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

With the largest high-risk prostate cancer (PCa) cohort to date undergoing Ga-68-prostate-specific membrane antigen (PSMA) PET/ CT primary staging, we aimed to, first, characterize the metastatic spread of PCa in relation to tumor 68Ga-PSMA uptake and the D'Amico classification and, second, compare Ga-68-PSMA PET/CT findings with radical prostatectomy and pelvic lymph node dissection (PLND) histopathology findings. Methods: The study included 691 consecutive newly diagnosed, biopsy-proven, treatment-naive, D'Amico high-risk PCa patients primary-staged by Ga-68-PSMA PET/CT. PSMA SUVmax and metastatic findings were compared with prostate-specific antigen level, International Society of Urological Pathology (ISUP) grade, and clinical stage as traditional risk stratification parameters. Moreover, 68Ga-PSMA PET/CT findings were compared with histology findings in radical prostatectomy 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 prostate-specific antigen level, ISUP grade, and clinical stage. 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 grades 2 and 3 were 10.8% (11/102) and 37.1% (33/89), respectively. Risk of advanced disease for cT2a, cT2b, and cT2c tumors was almost equal (24.2%, 27.9%, and 22.4%, respectively). We observed a weak correlation between SUVmax and biopsy ISUP grade (rho = 0.21; P < 0.001) and a modest correlation between SUVmax and postprostatectomy ISUP grade (rho = 0.38; P < 0.001). Sensitivity, specificity, positive and negative predictive value, and accuracy for LNM detection on 68Ga-PSMA PET/CT in the PLND cohort were 30.6%, 96.5%, 68.8%, 84.5%, and 83.1%, respectively. Undetected LNMs either were micrometastases located in the lymph node border or were 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 grades 2 and 3, as 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.

Automated summary

In this high-risk PCa cohort, advanced disease was identified in about one third of patients at diagnosis. ISUP grade was found to be the superior predictor for advanced disease at diagnosis. A significant difference in frequency of advanced disease was observed between ISUP grades 2 and 3, supporting the Gleason score 7 subdivision. Interestingly, no significant differences in risk of advanced disease were found when comparing the different cT2 stages. The undetected LNMs were either PSMA-negative or micrometastases.