Incremental Impact of [(68) Ga]Ga-PSMA-11 PET/CT in Primary N and M Staging of Prostate Cancer Prior to Curative-Intent Surgery: a Prospective Clinical Trial in Comparison with mpMRI

PURPOSE: The main objective of this prospective study was to assess the value of gallium-68 prostate-specific membrane antigen ([(68) Ga]Ga-PSMA-11) positron emission tomography/computed tomography (PET/CT) in primary N and M staging of intermediate- and high-risk prostate cancer (PCa) patients before planned curative-intent radical prostatectomy (RPE) and extended pelvic lymph node dissection (ePLND). The second objective was to compare the [(68) Ga]Ga-PSMA-11 PET/CT findings with standard of care pelvic multi-parametric magnetic resonance imaging (mpMRI) in the detection of locoregional lymph node metastases and intraprostatic prostate cancer. PROCEDURES: A total of 81 patients (mean age: 64.5 years, baseline mean trigger PSA (tPSA) 15.4 ng/ml, ± 15.9) with biopsy proven PCa (24 intermediate- and 57 high risk) scheduled for RPE and ePLND were enrolled in this prospective study. In 52 patients [(68) Ga]Ga-PSMA-11 PET/CT, pelvic mpMRI, and RPE with ePLND have been performed. Clinical risk stratification and related biomarkers as well as Gleason score (GS) were recorded. The location of the index lesion (IL) was documented systematically for each modality using a standardized segmentation of the prostate in six segments. Distant bone and lymph node metastasis detected by [(68) Ga]Ga-PSMA-11 PET/CT were documented. [(68) Ga]Ga-PSMA-11 PET/CT findings were correlated with results of mpMRI and histopathology. A consensus of imaging, clinical and/or follow-up findings were used for determining the distant metastases, which were not verified by histopathology. RESULTS: In the patient cohort who underwent RPE, [(68) Ga]Ga-PSMA-11 PET/CT and mpMRI detected the IL in 86.5% and 98.1% of the patients, respectively. The median of the maximum standardized uptake value (SUVmax) in the intraprostatic IL was 12 (range, 4.7–67.8). Intraprostatic IL of the high-risk patients showed significantly higher SUVmax than those in patients with intermediate risk for distant metastases (n = 48; median: 17.84 vs. 8.77; p = 0.02). In total 729 LN were removed by ePLND in 48 patients. The histopathology verified 26 pelvic lymph node metastases (pLNM) in 20.8% (10/48) of the patients, which have been correctly identified in 60% of the patients on [(68) Ga]Ga-PSMA-11 PET/CT, and in 50% on mpMRI. All but one pLNM had a maximum diameter below 10 mm. Bone metastases (BM) and distant LNM (dLNM) were found in 17.3% of the patients on [(68) Ga]Ga-PSMA-11 PET/CT imaging. 39.0% of the [(68) Ga]Ga-PSMA-11 PET-positive BM showed no suspicious morphological correlation on CT. CONCLUSION: [(68) Ga]Ga-PSMA-11 PET/CT shows high diagnostic performance for N and M staging of patients with intermediate- and high-risk prostate cancer and seems to be superior to pelvic mpMRI in the detection of locoregional lymph node metastases. A significant correlation was found between SUVmax of the intraprostatic index lesion and risk stratification based on tPSA level and GS. The results of this study emphasize again on the role of metabolic molecular imaging using specific tracers in selected patients, leading to tailored therapy approach. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11307-021-01650-9.