Hormone Treatment for Prostate Cancer Linked to Heightened Alzheimer’s Risk

E.J. Mundell wrote . . . . . . . . .

Soon after a man is diagnosed with prostate cancer, drugs that lower levels of testosterone are often offered as treatment, since testosterone fuels the cancer’s growth.

But a major new study suggests that this approach might have an unwanted side effect: Higher odds for Alzheimer’s disease and other dementias.

“Our results suggest that clinicians need to raise their awareness about potential long-term cognitive effects of hormone therapy and discuss these risks with their patients,” said study author Ravishankar Jayadevappa.

He’s a research associate professor of geriatrics at the University of Pennsylvania’s Perelman School of Medicine in Philadelphia.

One expert said it does raise troubling questions.

“Most of us are becoming as afraid of getting Alzheimer’s as we are of getting cancer,” said Dr. Elizabeth Kavaler, a urology specialist at Lenox Hill Hospital in New York City. “When a study pits one debilitating condition against another, it instills fear in patients.”

But the treatment — called androgen-deprivation therapy — remains the “gold standard” for many cases of prostate cancer, according to Kavaler. Therefore, the new data means “tough decision-making” for patients and their physicians, she said.

In the new study, Jayadevappa’s group took a look back at U.S. National Cancer Institute data on over 154,000 prostate cancer patients who were diagnosed between 1996 and 2003. About 62,000 received hormone-depleting therapy within two years of their diagnosis, while about 92,000 did not.

In total, 13% of men who had received the therapy went on to develop Alzheimer’s disease over eight years of follow-up, compared to 9% who hadn’t gotten the treatment, the study found. According to the researchers, the lifetime prevalence of Alzheimer’s disease in men generally is about 12%.

When the team looked at diagnoses of all forms of dementia, 22% of those who’d received the therapy received such a diagnosis, compared to 16% of those who hadn’t undergone hormonal therapy.

Jayadevappa’s team noted that earlier, smaller studies have found similar trends.

However, “to our knowledge, this is one of the largest studies to date examining this association, and it followed patients for an average of eight years after their prostate cancer diagnosis,” he said in a university news release.

As the researchers noted, androgen-deprivation therapy is an effective means of slowing the progress of prostate cancers. However, it is now typically only used in cases of advanced disease, or cases where the chances of a tumor recurrence are high.

The approach also has other deleterious side effects, including impaired sexual function, and potential harm to bones and cardiovascular health.

The study also can only point to an association between hormonal treatment and raised odds for dementia, it cannot prove cause and effect. But Jayadevappa’s team noted that they tried to account for other factors, such as age, the presence of other medical conditions and the severity of the prostate cancer.

Dr. Maria Torroella Carney is chief of geriatric and palliative medicine at Northwell Health in New Hyde Park, N.Y. Looking over the findings, she said they warrant further study, but it’s not time for men who’ve gotten hormonal therapy to panic.

Carney stressed that the study couldn’t prove cause and effect, and other factors might account for the higher risk of dementia.

Men receiving hormonal therapy tended to be “older, sicker and had more advanced prostate cancer,” Carney noted, and sicker patients already have higher odds of dementia.

In addition, the study didn’t reveal whether or not men who got the therapy lived longer than those who didn’t. If they did live longer, their odds of dementia would also increase over time, Carney explained.

Study co-author Dr. Thomas Guzzo agreed that no one should make rash decisions on prostate cancer care based on this study alone.

“I think we need to look at these patients on an individual level,” said Guzzo, who is chief of urology at the University of Pennsylvania. “Certainly, there are patients who need hormonal therapy and benefit from it greatly,” he said in a university news release. “There are others where the evidence is less clear, and in these patients, we should consider the risk of hormonal therapy versus the benefit in treating their prostate cancer. This should be a shared decision-making process with the patient.”

The study was published online in JAMA Network Open.

Source: HealthDay


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Interim Scan during Prostate Cancer Therapy Helps Guide Treatment

New prostate cancer research shows that adding an interim scan during therapy can help guide a patient’s treatment. Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) imaging of patients with metastatic castration-resistant prostate cancer after two cycles of lutetium-177 (177Lu)-PSMA radioligand therapy has shown a significant predictive value for patient survival. The research was presented at the 2019 Annual Meeting of the Society of Nuclear Medicine and Molecular Imaging (SNMMI).

According to the National Cancer Institute, currently the five-year survival rate for men with metastatic prostate cancer is 30.5 percent. Early assessment of treatment effectiveness is essential to providing optimal care.

In phase 2 trials, 177Lu-PSMA therapy has shown promising results in treating patients with metastatic castration-resistant prostate cancer. The therapy typically involves a preliminary PSMA PET scan to identify patients who are eligible for the treatment. While interim PET scans have shown high predictive value for lymphoma patients, this concept has not been previously explored in prostate cancer patients undergoing 177Lu-PSMA therapy.

The retrospective analysis was conducted at Klinikum rechts der Isar hospital, Technical University Munich, Germany including patients who underwent gallium-68 (68Ga)-PSMA11 PET/CT at baseline and after two cycles of 177Lu-PSMA RLT under a compassionate use program.

Instead of standardized uptake value, which is the parameter generally used in such analyses, researchers used qPSMA, an in-house developed software, to evaluate the whole-body tumor burden. “Tumor response was assessed by the changes in PSMA-avid tumor volume from baseline to the second PSMA PET using three classification methods,” explained Andrei Gafita, MD. “Subsequently, we found that tumor response assessed on interim PSMA PET after two RLT cycles was associated with overall survival.”

Gafita stated, “Our results therefore show that interim PSMA PET can be used for therapeutic response assessment in patients undergoing 177Lu-PSMA RLT. Furthermore, occurrence of new lesions in PSMA PET is a prognostic factor for disease progression and could be included in defining tumor response based on PSMA PET imaging.”

“While further analyses involving clinical parameters are warranted,” Gafita adds, “this analysis paves the way for use of interim PSMA PET in a prospective setting during 177Lu-PSMA radioligand therapy.”

Source: Society of Nuclear Medicine and Molecular Imaging


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2 Prostate Cancer Drugs Found to Fight Disease in Earlier Stages

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

Cutting-edge prostate cancer drugs that help extend life in the toughest cases might also be useful in fighting less aggressive tumors, two new clinical trials suggest.

Two drugs that interfere with cancer’s ability to use testosterone for fuel, apalutamide (Erleada) and enzalutamide (Xtandi), are already approved for use against more advanced prostate tumors that don’t respond to regular therapy.

But these trials show that the drugs also can improve survival and slow progression in prostate cancers that do respond to regular therapy, which typically involves medication that halts production of testosterone.

Both clinical trials involved patients with prostate cancer that had spread to other parts of their body but who still responded to androgen-deprivation therapy.

“We’re slowly starting to see a migration of drugs traditionally saved for advanced stages of disease, where we’re incorporating them into earlier stages of disease,” said Dr. Bobby Liaw, medical director of the Blavatnik Family Chelsea Medical Center at Mount Sinai, in New York City. He was not involved in the trials.

Apalutamide combined with androgen-deprivation therapy caused a 33% reduction in overall risk of death, compared against patients who received a placebo alongside their androgen-deprivation therapy, said the lead researcher of that clinical trial, Dr. Kim Chi.

Apalutamide also delayed progression of the cancer by 52%, and the length of time before patients required chemotherapy by 61%, said Chi, medical director of the Clinical Trials Unit at the BC Cancer Agency-Vancouver Prostate Center in Canada.

Adding the hormone blocker significantly improved patients’ outcomes with few side effects, Chi said.

“It’s well-tolerated, both from a side-effect profile and from a quality-of-life perspective,” Chi said, noting that side effects differ little from a placebo.

The second trial involved adding enzalutamide to androgen-deprivation therapy, and again positive results were found.

About 80% of men treated with enzalutamide were alive after three years, compared with 72% of men who received standard treatment, the researchers said.

Study co-chair Ian Davis is a professor at Monash University in Australia. “The actual result in patients starting hormonal therapy — noting patients had a 60% improvement in the time it takes to detect the cancer growing again along with a 33% increase chance of survival — was far higher than we expected,” he said in a news release.

In that trial, 1,125 men were randomly assigned to receive either enzalutamide or placebo, the study authors said.

The next step for researchers will be head-to-head comparisons that will help doctors decide which drugs would work best for specific patients, Liaw said.

“We don’t yet have any data to compare these drugs side-to-side. That’s where we’re going to start to see a bit of debate over which one is arguably the best drug to start with first,” Liaw said. “We’ve never had a lot of satisfying data to help us figure out what is the proper sequence, is there an optimal sequence, should we be combining certain drugs to get a better effect?”

Cost will also be an issue in using these new drugs to fight prostate cancer. “These are really expensive drugs,” Liaw said. “These are drugs that cost thousands for a month’s supply.”

Regardless, it is good for doctors to have more drugs on hand to help patients battle prostate cancer, he concluded.

“We’re certainly hoping to have their disease controlled, not just now but for the long haul, and that’s what these drugs are showing they have the capability of doing,” Liaw said.

Both trials were to be presented at the American Society for Clinical Oncology’s annual meeting, in Chicago, this weekend, and they will also be published in the New England Journal of Medicine.

Source: HealthDay

Chromosomes May Tell Is That Prostate Cancer Needs Treating

To treat, or not to treat: That remains one of the tough conundrums for men with prostate cancer and their doctors, because some tumors may be aggressive, while others may take decades to cause harm.

Now, new research suggests that tracking specific changes in the number of chromosomes inside prostate cancer cells might help solve the riddle.

Besides giving new insights into how prostate tumors form and spread, the chromosomal data might someday “be employed clinically to inform risk stratification and treatment” decisions for patients, according to a team led by Angelika Amon, of the Massachusetts Institute of Technology.

The research focuses on a genetic state known as aneuploidy — an abnormal number of chromosomes in cells. Aneuploidy is a known hallmark of cancer, but it’s unclear how it influences cancer progression, or whether tracking chromosome gains or losses might help guide treatment.

Treatment guidance for prostate cancer is sorely needed, said Dr. Manish Vira. He helps direct urologic research at Northwell Health’s Arthur Smith Institute for Urology, in Lake Success, N.Y.

That’s because use of the prostate-specific antigen (PSA) blood test has fallen out of favor somewhat as a means of gauging whether a man needs surgery or other treatment, Vira said. In many cases, the tumor might turn out to be “indolent” — so slow-growing that it’s better to leave it in place and simply “watch and wait.”

So, “the holy grail in prostate cancer remains to be finding a test, given at the time of diagnosis, that can identify the subset of patients that are at highest risk of dying of prostate cancer,” explained Vira, who wasn’t involved in the new study.

In this study, Amon’s group was seeking just such a test.

The investigators used prostate tumor samples from 333 men to develop a method to estimate a “signature” pattern of chromosomal gains and losses within cells.

They then applied this method to 404 prostate cancer patients who were followed for a median of 15 years.

Compared to those who had no predicted aneuploidy, the 23% of patients whose tumors had five or more predicted chromosome arm alterations at the time of diagnosis were 5.3 times more likely to die of prostate cancer during follow-up, the findings showed.

Even among high-risk patients, the degree of tumor aneuploidy predicted future deadly prostate cancer, according to the study published May 13 in the Proceedings of the National Academy of Sciences.

The findings suggest that aneuploidy does play a key role in aggressive prostate cancer, Amon’s team said, and that the extent of aneuploidy could be used to determine the level of risk from the cancer and to help make treatment decisions.

Vira agreed the tool has potential, and “could be used on prostate biopsy samples to further stratify patients at the time of diagnosis.”

Dr. Nicholas Karanikolas directs urologic oncology at Staten Island University Hospital in New York City. Reading over the new findings, he agreed that oncologists need “a broader understanding of the genetic makeup of the cancer itself” to help guide treatment.

Any test that might tell men they have a fivefold higher odds of dying from a prostate cancer “would provide further guidance as to those patients who would benefit from adjuvant treatments and/or inclusion in clinical trials,” Karanikolas said.

Source: HealthDay

Study Shows Safest Method for Prostate Cancer Biopsies

The Gale and Graham Wright Prostate Centre at North York General Hospital (NYGH) is advancing prostate cancer care with a new study that shows the benefits of transperineal prostate biopsies (TPBx) under local anesthetic.

Published online in the Journal of Urology the study, “Transperineal Prostate Biopsies Using Local Anesthesia: Experience in 1,287 Patients. Prostate Cancer Detection Rate, Complications and Patient Tolerability” provides evidence that the TPBx approach for testing and diagnosing prostate cancer is accurate and has significantly fewer complication rates compared to the traditional prostate biopsy method.

“After performing more than a thousand TPBx procedures under local anesthetic, the team at North York General has shown that it is the safest method of obtaining a biopsy for prostate cancer and patients tolerate the procedure well,” said Dr. Stan Flax, NYGH urologist and one of the study’s lead authors. “The clinical data provides the necessary evidence that the medical community needs in order to move toward a new standard of care for patients.”

In 2016, NYGH’s Gale and Graham Wright Prostate Centre became the first in Canada to use the TPBx approach, which involves obtaining the biopsy using a needle through the skin. Studies have shown that TPBx is a safer alternative for patients, as compared to transrectal biopsies, due to the lower risk of serious infections, which can result in hospitalization and admission to an intensive care unit.

In the very few settings where TPBx is performed, the procedure is done using general or spinal anesthetic, which typically requires more intensive resources. For the past three years, urologists at NYGH have exclusively used TPBx under local anesthetic and have tracked a total of 1,287 procedures as part of this study. The data shows this method of prostate biopsies has the same accuracy rate, if not better as transrectal, compared to the team’s previous series of transrectal biopsies.

Prostate cancer is the most commonly diagnosed cancer among North American men, with approximately one in seven men being diagnosed with this disease in their lifetime. It is also one of the more treatable cancers, if detected and treated in its early stages.

“Only one percent of testing for prostate cancer in North America is done using TPBx,” says Dr. Flax. “Given how often prostate biopsies are performed, there is a real opportunity to improve patient care with our research.”

Source: North York General Hospital


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