Most men who are diagnosed with prostate cancer can delay or avoid harsh treatments without harming their chances of survival, according to new results from a long-running study in the United Kingdom.
Men in the study who partnered with their doctors to keep a close eye on their low- to intermediate-risk prostate tumors – a strategy called surveillance or active monitoring – slashed their risk of the life-altering complications such as incontinence and erectile dysfunction that can follow aggressive treatment for the disease, but they were no more likely to die of their cancers than men who had surgery to remove their prostate or who were treated with hormone blockers and radiation.
“The good news is that if you’re diagnosed with prostate cancer, don’t panic, and take your time to make a decision” about how to proceed, said lead study author Dr. Freddie Hamdy, professor of surgery and urology at the University of Oxford.
Other experts who were not involved in the research agreed that the study was reassuring for men who are diagnosed with prostate cancer and their doctors.
“When men are carefully evaluated and their risk assessed, you can delay or avoid treatment without missing the chance to cure in a large fraction of patients,” said Dr. Bruce Trock, a professor of urology, epidemiology and oncology at Johns Hopkins University.
The findings do not apply to men who have prostate cancers that are scored through testing to be high-risk and high-grade. These aggressive cancers, which account for about 15% of all prostate cancer diagnoses, still need prompt treatment, Hamdy said.
For others, however, the study adds to a growing body of evidence showing that surveillance of prostate cancers is often the right thing to do.
“What I take away from this is the safety of doing active monitoring in patients,” said Dr. Samuel Haywood, a urologic oncologist at the Cleveland Clinic in Ohio, who reviewed the study, but was not involved in the research.
Results from the study were presented on Saturday at the European Association of Urology annual conference in Milan, Italy. Two studies on the data were also published in the New England Journal of Medicine and a companion journal, NEJM Evidence.
A common cancer that’s often low-risk
Prostate cancer is the second most common cancer in men in the United States, behind non-melanoma skin cancers. About 11% – or 1 in 9 – American men will be diagnosed with prostate cancer in their lifetime, and overall, about 2.5% – or 1 in 41 – will die from it, according to the National Cancer Institute. About $10 billion is spent treating prostate cancer in the US each year.
Most prostate cancers grow very slowly. It typically takes at least 10 years for a tumor confined to the prostate to cause significant symptoms.
The study, which has been running for more than two decades, confirms what many doctors and researchers have come to realize in the interim: The majority of prostate cancers picked up by blood tests that measure levels of a protein called prostate-specific antigen, or PSA, will not harm men during their lifetimes and don’t require treatment.
Dr. Oliver Sartor, medical director of the Tulane Cancer Center, said men should understand that a lot has changed over time, and doctors have refined their approach to diagnosis since the study began in 1999.
“I wanted to make clear that the way these patients are screened and biopsied and randomized is very, very different than how these same patients might be screened, biopsied and randomized today,” said Sartor, who wrote an editorial on the study but was not involved in the research.
He says the men included in the study were in the earliest stages of their cancer and were mostly low-risk.
Now, he says, doctors have more tools, including MRI imaging and genetic tests that can help guide treatment and minimize overdiagnosis.
The study authors say that to assuage concerns that their results might not be relevant to people today, they re-evaluated their patients using modern methods for grading prostate cancers. By those standards, about one-third of their patients would have intermediate or high-risk disease, something that didn’t change the conclusions.
When less treatment is better care
When the study began in 1999, routine PSA screening for men was the norm. Many doctors encouraged annual PSA tests for their male patients over age 50.
PSA tests are sensitive but not specific. Cancer can raise PSA levels, but so can things like infections, sexual activity and even riding a bicycle. Elevated PSA tests require more evaluation, which can include imaging and biopsies to determine the cause. Most of the time, all that followup just isn’t worth it.
“It is generally thought that only about 30% of the individuals with an elevated PSA will actually have cancer, and of those that do have cancer, the majority don’t need to be treated,” Sartor said.
Over the years, studies and modeling have shown that using regular PSA tests to screen for prostate cancer can do more harm than good.
By some estimates, as many as 84% of men with prostate cancer identified through routine screening do not benefit from having their cancers detected because their cancer would not be fatal before they died of other causes.
Other studies have estimated about 1 to 2 in every five men diagnosed with prostate cancer is overtreated. The harms of overtreatment for prostate cancer are well-documented and include incontinence, erectile dysfunction and loss of sexual potency, as well as anxiety and depression.
In 2012, the influential US Preventive Services Task Force advised healthy men not to get PSA tests as part of their regular checkups, saying the harms of screening outweighed its benefits.
Now, the task force opts for a more individualized approach, saying men between the ages of 55 and 69 should make the decision to undergo periodic PSA testing after carefully weighing the risks and benefits with their doctor. They recommend against PSA-based screening for men over the age of 70.
The American Cancer Society endorses much the same approach, recommending that men at average risk have a conversation with their doctor about the risks and benefits beginning at age 50.
Treatment had no impact on survival
The trial has been following more than 1,600 men who were diagnosed with prostate cancer in the UK between 1999 and 2009. All the men had cancers that had not metastasized, or spread to other parts of their bodies.
When they joined, the men were randomly assigned to one of three groups: active monitoring or using regular blood tests to keep an eye on their PSA levels; radiotherapy, which used hormone-blockers and radiation to shrink tumors; and prostatectomy, or surgery to remove the prostate.
Men who were assigned monitoring could change groups during the study if their cancers progressed to the point that they needed more aggressive treatment.
Most of the men have been followed for around 15 years now, and for the most recent data analysis, researchers were able get follow-up information on 98% of the participants.
By 2020, 45 men – about 3% of the participants – had died of prostate cancer. There were no significant differences in prostate cancer deaths between the three groups.
Men in the active monitoring group were more likely to have their cancer progress and more likely to have it spread compared with the other groups. About 9% of men in the active monitoring group saw their cancer metastasize, compared with 5% in the two other groups.
Trock points out that even though it didn’t affect their overall survival, a spreading cancer isn’t an insignificant outcome. It can be painful and may require aggressive treatments to manage at that stage.
Active surveillance did have important benefits over surgery or radiation.
As they followed the men over 12 years, the researchers found that 1 in 4 to 1 in 5 of those who had prostate surgery needed to wear at least one pad a day to guard against urine leaks. That rate was twice as high as the other groups, said Dr. Jenny Donovan of the University of Bristol, who led the study on patient-reported outcomes after treatment.
Sexual function was affected, too. It’s natural for sexual function to decline in men with age, so by the end of the study, nearly all the men reported low sexual function, but their patterns of decline were different depending on their prostate cancer treatment, she said.
“The men who have surgery have low sexual function early on, and that continues. The men in the radiotherapy group see their sexual function drop, then have some recovery, but then their sexual function declines, and the active monitoring group declines slowly over time,” Donovan said.
Donovan said that when she presents her data to doctors, they point out how much has changed since the study started.
“Some people would say, ‘OK, yeah, but we’ve got all these new technologies now, new treatments,’ ” she said, such as intensity-modulated radiation therapy, brachytherapy and robot-assisted prostate surgeries, “but actually, other studies have shown that the effects on these functional outcomes are very similar to the effects that we see our study,” she said.
Both Donovan and Hamby feel the study’s conclusions still merit careful consideration by men and their doctors as they weigh treatment decisions.
“What we hope that clinicians will do is use these figures that we’ve produced in these papers and share them with the men so that newly diagnosed men with localized prostate cancer can really assess those tradeoffs,” Donovan said.