In the past, even low-risk prostate cancer patients were often treated with surgery or radiation, as men opted for aggressive ways to get rid of the cancer, despite the potential for serious side effects of treatment.
But in recent years there has been a marked shift away from immediate treatment. About 60% of low-risk prostate cancer patients now forgo treatment in favor of active surveillance (AS).
The American Urological Association is urging further increases to reach at least 80% in the near future, as emerging research highlights the slow-growing and even non-malignant nature of most low-risk prostate tumors.
However, some researchers backed by pharmaceutical companies appear to be exploring a new treatment for these patients.
They do not advocate the use of AS only for this group of patients, but instead seek the use of oral androgen receptor inhibitors (ARI), a class of potent and expensive hormonal therapy including apalut amines, enzalutamide, and dalolutamide. So far, these drugs have only been approved to treat advanced prostate cancer. Wholesale prices for these drugs exceed $150,000 a year and can reach six figures.
The prospect of drug use in patients with less aggressive tumors has alarmed some cancer experts.
Christopher Booth, MD, of the Division of Cancer Care and Epidemiology at Queen’s University Cancer Institute in Kingston, Ontario, Canada, said he suspects drug companies may be trying to recover from growing early limitations Profits in the prostate cancer patient market they had previously overlooked.
“The adoption of active surveillance over the past two decades has been a huge step forward for patients with early-stage prostate cancer, as it has allowed us to lower the level of care, reduce side effects, and maintain good health results,” Booth told Medscape Medical News .
I don’t see how this represents an important advancement for patients. I fear that if clinicians start adopting this approach rather than true active monitoring, we’re going to go backwards. Dr. Christopher Booth
on Men prescribing ARIs, Booth said, “I don’t see this as an important advance for patients. I worry we’re going backwards if clinicians start adopting this approach rather than true active monitoring.”
Channing Paller, a medical oncologist at Johns Hopkins University in Baltimore, said she doesn’t think she would recommend hormone therapy for anyone with low- or intermediate-risk prostate cancer.
“I think patients will do well no matter what, and still have options for treatment if there is clinical progression,” Paller said. “I’m concerned about adding hormone therapy, even an oral drug, because it only gives individuals the side effects of clinically insignificant endpoints.”
Several recent studies have explored the effects of hormone therapy on men of low to intermediate risk prostate tumors. For example, in June, JAMA Oncology published the results of the ENACT trial, which compared the ARI enzalutamide with AS in 227 patients with low- and intermediate-risk prostate cancer.
The trial was launched in 2016, when AS was booming in the United States as a method of managing the disease.
On the surface, the study was a success. The drug reduced the risk of pathological or treatment progression of prostate cancer by 46% compared to AS alone.
However, the drug – which crosses the blood-brain barrier – is associated with significant side effects, including decreased energy and libido, increased abdominal visceral weight, as well as cardiovascular risk or complications, depression, bone Potential for worsening demineralization and hot flashes. Neal Shore, MD, ENACT principal investigator and medical director of the Carolina Urology Research Center in Myrtle Beach, SC, said not all patients want to go on with AS, which can lead to cancer anxiety and high dropout rates. About 30 percent of men with AS discontinue the approach within 5 years due to cancer progression, and some urologists urge patients with high-volume, low-risk prostate cancer to receive immediate treatment.
Michael Schweizer, MD, a medical oncologist at the University of Washington in Seattle, conducted a 2020 pilot study showing that another ARI, apalutamide, inhibits the Cancer in men with AS conditions.
“I think pharmaceutical companies are willing to enter the ‘active surveillance market.’ The challenge is that there is no clear path to FDA approval in this case because clinical trial endpoints have not been validated,” Schweizer Say. “I think drugs can be part of routine management in men with AS, but we need better ways to identify patients who need treatment.” Such patients include those who require surgery or radiation without treatment.
So far, drugmakers have said they have no interest in pursuing ARIs for low-risk cancers.
A spokesperson for Astellas, which partnered with Pfizer Oncology on the ENACT trial, said the company has no plans to conduct additional studies in early-stage prostate cancer or submit ENACT to global regulators data.
A spokesman for Bayer HealthCare, the maker of darolutamide, said the company does not sponsor any of its own investigations into the drug for low- or intermediate-risk localized prostate cancer. But Bayer supports the moderate-risk localized prostate cancer trial at the Dana-Farber Cancer Institute in Boston.
Pamela Munster, MD, is a medical oncologist at UCSF and founder of Alessa Therapeutics. The company has been developing Biolen silicon-based implantable seeds that deliver drugs directly into the prostate. She is conducting two proof-of-concept studies to determine whether locally available drugs can prevent the side effects of ARI.
ARI may have a future for patients with low- to intermediate-risk disease who would otherwise be AS or topical therapy will be chosen.
“Certainly any form of [ARI] is expected to slow prostate cancer progression, and favorable intermediate-risk disease does progress more frequently and more rapidly, so it’s really worth considering,” Catalona said . ” But what is the actual cost and the actual cost?”
Most of his patients taking enzalutamide” Not feeling well,” he said. “Many are extremely fatigued and some refuse to continue taking the drug. Gynecomastia is also a problem for most men.”
Although other drugs may slow progression and have fewer side effects “Most actively monitored patients have a strong incentive to avoid potentially adverse side effects associated with treating prostate cancer,” Catalona said.
He added that the final arbiter will be level 1 evidence from well-conducted prospective randomized trials by renowned researchers and published in prestigious journals. “Stay tuned,” he said.
Munster is the founder and owner of Alessa Therapeutics. Schweizer received a research grant from Janssen Pharmaceuticals. Shore received personal fees from Astellas and Pfizer, as well as from Bayer, AstraZeneca, Janssen, Dendreon, Sanofi, Myovant, and Merck, during the study period. Booth, Catalona and Paller report no relevant financial relationships.
Howard Wolinsky is a medical journalist in Chicago. You can read more of his prostate cancer story at TheActiveSurveillor.com.
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