The German Cancer Consortium (DKTK) multi-center prospective phase 1/2 68Ga-PSMA-11 PET-imaging trial in newly-diagnosed high-risk prostate cancer: Safety and diagnostic accuracy compared to histopathology and their impact on patient management

Purpose Clinically accurate detection of prostate cancer (PCa) metastases is crucial for management of high-risk PCa patients scheduled for radical prostatectomy. We determine the safety and diagnostic accuracy of pre-operative 68 Ga-PSMA-11 PET/CT imaging in newly diagnosed high-risk PCa and assess its impact on patient management. Methods Investigator-initiated prospective multi-center multinational single-arm open-label phase 1/2 imaging trial (EuRadCT 2016–001815-19). Patients with high-risk PCa scheduled for prostatectomy were enrolled at 9 institutions in Germany, Austria, and Switzerland to undergo 68 Ga-PSMA-11 PET/CT for primary staging. The primary objectives were the evaluation of 68 Ga-PSMA-11 PET/CT imaging to detect the primary tumor and lymph node disease and safety assessment. Secondary objectives included detection of distant metastases, correlation of 68 Ga-PSMA-11 uptake with Gleason Score, and determining the impact on clinical management. Impact of pre-operative 68 Ga-PSMA-11 PET/CT imaging on target volume definition for radiation therapy was assessed. Results 173 patients underwent 68 Ga-PSMA-11 PET/CT for primary staging. Histopathologic correlation was available in 139 patients (imaging dataset), with lymph node metastases in 55 patients (39.6%). 20 treatment-emergent AEs unrelated to the test item were reported in 14 of 173 (8.1%) patients and no SAE occurred. On a per-patient basis, sensitivity of 68 Ga-PSMA-11 PET for local disease was 0.971 (95% CI, 0.928–0.992). Sensitivity, specificity, PPV, NPV and accuracy to detect local lymph node disease on a per-patient basis were 0.400 (95% CI 0.271–0.529), 0.988 (95%CI 0.965–1.000), 0.957 (95% CI 0.873–1.000), 0.716 (95% CI 0.633–0.798) and 0.755 (95% CI 0.684–0.827), respectively. Considering the intrinsic PET resolution of 3–5 mm, the exclusion of lesions smaller than 3 or 5 mm on histopathology from the analysis led to increased sensitivity of 56.4% and 69.0%, respectively. Median SUVpeak of local disease was 6.4 (range 1.7–13.6), 8.4 (range 2.3–39.4), 10.7 (range 5.6–23.0), and 13.4 (range 3.8–56.9) for Gleason Score 7a, 7b, 8 and 9, respectively. Based on the results of 68 Ga-PSMA-11 PET/CT, surgical intervention was canceled in 23 patients (13.2%). 68 Ga-PSMA-11 PET/CT resulted in a change of target volume delineation for radiation therapy planning in 29 patients (20.9%). Conclusion In high-risk primary PCa, 68 Ga-PSMA-11 is safe and effective in local staging, resulting in changes in both surgical and radiation management. Moreover, 68 Ga-PSMA-11 uptake is positively correlated with tumor grade and its efficacy is dependent on the size of nodal lesions. 68 Ga-PSMA-11 PET/CT will be highly impactful in the management of newly diagnosed high risk prostate cancer patients. Funding The study was funded by the German Cancer Consortium (DKTK).