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

Close Monitoring for Heart Risk Needed if Breast, Prostate Cancer Treatment Includes Hormones

The hormonal therapies used to treat many breast and prostate cancers raise the risk of a heart attack and stroke, and patients should be monitored regularly and receive treatment to reduce risk and detect problems as they occur, according to a new American Heart Association scientific statement, published today in the Association’s journal Circulation: Genomic and Precision Medicine.

“The statement provides data on the risks of each type of hormonal therapy so clinicians can use it as a guide to help manage cardiovascular risks during cancer treatment,” said Tochi M. Okwuosa, D.O., FAHA, chair of the scientific statement writing group, an associate professor of medicine and cardiology and director of Cardio-Oncology Services at Rush University Medical Center in Chicago.

Hormone-dependent cancers, such as prostate and breast cancer, are the most common cancers in the United States and worldwide not including skin cancers. As improvements in treatment – including increased use of hormonal therapies – allow people with these cancers to live longer, cardiovascular disease has emerged as a leading cause of illness and death in these patients.

Hormonal treatments for breast cancer include selective estrogen receptor modulators (SERMs) and aromatase inhibitors (AIs). SERMs block estrogen receptors in cancer cells so the hormone can’t spur tumor growth, while letting estrogen act normally in other tissues such as bone and liver tissue; examples of SERMs include tamoxifen and raloxifene. Aromatase inhibitors lower the amount of estrogen produced in post-menopausal women and include exemestane, anastrozole and letrozole. Endocrine treatments for prostate cancer, called androgen deprivation therapy, include some medications that decrease production of testosterone by their action on the brain and others that block testosterone receptors found in prostate cells and some prostate cancer cells.

The writing group reviewed existing evidence from observational studies and randomized controlled trials and found that:

  • Tamoxifen increases the risk of blood clots, while aromatase inhibitors increase the risk of heart attack and stroke more than tamoxifen. For breast cancer patients who require more than one type of hormonal therapy because of developed resistance to the initial medication, , there is an improvement in cancer outcomes. However, treatment with multiple hormones is associated with higher rates of cardiovascular conditions such as high blood pressure, abnormal heart rhythms and blood clots.
  • Androgen deprivation therapy (to reduce testosterone) for prostate cancer increases cholesterol and triglyceride levels, adds body fat while decreasing muscle and impairs the body’s ability to process glucose (which may result in type 2 diabetes). These metabolic changes are associated with a greater risk of heart attacks, strokes, heart failure and cardiovascular death.
  • The longer people receive hormonal therapy, the greater the increased risk of cardiovascular problems. Further research is required to better define the risks associated with duration of treatment.
  • The hormonal therapy-associated increase in CVD risk was highest in people who already had heart disease or those who had two or more cardiovascular risk factors – such as high blood pressure, obesity, high cholesterol, smoking or a family history of heart disease or stroke – when they began treatment.

“A team-based approach to patient care that includes the oncology team, cardiologist, primary care clinician, dietician, endocrinologist and other health care professionals as appropriate is needed to work with each patient to manage and reduce the increased risk of heart disease and strokes associated with hormonal therapy in breast and prostate cancer treatment,” Okwuosa said.

There are currently no definitive guidelines for monitoring and managing hormonal therapy-related heart risks. The statement calls for clinicians to be alert for worsening heart problems in those with prior heart disease or risk factors, and to recognize that even those without pre-existing heart problems are at higher risk because of their exposure to hormonal therapies.

“For patients who have two or more cardiovascular risk factors, it is likely that referral to a cardiologist would be appropriate prior to beginning hormone treatment. For patients already receiving hormonal therapies, a discussion with the oncology team can help to determine if a cardiology referral is recommended,” Okwuosa said.

The statement also calls for additional research in several areas, including:

  • Further evaluation of racial and ethnic disparities among breast and prostate cancer patients who have received hormone therapy. In the few studies that exist, racial and ethnic differences detected may be related to health inequities and other factors, and these are important areas to address.
  • Heart disease and stroke outcomes and risks should be added as primary endpoints in randomized trials of hormonal therapies.
  • Studies of specific hormonal medications are needed since each one may have different heart risks even if they work in the same way to treat breast or prostate cancer.

Source: American Heart Association

Genomic Test Helps Estimate Risk of Prostate Cancer Metastasis, Death

A commercially available genomic test may help oncologists better determine which patients with recurrent prostate cancer may benefit from hormone therapy, according to new research from the Johns Hopkins Kimmel Cancer Center and 15 other medical centers.

Researchers studied prostate cancer samples from 352 participants in the NRG/RTOG 9601 clinical trial, which compared radiation therapy alone with radiation therapy combined with hormone therapy. The investigators found that the Decipher test, which measures the activity of 22 genes among seven known cancer pathways, independently estimated the participants’ risk of metastasis, death from prostate cancer and overall survival. Researchers say it also guided treatment recommendations for recurrence of prostate cancer after surgery, helping identify patients most likely to benefit from hormone therapy.

Results were published online in the journal JAMA Oncology.

“The findings may be practice-changing, and will give oncologists additional information to help guide decisions on whether to offer patients hormone therapy,” says senior study author Phuoc Tran, M.D., Ph.D., professor of radiation oncology and molecular radiation sciences and co-director of the Cancer Invasion and Metastasis Program at the Johns Hopkins Kimmel Cancer Center.

For the study, Tran and colleagues studied prostate cancer samples from 352 men whose prostate cancer recurred after surgery and who participated in the NRG/RTOG 9601 clinical trial of radiation therapy between March 1998 and March 2003. The participants were randomized to receive radiation with hormone therapy (150 milligrams of bicalutamide daily for two years) or radiation therapy without hormone therapy. The researchers ran genetic information called ribonucleic acid (RNA) from the tumor tissue through the Decipher test, which evaluates the activity of 22 genes to predict how aggressive the cancer is and its chances of metastasis.

The test uses “genomic classifier scores” determined from the genomic characteristics of the tumor to stratify patients into three groups. Lower scores correlate with a more favorable prognosis. Of the participants, 148 patients (42%) had low genomic classifier scores, below .45; 132 (38%) had intermediate genomic classifier scores, between .45 and .60; and 72 (20%) had high genomic classifier scores, above .60. These genomic classifiers helped predict the risk of distant metastases, prostate cancer-specific death and overall survival, even after adjusting for participants’ age, race/ethnicity, Gleason score, T stage of T1 to T4 to classify the extent of tumor spread, margin status, prostate-specific antigen level and whether they were receiving hormone therapy.

Specifically, patients with intermediate and high genomic classifier scores had an 88% increased risk of distant metastases versus those with low genomic classifier scores. The test also demonstrated that patients with lower genomic classifier scores had a 2.4% improvement in overall survival 12 years after treatment with radiation and hormone therapy, compared with an 8.9% improvement among those with higher genomic classifier scores. Additionally, patients receiving radiation therapy soon after recurrence benefited more from hormone therapy. Those with higher genomic classifier scores derived an 11.2% improvement in 12-year occurrence of distant metastasis and a 4.6% improvement in overall survival from taking hormone therapy.

“Patients with lower scores do better overall, but they do not benefit as much from adding on hormone therapy because they are low risk. Patients with higher scores have worse disease and, therefore, benefit the most from adding the hormone therapy,” explains Tran.

“The way that we treat many patients in the clinic now is based on pathological and clinical factors, such as age, stage, grade and imaging,” Tran says. “Those have been very helpful, but you can only go so far with these rough markers. Hormone therapy unfortunately has a whole host of side effects, such as lack of libido, lack of erections and fatigue, and over time can increase the risk of diabetes, heart attack or stroke, so you only want to prescribe it if it is clearly beneficial. Our study demonstrated that Decipher is prognostic in its ability to determine cancer metastasis and also prostate cancer-specific survival and overall survival. It also was able to determine the benefit of patients receiving hormones or no hormones.” Tran says the information the test provides guides precision medicine efforts to help physicians direct hormone therapies to those most likely to benefit from them.

Source: The Johns Hopkins University