The accuracy and intra- and interobserver variability of PSMA PET/CT for the local staging of primary prostate cancer

Abstract

Purpose: Prostate-specific membrane antigen (PSMA) positron emission tomography/ computed tomography (PET/CT) is recognized as the most accurate imaging modality for detection of metastatic high-risk prostate cancer (PCa). Its role in the local staging of disease is yet unclear. We assessed the intra- and interobserver variability, as well as the diagnostic accuracy of the PSMA PET/CT based molecular imaging local tumour stage (miT-stage) for the local tumour stage assessment in a large, multicentre cohort of patients with intermediate and high-risk primary PCa, with the radical prostatectomy specimen (pT-stage) serving as the reference standard.

Methods: A total of 600 patients who underwent staging PSMA PET/CT before robot-assisted radical prostatectomy was studied. In 579 PSMA positive primary prostate tumours a comparison was made between miT-stage as assessed by four nuclear physicians and the pT-stage according to ISUP protocol. Sensitivity, specificity and diagnostic accuracy were determined. In a representative subset of 100 patients, the intra-and interobserver variability were assessed using Kappa-estimates.

Results: The sensitivity and specificity of the PSMA PET/CT based miT-stage were 58% and 59% for pT3a-stage, 30% and 97% for ≥ pT3b-stage, and 68% and 61% for overall ≥ pT3-stage, respectively. No statistically significant differences in diagnostic accuracy were found between tracers. We found a substantial intra-observer agreement for PSMA PET/CT assessment of ≥ T3-stage (k 0.70) and ≥ T3b-stage (k 0.75), whereas the interobserver agreement for the assessment of ≥ T3-stage (k 0.47) and ≥ T3b-stage (k 0.41) were moderate.

Conclusion: In a large, multicentre study evaluating 600 patients with newly diagnosed intermediate and high-risk PCa, we showed that PSMA PET/CT may have a value in local tumour staging when pathological tumour stage in the radical prostatectomy specimen was used as the reference standard. The intra-observer and interobserver variability of assessment of tumour extent on PSMA PET/CT was moderate to substantial.

Keywords: Neoplasm Staging; Observer Variation; Positron Emission Tomography Computed Tomography; Prostatic Neoplasms.

Fig. 1

Example of PSMA PET based assessment of T3a-stage. A 78-year-old man presented with a clinical T1c ISUP grade 2 prostate cancer and an iPSA of 7.0, who underwent PSMA PET/ non-contrast enhanced CT using [¹⁸F]-JK-PSMA-7 as tracer because of a suspicious pelvic node on MRI. Attenuation-corrected PET reconstruction (a), fused PET – non-contrast enhanced CT (b) and non-contrast enhanced CT (c) at the same axial level of the prostate. These show an intensely PSMA-positive prostate tumour in the peripheral zone on the right (red arrow) and PET tumour activity extending outside the prostate contour as depicted on CT (green arrow), as well as asymmetrical bulging of the prostate contour on CT (blue arrow). According to the standardized assessment, a molecular imaging tumour-stage 3a (Likert score 2) was assigned. The patient underwent a robot-assisted radical prostatectomy after which a histopathologically confirmed pT3a, ISUP grade 3 acinar adenocarcinoma of the prostate with cribriform growth was found

Fig. 2

Example of PSMA PET based assessment of T3b-stage. A 61-year-old man presented with a clinical T2a ISUP grade 2 prostate cancer and an iPSA of 23.0, who underwent PSMA PET/ non-contrast enhanced CT using [⁶⁸Ga]Ga-PSMA-11 as tracer because of the presence of a high-risk factor (iPSA > 20 ng/ml). Attenuation-corrected PET reconstruction (a) and fused PET – non-contrast enhanced CT (b) at the same axial level of the prostate show an area of elevated uptake in the left seminal vesicle (red arrows). According to the standardized assessment, a molecular imaging tumour-stage 3b was assigned. The patient underwent a robot-assisted radical prostatectomy after which a histopathologically confirmed pT3b, ISUP grade 2 acinar adenocarcinoma of the prostate with cribriform growth was found