PSMA-PET vs Conventional Imaging: A Post Hoc Analysis of EMBARK Patients With nmHSPC

In the phase 3 EMBARK trial, the use of enzalutamide was shown to boost metastasis-free survival in patients with high-risk nonmetastatic hormone-sensitive prostate cancer (nmHSPC). Patient eligibility in the trial was determined by conventional imaging, yet this process can underdetect metastatic disease compared with prostate-specific membrane antigen–positron emission tomography (PSMA-PET). 

A recent cross-sectional post hoc analysis has examined the staging information obtained by PSMA-PET/computed tomography in a patient cohort eligible for the EMBARK trial to see what findings are present in patients with high-risk biochemically recurrent nmHSPC as determined by conventional imaging. 

The retrospective study involved 182 patients across four prospective studies conducted between September 2016 and September 2021. Each patient had recurrent prostate cancer and had undergone radical prostatectomy (RP), definitive radiotherapy (dRT), or salvage radiotherapy (SRT). 

Patients had increasing prostate-specific antigen (PSA) levels greater than 1.0 ng/mL after RP and SRT or 2.0 ng/mL above the nadir value after dRt, as well as a PSA doubling time of 9 months or less and a serum testosterone level of 150 ng/dL or greater. 

The median pre-scan PSA levels were 2.4 ng/mL (interquartile range [IQR], 1.4–4.8 ng/mL) after RP (n=91), 6.9 ng/mL (IQR, 3.5–18.5 ng/mL) after dRT (n=39), 2.6 ng/mL (IQR, 1.6–5.2 ng/mL) after RP and SRT (n=52), and 2.8 ng/mL (IQR, 1.7–6.6 ng/mL) overall (n=182). 

PSMA-PET results were positive in 80% (73 of 91) of patients after RP, 92% of patients (36 of 39) after dRT, 85% of patients (44 of 52) after RP and SRT, and 84% of patients (153 of 182) overall. Any distant metastatic disease was detected by PSMA-PET in 34% of patients (31 of 91) after RP, 56% of patients (22 of 39) after dRT, 60% of patients (31 of 52) after RP and SRT, and 46% of patients (84 of 182) overall.  

Polymetastatic disease, defined as having ≥5 lesions, was found in 19% of patients (17 of 91) after RP, 36% of patients (14 of 39) after dRT, 23% of patients (12 of 52) after RP and SRT, and 24% of patients (43 of 182) overall. 

Overall, PSMA-PET results were positive in 84% of patients and were able to detect M1 disease stage and polymetastatic disease in 46% and 24% of patients, respectively. These data suggest that conventional imaging may understage disease in patients with high-risk nmHSPC. Further studies are needed to determine the evolving role of PSMA-PET in patient selection and trial interventions.