# 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

## TL;DR

This study shows that 68Ga-PSMA-11 PET/CT imaging is safe and effective for detecting prostate cancer metastases, influencing treatment decisions in high-risk patients.

## Contribution

The study provides new evidence on the diagnostic accuracy and clinical impact of 68Ga-PSMA-11 PET/CT in high-risk prostate cancer staging.

## Key findings

- 68Ga-PSMA-11 PET/CT had high sensitivity for local disease detection (97.1%) and moderate sensitivity for lymph node metastases (40%).
- Imaging led to changes in surgical and radiation therapy plans in 13.2% and 20.9% of patients, respectively.
- PSMA uptake correlated with Gleason score, with higher SUVpeak values for higher-grade tumors.

## Abstract

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 68Ga-PSMA-11 PET/CT imaging in newly diagnosed high-risk PCa and assess its impact on patient management.

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 68Ga-PSMA-11 PET/CT for primary staging.

The primary objectives were the evaluation of 68Ga-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 68Ga-PSMA-11 uptake with Gleason Score, and determining the impact on clinical management. Impact of pre-operative 68Ga-PSMA-11 PET/CT imaging on target volume definition for radiation therapy was assessed.

173 patients underwent 68Ga-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 68Ga-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 68Ga-PSMA-11 PET/CT, surgical intervention was canceled in 23 patients (13.2%). 68Ga-PSMA-11 PET/CT resulted in a change of target volume delineation for radiation therapy planning in 29 patients (20.9%).

In high-risk primary PCa, 68Ga-PSMA-11 is safe and effective in local staging, resulting in changes in both surgical and radiation management. Moreover, 68Ga-PSMA-11 uptake is positively correlated with tumor grade and its efficacy is dependent on the size of nodal lesions. 68Ga-PSMA-11 PET/CT will be highly impactful in the management of newly diagnosed high risk prostate cancer patients.

The study was funded by the German Cancer Consortium (DKTK).

The online version contains supplementary material available at 10.1007/s00259-025-07540-4.