Prostate cancer presents a difficult screening challenge. Catching it early could mean dodging a painful journey with advanced cancer. Yet a significant majority of prostate cancers are ‘indolent’: slow-growing tumors that will most likely never metastasize during the patient’s lifetime, and whose treatment would do more harm than good.
Experts have long been conflicted about these considerations, with some arguing that the harms of PSA testing outweigh the benefits, while others are adamant that screening saves lives. The balance may now be shifting as researchers and physicians find methods that reduce the harms of screening, especially through the use of MRI. A new study published in the New England Journal of Medicine On Wednesday it emerged that the use of MRI scans can reduce unnecessary diagnosis and treatment of screening-detected prostate cancer by more than half.
That result should cause experts to reconsider prostate cancer screening guidelines with MRI in mind, said Jonas Hugosson, professor of urology at the University of Gothenburg in Sweden and lead author of the study. “In my opinion, this is the last piece of the puzzle that provides real evidence that the benefits of prostate screening outweigh the harms at a population level,” he said. “This document sends the message to healthcare authorities around the world to consider recommendations for men.”
That may be easier said than done, other experts said. There may not be sufficient MRI infrastructure to support a prostate screening program that requires the scans.
Prostate cancer is one of the most common cancers, affecting approximately one in eight men at some point in their lives. It is also the second highest cause of cancer-related deaths in men, killing approximately 35,000 people annually. The PSA test can help detect prostate cancer early, including aggressive diseases, but it mainly detects low-grade, indolent tumors that probably wouldn’t have been a problem for the patient. The problem then is that diagnosing these patients and treating them for cancer exposes them to radiation and surgery, which has side effects including damage to sexual health and urinary function.
That’s what scientists call overdiagnosis and overtreatment, and it probably would have been better if the patient had never been treated at all. Moreover, clinical trials in the late 2000s suggested that the PSA test likely produced only a modest reduction in mortality, said Paul Pinsky, chief of early detection at the National Cancer Institute, who did not participate in the study.
“When we started thinking about overdiagnosis and mortality reduction, which wasn’t great, some people started to sour on screening with PSA,” Pinsky said. Currently, most health authorities recommend that people make a decision about prostate screening with their doctor. “That’s mainly because we think there is some benefit, but we know there is a lot of harm.”
So scientists and doctors began working to reduce the harms of screening. Active surveillance was the first way to do that. Doctors would not treat low-grade prostate cancer unless it appeared to be progressing on subsequent testing. The problem with that is that patients may need to return several times a year for more PSA testing and possibly MRIs and more biopsies. In addition, the fear and pressure associated with a cancer diagnosis may prompt some people with low-grade prostate cancer to seek curative treatment. Since most of these cancers don’t evolve, experts began to wonder if it wouldn’t be better not to 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 sample just the lesion rather than systematically taking pieces from the entire prostate, which is typical. This is the route that Hugosson from the University of Gothenburg tested in the NEJM study.
About 13,000 men in Sweden took part in the study. For all men, if they had an elevated PSA of more than 3 nanograms per milliliter of blood, they would get an MRI. Then, about half were randomized to undergo a systematic biopsy regardless of MRI result – and a biopsy targeting a lesion if one was visible. The other half only received a targeted biopsy if a lesion was present on MRI. After an average of four years, Hugosson found that those in the biopsy-only group received significantly fewer biopsies and diagnoses of clinically insignificant cancers.
“We reduce the biopsy frequency by approximately 60%. If you look at the overdiagnosis rate, we reduce that by about 57%,” Hugosson said. “That is very valuable.”
That was to be expected, Hugosson said. Other scientists have shown that taking a biopsy only if the MRI is positive can reduce the harm of screening. “We wanted to show that it is a safe strategy because many urologists around the world are concerned that if you don’t biopsy MRI-negative men, some will definitely develop advanced cancer,” he said.
Strikingly, Hugosson saw no statistically significant increase in advanced, incurable cancers among men who had biopsies only if there was a visible lesion on MRI. In other words, using the MRI-targeted approach would allow 51 men out of every 1,000 men to undergo a biopsy and spare 14 men from being diagnosed with grade 1 prostate cancer. The strategy also missed some men with clinically significant prostate cancer on an initial screening, but was able to detect them on subsequent testing several years later. It delayed the diagnosis of clinically significant cancer in three men.
“They found no evidence that patients were being failed by the system at all because an MRI was negative,” says Tyler Seibert, a radiation oncologist and prostate cancer researcher at the University of California, San Diego, who did not participate in the study. Some patients can still slip through the cracks and develop 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 discovered during follow-up. However, four of them originally had a PSA below 3, and the last had a false-negative biopsy.
Overall, Seibert said, the strategy worked “to prevent clinically insignificant cancer. It seemed to find almost all cancers if you used the systematic biopsy approach. This is a great result for patients.”
The result may tip the balance toward a broader screening recommendation, if MRI is possible. “I think it swings the pendulum in a favorable direction,” said Oliver Sartor, an oncologist and cancer researcher at the Mayo Clinic, who did not participate in the study. “This method of screening reduces the risk of overdiagnosis. It reduces the risk of infections from biopsy.”
But it may not be feasible to implement a large-scale MRI program. Urologists and genitourinary oncologists have already started pushing for MRI before biopsy for prostate screening, Seibert said. This study strengthens the evidence that this strategy is a good strategy, but may not be feasible on a large scale. Currently, only a third of patients in urban areas receive an MRI before a prostate biopsy, and even fewer in rural areas.
“We know that MRI should be done before the biopsy. It’s already in the guidelines. That doesn’t happen because there are not enough MRI scanners,” said Seibert. Not only that, but getting a good scan of the prostate is not easy. “It’s not like pressing a button. These are like DSLR cameras on steroids. You need experts to do it, experts to interpret it, and that doesn’t exist everywhere yet.”
Scientists like Seibert are working to improve this by essentially creating presets for prostate imaging on MRI machines and AI for its interpretation. That could increase the efficiency of MRI scans 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 harm reduction actually changes whether people are screened may depend on their personal preferences, Seibert said. “This study will not ensure that everyone is in favor of screening. Some people will say, we’ll only do a big screening program if we save a lot of lives,” Seibert said. “If we don’t know that it will make you live longer, then it’s worth it to you, and opinions differ on that.”
For Seibert, he will personally be screened for prostate cancer because even if it doesn’t help him live a longer life, it will help him prevent 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 very difficult. So yes, I would prefer to be screened. But others don’t,” he said.
That’s why these conversations with doctors are important, he said. The only problem with that is finding a doctor who has time for it.