Søren Klingenberg1,2,3, Mads R Jochumsen4,2, Benedicte P Ulhøi5, Jacob Fredsøe2,3, Karina D Sørensen2,3, Michael Borre2,6, Kirsten Bouchelouche4,2. 1. Department of Nuclear Medicine and PET Centre, Aarhus University Hospital, Aarhus, Denmark soekli@rm.dk. 2. Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. 3. Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark. 4. Department of Nuclear Medicine and PET Centre, Aarhus University Hospital, Aarhus, Denmark. 5. Department of Pathology, Aarhus University Hospital, Aarhus, Denmark; and. 6. Department of Urology, Aarhus University Hospital, Aarhus, Denmark.
Abstract
With the largest high-risk prostate cancer (PCa) cohort to date undergoing 68Ga-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 68Ga-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-naïve, D'Amico high-risk PCa patients primary-staged by 68Ga-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 (ρ = 0.21; P < 0.001) and a modest correlation between SUVmax and postprostatectomy ISUP grade (ρ = 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.
With the largest high-risk prostate cancer (PCa) cohort to date undergoing 68Ga-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 68Ga-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-naïve, D'Amico high-risk PCa patients primary-staged by 68Ga-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 (ρ = 0.21; P < 0.001) and a modest correlation between SUVmax and postprostatectomy ISUP grade (ρ = 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.
Authors: Venkata Avinash Chikatamarla; Satomi Okano; Peter Jenvey; Alexander Ansaldo; Matthew J Roberts; Stuart C Ramsay; Paul A Thomas; David A Pattison Journal: EJNMMI Res Date: 2021-12-20 Impact factor: 3.138
Authors: Sui Wai Ling; Anouk C de Jong; Ivo G Schoots; Kazem Nasserinejad; Martijn B Busstra; Astrid A M van der Veldt; Tessa Brabander Journal: Eur Urol Open Sci Date: 2021-09-28
Authors: Melline G M Schilham; Patrik Zamecnik; Bastiaan M Privé; Bas Israël; Mark Rijpkema; Tom Scheenen; Jelle O Barentsz; James Nagarajah; Martin Gotthardt Journal: J Nucl Med Date: 2021-01-30 Impact factor: 10.057