PSMA PET has emerged as a crucial imaging modality for staging intermediate- and high-risk prostate cancer (PCa), yet its implementation varies globally. This study aims to assess the diagnostic consequence of omitting pre-operative PSMA PET/CT staging by comparing the radiological features and extent of disease in two cohorts of patients who subsequently developed PSA persistence (> 0.1 ng/mL) following radical prostatectomy (RP). Single-center, retrospective study (October 2019 to May 2025). The patient cohort included individuals who underwent radical prostatectomy and subsequently experienced PSA persistence, defined as a PSA value ≥ 0.1 ng/ml at the first measurement after 4–8 weeks after RP. Patients were divided into two groups: a Staging Cohort who underwent a pre-operative 68GaGa-PSMA-11 PET/CT and a Non-Staging Cohort who did not. All patients received a 68GaGa-PSMA-11PET/CT scan for PSA persistence. Clinical data, including PSA, TNM stage, and ISUP grade, as well as follow-up data were collected. The primary endpoints were the comparison of the overall PSMA PET positivity rate and the extent of both locoregional (N) and distant metastatic (M1) disease between the two cohorts. Secondary analysis included a comparison of baseline pathological characteristics and the evaluation of the potential for a theoretical change in initial patient management. 147 patients with PSA persistence after RP were included and divided into the Staging Cohort (n = 72, 49%) and a Non-Staging Cohort (n = 75, 51%). Baseline data showed the Staging Cohort had a higher proportion of high-grade (ISUP 4/5:72% vs. 45%; p < 0.05 ) and locally advanced (T3/T4: 78% vs. 61%; p < 0.05) disease. The Non-Staging Cohort had a higher rate of positive 68GaGa-PSMA-11 PET/CT scans for persistence (59%) compared to the Staging-Cohort (42%). The Non-Staging Cohort showed a markedly greater extent of disease, with a high proportion of patients (n = 34/75,45%) demonstrating findings consistent with M1 disease (bone or distant lymph nodes). The anatomical distribution of positive lymph node sites also differed: the Staging Cohort showed higher obturator nodes involvement (48% of positive sites), while the Non-Staging Cohort had a significantly higher proportion in common iliac (34%) and external/internal iliac sites. A retrospective evaluation of the Non-Staging Cohort suggested that a pre-operative 68GaGa-PSMA-11 PET/CT would have triggered a theoretical change of management in all 44 positive cases, primarily by suggesting systemic therapy instead of RP for M1 patients. The omission of pre-operative 68GaGa-PSMA-11 PET/CT is associated with a significantly higher incidence of PSMA-positive and extensive disease (locoregional and metastatic) at the time of PSA persistence. This suggests a critical diagnostic gap and potential under-staging in the Non-Staging Cohort, underscoring the vital role of early PSMA PET/CT utilization to optimize initial risk stratification and treatment planning.
Giorgio et al. (2026) studied this question.