For men with elevated prostate-specific antigen (PSA) levels who are at average risk for prostate cancer, evaluating suspicious lesions with MRI-directed targeted biopsy instead of systematic biopsy cuts the probability of detecting clinically insignificant tumors in half, a new analysis found.
However, there’s a tradeoff: MRI-directed targeted biopsy can also delay detection of a small number of intermediate-risk tumors.
The study is “important and it reinforces a shift that has occurred over the last few years amongst a subset of clinicians who are very focused on [moving] away from routine systematic biopsies,” Laurence Klotz, MD, who was not involved in the research, told Medscape Medical News.
“For the average patient whose risk is moderate, which is the majority of patients going through this process, it makes complete sense to just do the [MRI-directed] targeted biopsy,” said Klotz, chair of prostate cancer research, Sunnybrook Health Sciences Centre, Toronto, Canada.
However, Klotz noted, higher-risk patients will still need systematic biopsy. “This is basically a risk-stratified approach, meaning it’s not for everybody,” he said.
The findings from the trial were published online December 8 in The New England Journal of Medicine.
Prostate cancer screening remains a controversial area. Screening generates a high rate of overdiagnosis — detecting small, low-grade tumors that are often indolent but may be treated unnecessarily.
The current GÖTEBORG-2 trial tested whether a screening algorithm that includes PSA testing followed by targeted biopsy alone in men with positive MRI results led to less overdiagnosis than screening according to current recommendations, in which all men with elevated PSA are referred for systematic biopsy irrespective of the outcome of MRI.
Participants included 17,980 men with a PSA level ≥ 3 ng/mL who underwent MRI of the prostate.
The 5994 men in the reference group underwent systematic biopsy with 12 tissue samples taken from various parts of the prostate. If the MRI showed anything suspicious, another three to four targeted tissue samples were taken from the area of interest.
For the 11,986 men in the experimental group, only those with suspicious findings revealed by MRI were selected for tissue sampling, and four targeted tissue samples were taken from the suspicious area.
Clinically insignificant prostate cancer — defined as a Gleason 3+3 score — was detected in 66 (0.6%) men in the experimental group vs 72 (1.2%) men in the reference group (relative risk [RR], 0.46; P < .0001).
Clinically significant cancer — defined as Gleason scores of at least 3+4 — was detected on an almost equal scale in the two groups: 110 men (0.9%) in the experimental group and 68 (1.1%) in the reference group (RR, 0.81; 95% CI, 0.60-1.10).
“According to our results, systematic biopsies are doing more harm than benefit and changing to a strategy with MRI and targeted biopsies only in men with lesions visible at MRI would decrease the risk of overdiagnosis by 54%,” lead author Jonas Hugosson, MD, PhD, professor of urology at the University of Gothenburg and senior physician at Sahlgrenska University Hospital, Sweden, told Medscape Medical News.
This is “substantial and changes the balance of harms vs benefit with prostate cancer screening” and, in the investigators’ view, should lead to a change in prostate cancer screening recommendations, Hugosson added.
Still, 10 men had clinically significant prostate cancer detected only by systematic biopsy. These tumors were all intermediate-risk, mainly involving low-volume disease that could be managed with active surveillance.
Delayed diagnosis in these men is unlikely to be harmful, the study team said; however, future follow-up remains important.
Klotz agreed. “Even though there may be a handful of cases of invisible cancers that are missed if you don’t do a systematic biopsy, it may not really matter that much,” he said. “You can follow the patient, reimage, and if the cancer pops up, then do a biopsy.”
In an editorial, Roman Gulati, MD, commented that “the history of PSA screening has shown us that difficult trade-offs between too much and too little diagnosis are inevitable.”
Given the current analysis, “whether the trade-offs of omitting systematic biopsy are acceptable needs to be weighed by the clinical community in the context of contemporary standards of care,” said Gulati, of Fred Hutchinson Cancer Center, Seattle, Washington.
Support for the study was provided by the Karin and Christer Johansson’s Foundation, the Swedish Cancer Society, grants from the Swedish state, the ALF-agreement, the Swedish Research Council, Biocare, Regional Cancer Center Western Region Sweden, the Swedish Prostate Cancer Association, AFA Insurance, and the Nordic Cancer Union. Disclosures for authors are available with the full text of the article at NEJM.org. Klotz has no relevant disclosures.
N Engl J Med. Published online December 8, 2022. Abstract
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