing potentially unnecessary invasive prostate biopsies to determine who has the disease.
It is therefore for this group of men for whom the development of new and more accurate approaches to early cancer detection is a clearly unmet clinical need, and for whom the benefits of such an approach will be most relevant and significant.
The new thing about this approach is that it questions the immunological response to the tumor, not the tumor itself, and requires a simple blood test (liquid biopsy). Based on current practice, we expect this approach to prevent up to 70% of prostate biopsies, sparing men with benign prostate disease or low risk prostate cancer from unnecessary invasive procedures associated with significant side effects.
Do you believe this test can help to potentially limit the number of men who die from prostate cancer?
The test has the potential to identify high-risk prostate cancer at an early stage in asymptomatic men with moderately elevated PSA levels and thus has the potential to reduce the number of men who die from prostate cancer.
When will this test be immediately available for use?
We need the necessary funding to prove the test’s ability to accurately diagnose prostate cancer in a much greater number of patients – a critical step in making critical clinical decisions based on the results it generates. If funding is received, it is possible that the test could be conducted in formal clinical trials within 3-4 years.
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What are the next steps in your research?
The test is in the ‘experimental’ phase. We now need to validate the approach in a prospective (forward-looking) clinical trial in a larger number of men to demonstrate its effectiveness and gain approval for its use to make important clinical decisions.
We are currently trying to get funding for such a trial.
Where can readers find more information?
About Professor Pockley
Professor Pockley is a professor of immunobiology at Nottingham Trent University and director of the John van Geest Cancer Research Center. Research at the center focuses on the discovery and application of novel cancer biomarkers to detect cancer, monitor disease progression and develop new immunotherapy approaches. Progress in these areas is based on a fundamental understanding of cancer cell biology and immunobiology.
After obtaining a Doctor of Philosophy for studies on the immunomodulatory properties of human placental protein 14 from Sheffield City Polytechnic (now Sheffield Hallam University) in 1988, Professor Pockley attended a 2-year postdoctoral fellowship to study ocular mucosal immunoregulation in the Department of Immunology and Microbiology at Wayne State University, Detroit, USA.
In January 1990 he returned to the UK to pursue a professorship and lead the experimental transplantation program in the Professorial Surgical Unit of the Medical College of St. Bartholomew’s Hospital, London. He returned to Sheffield in September 1994 as a lecturer at the University of Sheffield Medical School, where he was promoted to Reader in Immunobiology in 1996 and to Professor of Immunobiology in 2004.
Professor Pockley became the assistant director of the John van Geest Cancer Research Center from Nottingham Trent University on May 1, 2012 and its Director in September 2016. He retains an honorary professorship in the Department of Oncology and Metabolism at the University of Sheffield (2012 – present).
Professor Pockley has published more than 200 articles and in 2019 PLOS Biology1 identified him as being among the top 0.5% (in terms of citation impact) of the ~ 6.9 million scientists who have published at least 5 papers in all disciplines since 1995.