New Tests for Colon, Prostate Cancer Show Promise

Dennis Thompson wrote . . . . . . . . .

A pair of experimental tests could help doctors detect colon or prostate cancer with just a sample of blood or saliva.

One test examines a person’s blood for four biomarkers linked to inflammation. In a small study, it outperformed the fecal blood test now used in colon cancer screening, said lead researcher Dr. Mona Eldeeb, of Alexandria University Medical Research Institute in Egypt.

“These combined blood base markers could detect early cancer [of the] colon, especially if applied in a screening program,” she said.

The other test uses a man’s saliva to look for genetic material linked to prostate tumor growth, according to the Iranian researchers who developed it.

If approved in the United States, the tests could make screening and diagnosis for these cancers easier on patients, without the need for needle biopsy or colonoscopy, experts said.

“The exciting part of this study is that the [prostate cancer] test truly is noninvasive, requiring no need for needles as it relies on saliva that can be easily and repeatedly obtained,” said Dr. Corey Speers, a radiation oncologist at the University of Michigan’s Rogel Cancer Center in Ann Arbor.

The colon cancer test uses microscopic, color-coded beads to capture four inflammatory proteins from a blood sample. Laser technology then provides a count of the beads.

Eldeeb and her team tried the test with 35 patients with colon cancer and 52 people who were cancer-free.

They found that the proteins were at higher levels in the cancer patients, indicating that they could be used to screen for colon cancer without resorting to colonoscopy, Eldeeb said.

“This new test showed higher accurate results than the routinely used stool-based noninvasive test, and if used in combination with the fecal occult blood test gives very strong and accurate sensitivity with less need for colonoscopy,” she said.

The prostate cancer test searches saliva for eight RNA samples that indicate whether a man has developed prostate cancer or is simply suffering from age-related enlarged prostate. The research was led by Jamal Amri and Mona Alaee, from Tehran University of Medical Sciences in Iran.

The researchers tried the test on 180 men between the ages of 45 and 50, including 60 diagnosed with prostate cancer and 60 with enlarged prostate.

The study found that the saliva panel accurately sorted the men with prostate cancer from those with an enlarged prostate — something that up to now has required a needle biopsy.

“Of course, with all such preliminary studies questions still remain as to the accuracy and reliability of the test when you expand to a larger group of patients, and it isn’t yet ready for general adoption, but this represents an exciting first step,” said Speers, a spokesman for the American Society for Clinical Oncology.

He said future studies would seek to confirm these initial findings in a larger and more diverse set of men. They will also seek to determine appropriate cutoffs for levels of RNA in the saliva samples.

“We look forward to these confirmatory studies being completed,” Speers said.

Both reports were presented this week at the American Association for Clinical Chemistry (AACC) annual meeting, in Atlanta. Findings presented at medical meetings are considered preliminary until published in a peer-reviewed journal.

“These reports are very interesting early observations, and it will be exciting to see how they perform in follow-up studies,” AACC President Dr. Stephen Master said in a statement. “Of course, it’s important to note that both of these studies are preliminary, and both tests will need to be validated in larger studies before we can really know if they can be used in clinical practice or not.”

Source: HealthDay

Metastatic Prostate Cancer Comes in Two Forms, Which Could Guide Treatment

Eric Hamilton wrote . . . . . . . . .

Scientists have identified two subtypes of metastatic prostate cancer that respond differently to treatment, information that could one day guide physicians in treating patients with the therapies best suited to their disease.

Building off of earlier studies that discovered clinically relevant subtypes of breast cancer and non-metastatic prostate cancer, researchers identified genetic signatures that can divide metastatic prostate tumors into two types known as luminal and basal.

Luminal tumors responded better to testosterone-blocking treatments, while basal tumors did not benefit as much from this hormone treatment. Basal tumors also included the particularly aggressive form of metastatic disease known as small cell neuroendocrine prostate cancer. Further clinical trials will be required before any new diagnostic-based treatment selection is available.

“The reason why these subtypes are important is they respond to hormone therapy very differently,” says Shuang Zhao, a professor of oncology in the University of Wisconsin School of Medicine and Public Health who helped direct the research. “In localized prostate cancer, we’ve shown that luminal tumors had a bigger benefit from anti-testosterone therapy. We wanted to know if the same pattern extended to metastatic disease.”

With colleagues at the University of California, San Francisco and other institutions, Zhao published his findings Sept. 23 in the journal JAMA Oncology. The work was co-led by Rahul Aggarwal of UCSF and Nicholas Rydzewski in the Department of Human Oncology at SMPH.

About 20 years ago, scientists discovered luminal and basal subtypes of breast cancer and found that each responds better to different therapies. This has given doctors greater precision in treating their breast cancer patients.

Since breast cancers and prostate cancers share many similarities, including their sensitivity to hormone treatment, in 2016 Zhao’s team looked at whether these similarities extended to different prostate cancer subtypes. They published the first report that identified the luminal and basal subtypes in localized prostate cancer, when the disease remains confined to the prostate.

The new study expanded the analysis to metastatic cancer, when the disease spreads from the prostate. Metastatic prostate cancer is much more lethal than its local version. It’s also more difficult to study, because small tumors can be in many different parts of the body and are harder to biopsy.

So, to identify enough samples to run their analysis, Zhao’s team turned to multiple large, national studies of metastatic prostate cancer patients. The largest of these studies was based out of UCSF and led by two of the current study’s senior authors, Eric Small and Felix Feng.

“We pooled all of the data together and assembled the largest metastatic prostate cancer cohort to date,” says Zhao. The team ended up with a total of 634 patient samples.

The scientists used computational methods to compare the patterns of gene expression in the tumor biopsies. A group of 50 genes determines the basal-or-luminal nature of breast and prostate cancer and, depending on how active each of these genes is, scientists can separate out the two subtypes.

As they had seen for localized prostate cancer, Zhao’s team identified luminal and basal types for metastatic cancer as well. They then asked how the subtypes affected patient survival and response to treatment.

Because the doctors treating the study’s patients did not know about the subtypes at the time, they had to decide what treatment they thought might work best without this information. The variation in treatment produced a natural experiment that the researchers could analyze.

“And we found that just like in localized prostate cancer, the hormone therapies seemed to work better in the luminal tumors than in the basal tumors,” says Zhao.

Although there were two clear subtypes, the researchers also saw that the tumors fell onto a spectrum depending on their degree of luminal-ness or basal-ness. At one extreme were the hormone-treatment-resistant small cell neuroendocrine prostate cancers, which appeared the most basal. At the other end were less aggressive luminal subtypes, which are much more sensitive to hormone therapy. But there were tumors in between the two extremes as well. It’s not yet clear how these middle-of-the-road cancers may benefit from different treatments.

Since metastatic tumors are so difficult to biopsy, Zhao is hoping to develop blood tests that could more easily determine the luminal-or-basal nature of metastatic prostate cancer. Such a biomarker test would make clinical trials testing the usefulness of subtyping metastatic tumors much more feasible. Similar clinical trials for local prostate cancer are currently underway.

“Now that we’ve discovered this pattern, how do we turn this into a test that metastatic patients can benefit from?” says Zhao, who is also the co-director of the Circulating Biomarker Core at the UW–Madison Carbone Cancer Center, which researches how to develop such blood tests. “The only way it can be used widely is if we make it easier.”

Source: University of Wisconsin-Madison

Adding MRI to Screening Can Cut Prostate Cancer Over Diagnosis in Half

Ernie Mundell and Robert Preidt wrote . . . . . . . . .

One of the big issues in prostate cancer care is over diagnosis — men who are treated for low-risk, slow-growing tumors that might be better left monitored and untreated.

Now, research out of Sweden suggests that having patients undergo MRI screening, along with targeted biopsies, could reduce the number of prostate cancer over diagnoses by half.

The new approach can detect just as many clinically significant tumors as current methods, but reduces unnecessary biopsies and the identification of minor low-risk tumors, according to the study presented recently at the European Association of Urology Congress. The findings were published simultaneously in the New England Journal of Medicine.

The findings show that “modern methods for prostate cancer screening maintain the benefits of screening, while decreasing the harms substantially,” said study co-leader Tobias Nordström. He is associate professor of urology at Danderyd Hospital at the Karolinska Institute.

“This addresses the greatest barrier to the introduction of nationwide screening,” Nordström explained in an institute news release.

One expert in the United States said the research holds real promise.

“For the past 20 years, urologists and researchers have been striving to improve prostate cancer screening to target men with clinically significant prostate cancer and avoid over diagnosis in men with low-risk prostate cancer,” said Dr. Manish Vira, system chief of urology at Northwell Health Cancer Institute in New Hyde Park, N.Y.

The Swedish findings show how the use of highly targeted MRI “has moved our field closer to the goal,” said Vira, who wasn’t involved in the new study.

As the Stockholm team explained, most countries no longer have nationwide prostate-cancer screening programs in place because current methods — PSA (prostate-specific antigen) blood testing plus traditional biopsies — often result in over diagnosis and unnecessary biopsies, meaning the risks of screening can outweigh the benefits.

In too many cases, so-called “indolent” prostate tumors grow at such a slow pace that treating them brings harms (such as urinary issues and impotence) that exceed any real risk from the tumor to the patient’s health.

But is there a better way to spot those higher-risk tumors that do need treatment?

In the new study, the Karolinska team tracked outcomes for 12,750 Swedish men between 2018 and 2021. Blood samples were collected from the men for PSA analysis, as well as analysis by the new Stockholm3 test, developed by institute researchers.

Men whose tests revealed elevated PSA levels were then randomly selected to undergo either traditional biopsies or they underwent MRI.

In the MRI group, biopsies were conducted only on suspected tumors identified by MRI.

The new approach can detect just as many clinically significant tumors as current methods, the researchers said, but it reduces unnecessary biopsies and the identification of minor low-risk tumors.

Vira explained that “by incorporating MRI into the prostate cancer screening process, we can better recommend biopsy in those men who are at high risk, and perhaps just as importantly, avoid unnecessary biopsies in men who don’t have prostate cancer or have indolent/insignificant disease.”

Dr. Art R. Rastinehad is associate professor of urology and radiology and vice chair of urology at Lenox Hill Hospital in New York City. He wasn’t involved in the Swedish research, but called it “another great study supporting the use of MRI before a prostate biopsy in men at risk of prostate cancer.”

He pointed out that “prostate cancer was the last solid organ malignancy that was diagnosed without imaging, so we are very excited to continue to use advanced imaging technologies to help our patients.”

The potential benefits to patients are clear, he added.

“It is estimated that up to 51% of patients having their prostate removed may be candidates for a less invasive, outpatient treatment that helps them get back to their normal lives with a lower risk of urinary incontinence and/or erectile dysfunction,” Rastinehad said.

Source: HealthDay

Targeted Radiotherapy Might Help Men Battling Advanced Prostate Cancer

Cara Murez wrote . . . . . . . . .

Patients with advanced prostate cancers may have newfound hope: Researchers identified a new potential treatment for men with metastatic castration-resistant prostate cancer, which has no cure.

Metastatic castration-resistant prostate cancer means the disease continues to spread despite therapies that deplete male hormones (androgens) such as testosterone, which are thought to “feed” tumors.

When added to standard care, this novel targeted radiotherapy improved survival for these cancer patients, researchers report.

The study “offers the treatment possibility where there was really very little for the most advanced patient, but it opens a doorway for exploring the benefits of this drug in multiple earlier patient populations,” said Dr. Michael Morris, head of the Prostate Cancer Section at Memorial Sloan Kettering Cancer Center in New York City.

In about 80% of prostate cancers, there is a protein on the surface of the cancer cell that is called prostate-specific membrane antigen (PSMA). It is also distributed on prostate cancer that has spread to the bone, lymph nodes or soft tissues. Yet, PSMA is not on normal tissues, so it was a good target for both diagnostics and therapeutics, Morris explained.

The new drug has two components, a targeting molecule and a payload delivers radiation. It is given intravenously.

“Each of the molecules of drug is seeking to bind with the cells containing PSMA, which generally are the prostate cancer cell. As the drug binds to it, the cell brings the drug into the interior of the cell. The radiation, which is attached to the drug, it’s the payload of the drug, is also brought into the interior of the cell. And there, it irradiates the cell and kills it as well as the cells that are neighboring to it,” Morris said.

To be a part of the trial, the patients had to have disease that had progressed through testosterone-lowering therapy, which has been the standard for decades, Morris said. They also had to have progressed through another class of drugs known as androgen-receptor pathway inhibitors and through chemotherapy.

“What happens when you go on to treatment with prostate cancer is that if you respond, you stay on that therapy or stay on that regimen until either side effects preclude continuing the therapy or it no longer works because the disease has become resistant to it,” Morris explained.

The trial included 831 participants. Patients were randomized two-to-one to receive the new treatment, called lutetium-labeled PSMA-617, plus standard care or just standard care between June 2018 and October 2019.

The new treatment increased overall median survival to 15.3 months versus 11.3 months for these patients who had very advanced disease. It also increased a measure called radiographic progression-free survival, which reflects disease control while on the drug, from a median of 3.4 months to 8.7 months.

The study is being presented online at the American Society of Clinical Oncology annual meeting, which will be held June 4-8. Findings presented at medical meetings are considered preliminary until published in a peer-reviewed journal. Drug maker Novartis funded the study and plans to submit the data to regulatory authorities for review and potential approval.

Prostate cancer is both the most common cancer in American men and the second leading cause of cancer-related death. The study’s positive results mean that patients who have very advanced disease might have a new treatment option.

“It also means that, usually in prostate cancer as well as other diseases, what you develop and discover as a new therapy for the most advanced patients usually benefits earlier patients and frequently we’ll see those benefits amplified in less sick patients who have less-resistant disease,” Morris said.

Current studies are now looking at the therapy for patients who have earlier disease who have not yet received chemotherapy, as well as those who are just beginning treatments for prostate cancer.

Dr. Ash Tewari, system chair in the Milton and Carroll Petrie Department of Urology at Mount Sinai Health System in New York City, said the study offers a lot of promise for patients, giving those with advanced prostate cancer new hope. It also has a reasonable side effect profile, said Tewari, who was not involved in the study.

“Androgen deprivation is the mainstay of therapy of advanced prostate cancer, but the cure rate is low and patients eventually become castrate-resistant,” Tewari said. “There is a need to more closely tailor therapies to individual patient profiles.”

Noting the median results for overall survival that the study found, Tewari said that extra four months of life can be very meaningful for someone who lives to see an important family milestone, such as a grandchild’s wedding.

“This is a good example of when a well-conducted clinical trial backed by scientific data can make an impact in patient’s life. And we should always be curiously, cautiously looking at these options,” he said.

Source: HealthDay

Thousands of Men to Trial Prostate Cancer Home Testing Kit

Thousands of men worldwide are to receive a home test kit for prostate cancer – thanks to pioneering research from the University of East Anglia and the Norfolk and Norwich University Hospital (NNUH).

The research team are trialling a new home-testing ‘Prostate Screening Box’ to collect men’s urine samples at-home. The urine samples will be used to analyse the health of the prostate in 2,000 men in the UK, Europe and Canada.

This simple urine test is intended to diagnose aggressive prostate cancer and in a pilot study predicted which patients required treatment up to five years earlier than standard clinical methods.

The Prostate Screening Box has been developed in collaboration with REAL Digital International Limited to create a kit that fits through a standard letterbox.

It means that men can provide a urine sample in the comfort of their own home, instead of going into a clinic or having to undergo an uncomfortable rectal examination. The research team hope that it could revolutionise diagnosis of the disease.

Lead researcher Dr Jeremy Clark, from UEA’s Norwich Medical School, said: “Prostate cancer is the most common cancer in men in the UK. However it usually develops slowly and the majority of cancers will not require treatment in a man’s lifetime. It is not a simple matter to predict which tumours will become aggressive, making it hard to decide on treatment for many men”.

“The most commonly used tests for prostate cancer include blood tests, a physical examination known as a digital rectal examination (DRE), an MRI scan or a biopsy”.

“We have developed the PUR (Prostate Urine Risk) test, which looks at gene expression in urine samples and provides vital information about whether a cancer is aggressive or ‘low risk’.

“The Prostate Screening Box part sounds like quite a small innovation, but it means that in future the monitoring of cancer in men could be so much less stressful for them and reduce the number of expensive trips to the hospital.

“The prostate lies just below the bladder. It constantly produces secretions which naturally flow into the urethra – the tube through which urine passes from the bladder. The prostatic secretions carry cells and molecules from all over the prostate which are flushed out of the body on urination. We collect these and examine them. It’s a way of sampling the whole prostate in one go.

“As the prostate is constantly secreting, the levels of biomarkers in the urethra will build up with time. Collecting from the first wee of the day means that overnight secretions can be collected which makes the analysis more sensitive.”

The team have previously trialled the kit with a small group of participants, but in the next phase of the research study are rolling it out to thousands.

Men taking part in the trial will receive a home urine-sampling kit and will be asked to provide two urine samples – one to be taken first thing in the morning and the second an hour later. The samples will then be sent back to the lab for analysis.

Dr Clark said: “Feedback from early participants showed that the at-home collection was much preferred over sample collection in a hospital.

“We hope that using our Prostate Screening Box could in future revolutionise how those on ‘active surveillance’ are monitored for disease progression, with men only having to visit the clinic after a positive urine result.

“This is in contrast to the current situation where men are recalled to the clinic every six to 12 months for a range of tests including DRE, PSA tests, painful and expensive biopsies and MRI. We are working to develop the test to help patients in three years’ time.

“A negative test could enable men to only be retested every two to three years, relieving stress to the patient and reducing hospital workload,” he added.

Robert Mills, Consultant Clinical Director in Urology at NNUH, said: “This simple, non-invasive urine test has the potential to significantly change how we diagnose and manage early prostate cancer for the benefit of patients and health care systems. It may enable us to avoid unnecessary diagnosis of low risk disease as well as managing patients more appropriately with surveillance for those with low risk of progression and early curative treatment for those at high risk of progression.”

Paul Villanti, executive director of programs at Movember, said: “The PUR test has great potential to transform the way prostate cancer is managed. Not only can it accurately predict when a man’s disease will become aggressive and require treatment, but it has the added advantage of allowing men to complete it at home.

“We are proud to have supported the development of the PUR test from its early stages as part of our Global Action Plan on Biomarkers, through to this trial involving thousands of men across the world.

“Through our Global Action Plan on active surveillance, we have been able to identify hundreds of men from the UK, Germany, Italy and Canada who are suitable to take part in this trial.

“We hope it will speed up the trial’s progress and get this test included as part of clinical care for men as quickly as possible.”

Source: University of East Anglia