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Fluorine-18 prostate-specific membrane antigen (PSMA)-1007 PET/CT was superior to multiparametric MRI for primary locoregional staging of prostate cancer, according to results from a phase II paired-cohort study.

Among 134 men undergoing radical prostatectomy, PSMA PET accurately identified pathological tumor stage in 45% of patients compared with 28% of patients with MRI (P=0.003), reported Adam Kinnaird, MD, PhD, of the University of Alberta in Edmonton, Canada, and colleagues.

PSMA PET was also superior to MRI for the accurate identification of the dominant nodule (94% vs 83%, P=0.01), laterality (64% vs 44%, P=0.001), and extracapsular extension (75% vs 63%, P=0.01), but not for seminal vesicle invasion (91% vs 85%, P=0.07), they wrote in .

Of note, PSMA PET and MRI underestimated the tumor stage in 41% and 64% of patients, respectively.

"These findings support PSMA PET in the preoperative workflow of intermediate-risk and high-risk tumors," Kinnaird and colleagues wrote.

In explaining the rationale behind the so-called the authors noted that while PSMA PET has been shown to be superior to conventional imaging (CT and bone scan) for nodal and metastatic staging, current guidelines recommend the use of multiparametric MRI for locoregional staging of prostate cancer before radical prostatectomy.

"For several factors, such as urinary accumulation of PSMA radioligands excreted by the kidneys, low-grade background prostatic activity, and lower resolution of PET compared to MRI, the accuracy of prostate cancer tumor staging has been limited," they added.

Fluorine-18 PSMA-1007 "is unique from other radioligands used in prostate cancer in that it is hepatically excreted," Kinnaird told MedPage Today. "This means significantly less background noise activity in the urinary bladder, which therefore improves that ability to discern true activity in the prostate gland, as the prostate is immediately adjacent to the bladder."

In this prospective study, the participants underwent both fluorine-18 PSMA-1007 PET/CT and multiparametric MRI within 2 weeks of one another and before radical prostatectomy. The 134 patients in the final analysis had a mean age of 62 years; 95% had Gleason grade group 2 or 3 disease, and 49% had extraprostatic extension (T3a or T3b).

While PSMA PET outperformed MRI in accurately identifying tumor stage, Kinnaird and colleagues acknowledged that accurate staging was observed in less than half of PSMA PET scans and slightly more than one-quarter of MRI scans.

"One explanation for this relatively low degree of overall accuracy is that blinding the radiologists and nuclear medicine physicians to biopsy results and other imaging data impaired the ability to make a diagnosis that would be possible outside of the trial in a standard clinical setting," they wrote.

Kinnaird and colleagues suggested that the study's findings have important implications for treatment decisions, pointing out that PSMA PET's superiority to MRI in detecting high-risk features such as extracapsular extension is "critical," since its presence alters surgical approach.

"For instance, preoperative knowledge of extracapsular extension may alter the decision to perform nerve-sparing techniques on the side with anticipated tumor extension," they wrote. "Similarly, it may alter the extent of margin that is sought during pericapsular dissection."

In addition, the authors noted that the superiority of PSMA PET in determining unilateral versus bilateral disease is important for novel treatments -- such as focal therapies -- for prostate cancer patients.

"The premise of focal therapy is to ablate only the side of the prostate where the cancer is present, thereby sparing the contralateral side from harmful treatment effects," they explained. "Therefore, the presence of bilateral disease is a contraindication to focal therapy."

As for safety, none of the patients experienced an adverse event related to either imaging modality.

The authors said that future research should focus on the accuracy of combining PET/CT and MRI, as well as the cost-effectiveness of PET/CT for the primary staging of prostate cancer.

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