⁶⁸Ga-PSMA PET/CT for Primary Lymph Node and Distant Metastasis NM Staging of High-Risk Prostate Cancer

Abstract

With the largest high-risk prostate cancer (PCa) cohort to date undergoing 68 Ga-prostate-specific membrane antigen (PSMA) PET/CT primary staging, we aimed to 1) characterize the metastatic spread of PCa in relation to tumor 68 Ga-PSMA-uptake and the D'Amico classification, and 2) compare 68 Ga-PSMA PET/CT findings with radical prostatectomy (RP) with pelvic lymph node dissection (PLND) histopathology. Methods A total of 691 consecutive newly diagnosed, biopsy-proven, treatment-naïve, D'Amico high-risk PCa patients primary staged by 68 Ga-PSMA PET/CT were included. PSMA maximum standardized uptake value (SUV max) and metastatic findings were compared to PSA level, International Society of Urologic Pathology (ISUP) grade, and clinical stage as traditional risk stratification parameters. Moreover, 68 Ga-PSMA PET/CT findings were compared with histology in RP patients undergoing PLND. Undetected lymph node metastases (LNMs) underwent immunohistochemical PSMA staining. Results Advanced disease (N1/M1) was observed in 35.3% of patients (244/691) and was associated with increasing PSA levels, ISUP grades, and clinical stages. LNMs (N1/M1a) were detected in 31.4% (217/691) and bone metastases (M1b) in 16.8% (116/691). Advanced disease frequencies in patients with ISUP grade 2 and 3 were 10.8% (11/102) and 37.1% (33/89), respectively. Risk of advanced disease for cT2a/cT2b/cT2c tumors were almost equal (24.2%, 27.9%, and 22.4%, respectively). We observed a weak correlation between SUV max and biopsy ISUP grade (ρ = 0.21; P < 0.001) and a modest correlation between SUV max and post-prostatectomy ISUP grade (ρ = 0.38; P < 0.001). Sensitivity, specificity, positive and negative predictive value, and accuracy for LNMs detection on 68 Ga-PSMA PET/CT in the PLND cohort were 30.6%, 96.5%, 68.8%, 84.5%, and 83.1%, respectively. Undetected LNMs were either micrometastases located in the lymph node border or without PSMA expression. Conclusion In this high-risk PCa cohort, we identified advanced disease in about one-third at diagnosis. ISUP grade was the superior predictor for advanced disease at diagnosis. We found a significant difference in frequency of advanced disease between ISUP grade 2 and 3, which supports the Gleason Score 7 subdivision. Interestingly, we observed no significant differences in risk of advanced disease when comparing the different cT2 stages. The undetected LNMs were either PSMA-negative or micrometastases.

Tumour blood flow for prediction of human prostate cancer aggressiveness: a study with Rubidium-82 PET, MRI and Na+/K+-ATPase-density

“…The primary tumour prostate-specific membrane antigen (PSMA) expression was also reported to correlate with the dominant intraprostatic lesion ISUP GG in a number of studies, however with substantial overlap between groups [45][46][47][48][49]. A direct comparison between 82 Rb and PSMA PET is needed to determine which physiologic parameter is closest related to the tumour aggressiveness and how they relate to each other.…”

The Role of 68Ga-PSMA Positron Emission Tomography/Computerized Tomography for Preoperative Lymph Node Staging in Intermediate/High Risk Patients With Prostate Cancer: A Diagnostic Meta-Analysis

“…Following the removal of duplicates, 307 records were screened by titles and abstracts, and 40 studies were deemed relevant for full-text assessment. Ultimately, 11 studies ( 21 – 31 ) fulfilled the inclusion criteria and were included in the meta-analysis ( Figure 1 ).…”

“…Overall, 11 studies comprising 904 patients who underwent 68 Ga-PSMA PET/CT before RP with PLND were included. All studies recruited patients with confirmed PCa of intermediate/high risk, and three studies ( 25 , 26 , 31 ) additionally applied nomogram tools ( 9 , 32 ) to identify patients of high risk of lymph node metastases. All studies set 68 Ga-PSMA PET/CT imaging as an index test and defined a positive test with increased 68 Ga-PSMA uptake above background.…”

“…For per-patient analysis, 11 studies ( 21 – 31 ) with 904 patients were assessed ( Table 2 ). Of the patients, 16.3% (147/904) and 23.7% (214/904) were diagnosed as positive by 68 Ga-PSMA PET/CT test and histology of PLND, respectively.…”

“…And in Herlemann's study, the authors included 14 patients receiving secondary PLND after primary treatment failure, and their final analysis was based on the mixed group ( 27 ). And Klingenberg et al only recruited those patients (177/691) who received PLND for final analysis ( 31 ). No publication bias was identified by Deek's funnel plot asymmetry test ( p = 0.54; Figure 5 ).…”