High Accuracy of PSMA PET in Initial Staging of High-Risk Prostate Cancer

Take-Away Points

• ■ Major Focus: This prospective randomized study aimed to compare the diagnostic utility of conventional imaging for initial staging of high-risk prostate cancer (CT and bone scintigraphy) with gallium 68 (⁶⁸Ga) prostate-specific membrane antigen (PSMA)-11 PET/CT.

• ■ Key Result: Compared to conventional imaging, ⁶⁸Ga-PSMA-11 PET/CT resulted in fewer equivocal imaging findings, less radiation exposure (8.4 mSv vs 19.2 mSv), and greater sensitivity (85% vs 38%) and specificity (98% vs 91%).

• ■ Impact: The results of prospective randomized studies, such as ProPSMA, may lead to the incorporation of PSMA PET into standard clinical management guidelines for the initial staging of prostate cancer due to its superior diagnostic accuracy over conventional imaging.

Prostate-specific membrane antigen (PSMA)–targeted PET is being increasingly used for localizing high-risk prostate cancer. Extensive evidence of its diagnostic use has led to the incorporation of PSMA PET into management guidelines for biochemically recurrent prostate cancer, but until recently there was insufficient evidence to effect a change in guidelines in other settings such as initial staging. The proPSMA study is a randomized controlled trial comparing the accuracy and diagnostic utility of conventional imaging (namely, CT and bone scintigraphy) with that of gallium 68 (⁶⁸Ga)-PSMA-11 PET/CT for the initial staging of prostate cancer. The patient cohort included 300 men (mean age, 69.0 years) with histopathologically confirmed prostate cancer who were under consideration for prostatectomy or radiotherapy. Each patient was randomized to initially undergo either conventional imaging (control group) or PSMA PET/CT within 21 days of randomization. Then, all men who did not have greater than three unequivocal distant metastases underwent second-line crossover imaging 6 months later.

PSMA PET/CT had an accuracy (calculated as the mean of the sensitivity and specificity) of 92% compared to 65% for conventional imaging. This 27% difference reflects the finding that, compared to conventional imaging, PSMA PET/CT had both a higher sensitivity (85% vs 38%) and specificity (98% vs 91%) for metastases than conventional imaging. Additionally, results demonstrated that PSMA PET/CT resulted in fewer equivocal imaging findings than conventional imaging for metastatic disease and pelvic nodes. PSMA PET/CT also resulted in less radiation exposure than conventional imaging (a mean of 8.4 mSv vs 19.2 mSv). Neither PSMA PET/CT nor conventional imaging was associated with any adverse events. Finally, patients who underwent first-line PSMA PET/CT imaging also resulted in a higher percentage of high-effect or medium-effect management changes (28%) compared to conventional imaging (15%). High-effect changes were defined as changes in management intent (eg, curative to palliative), while medium-effect changes were changes in modality delivery.

Together, these results demonstrate that PSMA PET/CT has superior diagnostic accuracy for prostate cancer compared to conventional imaging. As a whole, the findings of this study demonstrate that PSMA PET/CT is a viable replacement for conventional imaging for prostate cancer and suggest that PSMA PET has value for incorporation into standard clinical management guidelines for the initial staging of prostate cancer.

Highlighted Article

• Hofman MS, Lawrentschuk N, Francis RJ, et al. Prostate-specific membrane antigen PET-CT in patients with high-risk prostate cancer before curative-intent surgery or radiotherapy (proPSMA): a prospective, randomised, multicentre study. Lancet 2020;395(10231):1208–1216. doi: https://doi.org/10.1016/S0140-6736(20)30314-7