Genetic test that analyzes DNA to identify men at greatest risk for developing the disease could become common clinical laboratory screen for cancer
Researchers in the UK believe a common spit test can be more accurate at determining which men are more likely to develop prostate cancer than the clinical laboratory prostate-specific antigen (PSA) blood test currently used by the National Health Service (NHS) for that diagnosis.
During a recent study, scientists at the Institute of Cancer Research, London (ICR), found that germline DNA extracted from saliva, which was then used to derive polygenic risk scores for cancer, resulted in a higher percentage of participants “found to have clinically significant disease” than the percentage that would have been identified with the use of PSA or MRI.
The salvia test works by analyzing men’s DNA to find out if they are genetically pre-disposed to developing the disease. Men who find out they are likely to develop prostate cancer can then pursue further testing and scans.
“The test assesses 130 genetic variants to provide a risk score for prostate cancer, which is the second most common cause of cancer deaths in men in the UK,” The Guardian reported.
The study found that 187 of the men in the study had prostate cancer. According to the American Cancer Society, one in eight men will be diagnosed with prostate cancer in their lifetime.
“We can identify men at risk of aggressive cancers who need further tests and spare the men who are at lower risk from unnecessary treatments,” said study leader Rosalind Eeles, PhD, of the ICR London, in The Guardian.
“With this test, it could be possible to turn the tide on prostate cancer,” Rosalind Eeles, PhD, of the Institute of Cancer Research, London, told the BBC. (Photo copyright: Prostate Cancer UK.)
Landmark Discovery
Michael Inouye, PhD, professor of systems genomics and population health at the University of Cambridge, told the BBC that researchers will look back on this study “as a landmark.” He also acknowledged that it would be a long road before widespread implementation of the test.
While some sources call the ICR’s test promising, they also acknowledge it may only have a modest effect and that there may be possible racial disparities in the findings. The study was primarily based on people with European ancestry. According to Prostate Cancer UK, black men in the UK have double the risk of developing the disease. A similar trend can be observed in the US, Statistica reported.
Dusko Ilic, PhD, professor in stem cell sciences at King’s College London, told the BBC that there was “no direct evidence” of these findings having an effect on survival or quality of life. He stressed the need for more studies to better assess the value of the test.
The salvia test is expected to be included in Prostate Cancer UK’s TRANSFORM trial, a $58 million research program partly funded by the NHS to determine the best way to screen for cancer in the UK.
Effect on Clinical Pathologists
Prostate cancer is expected to surge in the US over the next 15 years, according to UC Davis Health. Thus, pathologists should expect more men to seek ways to assess their risk. Pathologists would be wise to educate themselves fully on new and emerging tests and tools to best meet the needs of their patients.
Given the publicity generated by former President Biden’s announcement that he has an advanced case of prostate cancer, clinical laboratories should also expect more patients to request diagnostic tests that either screen for or confirm the presence of the disease.
Researchers in Sweden develop urine test that more effectively screens for prostate cancer than standard PSA test
Clinical laboratories may soon have a new inexpensive, non-invasive urine test to screen for prostate cancer that produces superior results compared to the standard PSA test.
An international team of scientists led by researchers at the Karolinska Institutet in Sweden found they could use machine learning to not only accurately identify the presence of a new set cancer biomarkers in urine samples but also determine the stage or grade of the cancer.
“There are many advantages to measuring biomarkers in urine,” said Mikael Benson, principal researcher in the Department of Clinical Science, Intervention and Technology at Karolinska Institutet and senior investigator for the study, in a news release. “It’s non-invasive and painless and can potentially be done at home. The sample can then be analyzed using routine methods in clinical labs.”
“New, more precise biomarkers than PSA can lead to earlier diagnosis and better prognoses for men with prostate cancer,” said Mikael Benson, principal researcher at Karolinska Institutet and senior investigator for the study, in a news release. “Moreover, it can reduce the number of unnecessary prostate biopsies in healthy men.” (Photo copyright: Karolinska Institutet.)
New Prostate Cancer Biomarkers
According to the American Cancer Society, there will be approximately 313,780 new cases of prostate cancer diagnosed this year in the US with about 35,770 deaths due to the disease. About one in eight US men will be diagnosed with prostate cancer in their lifetime, and the lifetime risk of dying from prostate cancer is one in 44 men.
“Early cancer diagnosis is crucial but challenging owing to the lack of reliable biomarkers that can be measured using routine clinical methods. The identification of biomarkers for early detection is complicated by each tumor involving changes in the interactions between thousands of genes. In addition to this staggering complexity, these interactions can vary among patients with the same diagnosis as well as within the same tumor,” the researchers wrote in Cancer Research.
The scientists “hypothesized that reliable biomarkers that can be measured with routine methods could be identified by exploiting three facts:
The same tumor can have multiple grades of malignant transformation;
These grades and their molecular changes can be characterized using spatial transcriptomics; and,
These changes can be integrated into models of malignant transformation using pseudotime models to prioritize the genes that were most correlated with malignant transformation.”
To perform their study, the scientists analyzed the mRNA activity of cells in prostate tumors to construct digital models of prostate cancer. These models were then examined using machine learning, a type of artificial intelligence (AI), to locate specific proteins that could be used as biomarkers.
The researchers evaluated these new biomarkers in urine, blood, and tissue samples from more than 2,000 prostate cancer patients along with a control group. The team’s final calculations found the results of the urine test surpassed the current PSA test traditionally used for diagnosing prostate cancer.
“Prostate cancer can be effectively identified by analyzing the expression of candidate biomarkers in urine,” lead study author Martin Smelik, PhD student at Karolinska Institutet, told Fox News. “This approach outperforms the current blood tests based on PSA, but at the same time keeps the advantages of being non-invasive, painless, and relatively cheap.”
Advancements over Traditional PSA Test
Although the prostate-specific antigen (PSA) test typically used by doctors to diagnose prostate cancer can screen for the disease and monitor its progression, it has limitations.
“While PSA is an incredibly sensitive tool for issues related to the prostate, it is not specific to prostate cancer,” Matthew Abramowitz, MD, associate professor in the Department of Radiation Oncology at the Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, told Fox News. “The techniques proposed in the current study suggest the promise of identifying specific cancer markers in the urine, minimizing some of the specificity concerns associated with PSA.”
“This study highlights the power of machine learning applied to patient data in identifying breakthroughs that can help us diagnose cancer earlier, when our treatments are most effective,” Timothy Showalter, MD, a radiation oncologist at UVA Health in Virginia, told Fox News. “Prostate cancer screening has not seen a transformative advance in decades, and current approaches still rely on the PSA blood test, which is known to have low specificity for clinically significant cancers.”
“Overall, this study demonstrates the diagnostic potential of combining spatial transcriptomics, pseudotime, and machine learning for prostate cancer, which should be further tested in prospective studies,” the researchers wrote.
The Karolinska Institutet team is planning large-scale clinical trials as the next phase of their exploration.
Nearly 100,000 patients submitted saliva samples to a genetic testing laboratory, providing insights into their disease risk
Researchers at Mayo Clinic have employed next-generation sequencing technology to produce a massive collection of exome data from more than 100,000 patients, offering a detailed look at genetic variants that predispose people to certain diseases. The study, known as Tapestry, was administered by doctors and scientists from the clinic’s Center for Individualized Medicine and produced the “largest-ever collection of exome data, which include genes that code for proteins—key to understanding health and disease,” according to a Mayo Clinic news release.
For our clinical laboratory professionals, this shows the keen interest that a substantial portion of the population has in using their personal genetic data to help physicians identify their risk for many diseases and types of cancer. This support by healthcare consumers is a sign that labs should be devoting attention and resources to providing these types of gene sequencing services.
As Mayo explained in the news release, the exome includes nearly 20,000 genes that code for proteins. The researchers used the dataset to analyze genes associated with higher risk of heart disease and stroke along with several types of cancer. They noted that the data, which is now available to other researchers, will likely provide insights into other diseases as well, the news release notes.
“What we’ve accomplished with the Tapestry study is a blueprint for future endeavors in medical science,” said gastroenterologist and lead researcher Konstantinos Lazaridis, MD (above), in the news story. “It demonstrates that through innovation, determination and collaboration, we can deeply advance our understanding of DNA function and eventually other bio-molecules like RNA, proteins and metabolites, turning them into novel diagnostic tools to improve health, prevent illness, and even treat disease.” Some of these newly identified genetic markers may be incorporated into new clinical laboratory assays. (Photo copyright: Mayo Clinic.)
How Mayo Conducted the Tapestry Study
One notable aspect of the study was its methodology. The study launched in July 2020 during the COVID-19 pandemic. Since many patients were quarantined, researchers conducted the study remotely, without the need for the patients to visit a Mayo facility. It ran for five years through May 31, 2024. The news release notes that it’s the largest decentralized clinical trial ever conducted by the Mayo Clinic.
The researchers identified 1.3 million patients from the main Mayo Clinic campuses in Minnesota, Arizona, and Florida who met the following eligibility criteria:
Participants had to be 18 or older,
they had to have internet and email access, and
be sufficiently proficient in speaking and reading English.
More than 114,000 patients consented to participate, but some later withdrew, resulting in a final sample of 98,222 individuals. Approximately two-thirds were women. Mean age was 57 (61.9 for men and 54.3 for women).
“It was a tremendous effort,” said Mayo Clinic gastroenterologist and lead researcher Konstantinos Lazaridis, MD, in the news release. “The engagement of such a number of participants in a relatively short time and during a pandemic showcased the trust and the dedication not only of our team but also of our patients.”
He added that the researchers “learned valuable lessons about some patients’ decisions not to participate in Tapestry, which will be the focus of future publications.”
Three Specific Genes
Enrolled patients were invited to visit a website, where they could view a video and submit an eligibility form. Once approved, they completed a digital consent agreement and received a saliva collection kit. Participants were also invited to provide information about their family history.
Helix, a clinical laboratory company headquartered in San Mateo, Calif., performed the exome sequencing.
Though Helix performed whole exome sequencing, the researchers were most interested in three specific sets of genes:
Patients received clinical results directly from Helix along with information about their ancestry. Clinical results were also transmitted to Mayo Clinic for inclusion in patients’ electronic health records (EHRs).
Among the participants, approximately 1,800 (1.9%) had what the researchers described as “actionable pathogenic or likely pathogenic variants.” About half of these were BRCA1/2.
These patients were invited to speak with a genetic counselor and encouraged to undergo additional testing to confirm the variants.
Tapestry Genomic Registry
In addition to the impact on the participants, Mayo Clinic’s now has an enormous amount of raw sequencing data stored in the Tapestry Genomic Registry, where it will be available for future research.
The database “has become a valuable resource for Mayo’s scientific community, with 118 research requests submitted,” the researchers wrote in the news release. Mayo has distribution more than a million exome datasets to other genetic researchers.
“What we’ve accomplished with the Tapestry study is a blueprint for future endeavors in medical science,” Lazaridis noted. “It demonstrates that through innovation, determination, and collaboration, we can deeply advance our understanding of DNA function and eventually other bio-molecules like RNA, proteins and metabolites, turning them into novel diagnostic tools to improve health, prevent illness, and even treat disease.”
Everything about this project is consistent with precision medicine, and the number of individuals discovered to have risk of cancers is relevant. Clinical laboratory professionals understand these ratios and the importance of early detection and early intervention.
Study findings could lead to new clinical laboratory screening tests that determine risk for cancer
New disease biomarkers generally lead to new clinical laboratory tests. Such may be the case in an investigational study conducted at the University of Oxford in the United Kingdom (UK). Researchers in the university’s Cancer Epidemiology Unit (CEU) have discovered certain proteins that appear to indicate the presence of cancer years before the disease is diagnosed.
The Oxford scientists “investigated associations between 1,463 plasma proteins and 19 cancers, using observational and genetic approaches in participants of the UK Biobank. They found 618 protein-cancer associations and 317 cancer biomarkers, which included 107 cases detected over seven years before the diagnosis of cancer,” News Medical reported.
To conduct their study, the scientists turned to “new multiplex proteomics techniques” that “allow for simultaneous assessment of proteins at a high-scale, especially those that remain unexplored in the cancer risk context,” News Medical added.
Many of these proteins were in “blood samples of people who developed cancer more than seven years before they received a diagnosis,” an Oxford Population Health news release notes.
“To be able to prevent cancer, we need to understand the factors driving the earliest stages of its development. These studies are important because they provide many new clues about the causes and biology of multiple cancers, including insights into what’s happening years before a cancer is diagnosed,” said Ruth Travis, BA, MSc, DPhil, senior molecular epidemiologist at Oxford Population Health and senior study author, in the news release.
“We now have technology that can look at thousands of proteins across thousands of cancer cases, identifying which proteins have a role in the development of specific cancers and which may have effects that are common to multiple cancer types,” said Ruth Travis, BA, MSc, DPhil (above), senior molecular epidemiologist, Oxford Population Health, in a news release. The study findings could lead to new clinical laboratory screening tests for cancer. (Photo copyright: University of Oxford.)
Proteomics to Address Multiple Cancers Analysis
In their published paper, the Oxford scientists acknowledged other research that identified links between blood proteins and risk for various cancers, including breast, colorectal, and prostate cancers. They saw an opportunity to use multiplex proteomics methods for the simultaneous measurement of proteins “many of which have not previously been assessed for their associations with risk across multiple cancer sites,” the researchers noted.
The researchers described “an integrated multi-omics approach” and the use of the Olink Proximity Extension Assay (PEA) to quantify 1,463 proteins in blood samples from 44,645 participants in the UK Biobank, a large biomedical database and resource to scientists.
Olink, a part of Thermo Fisher Scientific in Waltham, Mass., explains on its website that PEA technology “uniquely combines specificity and scalability to enable high-throughput, multiplex protein biomarker analysis.”
The researchers also compared proteins of people “who did and did not go on to be diagnosed with cancer” to determine differences and identify proteins that suggest cancer risk, News Medical reported.
Proteins Could Assist in Cancer Prevention
“To save more lives from cancer, we need to better understand what happens at the earliest stages of the disease. Data from thousands of people with cancer has revealed really exciting insights into how the proteins in our blood can affect our risk of cancer. Now we need to study these proteins in depth to see which ones could be reliably used for cancer prevention,” Keren Papier, PhD, senior nutritional epidemiologist at Oxford Population Health and joint lead author of the study, told News Medical.
While further studies and regulatory clearance are needed before the Oxford researchers’ approach to identifying cancer in its early stages can be used in patient care, their study highlights scientists’ growing interest in finding biomarker combinations that can predict or diagnose cancer even when it is presymptomatic. By focusing on proteins rather than DNA and RNA, researchers are turning to a source of information other than human genes.
For anatomic pathologists and clinical laboratory leaders, the Oxford study demonstrates how scientific teams are rapidly developing new knowledge about human biology and proteins that are likely to benefit patient care and diagnostics.
Anatomic pathologists understand that, along with breast cancer, diagnostic testing for prostate cancer accounts for a high volume of clinical laboratory tests. Thus, a recent study indicating that a new artificial intelligence (AI)-based software tool can dramatically improve physicians’ ability to identify the extent of these cancers will be of interest.
“The study found that Unfold AI’s patient-specific encapsulation confidence score (ECS), which is generated based on multiple patient data points, including MRI scans, biopsy results, PSA [prostate-specific antigen] data, and Gleason scores, is critical for predicting treatment success,” an Avenda press release states. “These findings emphasize the importance of Unfold AI’s assessment of tumor margins in predicting treatment outcomes, surpassing the predictive capability of conventional parameters.”
“Unfold AI’s ability to identify tumor margins and provide the ECS will improve treatment recommendations and allow for less-invasive interventions,” said study co-author Wayne Brisbane, MD, a urologic oncologist and UCLA medical professor, in another press release. “This more comprehensive approach enhances our ability to predict treatment outcomes and tailor interventions effectively to individual patient needs.”
“This study is important because it shows the ability of AI to not only replicate expert physicians, but to go beyond human ability,” said study co-author Wayne Brisbane, MD (above), a urologic oncologist and UCLA medical professor, in a press release. “By increasing the accuracy of cancer identification in the prostate, more precise and effective treatment methods can be prescribed for patients.” Clinical laboratories that work with anatomic pathologists to diagnose prostate and other cancers may soon have a new AI testing tool. (Photo copyright: UCLA.)
How Unfold AI Works
To gauge the extent of prostate tumors, surgeons typically evaluate results from multiple diagnostic methods such as PSA tests and imaging scans such as MRIs, according to a UCLA press release. However some portions of a tumor may be invisible to an MRI, causing doctors to underestimate the size.
Unfold AI, originally known as iQuest, was designed to analyze data from PSA, MRI, fusion biopsy, and pathology testing, according to a company brochure. From there, it generates a 3D map of the cancer. Avenda’s website says the technology provides a more accurate representation of the tumor’s extent than conventional methods.
“Accurately determining the extent of prostate cancer is crucial for treatment planning, as different stages may require different approaches such as active surveillance, surgery, focal therapy, radiation therapy, hormone therapy, chemotherapy, or a combination of these treatments,” Brisbane said in the UCLA press release.
Putting AI to the Test
In the new study, the UCLA researchers enlisted seven urologists and three radiologists to review 50 prostate cancer cases. Each patient had undergone prostatectomy—surgical removal of all or part of the prostate—but might have been eligible for focal therapy, a less-aggressive approach that uses heat, cryotherapy, or electric shocks to attack cancer cells more selectively.
The physicians came from five hospitals and had a wide range of clinical experience from two to 23 years, the researchers noted in The Journal of Urology.
They reviewed clinical data and examined MRI scans of each patient, then “manually drew outlines around the suspected cancerous areas, aiming to encapsulate all significant disease,” the press release states. “Then, after waiting for at least four weeks, they reexamined the same cases, this time using AI software to assist them in identifying the cancerous areas.”
The researchers analyzed the physicians’ work, evaluating the accuracy of the cancer margins and the “negative margin rate,” indicating whether the clinicians had identified all of the cancerous tissue. Using conventional approaches, “doctors only achieved a negative margin 1.6% of the time,” the press release states. “When assisted by AI the number increased to 72.8%.”
The clinicians’ accuracy was 84.7% when assisted by AI versus 67.2% to 75.9% for conventional techniques.
They also found that clinicians who used the AI software were more likely to recommend focal therapy over more aggressive forms of treatment.
“We saw the use of AI assistance made doctors both more accurate and more consistent, meaning doctors tended to agree more when using AI assistance,” said Avenda Health co-founder and CEO Shyam Natarajan, PhD, who was senior author of the study.
“These results demonstrate a marked change in how physicians will be able to diagnose and recommend treatment for prostate cancer patients,” said Natarajan in a company press release. “By increasing the confidence in which we can predict a tumor’s margins, patients and their doctors will have increased certainty that their entire tumor is treated and with the appropriate intervention in correlation to the severity of their case.”
UCLA’s study found that AI can outperform doctors both in sensitivity (a higher detection rate of positive cancers) and specificity (correctly detecting the sample as negative). That’s relevant and worth watching for further developments.
Pathologists and clinical laboratory managers should consider this use of AI as one more example of how artificial intelligence can be incorporated into diagnostic tests in ways that allow medical laboratory professionals to diagnose disease earlier and more accurately. This will improve patient care because early intervention for most diseases leads to better outcomes.
