Prostate cancer presents a tricky screening challenge. Catching it early could mean dodging a painful journey with advanced cancer. Yet a sizable majority of prostate cancers are “indolent” — slow growing tumors that most likely would never metastasize during the patient’s lifetime, and whose treatment would do more harm than good.
Experts have long clashed over these considerations, with some arguing that the harms of PSA testing outstrip the benefits and others adamant that lives are saved with screening. The balance may now be shifting as researchers and physicians find methods that reduce the harms of screening, in particular with the use of MRI. A new study published in the New England Journal of Medicine on Wednesday showed using MRI scans can reduce unnecessary diagnosis and treatment of screen-detected prostate cancer by more than half.
That result should be a reason for experts to rethink prostate cancer screening guidelines with MRI in mind, according to Jonas Hugosson, a professor of urology at the University of Gothenburg in Sweden and the study’s lead author. “In my opinion, this is the last piece of the puzzle to have real evidence that the benefits of prostate screening exceed the harms on a population level,” he said. “This paper is the message to healthcare authorities around the world to look over recommendations for men.”
That may be easier said than done, other experts said. There may not be enough MRI infrastructure to support a prostate screening program requiring the scans.
Prostate cancer is one of the most common cancers, afflicting about one in eight men at some point in their lifetimes. It’s also the second highest cause of cancer-related death in men, killing roughly 35,000 people each year. The PSA test can help detect prostate cancer early, including aggressive disease, but it mostly catches low-grade, indolent tumors that probably wouldn’t have been an issue for the patient. The problem then is that diagnosing these patients and treating them for cancer subjects them to radiation and surgery, which has side effects including harming sexual health and urinary function.
That’s what scientists call overdiagnosis and overtreatment, and it probably would’ve been better if the patient had never been treated at all. On top of that, clinical trials in the late 2000s suggested that the PSA test likely only had a modest reduction in mortality, said Paul Pinsky, chief of early detection at the National Cancer Institute, who did not work on the study.
“When we thought about overdiagnosis and mortality reduction which was not great, some people started to sour on screening with PSA,” Pinsky said. Currently, most health authorities recommend people make a shared decision with their physician about prostate screening. “That’s mainly because we think there’s some benefit, but we know there’s a lot of harm.”
So scientists and clinicians began pushing to reduce the harms of screening. Active surveillance was the first way to do that. Doctors wouldn’t treat low-grade prostate cancer unless it seemed to progress on subsequent testing. The problem with that is patients may need to come back multiple times a year for more PSA testing and potentially MRIs and more biopsies, too. Plus, the anxiety and pressure of having a cancer diagnosis can drive some people with low-grade prostate cancer to seek curative treatment anyway. Considering most of these cancers don’t progress, experts began wondering if it’d be better to not even bother finding low-grade cancers in the first place.
One way to do that is to only biopsy men who have a suspicious lesion on an MRI scan, and only sample the lesion instead of systematically taking pieces from all around the prostate, which is typical. This is the route that University of Gothenburg’s Hugosson tested in the NEJM study.
The study enrolled about 13,000 men in Sweden. For all the men, if they had an elevated PSA of over 3 nanograms per milliliter of blood, they would receive an MRI. Then, about half were randomized to get systematic biopsy regardless of the MRI result — as well as a biopsy targeted on a lesion if one was visible. The other half received a targeted biopsy only if a lesion was present on MRI. After a median of four years, Hugosson found that those in the targeted biopsy-only group got significantly fewer biopsies and diagnoses of clinically insignificant cancers.
“We reduce biopsy frequency by about 60%. If you look at the overdiagnosis rate, we reduce that by approximately 57%,” said Hugosson. “That is very valuable.”
That was expected, Hugosson said. Other scientists have shown that only taking a biopsy if the MRI is positive can reduce the harms of screening. “We wanted to show that it’s a safe strategy, because many urologists around the world have been afraid that if you do not biopsy MRI-negative men, some will develop advanced cancers for sure,” he said.
Notably, Hugosson didn’t see a statistically significant increase in advanced, incurable cancers among men who only had biopsies when there was a visible lesion on MRI. Put another way, using the MRI-targeted approach would spare 51 men from undergoing biopsy and 14 men from receiving grade 1 prostate cancer diagnoses out of every 1,000 men. The strategy also missed a few men with clinically significant prostate cancer on a first screen, but was able to catch them on subsequent testing some years later. It delayed the diagnosis of clinically significant cancer in three men.
“They did not find evidence that patients were at all failed by the system because an MRI was negative,” said Tyler Seibert, a radiation oncologist and prostate cancer researcher at the University of California, San Diego who didn’t work on the study. Some patients might still slip through the cracks and present with incurable cancer, but Seibert said it’s impossible to prevent every single case. In the MRI-targeted group, five men had advanced or incurable cancer detected in a follow-up. Four of them originally had a PSA under 3, however, and the last had a false-negative biopsy.
Overall, Seibert said, the strategy “worked to avoid clinically insignificant cancer. It seemed to find almost all the cancers if you did the systematic biopsy approach. This is a great result for patients.”
The result may tip the balance towards a broader screening recommendation, if MRI can be done. “I think it does swing the pendulum in a favorable direction,” said Oliver Sartor, an oncologist and cancer researcher at the Mayo Clinic who did not work on the study. “This method of screening diminishes the risk of overdiagnosis. It diminishes the risk of infections from biopsy.”
But it simply may not be feasible to implement a wide-scale MRI program. Urologists and genitourinary oncologists have already begun pushing for MRI before biopsy for prostate screening, Seibert said. This study strengthens the evidence that this strategy is a good one, but it may not be feasible on a large scale. Currently, only a third of patients in urban areas receive MRI before a prostate biopsy, even less in rural areas.
“We know MRI should happen before biopsy. It’s already in the guidelines. It’s not happening because there aren’t enough MRI scanners,” Seibert said. Not only that, but getting a good scan on the prostate isn’t straightforward. “It’s not like pushing a button. These are like DSLR cameras on steroids. You need experts to do it, experts to interpret it, and that just doesn’t exist everywhere yet.”
Scientists like Seibert are working on improving this by essentially creating presets for prostate imaging on MRI machines and AI for interpreting them. That could increase the efficiency of MRI scanning for prostate screening and reduce the need for specialized radiologists for this strategy. Researchers are also working on ways other than MRI to reduce the harms of prostate screening, including developing other blood or urine biomarkers or personalized prostate screening programs based on individual genetic risk factors.
Whether all this reduction in harms actually changes whether people get screened may depend on their personal preferences, Seibert said. “This study won’t make it so that everybody jumps on the pro-screening side of things. Some people will say, we’re only doing a big screening program if we save lots of lives,” Seibert said. “If we don’t know that this will make you live longer, then is it worth it to you, and opinions vary on that.”
For Seibert, personally, he will be getting screened for prostate cancer, because even if it doesn’t help him live a longer life, it will help him avoid metastatic prostate cancer. “Even if I die of a heart attack, I don’t want to spend those years being treated for metastatic prostate cancer, because the treatment is really rough. So yes, I would prefer to be screened. But others do not,” he said.
That’s why these conversations with physicians are important, he said. The only problem with that is finding a primary care physician with the time for it.
