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.
As before, the ongoing strikes continue to cause delays in critical clinical laboratory blood testing and surgical procedures
After seven months of failed negotiations, New Zealand’s blood workers, clinical laboratory technicians, and medical scientists, are once again back on strike. According to Star News, hundreds of lab workers walked off the job on May 31, 2024, with another longer walkout planned for June to protest pay disparities.
New Zealand Blood Service (NZBS) workers, who are represented by the Public Service Association or PSA (Māori: Te Pūkenga Here Tikanga Mahi), collect and process blood and tissue samples from donors to ensure they are safe for transfer.
“Our colleagues at Te Whatu Ora [Health New Zealand] are being paid up to 35% more than us and we want to be paid too. We want fair pay,” Esperanza Stuart, a New Zealand Blood Service scientist, told Star News.
“The stall in negotiations is largely attributed to a lack of movement from NZBS on the principal issue of parity with Te Whatu Ora laboratory workers rates of pay. There is currently a 21-28% pay differential between NZBS and Te Whatu Ora laboratory workers, despite both groups of workers performing essentially the same work,” NZ Doctor noted.
Health New Zealand is the country’s government-run healthcare system.
The first strike took place on May 31 from 1-5 pm. A second 24-hour strike is planned for June 4. The strikers outlined the rest of their strike schedule as follows:
The PSA union claims that the pay disparity workers are experiencing is pushing veteran workers out and complicating recruitment of new workers.
New Zealand Blood Service workers and junior doctors are once again back on the picket line to protest wage cuts and pay disparities. “I think it should be a signal that things are not right in our health system when there are multiple groups of workers going on strike simultaneously,” said PSA union organizer Alexandra Ward. Clinical laboratory workers in the US are closely monitoring the goings on in New Zealand as pressure over staff shortages and working conditions continue to mount in this country as well. (Photo copyright: RNZ.)
Clinical Laboratory Worker Strikes Ongoing in New Zealand
This is far from the first time New Zealand lab workers have hit the picket line.
In “Medical Laboratory Workers Again on Strike at Large Clinical Laboratory Company Locations around New Zealand,” Dark Daily reported on a medical laboratory workers strike that took place in 2023 in New Zealand’s South Island and Wellington regions. The workers walked off the job after a negotiated agreement was not reached between APEX, a “specialist union representing over 4,000 allied, scientific, and technical health professionals,” according to the union’s website, and Awanui Labs, one of the country’s largest hospital and clinical laboratory services providers.
This latest strike is likely to cause delays in vital surgeries and risk the nation’s critical blood supply. All of these strikes were spurred on by low pay, negative working conditions and worker burnout. Similar issues have caused labor actions in the United Kingdom’s National Health Service in recent years.
Junior Doctors Join Blood Service Workers on Picket Line
Blood service workers aren’t the only healthcare employees in New Zealand’s medical community taking action. In May about half of the nation’s junior doctors walked off the job for 25 hours to protest proposed pay cuts, NZ Herald reported.
In a letter to the nation’s public hospitals, Sarah Morley, PhD, NZBS’s Chief Medical Officer, “warned [that] even high priority planned surgeries should be deferred because they did not meet the definition of a ‘life-preserving service,’” and that “only surgeries where there is less than a 5% risk that patients may need a transfusion should be carried out,” RNZ reported.
According to an internal memo at Mercy Ascot, NZBS “did not consider cancers and cardiac operations in private hospitals to be a life-preserving service,” RNZ noted.
The situation may be more dangerous than officials are letting on, NZ Herald noted. A senior doctor at Waikato Hospital told reporters, “There are plenty of elective services cancelled today—clinics, surgery, day stay procedures etc. … And although I can only speak for my department, we are really tight for cover from SMO [senior medical officers] staff for acute services and pretty much all elective work has been cancelled. So, it’s actually pretty dire, and if next week’s planned strike goes ahead it’s going to be worse. I’d go as far as to say that it’s bordering on unsafe.”
The strike did take place, and the junior doctors went back on strike at the end of May as well, according to RNZ.
Support from Patients
Eden Hawkins, a junior doctor on strike at Wellington Hospital told RNZ that patient wellbeing is a top concern of striking workers and that patients have shown support for the doctors.
“When patients have brought it up with me on the wards or in other contexts there seems to be a bolstering sense of support around us, which is really reassuring and heartening because there’s obviously a conflict within ourselves when we strike, we don’t want to be doing that,” she said. Hawkins also makes the argument that striking workers can improve patient wellbeing in the long run. Improvement of pay and conditions could lessen staff turnover and overall improve the standard of care.
New Zealand healthcare workers haven’t been shy when it comes to fighting for the improved working conditions and fair pay. And their problems are far from unique. American healthcare workers have been struggling with worker burnout, pay disparities, high turnover as well. Clinical laboratory and other healthcare professionals in the US would be wise to keep an eye on their Kiwi counterparts.
Norwegian researchers reviewed large clinical trials of six common cancer screenings, including clinical laboratory tests, but some experts question the findings
Cancer screenings are a critical tool for diagnosis and treatment. But how much do they actually extend the lives of patients? According to researchers at the University of Oslo in Norway, not by much. They recently conducted a review and meta-analysis of 18 long-term clinical trials, five of the six most commonly used types of cancer screening—including two clinical laboratory tests—and found that with few exceptions, the screenings did not significantly extend lifespans.
The 18 long-term clinical trials included in the study were randomized trials that collectively included a total of 2.1 million participants. Median follow-up periods of 10 to 15 years were used to gauge estimated lifetime gain and mortality.
“The findings of this meta-analysis suggest that current evidence does not substantiate the claim that common cancer screening tests save lives by extending lifetime, except possibly for colorectal cancer screening with sigmoidoscopy,” the researchers wrote in their published paper.
The researchers noted, however, that their analysis does not suggest all screenings should be abandoned. They also acknowledged that some lives are saved by screenings.
“Without screening, these patients may have died of cancer because it would have been detected at a later, incurable stage,” the scientists wrote, MedPage Today reported. “Thus, these patients experience a gain in lifetime.”
Still, some independent experts questioned the validity of the findings.
Gastroenterologist Michael Bretthauer, MD, PhD (above), a professor at the University of Oslo in Norway led the research into cancer screenings. In their JAMA Internal Medicine paper, he and his team wrote, “The findings of this meta-analysis suggest that colorectal cancer screening with sigmoidoscopy may extend life by approximately three months; lifetime gain for other screening tests appears to be unlikely or uncertain.” How their findings might affect clinical laboratory and anatomic pathology screening for cancer remains to be seen. (Photo copyright: University of Oslo.)
Pros and Cons of Cancer Screening
The clinical trials, according to MedPage Today and Oncology Nursing News covered the following tests:
Mammography screening for breast cancer (two trials).
As reported in these trials, “colorectal cancer screening with sigmoidoscopy prolonged lifetime by 110 days, while fecal testing and mammography screening did not prolong life,” the researchers wrote. “An extension of 37 days was noted for prostate cancer screening with prostate-specific antigen testing and 107 days with lung cancer screening using computed tomography, but estimates are uncertain.”
The American Cancer Society (ACS) recommends certain types of screening tests to detect cancers and pre-cancers before they can spread, thus improving the chances for survival.
The ACS advises screenings for breast cancer, colorectal cancer, and cervical cancer regardless of whether the individual is considered high risk. Lung cancer screenings are advised for people with a history of smoking. Men who are 45 to 50 or older should discuss the pros and cons of prostate cancer screening with their healthcare providers, the ACS states.
A CNN report about the University of Oslo study noted that the benefits and drawbacks of cancer screening have long been well known to doctors.
“Some positive screening results are false positives, which can lead to unnecessary anxiety as well as additional screening that can be expensive,” CNN reported. “Tests can also give a false negative and thus a false sense of security. Sometimes too, treatment can be unnecessary, resulting in a net harm rather than a net benefit, studies show.”
In their JAMA paper, the University of Oslo researchers wrote, “The critical question is whether the benefits for the few are sufficiently large to warrant the associated harms for many. It is entirely possible that multicancer detection blood tests do save lives and warrant the attendant costs and harms. But we will never know unless we ask,” CNN reported.
Hidden Impact on Cancer Mortality
ACS Chief Scientific Officer William Dahut, MD, told CNN that screenings may have an impact on cancer mortality in ways that might not be apparent from randomized trials. He noted that there’s been a decline in deaths from cervical cancer and prostate cancer since doctors began advising routine testing.
“Cancer screening was never really designed to increase longevity,” Dahut said. “Screenings are really designed to decrease premature deaths from cancer.” For example, “if a person’s life expectancy at birth was 80, a cancer screening may prevent their premature death at 65, but it wouldn’t necessarily mean they’d live to be 90 instead of the predicted 80,” CNN reported.
Dahut told CNN that fully assessing the impact of cancer screenings on life expectancy would require a clinical trial larger than those in the new study, and one that followed patients “for a very long time.”
“From its title, one would have expected this paper to be based on analysis of individual lifetime data. However, it is not,” he wrote in a compilation of expert commentary from the UK’s Science Media Center. “The paper’s conclusions are based on arithmetic manipulation of relative rates of all-cause mortality in some of the screening trials. It is therefore difficult to give credence to the claim that screening largely does not extend expected lifetime.”
He also questioned the inclusion of one particular trial in the University of Oslo study—the Canadian National Breast Screening Study—“as there is now public domain evidence of subversion of the randomization in this trial,” he added.
Another expert, Leigh Jackson, PhD, of the University of Exeter in the UK, described the University of Oslo study as “methodologically sound with some limitations which the authors clearly state.”
But he observed that “the focus on 2.1 million individuals is slightly misleading. The study considered many different screening tests and 2.1 million was indeed the total number of included patients, however, no calculation included that many people.”
Jackson also characterized the length of follow-up as a limitation. “This may have limited the amount of data included and also not considering longer follow-up may tend to underestimate the effects of screening,” he said.
This published study—along with the range of credible criticisms offered by other scientists—demonstrates how analysis of huge volumes of data is making it possible to tease out useful new insights. Clinical laboratory managers and pathologists can expect to see other examples of researchers assembling large quantities of data across different areas of medicine. This huge pools of data will be analyzed to determine the effectiveness of many medical procedures that have been performed for years with a belief that they are helpful.
Though still in trials, early results show tests may be more accurate than traditional clinical laboratory tests for detecting prostate cancer
Within weeks of each other, different research teams in the US and UK published findings of their respective efforts to develop a better, more accurate clinical laboratory prostate cancer test. With cancer being a leading cause of death among men—second only to heart disease according to the Centers for Disease Control and Prevention (CDC)—new diagnostics to identify prostate cancer would be a boon to precision medicine treatments for the deadly disease and could save many lives.
Thus, these are two different pathways toward the goal of achieving earlier, more accurate diagnosis of prostate cancer, the holy grail of prostate cancer diagnosis.
“There is currently no single test for prostate cancer, but PSA blood tests are among the most used, alongside physical examinations, MRI scans, and biopsies,” said Dmitry Pshezhetskiy, PhD (above), Professorial Research Fellow at University of East Anglia and one of the authors of the UEA study. “However, PSA blood tests are not routinely used to screen for prostate cancer, as results can be unreliable. Only about a quarter of people who have a prostate biopsy due to an elevated PSA level are found to have prostate cancer. There has therefore been a drive to create a new blood test with greater accuracy.” With the completion of the US and UK studies, clinical laboratories may soon have a new diagnostic test for prostate cancer. (Photo copyright: University of East Anglia.)
East Anglia’s Research into a More Accurate Blood Test
Scientists at the University of East Anglia (UEA) worked with researchers from Imperial College in London, Imperial College NHS Trust, and Oxford BioDynamics to develop a new precision medicine blood test that can detect prostate cancer with greater accuracy than current methods.
The researchers evaluated their test in a pilot study involving 147 patients. They found their testing method had a 94% accuracy rate, which is higher than that of PSA testing alone. They discovered their test significantly improved the overall detection of prostate cancer in men who are at risk for the disease.
“When tested in the context of screening a population at risk, the PSE test yields a rapid and minimally invasive prostate cancer diagnosis with impressive performance,” Dmitry Pshezhetskiy, PhD, Professorial Research Fellow at UEA and one of the authors of the study told Science Daily. “This suggests a real benefit for both diagnostic and screening purposes.”
The UK scientists hope their test can eventually be used in everyday clinical practice as there is a need for a highly accurate method for prostate cancer screening that does not subject patients to unnecessary, costly, invasive procedures.
Cedars-Sinai’s Research into Nanotechnology Cancer Testing
Researchers from Cedars-Sinai Cancer took a different approach to diagnosing prostate cancer by developing a nanotechnology-based liquid biopsy test that detects the disease even in microscopic amounts.
Their test isolates and identifies extracellular vesicles (EVs) from blood samples. EVs are microscopic non-reproducing protein and genetic material shed by all cells. Cedars-Sinai’s EV Digital Scoring Assay accurately extracts EVs from blood and analyzes them faster than similar currently available tests.
“This research will revolutionize the liquid biopsy in prostate cancer,” said oncologist Edwin Posadas, MD, Medical Director of the Urologic Oncology Program and co-director of the Experimental Therapeutics Program in Cedars-Sinai Cancer in a press release. “The test is fast, minimally invasive and cost-effective, and opens up a new suite of tools that will help us optimize treatment and quality of life for prostate cancer patients.”
The researchers tested blood samples from 40 patients with prostate cancer. They found that their EV test could distinguish between cancer localized to the prostate and cancer that has spread to other parts of the body.
Microscopic cancer deposits, called micrometastases, are not always detectable, even with advanced imaging methods. When these deposits spread outside the prostate area, focused radiation cannot prevent further progression of the disease. Thus, the ability to identify cancer by locale within the body could lead to new precision medicine treatments for the illness.
“[The EV Digital Scoring Assay] would allow many patients to avoid the potential harms of radiation that isn’t targeting their disease, and instead receive systemic therapy that could slow disease progression,” Posadas explained.
Other Clinical Laboratory Tests for Prostate Cancer Under Development
According to the American Cancer Society, the number of prostate cancer cases is increasing. One out of eight men will be diagnosed with the illness during his lifetime. Thus, developers have been working on clinical laboratory tests to accurately detect the disease and save lives for some time.
In “University of East Anglia Researchers Develop Non-Invasive Prostate Cancer Urine Test,” Dark Daily reported on a urine test also developed by scientists at the University of East Anglia that clinical laboratories can use to not only accurately diagnose prostate cancer but also determine whether it is an aggressive form of the disease.
And in “UPMC Researchers Develop Artificial Intelligence Algorithm That Detects Prostate Cancer with ‘Near Perfect Accuracy’ in Effort to Improve How Pathologists Diagnose Cancer ,” we outlined how researchers at the University of Pittsburgh Medical Center (UPMC) working with Ibex Medical Analytics in Israel had developed an artificial intelligence (AI) algorithm for digital pathology that can accurately diagnose prostate cancer. In the initial study, the algorithm—dubbed the Galen Prostate AI platform—accurately detected prostate cancer with 98% sensitivity and 97% specificity.
More research and clinical trials are needed before the new US and UK prostate cancer testing methods will be ready to be used in clinical settings. But it’s clear that ongoing research may soon produce new clinical laboratory tests and diagnostics for prostate cancer that will steer treatment options and allow for better patient outcomes.
Study may lead to clinical laboratory involvement in repurposing hormonal treatments to prevent cancer treatment resistance
Diagnosing prostate cancer and identifying which patients have aggressive forms of the cancer has been a challenge. But new insights into how aggressive cancers become resistant to drug therapies—and the discovery of a way to repurpose hormonal treatment to block or slow aggressive prostate cancer—may lead to clinical laboratories monitoring the progress of patients’ being treated with this new type of therapy.
Instead of treating tumors directly, the new approach developed by an international team of scientists would target proteins that typically regulate a cell’s circadian rhythm, but which have been found to be helping cancerous cells become resistant to treatment therapies.
“Our discovery has shown us that we will need to start thinking outside the box when it comes to new drugs to treat prostate cancer and test medicines that affect the circadian clock proteins in order to increase sensitivity to hormonal therapy in prostate cancer,” said Wilbert Zwart, PhD (above), Lead Researcher and Senior Group Leader Oncogenomics Division at NKI, in a news release. This discovery could give clinical laboratories and anatomic pathology groups an effective way to monitor new forms of cancer hormonal treatments. (Photo copyright: Netherlands Cancer Institute.)
Breakthrough Could Mean New Treatment for Aggressive Cancer
The aim of prostate cancer hormone therapy (AKA, androgen suppression therapy) is to halt signals by male hormones (usually testosterone) that stimulate tumor growth. This approach works until cancer becomes resistant to the drug therapy.
So, the challenge in metastatic prostate cancer treatment is finding a drug that prevents resistance to hormonal therapy.
In addressing the challenge, the researchers made a surprising discovery about what exactly dilutes anti-hormonal therapy’s effectiveness. Proteins that regulate the body’s sleep-wake cycle, or circadian rhythm, were found to also “dampen the effects of the anti-hormonal therapy,” according to the study.
“Prostate cancer cells no longer have a circadian rhythm. But these ‘circadian clock’ proteins acquire an entirely new function in the tumor cells upon hormonal therapy: they keep these cancer cells alive, despite treatment. This has never been seen before,” said Wilbert Zwart, PhD, Lead Researcher and Senior Group Leader Oncogenomics Division, NKI, in the news release.
The research suggests treatment for metastatic prostate cancer requires drugs “which influence the day-and-night rhythm of a cell,” and not necessarily medications that fight cancer, Technology Networks noted.
“Fortunately, there are already several therapies that affect circadian proteins, and those can be combined with anti-hormonal therapies. This lead, which allows for a form of drug repurposing, could save a decade of research,” Zwart added.
Questioning Hormonal Therapy Resistance
In their paper, the Dutch researchers acknowledged that androgen receptor (AR)-targeting agents are effective in prostate disease stages. What they wanted to learn was how tumor cells bypass AR suppression.
For the study, the scientists enrolled 56 patients with high-risk prostate cancer in a neoadjuvant clinical trial. Unlike adjuvant therapy, which works to lower the risk that cancer will return following treatment, the purpose of neoadjuvant therapy is to reduce the size of a tumor prior to surgery or radiation therapy, according to the National Institute of Health (NIH) National Cancer Institute (NCI).
The researchers performed DNA analysis of tissue samples from patients who had three months of anti-hormonal therapy before surgery. They observed that “genes keeping tumor cells alive were controlled by a protein that normally regulates the circadian (body) clock,” said Simon Linder, PhD student and researcher at NKI, in the news release.
“We performed integrative multi-omics analyses on tissues isolated before and after three months of AR-targeting enzalutamide monotherapy from patients with high-risk prostate cancer enrolled in a neoadjuvant clinical trial. Transcriptomic analyses demonstrated that AR inhibition drove tumors toward a neuroendocrine-like disease state,” the researchers wrote in Cancer Discovery.
“Understanding how prostate cancers adapt to AR-targeted interventions is critical for identifying novel drug targets to improve the clinical management of treatment-resistant disease. Our study revealed an enzalutamide-induced epigenomic plasticity toward pro-survival signaling and uncovered the circadian regulator ARNTL [Aryl hydrocarbon receptor nuclear translocator-like protein 1] as an acquired vulnerability after AR inhibition, presenting a novel lead for therapeutic development,” the scientists concluded.
More Research Planned
The scientists expressed intent to follow-up with Oncode to develop a drug therapy that would increase anti-hormonal therapy’s effectiveness in prostate cancer patients.
Given the molecular processes involved in the researchers’ discovery, there may be a supportive role for clinical laboratories and anatomic pathology groups in the future. But that can only happen after more studies and a US Food and Drug Administration (FDA) review of any potential new therapy to combat hormonal treatment resistance in prostate cancer patients.
