Optimization of staging algorithm for newly detected prostate cancer by using PET/CT with <sup>68</sup>Ga-PSMA: a retrospective study
Authors: Dolbov A. L. , Stanzhevskii A. A. , Maistrenko D. N. , Shkolnik M. I. , Rozengauz E. V. , Bogomolov O. A. , Sysoev D. S. , Mus V. F. 
Published: January 2023

INTRODUCTION: Prostate cancer (PC) is the most common malignancy in men worldwide and ranks third in mortality. Improvement of the results of staging of newly detected prostate cancer is rightfully associated with the active use in clinical practice of positron emission tomography combined with computed tomography (PET/CT) with radiotracers based on prostate-specific membrane antigen (PSMA) ligands.

OBJECTIVE: The aim of the study was to determine the capabilities of PET/CT with 68Ga-PSMA in evaluating the prevalence of newly diagnosed breast cancer in comparison with traditional imaging techniques (computed tomography, magnetic resonance imaging and bone scan) and to determine the role of this technology in the choice of treatment algorithm.

MATERIALS AND METHODS: 120 patients aged 46 to 74 years (median age 62.5 years) with histologically verified prostate cancer underwent PET/CT with 68Ga-PSMA in our center to assess disease prevalence. The selection criteria for the study were: prostate-specific antigen (PSA) level of 5 ng/ml and above, presence of newly detected, histologically verified prostate cancer, no treatment, suspected metastatic lesion of pelvic and skeletal lymph nodes according to CT, MRI and OSG. All patients were divided into groups according to PSA level and Gleason score. Statistics: Statistical processing of the results was performed by methods of variance statistics using Statistica 10.0, GraphPad Prism 9.3.1. Wilcoxon-Mann-Whitney and Friedman tests for ANOVA were used to determine the significance of differences between comparison groups. The chi-square test with Yates correction was used to determine the reliability of intergroup differences for nominal measures (such as the presence of previous recurrences). The level of correlation was assessed using Spearman criterion.

RESULTS: PET/CT imaging analysis in addition to MRI, CT, and OSG data showed TNM staging changes in 63 of 120 patients (52.3%) due to the detection of additional foci of metastatic lesions. Change of data about local spread of tumor with increasing of TNM stage due to detection of pathological RFP accumulation in seminal vesicles in 10 of 120 patients (8.3%), without structural changes using conventional imaging methods. In 20 of 64 patients (31.3%), PET/CT revealed lesions of regional lymph nodes (N) that were not visualized by conventional imaging methods due to their small size. Metastatic lesions of distant lymph nodes (M1a) and bones (M1b) undetected by CT, MRI, and OSG were found in 27 (22.5%) and 32 (26.7%) of 120 patients, respectively. At the same time, foci of pathological accumulation of 68Ga-PSMA in the bones without structural changes on CT were detected in 7 and 32 patients (21.8%).

DISCUSSION: One of the objectives of this study was to compare the diagnostic capabilities of standard diagnostic imaging techniques, in particular MRI, CT and Bone scan, with the hybrid technology of PET/CT with 68Ga-PSMA to improve the accuracy of PCa staging in order to determine treatment tactics. The results demonstrate minimal superiority of PET/CT with 68Ga-PSMA over MRI in terms of sensitivity (96% and 94%, respectively) in assessing local disease prevalence. Tumor invasion of the seminal vesicles, in most cases, was detected in patients with a Gleason score greater than 8. At the same time there was a tendency for an increase in the level of radiotracer accumulation in the tumor tissue of the seminal vesicles depending on the differentiation group of PCa. Analysis of the histological material obtained after the prostatectomy demonstrated tumorous invasion of the seminal vesicles in 26 (37.1%) out of 70 operated patients. Coincidence of histological examination results with PET/CT data was found in 22 patients, with MRI data — in 20 patients. The sensitivity, specificity, positive predictive value, and negative predictive value of PET/CT were 85%, 92%, 85%, and 92%, while the corresponding values from MRI were as follows: 77%, 88%, 77%, and 88%. Analyzing the levels of 68Ga-PSMA uptake in the tumor tissue, we found that with increasing prostate differentiation group, there was a persistent increase in radiotracer accumulation in the prostate tumor tissue. We also evaluated the interrelation of RFP accumulation with PSA level. The patients with PCa with PSA level ≥10.0 ng/ml demonstrated high accumulation of radiotracer accumulation compared to those with PSA <10.0 ng/ml (p<0.001).

CONCLUSIONS: The use of 68Ga-PSMA PET/CT in the staging of newly diagnosed and untreated cancers provides comprehensive information on the local, regional, and distant extent of the disease, and in some cases contributes to a change in TNM stage of the disease in a single study. The use of this method before planned surgical treatment of PCa can significantly reduce the risk of early postoperative relapse, especially in patients with a Gleason score of more than 7 and a PSA level greater than 20 ng/ml.