⁶⁸Ga-PSMA-11 PET/CT Interobserver Agreement for Prostate Cancer Assessments: An International Multicenter Prospective Study

Abstract

The interobserver agreement for Ga-PSMA-11 PET/CT study interpretations in patients with prostate cancer is unknown.Ga-PSMA-11 PET/CT was performed in 50 patients with prostate cancer for biochemical recurrence ( = 25), primary diagnosis ( = 10), biochemical persistence after primary therapy ( = 5), or staging of known metastatic disease ( = 10). Images were reviewed by 16 observers who used a standardized approach for interpretation of local (T), nodal (N), bone (Mb), or visceral (Mc) involvement. Observers were classified as having a low (<30 prior Ga-PSMA-11 PET/CT studies; = 5), intermediate (30-300 studies; = 5), or high level of experience (>300 studies; = 6). Histopathology ( = 25, 50%), post-external-beam radiation therapy prostate-specific antigen response ( = 15, 30%), or follow-up PET/CT ( = 10, 20%) served as a standard of reference. Observer groups were compared by overall agreement (% patients matching the standard of reference) and Fleiss' κ with mean and corresponding 95% confidence interval (CI). Agreement among all observers was substantial for T (κ = 0.62; 95% CI, 0.59-0.64) and N (κ = 0.74; 95% CI, 0.71-0.76) staging and almost perfect for Mb (κ = 0.88; 95% CI, 0.86-0.91) staging. Level of experience positively correlated with agreement for T (κ = 0.73/0.66/0.50 for high/intermediate/low experience, respectively), N (κ = 0.80/0.76/0.64, respectively), and Mc staging (κ = 0.61/0.46/0.36, respectively). Interobserver agreement for Mb was almost perfect irrespective of prior experience (κ = 0.87/0.91/0.88, respectively). Observers with low experience, when compared with intermediate and high experience, demonstrated significantly lower median overall agreement (54% vs. 66% and 76%, = 0.041) and specificity for T staging (73% vs. 88% and 93%, = 0.032). The interpretation of Ga-PSMA-11 PET/CT for prostate cancer staging is highly consistent among observers with high levels of experience, especially for nodal and bone assessments. Initial training on at least 30 patient cases is recommended to ensure acceptable performance.

Optimization of PET protocol and interrater reliability of 18F-PSMA-11 imaging of prostate cancer

“…6 clearly shows improvement in each category where κ statistics were determined. This was in concordance with the interobserver agreement study by Fendler et al [27] who also found that observers with less than 30 previous PSMA image readings only showed moderate interrater reliability contrary to more experienced observers who achieved substantial to almost perfect agreement. Retrospectively, all observed lesions from the original Phase 2 were discussed with both observers.…”

“…It may be more appropriate to administer a lower furosemide dose simultaneously with the radiotracer administration for the comfort of the patient, which is also recommended in the guidelines of EANM and SNMMI for administration of 68 Ga-PSMA [14]. PSMA expression is not specific to the prostate only; physiological background uptake is seen in the kidneys, bladder, intestines, and salivary glands as well as in pathological conditions such as Paget's bone disease and neovasculature of several solid tumours such as highgrade sarcomas [27][28][29][30][31]. Moreover, some prostatic malignant lesions exhibit minimal PSMA expression and can be difficult to detect on PET [32].…”

Prostate Specific Membrane Antigen Targeted 18 F-DCFPyL Positron Emission Tomography/Computerized Tomography for the Preoperative Staging of High Risk Prostate Cancer: Results of a Prospective, Phase II, Single Center Study

“…In fact, recent data on 68 Ga-PSMA-11 PET/CT showed that increasing reader experience positively correlated with interreader agreement and presumably with accuracy to determine clinical stage. 25 The specificity of 18 F-DCFPyL PET/CT may also be improved through concurrent use of pelvic MRI, multiple imaging time points and/or administration of diuretics.…”

Impact of 68Ga-PSMA-11 PET/CT on the Management of Prostate Cancer Patients with Biochemical Recurrence

“…Standard image reconstruction parameters were used (16,18). 68 Ga-PSMA-11 PET/CT Image Analysis 68 Ga-PSMA-11 PET/CT images were analyzed according to recent guidelines during clinical readouts by an experienced nuclear medicine physician who had unlimited access to all medical records (16,18,19): any focal uptake of 68 Ga-PSMA-11 PET/CT above the background level and not associated with physiologic uptake or known pitfalls (6,18) was considered PSMA-positive.…”

“…Compar ed with conventional imaging, 68 Ga-PSMA-11 PET/ CT is superior for detecting sites of prostate cancer biochemical recurrence (BCR) (1)(2)(3)(4), is sensitive for detecting regional and distant metastatic disease (3,5), is highly specific (4,) and is associated with a low interreader variability (6).…”