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MRI combined with prostate-specific membrane antigen (PSMA) PET improved the detection of clinically significant prostate cancer compared with MRI alone, and can potentially allow for a reduction in the number of biopsies needed for diagnosis, according to results from the PRIMARY trial.

The combined approach demonstrated an increase in negative predictive value for detecting prostate cancer (91% vs 72% for MRI alone; P<0.001) and improved sensitivity (97% vs 83%, respectively; P<0.001), reported Louise Emmett, MD, of St. Vincent's Hospital in Sydney, and colleagues.

However, specificity was reduced with the combination (40% vs 53% with MRI alone; P=0.011), and positive predictive value was similar (67% vs 65%, respectively; P=0.4).

"The findings from this trial suggest that the combination of PSMA+MRI may further shift the paradigm in prostate cancer diagnosis towards imaging and warrants further investigation in randomized trials," the authors wrote in .

Emmett and colleagues noted that the PRECISION trial demonstrated that MRI was able to increase the detection rate of clinically significant prostate cancers, while reducing the detection of clinically insignificant disease, compared with transrectal ultrasound-guided biopsy. However, they also pointed out that the positive predictive value of MRI remains low, resulting in unnecessary biopsies, and that MRI can miss clinically significant cancers in up to 13% of cases.

"PSMA PET is transforming the staging of both newly diagnosed and biochemically recurrent prostate cancer," they wrote. "The next question is whether it can improve upon the diagnosis of clinically significant prostate cancer."

Asked for his perspective, Thomas Hope, MD, of the University of California San Francisco, noted that the PRIMARY study is the first to truly evaluate the role of PSMA PET in the screening population.

"One of the central conundrums in prostate cancer is determining who has clinically significant prostate cancer, and therefore needs treatment," said Hope, who was not involved in the research. "It remains unclear, even in light of this study, what role PSMA PET will have in patients on active surveillance and undergoing biopsy, but the results provide insight into the potential benefit of adding PSMA PET to MRI in order to better select patients for biopsy."

PRIMARY was a prospective, multicenter, phase II trial conducted across three institutions in Australia. Men were eligible if they were suspected of having prostate cancer based on abnormal prostate-specific antigen (PSA) levels (<20 ng/mL) or an abnormal digital rectal examination, and were excluded if they had a prior diagnosis of prostate cancer, a prostate biopsy, or prostate MRI. All participants underwent prostate MRI within 6 months, and underwent biopsy based on clinical risk and MRI results.

PSMA PET plus MRI was defined as negative for PSMA-negative Prostate Imaging Reporting and Data System (PI-RADS) 2/3 and positive for either MRI PI-RADS 4/5 or PSMA-positive PI-RADS 2/3. Clinically significant prostate cancer was defined as any International Society of Urological Pathology (ISUP) grade group ≥2.

A total of 291 men underwent MRI, PSMA PET, and biopsy. Of these patients, 56% had clinically significant prostate cancer, 67% had a positive MRI (PI-RADS 3-5), 73% had a positive PSMA PET, and 81% had a positive combined PSMA PET plus MRI.

Of these men, 27 of 95 with PI-RADS 2 and 25 of 53 with PI-RADS 3 had clinically significant prostate cancer, and PSMA PET was positive in 90% of these patients. Of the PI-RADS 2 and 3 patients, 38% were negative on PSMA plus MRI; of these cases, five clinically significant cancers were missed. The missed cancers included four ISUP grade group 2 cancers, and one ISUP grade group 3 cancer.

Thus, of the 291 men in the study, 19% were negative on PSMA plus MRI and "could potentially have avoided biopsy," risking delayed detection in 3.1% of patients with clinically significant prostate cancer, or 1.7% of men in the entire study cohort, Emmett and team observed.

The authors acknowledged that specificity was relatively low for both PSMA PET and the combination of PSMA PET and MRI in the study. "This is not unexpected considering this being the first trial evaluating PSMA in a low prevalence population, with previous estimates of intraprostatic specificity likely being overestimated," they wrote, adding that the specificity of the combination "may be underestimated as the modalities were reported separately, with the algorithm compounding false positives."

Nevertheless, "given the high sensitivity of PSMA+MRI in detection of clinically significant prostate cancer and the predominately low-grade characteristics of the cancers missed, it appears acceptable to avoid biopsy in men with negative PSMA+MRI findings, in the absence of subsequent concerning PSA kinetics," they concluded.

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