Prostatic Specific Membrane Antigen Reporting and Data System (PSMA-RADS) Version 1.0: Prospective Validation and Comparison to Updated Version (v2.0)
Conditions: Cancer Prostate
Sponsor: Zagazig University

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Prostatic Specific Membrane Antigen Reporting and Data System 
(PSMA-RADS) Version 1.0: A Prospective Validation and 
Comparison to Updated Version (v2.0)  
NCT number: No available 
Date: 21/01/2024 
 
 
 
 
 
 
 
 
 
 
 

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Introduction 
In recent years, positron emission tomography (PET) imaging with radiotracers targeting 
the prostate-specific membrane antigen (PSMA) has emerged as a promising tool for detecting and 
staging prostate cancer (PCa) [1-3]. Several PSMA-targeted PET radiotracers, such as 68Ga-
PSMA-11 and 18F-DCFPyL, have demonstrated superior diagnostic performance compared to 
conventional imaging modalities [4-9]. However, the interpretation of PSMA-PET imaging can be 
subjective and prone to variability among readers, hindering its widespread clinical adoption [10-
13]. To address this challenge, different standardized framework systems have been developed for 
interpreting PSMA-PET imaging, such as the PROstate cancer Molecular Imaging Standardization 
Evaluation (PROMISE) [14, 15] and the standardized reporting guidelines endorsed by the 
European Association of Nuclear Medicine (E-PSMA) [16]. While these systems aim to improve 
consistency and accuracy in interpretation, they are specific to certain imaging agents, requiring 
interpreting specialists to become familiar with multiple non-overlapping standardization 
frameworks [13].  
In light of this, Rowe et al. proposed a Reporting and Data System (RADS) specifically 
for PSMA-PET/CT imaging, called PSMA-RADS version 1.0 [17, 18]. Like other RADS, the 
PSMA-RADS aims to reduce interpretation variability, standardize the reporting and interpretation 
of PSMA-PET findings, facilitate effective communication among healthcare professionals, and 
provide clear guidelines for clinical decision-making [13]. PSMA-RADS categorizes PSMA-PET 
scans and individual findings on these images into categories that reflect the likelihood of the 
presence of PCa. PSMA-RADS version 1.0 is organized around a 5-point scale, with higher 
numbers indicating a greater probability of PCa. PSMA-RADS-1 (certainly benign) indicates an 
absence of PCa. PSMA-RADS-2 (likely benign) suggests a low probability of PCa. PSMA-RADS-

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3 (equivocal) indicates a moderate probability of PCa. PSMA-RADS-4 (highly likely malignant) 
suggests a high probability of PCa. PSMA-RADS-5 (almost certainly malignant) indicates the 
presence of PCa [17, 18]. 
Since its first publication in 2018, numerous studies [19-35] have been conducted to 
investigate the potential of PSMA-RADS v1.0 to improve diagnostic accuracy and inter-reader 
agreement in PSMA-PET imaging. These studies consistently demonstrated the excellent 
diagnostic accuracy and reliability of PSMA-RADS v1.0. However, most of these studies were 
retrospective or limited to case reports, highlighting the need for further research to establish the 
clinical utility and performance characteristics of PSMA-RADS. In 2023, an updated version of 
PSMA-RADS (v2.0) was developed. This version updated the PSMA-RADS framework to 
include a refined set of categories for optimizing lesion-level characterization, addressing 
deficiencies, and aiding clinical decision-making [36]. In this prospective multicenter study, we 
aimed to evaluate the diagnostic accuracy and reliability of PSMA-RADS v1.0 in evaluating PCa 
using 68Ga-PSMA-11 and to compare its performance with the updated version (v2.0). 
 
 
 
 
 
 
 
 
 

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Patients and Methods 
Ethical Considerations  
This prospective study was conducted in accordance with international guidelines 
approved by the Institutional Review Board (approval number: ZU-10490). Informed consent 
was obtained from all patients prior to their participation in the study. Our study adhered to the 
ethical principles outlined in the Declaration of Helsinki. 
Study Population 
Between January 2023 and March 2024, a total of 208 consecutive patients were recruited 
from three institutions. The study cohort included patients with newly diagnosed Pca and patients 
with biochemical recurrence (BCR). Patients were excluded based on the following criteria: 
inability to undergo PET/CT scan due to weight (e.g.,>180 kg) (n= 5), claustrophobia or inability 
to lie still throughout the scanning duration (n= 3), allergy to contrast media (n= 2), hepatic 
impairment (n= 5), renal failure (n= 2), and patients lost during follow-up (n= 7). This resulted in 
a final cohort of 186 patients (52 with a new diagnosis and 134 with biochemical recurrence). The 
flowchart of the study is illustrated in Fig. 1. Once enrolled, all patients underwent a 68Ga-PSMA-
11 PET/CT scan. For each patient, we determined the prostate-specific antigen (PSA) value, 
Gleason score (GS), and disease stage according to the TNM classification (molecular imaging 
TM (miTNM)), as proposed by PROMISE criteria [37].  
68Ga-PSMA-11 PET/CT Imaging Protocol 
All 68Ga-PSMA PET/CT images were performed using two integrated PET/CT scanners 
(Ingenuity TF 128; Philips Healthcare, Cleveland, OH, USA). All patients were instructed to fast 
and rest for at least 6 hours before the examination. Activities, including talking, chewing, and 
walking, were restricted. In addition, all patients were instructed to void preceding the 

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examination. The patients were in a supine position with their arms above their heads. An average 
of 4.0 mCi 68Ga-PSMA was administered intravenously (IV) according to the body weight, and 
the image started after almost 60 min. A low dose non-contrast CT for attenuation correction and 
anatomic localization from the skull vault to the mid-thigh were obtained (tube rotation time of 1 
sec per revolution; 120 kV; 60 mA; 7.5 mm per rotation; and an acquisition time of 60.9 sec for a 
scan length of 867 mm). Immediately after CT scanning, seven or eight frames (3 min/frame) of 
emission PET data were obtained in the three-dimensional mode. Images of CT and corresponding 
functional PET images are taken in axial, coronal and sagittal planes. Diagnostic contrast-
enhanced CT (CECT) scans of the thorax, abdomen, and pelvis were acquired in all patients after 
IV administration of 60-120 ml of non-ionic contrast agent (Ultravist 370, Bayer Schering Pharma 
AG, Berlin, Germany) depending on patient body weight. The CECT parameters were: 120 kV, 
250 mAs, 128x0.625 collimation, 5.0 mm slice thickness and interval, 0.993 pitch, 42 cm2 field 
of view, 512×512 matrix, and 330 ms gantry rotation. 
Image Analysis and PSMA-RADS Evaluation 
All CT, attenuation-corrected PET, and fused PET/CT images were anonymized and 
transmitted for central review on an interactive workstation (IntelliSpace Portal V4.0; Philips 
Healthcare, Cleveland, Ohio, USA). Three nuclear medicine radiologists with over five years of 
experience independently evaluated all PET/CT images in random presentations during separate 
reading sessions. Before the study commenced, the radiologists underwent five hours of lecture-
based and practical training, which provided detailed explanations of the PSMA-RADS 
classification. They were blinded to clinical data and biopsy reports. For each patient, the PET/CT 
scan was divided into four regions: prostate/prostate bed, regional lymph nodes (LNs), bone 
structures, and soft tissue (visceral structures and non-pelvic LNs). Each region was individually 

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evaluated for (i) the presence and intensity of uptake (none, equivocal, or intense), (ii) the 
relevance of the sites (typical or atypical for PCa metastases), and (iii) the clarity of the lesions on 
corresponding CT images (defined or not defined). The disease activity in each region was 
determined through qualitative and quantitative methods. The qualitative analysis was based on 
identifying focal 68Ga-PSMA-11 uptake that exceeded background levels and was distinct from 
known physiological tracer uptake areas. The quantitative analysis involved measuring the 
maximum standardized uptake value (SUVmax). Subsequently, each radiologist independently 
assigned a PSMA-RADS category to each region and an overall PSMA-RADS score to each 
patient using the PSMA-RADS v1.0 criteria [14, 15]. Since the updated PSMA-RADS v2.0 was 
published in July 2023 during this study, the same three nuclear medicine radiologists 
retrospectively and independently re-reviewed the images for all patients. Using the updated 
PSMA-RADS v2.0 criteria [16], they independently reassigned PSMA-RADS categories to each 
patient. Any disagreement between the three radiologists was discussed until a consensus was 
reached. 
Reference Standard 
The primary endpoint was diagnostic accuracy on a per-patient basis. For newly 
diagnosed patients, the definitive diagnosis was validated by histopathological results after biopsy. 
Biopsies were obtained through a transrectal ultrasound (TRUS) guided procedure within two 
weeks before 68Ga-PSMA-11 PET/CT imaging. For patients with biochemical recurrence, the final 
diagnosis was confirmed based on the following: (i) Histopathological findings after biopsy (n= 
151 patients (55 locoregional, 96 lymph nodes, 45 bone lesions, and 42 visceral soft tissue 
lesions)). Biopsies were taken by ultrasound-guided (n=78) or CT-guided (n=73) procedure within 
two weeks before 68Ga-PSMA-11 PET/CT imaging. Two experienced pathologists evaluated all 

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specimens, and the results were obtained by consensus. In patients with multiple lesions, the biopsy 
result of one lesion was considered representative of all lesions. Biopsies were performed to 
determine the lesion type as per the doctor's request. (ii) One year of clinical and imaging follow-
up (n= 37). Follow-up imaging was completed every six months via 68Ga-PSMA PET/CT analysis. 
It was interpreted by a panel of expert readers who were informed of the locations of the lesions 
described by the blinded readers at initial imaging. 
Statistical Analysis 
Statistical analysis was performed using MedCalc version 20.022 (Ltd., Ostend, Belgium) 
and SPSS version 26 (IBM, Armonk, NY). Continuous variables were presented as means and 
standard deviations, while categorical variables were presented as numbers and percentages. To 
compare categorical variables, we used the chi-square test; for continuous variables, we used the 
one-way ANOVA test. The receiver operating characteristic (ROC) curve was utilized to identify 
the best cut-off value and the area under the curve (AUC) for detecting PCa. To evaluate the 
diagnostic accuracy of both PSMA-RADS versions in categorizing PCa, we employed a four-fold 
table test with histopathology and follow-up as the reference standards. We used Fleiss kappa (κ) 
statistics to assess the inter-rater agreement (IRA) of PSMA-RADS scoring results in detecting 
PCa. The κ values were interpreted as follows: 0.01–0.20= poor agreement, 0.21–0.40= fair 
agreement, 0.41–0.60= moderate agreement, 0.61–0.80= good agreement, and 0.81–1.0= perfect 
agreement. Statistical significance was set at P ≤ 0.05. 
 
 
 
 

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