68Ga-PSMA PET Research Articles

Utility of Multiparametric Prostate MRI to Predict Regional or Distant Metastatic Disease Against Conventional Staging Using CT and Bone Scintigraphy or 68Ga-PSMA PET in Intermediate-to-High-Risk Prostate Cancer

Utility of Multiparametric Prostate MRI to Predict Regional or Distant Metastatic Disease Against Conventional Staging Using CT and Bone Scintigraphy or 68Ga-PSMA PET in Intermediate-to-High-Risk Prostate Cancer

Comparison of 68Ga-PSMA PET and mpMRI for prostate cancer local staging: a comprehensive review and direct meta-analysis

Comparison of 68Ga-PSMA PET and mpMRI for prostate cancer local staging: a comprehensive review and direct meta-analysis

Histopathological Correlation of Robotic-Assisted Radical Prostatectomy Specimen with Simultaneous 68GA-PSMA PET/MRI Findings in Cases of Adenocarcinoma Prostate

Background and Aims: 68Ga-PSMA PET represents a reasonable biomarker for presence of cancer of prostate (CaP). 68Ga-PSMA PET combined with simultaneous ‘multiparametric MRI’ (mpMRI) has the potential to be used for the detection and localisation of primary prostate cancer. It is therefore essential to correlate the histopathological findings of robotic-assisted radical prostatectomy (RARP) specimens with pre-operative PSMA PET/MRI. In addition, imaging with PSMA could be useful in estimating the aggressiveness of CaP. The current study aims at the correlation of histopathologic findings of RARP specimens with pre-operative combined 68Ga-PSMA PET/MRI imaging. Materials and Methods: Specimens retrieved after RARP in 38 patients of localised CaP were synchronised with pre-operative images obtained with simultaneous 68Ga-PSMA PET/MRI. Maximum scores of individual parameters such as PI-RADS, Gleason’s score and PSMA uptake (in SUV) were taken for each sector and used for statistical analysis. Results: The positive predictive value (PPV) and negative predictive value (NPV) of simultaneous 68Ga-PSMA PET and MRI in detecting malignancy were found to be 84.23% (95% CI: 80.74%–87.18%) and 63.92% (95% CI: 57.77%–69.65%), respectively. Combining 68Ga-PSMA PET and mpMRI improves the sensitivity to 81.48% (95% CI: 76.70%–85.67%), but the specificity was found to be 68.24% (95% CI: 60.09%–75.64%). It was found that SUV max correlated with the severity of GS ( P value < .001). Conclusion: Prediction and localisation of histological malignancy in the prostate could be improved pre-operatively by adding 68Ga-PSMA PET to mpMRI imaging. The SUV of abnormal uptake of 68Ga-PSMA radiotracer is predictive of aggressiveness of tumour as reflected in the Gleason score.

Evaluation of the prostate cancer and its metastases in the [ 68 Ga]Ga-PSMA PET/CT images: deep learning method vs. conventional PET/CT processing.

This study demonstrates the feasibility and benefits of using a deep learning-based approach for attenuation correction in [ 68 Ga]Ga-PSMA PET scans. A dataset of 700 prostate cancer patients (mean age: 67.6 ± 5.9 years, range: 45-85 years) who underwent [ 68 Ga]Ga-PSMA PET/computed tomography was collected. A deep learning model was trained to perform attenuation correction on these images. Quantitative accuracy was assessed using clinical data from 92 patients, comparing the deep learning-based attenuation correction (DLAC) to computed tomography-based PET attenuation correction (PET-CTAC) using mean error, mean absolute error, and root mean square error based on standard uptake value. Clinical evaluation was conducted by three specialists who performed a blinded assessment of lesion detectability and overall image quality in a subset of 50 subjects, comparing DLAC and PET-CTAC images. The DLAC model yielded mean error, mean absolute error, and root mean square error values of -0.007 ± 0.032, 0.08 ± 0.033, and 0.252 ± 125 standard uptake value, respectively. Regarding lesion detection and image quality, DLAC showed superior performance in 16 of the 50 cases, while in 56% of the cases, the images generated by DLAC and PET-CTAC were found to have closely comparable quality and lesion detectability. This study highlights significant improvements in image quality and lesion detection capabilities through the integration of DLAC in [ 68 Ga]Ga-PSMA PET imaging. This innovative approach not only addresses challenges such as bladder radioactivity but also represents a promising method to minimize patient radiation exposure by integrating low-dose computed tomography and DLAC, ultimately improving diagnostic accuracy and patient outcomes.

Prognostic Significance of Baseline Clinical and [68Ga]Ga-PSMA PET Derived Parameters on Biochemical Response, Overall Survival, and PSA Progression-Free Survival in Metastatic Castration-Resistant Prostate Cancer (mCRPC) Patients Undergoing [177Lu]Lu-PSMA Therapy.

In this study, we sought to identify the clinical baseline characteristics and pre-therapy 68Ga-PSMA PET derived parameters that can have impact on PSA (biochemical) response, OS and PSA PFS in patients with metastatic castration-resistant prostate cancer (mCRPC) who undergo RLT with [177Lu]Lu-PSMA-617. Various pre-treatment clinical and PSMA PET derived parameters were gathered and computed. We used PSA response as the criteria for more than a 50% decrease in PSA level, and OS and PSA PFS as endpoints. We assessed the collected parameters in relation to PSA response. Additionally, we employed univariable Cox regression and Kaplan-Meier analysis with log rank to evaluate the influence of the parameters on OS and PFS. A total of 125 mCRPC patients were included in this study. The median age was 68 years (range: 49-89). Among the cases, 77 patients (62%) showed PSARS, while 48 patients (38%) did not show PSA response. The median OS was 14 months (range: 1-60), and the median PSA-PFS was 10 months (range: 1-56). Age, prior history of chemotherapy, and SUVmax had a significant impact on PSA response (p<0.05). PSA response, RBC count, hemoglobin, hematocrit, neutrophil to lymphocyte ratio (NLR), alkaline phosphatase (ALP), number of metastases, wbPSMA-TV, and wbTL-PSMA significantly affected OS. GS, platelet count, NLR, and number of metastases were found to have a significant impact on PSA PFS. We have identified several baseline clinical and PSMA PET derived parameters that can serve as prognostic factors for predicting PSA response, OS, and PSA PFS after RLT. Based on the findings, we believe that these clinical baseline characteristics can assist nuclear medicine specialists in identifying RLT responders who have long-term survival and PFS.

Correlation of [68Ga]Ga-PSMA PET/CT response and PSA decline in first-line enzalutamide for metastatic castration-resistant prostate cancer patients.

to assess the utility of response monitoring to enzalutamide by using [68Ga]Ga-PSMA PET in mCRPC patients treated with enzalutamide as first-line therapy. patients underwent [68Ga]Ga-PSMA PET less than 8 weeks before and 3 months after starting enzalutamide. On the basis of EAU/EANM criteria, patients were categorized as PSMA responders (PET-R) or PSMA non-responders (PET-NR), whilst, based on PSA, they were classified as biochemical responders (PSA-R) or non-responders (PSA-NR). Survival analysis was performed using the Cox regression hazard model and the Kaplan-Meier method. 69 patients were considered fully evaluable. We observed 47.8% of concordance between [68Ga]Ga-PSMA PET and PSA monitoring at 3 months after starting enzalutamide. For discordant cases, the PSA reduction has a weak impact on PFS and a significant impact on OS in PET-NR patients, whilst this change has no impact either for PFS and OS in PET-R ones. [68Ga]Ga-PSMA PET could be a useful imaging tool for monitoring response to enzalutamide in mCRPC patients, being more informative than PSA in this setting, and possibly better guiding clinicians in therapeutic decisions.

Primary tumor heterogeneity on pre-treatment [68Ga]Ga-PSMA PET/CT for the prediction of biochemical recurrence in prostate cancer

PurposeThe aim of this study is to research the value of the texture analysis of primary tumors in pre-treatment [68Ga]Ga-PSMA PET in the prediction of the development of biochemical recurrence (BCR) in prostate cancer patients who underwent definitive therapies. Methods51 patients with prostate adenocarcinoma who had a pre-treatment [68Ga]Ga-PSMA-11 PET/CT and underwent definitive radiotherapy (RT) or radical prostatectomy (RP) were included in the study. Demographics, clinicopathologic features, the presence of BCR, and the last follow-up date of patients were recorded. Textural and conventional PET parameters (maximum standardized uptake value (SUVmax), total lesion-PSMA (TL-PSMA), and PSMA-tumor volume (PSMA-TV)) were obtained from PET/CT images using LifeX program. Parameters were grouped using the Youden index in ROC analysis. Factors predicting the BCR were determined using Cox regression analyses. Results29 (56.9%) patients have received primary curative RT, while the remaining 22 (43.1%) patients have undergone RP. 5 (22.7%) patients with RP and 3 (10.3%) patients with curative RT have developed BCR during the follow-up. INTENSITY-BASED-minimum grey level (P=.050), GLCM-sum variance (P=.019), and GLCM-cluster prominence (P=.050) were associated with BCR in univariate analysis. INTENSITY-BASED-minimum grey level (P=.009) and GLCM-sum variance (P=.004) were found as independent predictors of BCR in the multivariate analysis. ConclusionTumor heterogeneity on pre-treatment [68Ga]Ga-PSMA PET is associated with a high risk of BCR in PCa patients who underwent definitive therapies.

Ga68-PSMA PET for lymph node staging in intermediate and high-risk prostate cancer patients undergoing robotic assisted radical prostatectomy.

In intermediate/high risk prostate cancer, preoperative staging exams are mandatory. The aim of these imaging studies is to evaluate eventual lymph nodes involvement and/or metastatic spread of the tumor. Nevertheless, computed tomography (CT), magnetic resonance imaging (MRI), bone scan modalities have controversial sensitivity. Introduction of PET-PSMA and its use also as preoperative exam, seems to improve diagnostic accuracy due to favorable negative predictive value. The aim of this study was to evaluate the accuracy of PET-PSMA as a preoperative staging exam and its accuracy in predicting lymph nodes involvement in intermediate/high risk prostate cancer (PCa) patients. A retrospective analysis of 50 patients diagnosed with intermediate/high risk PCa between 2018 and 2022 has been performed. All patients underwent preoperative 68Ga-PSMA PET/CT prior to robot-assisted radical prostatectomy (RARP) + extended pelvic lymph node dissection (ePLND). The cohort was categorized into two groups: pathologically negative lymph nodes (pN0) vs. positive nodes (pN1). A descriptive and comparative analysis was conducted. Correlation analysis between continuous variables was performed using the Spearman's Rank Test. Using lymph nodes histopathological results as reference standard, the diagnostic performance of 68Ga-PSMA PET/CT was calculated. Overall, 50 patients were included. The mean age was 63.3 years with a median prostatic specific antigen (PSA) of 7.7 ng/dL. Forty-four percent of the patients exhibited an International Society of Urological Pathology (ISUP) score of 4 or higher, and 28% had a pT3 stage. Overall, 43 (86%) patients submitted to ePLND did not present lymph node metastases (pN0), while 8 (14%) patients were pN1. PET-PSMA showed low sensitivity in detecting lymph node metastases (25%) while a high specificity in excluding lymph-node disease (88.1%) has been observed. Finally, we noted a significant positive correlation between the total SUV<inf>max</inf> of the prostate and the initial total PSA (r=0.38; P=0.019), as well as the percentage of tumor involvement (r=0.383; P=0.022). Evidence on the role of PET-PSMA in the primary staging of PCa is steadily building up. A positive correlation between SUV and prostate involvement indicates that PET-PSMA could reflect, with a good approximation, the pathological features of the prostate. However, the low sensitivity depicted remains the main limitation. Future prospective studies are needed to determine the impact on patient outcome.

Molecular imaging with 68Ga-PSMA PET/CT in high grade glioma: A biomarker for tumour neo-angiogenesis.

There are several promising radiotracers used for both staging and restaging of primary and recurrent brain tumours based on various mechanisms of tracer localization in tumour cells. 68Ga-PSMA PET has extremely low background uptake in normal brain tissue and consequently high tumour-to-brain ratio making it a promising imaging radiotracer for gliomas. 68Ga-PSMA demonstrates utility in evaluating high grade glioma during both initial workup or when suspecting recurrence. Herein the authors evaluate the role of this imaging modality and the potential future it holds in the management of high grade gliomas.

[68Ga]Ga‑PSMA‑617 PET-based radiomics model to identify candidates for active surveillance amongst patients with GGG 1–2 prostate cancer at biopsy

PurposeTo develop a radiomics-based model using [68Ga]Ga-PSMA PET/CT to predict postoperative adverse pathology (AP) in patients with biopsy Gleason Grade Group (GGG) 1–2 prostate cancer (PCa), assisting in the selection of patients for active surveillance (AS).MethodsA total of 75 men with biopsy GGG 1–2 PCa who underwent radical prostatectomy (RP) were enrolled. The patients were randomly divided into a training group (70%) and a testing group (30%). Radiomics features of entire prostate were extracted from the [68Ga]Ga-PSMA PET scans and selected using the minimum redundancy maximum relevance algorithm and the least absolute shrinkage and selection operator regression model. Logistic regression analyses were conducted to construct the prediction models. Receiver operating characteristic (ROC) curve, decision curve analysis (DCA), and calibration curve were employed to evaluate the diagnostic value, clinical utility, and predictive accuracy of the models, respectively.ResultsAmong the 75 patients, 30 had AP confirmed by RP. The clinical model showed an area under the curve (AUC) of 0.821 (0.695–0.947) in the training set and 0.795 (0.603–0.987) in the testing set. The radiomics model achieved AUC values of 0.830 (0.720–0.941) in the training set and 0.829 (0.624–1.000) in the testing set. The combined model, which incorporated the Radiomics score (Radscore) and free prostate-specific antigen (FPSA)/total prostate-specific antigen (TPSA), demonstrated higher diagnostic efficacy than both the clinical and radiomics models, with AUC values of 0.875 (0.780–0.970) in the training set and 0.872 (0.678–1.000) in the testing set. DCA showed that the net benefits of the combined model and radiomics model exceeded those of the clinical model.ConclusionThe combined model shows potential in stratifying men with biopsy GGG 1–2 PCa based on the presence of AP at final pathology and outperforms models based solely on clinical or radiomics features. It may be expected to aid urologists in better selecting suitable patients for AS.

Dosimetry of lutetium-177-PSMA-I&amp;T radioligand therapy in recurrent/metastatic adenoid cystic carcinoma.

6093 Background: There is a high unmet need for effective systemic therapies for recurrent and/or metastatic (R/M) adenoid cystic carcinoma (AdCC), as no standard-of-care exists. AdCC frequently expresses prostate-specific membrane antigen (PSMA), providing rationale for PSMA-targeted therapies, which have demonstrated significant efficacy in prostate cancer. In our phase 2 pilot trial (EudraCT 2019-003857-27), we assessed the safety, efficacy and feasibility of lutetium-177 (177Lu)-PSMA-I&amp;T in R/M AdCC patients. Despite well-tolerated, the efficacy was limited. To gain further insight into causes of the limited efficacy, we measured absorbed 177Lu-PSMA-I&amp;T radiation doses in tumors and organs at risk. Methods: Dosimetry was feasible and was performed in all 10 enrolled AdCC patients. They received 177Lu-PSMA-I&amp;T with a median activity of 7.40 (range 6.78-7.49) GBq and a median of 4 (range 1-4) cycles. For bone marrow dosimetry, blood samples were collected during cycle 1. Single-photon emission CT/CT (SPECT/CT) was performed at 1, 24, 48, 72 and 168 hours after 177Lu-PSMA-I&amp;T injection at cycle 1. Tumors &gt;1 cm were categorized based on gallium-68 (68Ga)-PSMA PET mean standardized uptake value (SUVmean): above, at (±10%), and below liver SUVmean. Per site, up to 3 index lesions per category were selected. Volumes of interest with ~1 cm margin were drawn on SPECT/CT. Background correction was applied. Salivary gland and bone lesion volume were determined by iterative thresholding on 68Ga-PSMA PET. Other tumor volumes were determined on CT. Hermes dosimetry software and Olinda 2.2 software were used to estimate doses according to the Medical Internal Radiation Dose scheme. Results were reported as the absorbed dose at cycle 1 (Gy). Results: In total, 66 tumor lesions were analyzed. Tumor sites included lung (n=35), pleura (n=16), liver (n=5), bone (n=4), lymph node (n=3), local recurrence (n=2) and thoracic wall (n=1). The median 68Ga-PSMA PET tumor/liver SUVmean ratio was 0.94 (range 0.33-2.62). The median tumor-absorbed dose was 0.47 (range, 0.01-4.66) Gy. Highest median doses by tumor site were 1.84 (range, 0.76-2.92) Gy in local recurrences and 1.35 (range, 0.33-2.62) Gy in bone lesions. Lowest median doses by tumor site were 0.18 (range, 0.14-0.27) Gy in lymph node lesions and 0.21 (range, 0.12-0.79) Gy in liver lesions. In organs at risk, the absorbed dose was highest in the kidneys, followed by the salivary glands, with mean values of 6.29 (standard deviation [SD], 2.32) Gy and 5.07 (SD, 2.47) Gy, respectively. The mean bone marrow absorbed dose was 0.53 (SD, 0.14) Gy. Conclusions: Tumor-absorbed radiation doses in our AdCC patient cohort receiving 177Lu-PSMA-I&amp;T were significantly lower than in prostate cancer (~10-40 Gy per cycle), likely due to lower and heterogeneous PSMA expression. This could explain the limited efficacy. Organ-absorbed doses aligned with studies in prostate cancer. Clinical trial information: NCT04291300 .

The superior detection rate of total-body [68Ga]Ga-PSMA-11 PET/CT compared to short axial field-of-view [68Ga]Ga-PSMA-11 PET/CT for early recurrent prostate cancer patients with PSA < 0.2ng/mL after radical prostatectomy.

[68Ga]Ga-PSMA PET imaging has been extensively utilized for the detection of biochemical recurrence (BCR) in prostate cancer. However, the detection rate declines to merely 10-40% when PSA levels are < 0.2ng/mL employing short axial field-of-view (SAFOV) PET. Prior studies exhibited superior detection rates with total-body [68Ga]Ga-PSMA-11 PET compared to SAFOV [68Ga]Ga-PSMA-11 PET in BCR patients with PSA > 0.2ng/mL. Nevertheless, the diagnostic utility of total-body [68Ga]Ga-PSMA-11 PET for BCR patients when PSA is < 0.2ng/mL remains unclear. This study aimed to assess whether total-body [68Ga]Ga-PSMA-11 PET/CT could improve the detection rate compared to SAFOV [68Ga]Ga-PSMA-11 PET/CT in BCR patients with PSA < 0.2ng/mL. Eighty BCR patients with PSA < 0.2ng/mL underwent total-body [68Ga]Ga-PSMA-11 PET/CT. These patients were matched by baseline qualities to another 80 patients who received SAFOV [68Ga]Ga-PSMA-11 PET/CT. The detection rates of total-body [68Ga]Ga-PSMA-11 PET/CT and SAFOV [68Ga]Ga-PSMA-11 PET/CT were compared utilizing a chi-square test and stratified analysis. Image quality of total-body [68Ga]Ga-PSMA PET/CT and SAFOV [68Ga]Ga-PSMA-11 PET/CT was assessed based on subjective scoring and objective parameters. The objective parameters measured were SUVmax, SUVmean, standard deviation (SD) of SUV, and signal-to-noise ratio (SNR) of liver and gluteus maximus. The image quality of total-body [68Ga]Ga-PSMA PET/CT was superior to that of SAFOV [68Ga]Ga-PSMA-11 PET/CT in both early and delayed scans. The detection rate of total-body [68Ga]Ga-PSMA PET/CT for BCR patients with PSA < 0.2ng/mL was significantly higher than that of SAFOV [68Ga]Ga-PSMA-11 PET/CT (73.75% vs. 43.75%, P < 0.001). Total-body [68Ga]Ga-PSMA PET/CT resulted in noteworthy modifications to the treatment regimen when contrasted with SAFOV [68Ga]Ga-PSMA-11 PET/CT. In BCR patients with PSA < 0.2ng/mL, total-body [68Ga]Ga-PSMA-11 PET/CT not only demonstrated a significantly higher detection rate compared to SAFOV [68Ga]Ga-PSMA-11 PET/CT but also led to significant alterations in treatment regimens.

A multicentric, single arm, open-label, phase I/II study evaluating PSMA targeted radionuclide therapy in adult patients with metastatic clear cell renal cancer (PRadR)

BackgroundDespite advancements in managing metastatic clear cell renal carcinoma (mccRCC) through antiangiogenic tyrosine kinase inhibitors and immunotherapy, there remains a demand for novel treatments for patients experiencing progression despite the use of these medications. There is currently no established standard treatment for patients receiving third therapy line. Prostate Specific Membrane Antigen (PSMA) whose high expression has been demonstrated in metastatic aggressive prostate adenocarcinoma is also highly expressed in neovessels of various solid tumors including renal cell carcinoma (RCC): 86% of clear cell RCC, 61% of chromophobe RCC, and 28% of papillary RCC. Therefore, PSMA may be a target expressed in metastatic ccRCC for radionuclide therapy using PSMA ligands radiolabeled with Lutetium-177 (PRLT). 177Lu-PSMA delivers ß-particle radiation to PSMA-expressing cells and the surrounding microenvironment with demonstrated efficacy in metastatic prostate cancer.MethodsThis is a multicenter phase I/II study designed to assess the tolerability and effectiveness of 177Lu-PSMA-1 in individuals with PSMA-positive metastatic clear cell renal cell carcinoma (ccRCC), identified through 68Ga-PSMA PET, conducted in France (PRadR). 48 patients will be treated with 4 cycles of 7.4 GBq of 177Lu-PSMA-1 every 6 weeks. The primary objective is to evaluate the safety of 177Lu-PSMA-1 (phase I) and the efficacy of 177Lu-PSMA-1 in mccRCC patients (phase II). Primary endpoints are incidence of Severe Toxicities (ST) occurring during the first cycle (i.e. 6 first weeks) and disease Control Rate after 24 weeks of treatment (DCR24w) as per RECIST V1.1. Secondary objective is to further document the clinical activity of 177Lu-PSMA-1 in mccRCC patients (duration of response (DoR), best overall response rate (BORR), progression fee survival (PFS) and overall survival (OS).DiscussionOur prospective study may lead to new potential indications for the use of 177Lu-PSMA-1 in mccRCC patients and should confirm the efficacy and safety of this radionuclide therapy with limited adverse events. The use of 177Lu-PSMA-1may lead to increase disease control, objective response rate and the quality of life in mccRCC patients.Trial registrationClinicalTrials.gov: NCT06059014.

18F-FDG PET Is Not Inferior to 68Ga-PSMA PET for Detecting Biochemical Recurrent Prostate Cancer with a High Gleason Score: A Head-to-Head Comparison Study.

Previous studies have indicated that 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) in biochemical recurrence (BCR) patients with poorly differentiated prostate adenocarcinoma had higher diagnostic sensitivity than those with well differentiated adenocarcinoma, but whether the performance of FDG PET can achieve the effect of prostate-specific membrane antigen (PSMA) PET in BCR patients with a high Gleason score remains poorly understood. This study aimed to compare the efficacies of 18F-FDG PET/CT and 68Ga-PSMA PET/CT for BCR patients and evaluate whether 18F-FDG PET was not inferior to 68Ga-PSMA PET for detecting BCR with a high Gleason score. This was a retrospective, head-to-head comparative study completed at Ren Ji Hospital between May 2018 and June 2021. Patients underwent both 18F-FDG and 68Ga-PSMA PET/CT. The detection rate of BCR at the patient level and at the anatomical region level was evaluated. In total, 145 patients were enrolled in this study. 18F-FDG PET/CT (24.1%, 35/145) had lower detection rates than 68Ga-PSMA PET/CT (59.3%, 86/145; p < 0.001) at the patient level and at any anatomical region (p < 0.05). The PSA level (p < 0.001, OR = 11.026, 95% CI: 3.214-37.824) and the Gleason score (p < 0.001, OR = 20.227, 95% CI: 5.741-71.267) were independent predictive factors of the detection rate on 18F-FDG PET/CT, while the PSA level (p < 0.001, OR = 4.862, 95% CI: 2.338-10.110) was the only predictor of the detection rate on 68Ga-PSMA PET/CT. 18F-FDG PET/CT had a similar detection rate as 68Ga-PSMA PET/CT in patients with a Gleason score of 9 at the patient level (64.3% vs. 71.4%, p = 0.567) and any anatomical region (all p > 0.05), but 18F-FDG PET/CT had a lower detection rate than 68Ga-PSMA PET/CT in patients with a Gleason score of 6-8. 18F-FDG PET is not inferior to 68Ga-PSMA PET for detecting BCR with a Gleason score of 9; therefore, 18F-FDG PET/CT could be considered in BCR patients with a Gleason score of 9. However, 68Ga-PSMA is a better tracer than 18F-FDG in PET/CT for treatment decision making in BCR patients with a Gleason score of 6-8.

Reproducibility and Accuracy of the PRIMARY Score on PSMA PET and of PI-RADS on Multiparametric MRI for Prostate Cancer Diagnosis Within a Real-World Database.

The PRIMARY score is a 5-category scale developed to identify clinically significant intraprostate malignancy (csPCa) on 68Ga-prostate-specific membrane antigen (PSMA)-11 PET/CT (68Ga-PSMA PET) using a combination of anatomic site, pattern, and intensity. Developed within the PRIMARY trial, the score requires evaluation in external datasets. This study aimed to assess the reproducibility and diagnostic accuracy of the PRIMARY score in a cohort of patients who underwent multiparametric MRI (mpMRI) and 68Ga-PSMA PET before prostate biopsy for the diagnosis of prostate cancer. Methods: In total, data from 242 men who had undergone 68Ga-PSMA PET and mpMRI before transperineal prostate biopsy were available for this ethics-approved retrospective study. 68Ga-PSMA PET and mpMRI data were centrally collated in a cloud-based deidentified image database. Six experienced prostate-focused nuclear medicine specialists were trained (1 h) in applying the PRIMARY score with 30 sample images. Six radiologists experienced in prostate mpMRI read images as per the Prostate Imaging-Reporting and Data System (PI-RADS), version 2.1. All images were read (with masking of clinical information) at least twice, with discordant findings sent to a masked third (or fourth) reader as necessary. Cohen κ was determined for both imaging scales as 5 categories and then collapsed to binary (negative and positive) categories (score 1 or 2 vs. 3, 4, or 5). Diagnostic performance parameters were calculated, with an International Society of Urological Pathology grade group of at least 2 (csPCa) on biopsy defined as the gold standard. Combined-imaging-positive results were defined as any PI-RADS score of 4 or 5 or as a PI-RADS score of 1-3 with a PRIMARY score of 3-5. Results: In total, 227 patients with histopathology, 68Ga-PSMA PET, and mpMRI imaging before prostate biopsy were included; 33% had no csPCa, and 67% had csPCa. Overall interrater reliability was higher for the PRIMARY scale (κ = 0.70) than for PI-RADS (κ = 0.58) when assessed as a binary category (benign vs. malignant). This was similar for all 5 categories (κ = 0.65 vs. 0.48). Diagnostic performance to detect csPCa was comparable between PSMA PET and mpMRI (sensitivity, 86% vs. 89%; specificity, 76% vs. 74%; positive predictive value, 88% vs. 88%; negative predictive value, 72% vs. 76%). Using combined imaging, sensitivity was 94%, specificity was 68%, positive predictive value was 86%, and negative predictive value was 85%. Conclusion: The PRIMARY score applied by first-user nuclear medicine specialists showed substantial interrater reproducibility, exceeding that of PI-RADS applied by mpMRI-experienced radiologists. Diagnostic performance was similar between the 2 modalities. The PRIMARY score should be considered when interpreting intraprostatic PSMA PET images.

Correlation between Prostate Cancer Positive Cores and 68Ga-PSMA Distribution in Prostate Gland

Introduction: The purpose of our study was to evaluate reliability of ⁶⁸Ga-labeled prostate-specific membrane antigen positron emission tomography (⁶⁸Ga-PSMA PET/CT) and identify appropriate SUV_max cutoff values in order to use for diagnosis, especially in patients remained clinically suspicious for prostate cancer (PCa). Methods: Eighty-four patients applied ⁶⁸Ga-PSMA PET/CT subsequent to transrectal ultrasound-guided prostate biopsy (TRUS-bx) involved in this study retrospectively. ⁶⁸Ga-PSMA PET/CT imagings were analyzed by a nuclear medicine physician, and region of interests were drawn manually in prostate diagrams including 6 segments for each patient. These marked diagrams were analyzed with histopathology reports TRUS-bx. 504 segments were grouped with Gleason scoring system, and all groups were compared with mean SUV_max values. Results: Mean SUV_max value of Gleason grade group 1 (GG1, n: 352 segments) was 6.6 (±4.6) and significantly lower than the other groups (p < 0.001). No significant difference was detected within GG2–5 groups (p > 0.05). According to receiver operating characteristic curve analysis, SUV_max cutoff values were 1.0 (AUC: 0.961) for tumor detection, yielding a sensitivity, specificity, positive predictive value, negative predictive value of 99.4%, 92.1%, 96.5%, 98%, respectively, and 4.2 (AUC: 0.853) for detection of clinically significant PCa with 88.8%, 62.4%, 84.5%, and 71%, respectively. Although tumor percentage of biopsy core and Gleason group were correlated with SUV_max uptake, but patient age was not. Conclusion: ⁶⁸Ga-PSMA PET appears to be a reliable option for diagnosis and disease management in PCa and can be considered especially in discrimination of csPCa, and patients remained suspicious for disease.

Enhancing PSMA PET/CT imaging of prostate cancer: investigating the impact of multiple time point evaluation, diuretic administration, cribriform pattern, and intraductal carcinoma.

Our objective was to correlate staging PSMA PET imaging parameters to final histopathology. Second objective was to assess the performance of standard versus delayed PSMA PET to detect primary prostate tumor. Thirty-one patients (mean age, 61.4 ± 8.2) who underwent radical prostatectomy and preoperative staging PSMA PET scans were included in the study. After defining dominant lesion in pathology, correlations with PET images were performed. Additionally, two physicians blind to clinical and pathological information retrospectively reviewed staging Ga-68 PSMA PET scans with standard and delayed imaging. Dominant lesion SUV's increased with time 8.2(± 4.5), 10(± 7.1), and 10.2(± 7.8) at 1, 2, and 3h (P = .03 T1-T3). WHO Grade group 3 had highest SUV (group 3 11.9 ± 5.6 vs. group 2 7.9 ± 1.5, p = .02). Addition of cribriform pattern on intraductal component was associated with higher SUV's (11 ± 2.9 vs. 6.5 ± 2.1, p = .01) and higher Gleason four ratios (64 ± 9% vs. 37 ± 17%, p = .01). Intraductal carcinoma was associated with larger tumors (6.3 ± 2.3cm3 vs. 2.6 ± 1.7cm3, p < .001). Physician sensitivities ranged from 61 to 81%. Excluding Gleason 3 + 3 lesions and small lesions (< 1cm3), sensitivities increased to 80-100%. Differences of sensitivity between different time points were not significant. Combined evaluation of all time points did not increase sensitivity. Cribriform pattern correlates with higher Gleason 4 ratios and SUVs in PSMA PET. Intraductal carcinoma is associated with larger tumors but not higher Gleason 4 ratios and SUVs. Multiple late imaging times did not enhance tumor detection and may pose tolerability issues for some patients.

Intraoperative Frozen Section via Neurosafe During Robotic Radical Prostatectomy in the Era of Preoperative Risk Stratifications and Primary Staging With mpMRI and PSMA-PET CT: Is There a Perfect Candidate?

We aimed to analyze the effect of preoperative risk assessment including Ga-68 PSMA PET and multiparametric magnetic resonance imaging (mpMRI) on nerve sparing practices, positive surgical margin (PSM) rates and oncological outcomes based on a comparison between patients underwent RARP with and without Neurosafe (NS). Patients underwent RARP with NS (RARP-NS) or without (RARP-only) NS retrospectively evaluated. Suspicion for extracapsular extension on mpMRI and/or Ga-68 PSMA PET was recorded as i(imaging)T3. NS was performed according to the Martini-Klinik technique. PSM at preserved bundle side were called PSM at region of interest (ROI) while the others were elsewhere. A total of 208 patients (90 in RARP-NS, 118 in RARP-only groups) were included. Preoperatively the RARP-only group showed significantly higher mean PSA (p=.01) and PIRADS 5 (p=.002) findings and had more D'Amico high risk (DAHR) patients (p=.08). The overall PSM rates for pT2 versus pT3 disease were 7.5% versus 21.6 and 15.6% versus 55% in RARP-NS and RARP-only groups, respectively. NS resulted in more bilaterally preserved bundles (81.1% vs. 66.3%) and less PSM at the ROI (3.3% vs. 23.4%) than RARP-only group. NS outperformed RARP-only in all clinical settings had its highest differential benefit in more bilateral nerve sparing and less PSM at ROI in patients with both DAHR and iT3 disease. BCR rates were 2.2% and 2.5% for RARP-NS and RARP only groups, respectively (p=.4). One patient in RARP-NS and 9 in RARP-only groups had PSA persistence (p=.02). RARP-NS led to more preserved bundles with less PSM. It was especially useful in DAHR patients with preoperative extracapsular extension suspicion in imaging simultaneously.

UP40 - Evaluation of imaging, clinical and pathological factors associated with 2-year biochemical recurrence in surgical patients with intermediate- to high-risk prostate cancer: A focus on 68Ga-PSMA PET and pelvic 3Tesla mpMRI

UP40 - Evaluation of imaging, clinical and pathological factors associated with 2-year biochemical recurrence in surgical patients with intermediate- to high-risk prostate cancer: A focus on 68Ga-PSMA PET and pelvic 3Tesla mpMRI

A Pilot Study of Stereotactic Body Radiotherapy and 177Lu-PSMA-617 for Oligometastatic Hormone Sensitive Prostate Cancer

Stereotactic body radiotherapy (SBRT) is increasingly used for oligorecurrent prostate cancer (OPC). Despite excellent local control, distant metastasis free survival rates are more modest. We hypothesized SBRT outcomes could be optimized with improved staging imaging and integration of a well-tolerated targeted radiopharmaceutical therapy (RLT) for microscopic disease. We report initial results of a prospective, single-institution pilot (NCT05079698) of a novel, PSMA-based theranostic strategy for OPC. Men with castrate sensitive OPC and 1-3 sites of PSMA PET avid disease ("index lesions") and no PSMA non-avid sites were eligible. No androgen deprivation therapy was permitted. Subjects first received 2 cycles of 177Lu-PSMA-617 RLT (7.47±0.14 GBq) spaced 6 weeks apart. In vivo dosimetry was performed during cycle 1. Four weeks post-cycle 2, patients were restaged with 68Ga-PSMA PET for an interim (post-RLT) response assessment. Index lesions were then consolidated with SBRT (9 Gy x 3) irrespective of post-RLT PET response. The primary outcome was feasibility defined as successful completion of protocol-mandated therapy without intercurrent distant failure on post-RLT PET. Six men were treated with nine total index lesions (5 nodal, 3 osseous, 1 visceral). The study met its primary endpoint; all completed required interventions and no distant progression was seen on interim PSMA PET. Treatment was well tolerated; no grade 3+ toxicities, 2/6 had grade 2 toxicities (transient anemia and hyperbilirubinemia) and 5/6 had grade 1 toxicities. Median baseline lesion-level PSMA SUVmax was 16.8±8.7. Median interim SUVmax was 6.2±2.5 and declined for all but one lesion post-RLT (median -65%). Median SUVmax at 3-mos post-SBRT was 3.3±2.5 and decreased for all evaluable lesions (median -80%). Median baseline PSA was 2.01 ng/mL (range: 0.72-4.56) which declined in 5/6 post-RLT. The 6th patient experienced biochemical rise with interim PET showing only greater avidity in the known index lesion and SBRT was completed per protocol. All 4 evaluable patients with at least one post-SBRT follow-up have improved PSA at last visit (range 5.5-12 mos from cycle 1), and 2/4 have undetectable PSA. Composite dosimetry, correlatives and quality of life studies are forthcoming. Our pilot study demonstrates the feasibility of a novel PSMA anchored theranostic strategy combining SBRT with targeted RLT for OPC. Preliminary data suggests promising outcomes, including the possibility of achieving an undetectable biochemical disease state without hormone therapy.