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.
CDC advises clinical laboratories and microbiologists encountering C. auris to follow their own protocols before adopting federal agency guidelines
In July, the Centers for Disease Control and Prevention (CDC) warned healthcare facilities and clinical laboratories to be on the alert for Candida auris (C. auris) infections in their patients. An outbreak of the drug resistant and potentially deadly fungus had appeared in two Dallas hospitals and a Washington D.C. nursing home.
Since those outbreaks, researchers have studied with urgency the “superbug’s” emergence in various types of healthcare facilities around the nation, not just hospitals. Their goal was to discover how it was successfully identified and contained.
“Seeing what was happening in New York, New Jersey, and Illinois [was] pretty alarming for a lot of the health officials in California [who] know that LTACHs are high-risk facilities because they take care of [very] sick people. Some of those people are there for a very long time,” the study’s lead author Ellora Karmarkar, MD, MSc, told Medscape. Karmarkar is an infectious disease fellow with the University of Washington and formerly an epidemic intelligence service officer with the CDC.
“One of the challenges was that people were so focused on COVID that they forgot about the MDROs (multi-drug resistant organisms] … Some of the things that we recommend to help control Candida auris are also excellent practices for every other organism including COVID care,” she added.
According to Medscape, “The OCHD researchers screened LTACH and vSNF patients with composite cultures from the axilla-groin or nasal swabs. Screening was undertaken because 5%–10% of colonized patients later develop invasive infections, and 30%–60% die.
Medscape also reported that the first bloodstream infection was detected in May 2019, and that, according to the Annals of Internal Medicine study, as of January 1, 2020, of 182 patients:
22 (12%) died within 30 days of C. auris identification,
“This is really the first time we’ve seen clustering of resistance in which patients seemed to be getting the infections from each other,” Meghan Lyman, MD, Medical Officer in the Mycotic Diseases Branch of the CDC, told Fox News.
The graphic above illustrates how Candida auris is “spanning the globe,” The New York Times reported. Clinical laboratories that encounter this potentially deadly fungus are advised to contact the CDC immediately for guidance and to take proactive steps to prepare for the “superbug’s” arrival. (Graphic copyright: The Scottish Sun.)
Be More Proactive than Reactive in Identifying C. Auris, CDC Says
C. auris is a type of yeast infection that can enter the bloodstream, spread throughout the body, and cause serious complications. People who appear to have the highest risk of contracting the infection are those:
Who have had a lengthy stay in a healthcare facility,
Individuals connected to a central venous catheter or other medical tubes, such as breathing or feeding tubes, or
Have previously received antibiotics or antifungal medications.
It tends to be resistant to the antifungal drugs that are commonly used to treat Candida infections.
It can be difficult to identify via standard laboratory testing and is easily misidentified in labs without specific technology.
It can quickly lead to outbreaks in healthcare settings.
“With all this spread that we’ve been seeing across the country we’re really encouraging health departments and facilities to be more proactive instead of reactive to identifying Candida auris in general,” Lyman told STAT. “Because we’ve found that controlling the situation and containing spread is really easiest when it’s identified early before there’s widespread transmission.”
There continues to be concerns over this highly drug-resistant infection among hospital physicians and medical laboratories. “Acute care hospitals really ought to be moving toward doing species identification of Candida from nonsterile sites if they really want to have a better chance of detecting this early,” Dan Diekema, MD (above), an epidemiologist and clinical microbiologist at the University of Iowa, told Medscape. (Photo copyright: University of Iowa.)
Candia Auris versus Other Candida Infections
C. auris can cause dangerous infections in the bloodstream and spread to the central nervous system, kidneys, liver, spleen, bones, muscles, and joints. It spreads mostly in long-term healthcare facilities among patients with other medical conditions.
The symptoms of having a Candida auris infection include:
Fever
Chills
Pain
Redness and swelling
Fluid drainage (if an incision or wound is present)
General feeling of tiredness and malaise
C. auris infections are typically diagnosed via cultures of blood or other bodily fluids, but they are difficult to distinguish from more common types of Candida infections, and special clinical laboratory tests are needed to definitively diagnose C. auris.
Whole-genome Sequencing of C. Auris and Drug Resistance
The CDC conducted whole-genome sequencing of C. auris specimens gathered in Asia, Africa, and South America and discovered four different strains of the potentially life-threatening Candida species. All four detected strains have been found in the United States.
There are only three classes of antifungal drugs used to treat Candida auris infections:
However, 85% of the infections in the US have proven to be resistant to azoles and 38% are resistant to polyenes. Patients respond well to echinocandins, but more effective therapies are needed especially as some isolates may become resistant while a patient is on drug therapy, STAT reported.
“Even while it might be susceptible upfront, after a week or two of therapy, we may find that the patient has an infection now caused by an isolate of the same Candida auris that has become resistant to the echinocandins and we are really left with nothing else,” Jeffrey Rybak, PhD, PharmD, Instructor, Department of Pharmaceutical Sciences, St. Jude Children’s Research Hospital, told Infection Control Today.
Although relatively rare, C. auris infections are on the rise. The good news is that there may be further pharmaceutical help available soon. New antifungal agents, such as Ibrexafungerp (Brexafemme) show promise in fighting C. auris infections, but more research is needed to prove their efficacy.
What Should Clinical Laboratories Do?
The CDC stresses that clinical laboratories and microbiologists working with known or suspected cases of Candida auris should first adhere to their own safety procedures. The CDC issued guidelines, but they are not meant to supersede the policies of individual labs.
The CDC also recommends that healthcare facilities and clinical laboratories that suspect they have a patient with a Candida auris infection immediately contact the CDC and state or local public health authorities for guidance.
In the future, pathologists and clinical laboratory administrators may need to plan for a canine addition to their traditional laboratory staff
See Cliff sniff C. diff! No, that’s not a line from a new reading primer. In fact, it refers to one hospital’s innovation for early detection of Clostridium difficile (C. diff): a two-year-old beagle named Cliff. Cliff the Beagle is faster at detecting certain infections than the standard clinical laboratory tests used daily in hospitals throughout the world.
Researchers from Vrije University Medical Center (VUMC) in Amsterdam successfully used the trained beagle to detect the smell of C. difficile in hospitals. The researchers believe trained canine disease detectives like Cliff could be a cheap and effective way to conduct routine C. diff screening in hospitals. (more…)
Still not known is how pathologists and clinical laboratories will be paid for medical lab tests
In classic cart-before-the-horse thinking, Vermont enacted a law to institute a single-payer universal-coverage healthcare system within the state, starting in 2017. However, this law does not specify how the new healthcare system will be funded. That is the next challenge for the Vermont legislature.
Dark Daily suspects that anatomic pathology groups and clinical laboratories in the Green Mountain State will have a keen interest in learning how this new healthcare system will be funded—and how pathology services and medical laboratory tests will be reimbursed.
Vermont’s governor—Peter Shumlin—signed H.202 on May, 26, 2011. It is a bit surprising that this news has not gotten much coverage by national news outlets. After all, this is a major innovation at the state level that will definitely re-shape healthcare services in the Green Mountain State.
