Here’s welcome news for men of a certain age: new results support a less invasive approach to investigations for suspicion of prostate cancer.
An approach using MRI of the prostate followed by targeted biopsy (TB) in men with images suggesting a high risk beat the conventional approach of using transrectal ultrasound (TRUS)-guided 12-core systematic biopsy.
The results come from the randomized phase 3 PRECISION trial, and were published online in JAMA Oncology.
“What the trial showed is that by taking an imaging-first strategy, you could reduce the number of patients needing a biopsy by about 40% and actually find more significant cancer (35% vs 30%) and reduce the diagnosis of grade group 1 cancers that we don’t want to find by more than half,” lead author Laurence Klotz, CM, MD, from the Sunnybrook Health Sciences Centre in Toronto, Canada, commented in an interview with Medscape Medical News.
These results from the PRECISE trial support and slightly improve upon findings from the European-based PRECISION trial.
That European trial had already provided “compelling evidence in favor of MRI and targeted biopsy,” notes Olivier Rouvière, MD, PhD, from the University of Lyon, Lyon, France, writing an accompanying editorial. But he argues that it was worth duplicating the trial, as “it must not be forgotten that in science, testing the robustness of an effect and the factors influencing it is are as important as demonstrating this effect in the first place.”
The results from both trials suggest that, instead of replacing TRUS biopsy entirely, MRI results could be used to guide patients to the appropriate diagnostic pathway, Rouvière comments.
“Using only MRI findings to decide which patients should undergo biopsy is probably insufficient,” he adds. “Most likely, MRI findings will be used in conjunction with other biomarkers such as PSA density to select, among the patients with positive MRI findings, those who need targeted biopsy (and those who may safely avoid it), and among the patients with negative MRI findings, those who may still deserve systematic biopsy,” he writes.
Details of PRECISE Findings
The Canadian PRECISE study was developed as a noninferiority trial in coordination with the European PRECISION study, but the Canadian version had several additional features: It added risk-based eligibility, systematic follow-up of all patients for 2 years, a repeat MRI in all untreated patients, investigation of fluid- and tissue-based biomarkers in the cohort, and an economic analysis.
PRECISE was conducted in five Canadian academic health sciences centers from January 2017 through November 2019. A total of 453 biopsy-naive men with a clinical suspicion of prostate cancer who were referred for prostate biopsy were enrolled. Of this group, 421 were evaluable per protocol.
The investigators defined clinical suspicion as a ≥5% chance of grade group 2 or greater prostate cancer. Patients were also required to have serum prostate-specific antigen (PSA) levels of 20 ng/mL or less and no contraindication to MRI.
The patients randomly assigned to MRI underwent an MRI-targeted biopsy only if a lesion with a Prostate Imaging Reporting and Data System (PI-RADS) score of 3 or greater was identified, whereas all men in the other arm of the trial underwent a systematic TRUS-guided 12-core biopsy.
The MRI approach identified more clinically significant cancers. Grade 2 or higher tumors were found in 79 (35%) of 227 men allocated to MRI-TB, vs 67 (30%) of 225 men who underwent TRUS biopsy.
MRI also reduced the need for a biopsy, allowing many men to avoid the associated pain, discomfort, and infection risks. Of 221 men who were randomly assigned to the MRI group, 83 (37%) had a negative MRI result and avoided biopsy. In contrast, all men in the TRUS group had a biopsy.
In addition, MRI was associated with a marked reduction in the diagnosis of clinically insignificant International Society of Urological Pathology (ISUP) grade group 1 cancers (10% with MRI-TB vs 22% with TRUS). Detection of such early cancers, under conventional protocols, often leads to unnecessary therapies or invasive procedures with significant side effects.
These results led the researchers to conclude that the strategy of MRI followed by MRI-guided biopsy only in men at risk of prostate cancer “offers substantial advantages over an initial systematic biopsy.”
The MRI strategy “results in similar detection rates of clinically significant prostate cancer…while avoiding biopsy in more than one third of men and reducing the diagnosis of clinically insignificant cancer,” the investigators point out.
The investigators acknowledged that the performance of the MRI-target biopsy varied between centers, with differences in both positive MRI rates and target biopsy yields.
“This difference occurred despite the fact that all MRIs were reviewed, and biopsies performed, by experienced radiologists or urologists. This underscores the need for quality control measures to enable the broad application of MRI,” they write.
Klotz noted that an important addition to PRECISE is the planned follow-up of patients who did not receive treatment on study.
“We know MRI is not perfect, so what happens to the guys who avoid the biopsy? How much at risk are they of having something missed? So the only way to know that really is with long-term follow-up on the patients,” he told Medscape.
In addition to repeat MRI at 2 years, the investigators plan to follow these patients for up to 8 years.
“But certainly, compared to the traditional strategy of systematic biopsy, this looks a lot better,” Klotz commented.
In his editorial, Rouvière commented that the intersite variability seen in the study “sounds like a warning to the MRI pathway.”
“Considering that all participating centers were experienced high-volume tertiary centers, the intersite variability is probably much higher among less experienced centers,” he wrote. “Thus, whatever the diagnostic pathway, continuing education and quality insurance programs will become major issues in the future, not only for prostate MRI interpretation, but also for targeted biopsy, which does have a learning curve even with magnetic resonance and ultrasound fusion systems, and even for systematic biopsy.”
PRECISE was funded by the Ontario Institute of Cancer Research and Prostate Cancer Canada. Klotz and Rouvi ère have disclosed no relevant financial relationships.