Diagnostic value of two-time point [68Ga]Ga-PSMA-11 PET/CT in the primary staging of untreated prostate cancer – Scientific Reports

This retrospective study included 100 patients from January 2017 to October 2019 with untreated PCa referred to our division for primary staging with [⁶⁸Ga]Ga-PSMA-11 PET/CT. Patients were referred for primary staging after establishing diagnosis via trans-rectal biopsy and performing pre-staging via MRI and/or CT of the pelvis.

All procedures performed in this study were in accordance with the ethical standards of the institutional research committee (Ethikkommission der Medizinischen Universität Graz—Ethics Committee at Medical University of Graz). Being a retrospective study the need for written informed consent was waived by the Ethics Committee at Medical University of Graz.

The Gallium-68 labelled PSMA-11 ligand was prepared in-house according to the established EANM guideline on current good radiopharmacy practice (cGRPP)¹⁸ by the chelation of the HBED-CC precursor molecule (ABX, Radeberg, Germany) via a GMP-compliant fully automated radiopharmaceutical synthesizer (GRP Module, Scintomics, Fuerstenfeld-Bruck, Germany). Gallium-68 was obtained from a Germanium-68/Gallium-68 Generator (Galli Ad, IRE, Fleurus, Belgium). Quality control was successfully carried out according to the European Pharmacopeia. All prepared products were apyrogenic and sterile with a radiochemical purity > 91%.

All PET/CT examinations were performed on two dedicated PET/CT systems in 3D mode (Discovery MI, GE Healthcare, Milwaukee, WI, U.S.A.; Biograph mCT, Siemens, Erlangen, Germany); patients were unsystematically referred to each scanner. Target dose was 2 MBq kg body weight range 80–200 MBq according to established EANM dose recommendations¹⁹. The early phase consisted of a static image acquired 6 min post-injection over the pelvis with one bed position and an acquisition time of 2 min. The late phase consisted of static whole-body imaging starting 60 min post-injection by discontinuously craniocaudal bed movement and an acquisition time of 2 min per bed position. Transmission CT scans for attenuation correction were acquired using helical mode without the use of a contrast agent. Both PET and CT scans were reconstructed with a slice thickness of 3.75 mm. All studies were interpreted by at least two experienced Nuclear Medicine physicians in consensus reading, seldom discrepancies were solved by adding a third experienced Nuclear Medicine physician.

[⁶⁸Ga]Ga-PSMA-11 positive tumor lesions were visually identified as focal uptake higher than adjacent background activity, not associated with physiological uptake as recommended by the generally accepted international EANM/SNMMI criteria²⁰. Volumes of interest (VOI) to acquire SUVmax, SUVmean and TTV were manually drawn over pathological uptake in the prostate gland in both early and late images, avoiding the very high physiological bladder activity. VOIs were also drawn to acquire SUVmax, SUVmean and TTV in up to five extra-prostatic non-physiological uptakes in the whole-body late phase PET image to document nodal and bone metastasis.

Semi-quantitative data for both primary tumor and metastasis was acquired on AW Server 3.2 Ext. 4.0, GE Healthcare, Milwaukee, WI, U.S.A. using the manufacturer provided auto-snake tool with automatic threshold definition pre-set to 42% of SUVmax.

Risk stratification was based on the generally accepted criteria proposed by D’Amico in 1998²¹: The definition of (a) low risk are Gleason grade group 6, prostate specific antigen (PSA) level < 10 ng/mL, and clinical stage cT1c or cT2a, (b) intermediate risk are Gleason grade group 7 or PSA level 10-20 ng/mL or clinical stage cT2b, and (c) high risk are Gleason grade group ≥ 8 or PSA level > 20 ng/mL or clinical stage cT2c or higher. Patients with a history of previous or present other neoplastic disease were dismissed. Patients were included regardless of newly started anti-hormone treatment or pre-existing benign prostatic disorders. Anti-hormone treatment was started in all cases in less than a month before PET/CT examination, therefore a significant impact on results was deemed insignificant.

Therapy changes due to PET/CT outcomes were performed by the referring urologist; however complex cases and equivocal findings were discussed in the weekly tumor-board held for urological tumors held at the University Department of Urology including one nuclear medicine physician.

Statistical analysis was performed using SAS™ version 9.4 (SAS Institute Inc., Cary, NC, U.S.A.) by a professional statistician. Continuous parameters are presented as median, minimum and maximum, categorical parameters as frequency and percent. Wilcoxon signed-rank test was used to compare late and early phase semi-quantitative parameters. For group comparisons (i.e., PSA levels between patients with and without metastasis, semi-quantitative parameters between Gleason and D’Amico grading groups), Mann–Whitney-U-test and Kruskal–Wallis test were used. Additionally, Spearman’s rank correlation coefficient was calculated for PSA levels and semi-quantitative parameters.

Ethics approval

This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee at the Medical University of Graz. Being a retrospective study the need for written informed consent was waived by the Ethics Committee at Medical University of Graz.