Specific Membrane Antigen Positron Emission Research Articles

Predictors of Metastasis in 68GA-Prostate Specific Membrane Antigen Pet-CT in the Primary Staging of Prostate Cancer

Background: The objective of this study was to investigate factors influencing Gallium 68 Prostate Specific Membrane Antigen Positron Emission Tomography (Ga68 PSMA PET-CT) uptake for primary staging in prostate cancer. Methods: Retrospective analysis was conducted on 499 non-metastatic and 243 de novo metastatic prostate cancer cases undergoing Ga68 PSMA PET-CT. Demographic, clinical, and imaging data were collected and analyzed. Multivariate logistic regression determined independent risk factors for metastasis detection on Ga68 PSMA PET-CT. Results: Metastatic cases showed higher levels of total PSA, PSA density (dPSA) and biopsy ISUP grade group compared to non-metastatic cases. Multivariate analysis identified cT2 stage and dPSA as independent predictors of metastasis detection on Ga68 PSMA PET-CT. Conclusions: Ga68 PSMA PET-CT plays a crucial role in prostate cancer staging, with identified factors such as clinical T stage and dPSA significantly impacting its diagnostic accuracy. These findings underscore the importance of Ga68 PSMA PET-CT in refining clinical staging and guiding treatment decisions for prostate cancer patients.

Association of Pre-Treatment Serum Testosterone Levels with Prostate Cancer: A Prospective Study

Introduction: It has been widely accepted that prostate cancer (PCa) growth is related to serum testosterone (ST). A direct correlation between pre-treatment ST level and PCa growth and progression has been reported. However, recent studies have shown that pre-treatment ST levels have a negative correlation with PCa. Thus, the literature is, at best, conflicting. In this study, we examined the pre-treatment serum total testosterone (ST) levels in PCa. Methods: In this prospective observational study, suspected cases of PCa underwent digital rectal examination, routine blood investigation, Prostate-Specific Antigen (PSA) measurement, and prostate biopsy. Diagnosed cases of PCa without any risk factors affecting testosterone levels were included. Their pre-treatment total ST levels were measured. All patients underwent staging evaluation with either Magnetic Resonance Imaging (MRI) & Bone scan or Ga-68 Prostate Specific Membrane Antigen Positron Emission Tomography (PSMA PET). ST levels were also measured in patients with Benign Prostatic Hyperplasia (BPH) and compared with those in PCa patients. ST levels were also assessed according to Gleason Score (GS) and clinical stage in PCa. Results: 110 cases and 54 patients with BPH were included in the study. The median ST level in PCa patients was significantly lower as compared to BPH patients [352.28 ng/dL (Interquartile Range (IQR) 224.99-563.17) vs. 448.29 ng/dL (IQR 400.97-596.42) (p =0.004)]. The median ST level in metastatic PCa was significantly lower than the localized PCa group [298.20 ng/dL vs. 452.30 ng/dL (p=0.0001)]. Moreover, the median ST level was also significantly lower in patients with Gleason Score ≥ 8 than those with Gleason Score ≤ 7 [285.92 ng/dL (149.97-560.40) vs. 425.13 ng/dL (320.43-571.46) (p=0.002)]. Conclusion: This study shows lower ST levels in patients with PCa compared to patients with BPH, thus supporting a potential association as described in previous studies. ST levels may have prognostic value since a low pre-treatment ST level is associated with a higher clinical stage and aggressive PCa.

Abstract 4150: Development of a three-dimensional spatialomics map of lethal prostate cancer driven by clinical imaging

Abstract Prostate adenocarcinoma (PCa) is the most common malignancy and the second leading cause of cancer-related mortality in United States men. Following treatment for localized PCa, up to 50% of these men can experience disease recurrence, with subsequent metastasis and death. This indicates that there is suboptimal identification of lethal PCa at the time of diagnosis, despite advancements in imaging, genomics, and biomarkers. To improve the noninvasive diagnosis of lethal PCa at initial diagnosis, we have developed a novel magnetic resonance imaging (MRI) method, diffusion basis spectrum imaging (DBSI), that noninvasively measures cancer, stromal, and immune cell contributions to the prostate tumor microenvironment (TME). To validate DBSI for PCa, we have applied novel technologies to matched prostatectomy specimens that include (i) fully automated tissue section processing with serial 2-photon tomographic (STP) imaging of the sections to generate 3D volumetric structural maps of the tumor tissue and (ii) multiplex MALDI mass spectrometry imaging of untargeted glycans and extracellular matrix (ECM) peptides and of proteins targeted with novel photocleavable-mass-tagged antibodies (MALDI-IHC) to spatially resolve hundreds of biomolecules from the TME. To establish the feasibility of this approach, we recruited a patient with an unusually aggressive prostate cancer consisting of Gleason 5+4 acinar adenocarcinoma histology with intraductal growth that was locally invasive and lymph node positive at prostatectomy (stage T3bN1). This patient also had the unusual finding of low activity on prostate specific membrane antigen positron emission tomography (PSMA-PET). Following gross sectioning of the prostate with MRI-guided 3D printed molds to co-register clinical DBSI with histology, a 5-mm thick tissue cross-section containing tumor and normal prostate was imaged with high resolution ex vivo DBSI followed by 3D structural mapping with STP imaging. Selected slides in the 3D stack were subject to multiplexed MALDI imaging to identify relationships between cellular and molecular heterogeneity with tumor structure identified with DBSI and STP imaging. We discovered unique structural differences in the prostate tumor compared with the surrounding stroma based upon collagen and glycan modifications to the ECM that were recapitulated with second harmonic maps of collagen from STP imaging as well as stromal maps generated from DBSI imaging. Additional novel protein and glycan ECM components were expressed in this tumor known to be associated with poor patient outcomes. Together, these data represent the first evidence successfully linking noninvasive in vivo clinical imaging and de novo spatialomics technologies with potential to improve PCa diagnostics. This advanced imaging workflow can be applied to any tissue type, underscoring its relevance to translational cancer research. Citation Format: Joseph E. Ippolito, David H. Ballard, Karla Bergeron, Ritesh Chidambaram, Anusha Elumalai, Tyler J. Fraum, Huaping Jing, Peter Kamelin, Eric H. Kim, Catherine Kita, Aleksandra Klim, Anthony Knesis, Mark Lim, José Marcio Luna, Hani Nakhoul, Timothy Ragan, Kenneth J. Rothschild, Sheng-Kwei Song, Kainen Utt, Cody Weimholt, Gargey Yagnik, Elijah Yew, Peggi M. Angel, Richard R. Drake. Development of a three-dimensional spatialomics map of lethal prostate cancer driven by clinical imaging [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4150.

Neural blind deconvolution for deblurring and supersampling PSMA PET.

Objective. To simultaneously deblur and supersample prostate specific membrane antigen (PSMA) positron emission tomography (PET) images using neural blind deconvolution.Approach. Blind deconvolution is a method of estimating the hypothetical 'deblurred' image along with the blur kernel (related to the point spread function) simultaneously. Traditionalmaximum a posterioriblind deconvolution methods require stringent assumptions and suffer from convergence to a trivial solution. A method of modelling the deblurred image and kernel with independent neural networks, called 'neural blind deconvolution' had demonstrated success for deblurring 2D natural images in 2020. In this work, we adapt neural blind deconvolution to deblur PSMA PET images while simultaneous supersampling to double the original resolution. We compare this methodology with several interpolation methods in terms of resultant blind image quality metrics and test the model's ability to predict accurate kernels by re-running the model after applying artificial 'pseudokernels' to deblurred images. The methodology was tested on a retrospective set of 30 prostate patients as well as phantom images containing spherical lesions of various volumes.Main results. Neural blind deconvolution led to improvements in image quality over other interpolation methods in terms of blind image quality metrics, recovery coefficients, and visual assessment. Predicted kernels were similar between patients, and the model accurately predicted several artificially-applied pseudokernels. Localization of activity in phantom spheres was improved after deblurring, allowing small lesions to be more accurately defined.Significance. The intrinsically low spatial resolution of PSMA PET leads to partial volume effects (PVEs) which negatively impact uptake quantification in small regions. The proposed method can be used to mitigate this issue, and can be straightforwardly adapted for other imaging modalities.

THE DIAGNOSTIC ACCURACY OF A COMBINATION OF PREOPERATIVE 68-Ga PSMA PET/CT AND MULTIPARAMETRİC MRI IN LOCALIZED PROSTATE CANCER.

Prostate cancer (PCa) is a common and leading course of cancer-related death in men. Although there are studies on multiparametric magnetic resonance imaging (MpMRI) with good diagnostic results in detecting clinically significant prostate cancer, new methods have been investigated due to the low positive predictive values. In this context, Prostate Specific Membrane Antigen Positron Emission Tomography (PSMA PET) emerges as an alternative imaging method to MpMRI. This study aims to compare 68Ga PSMA I&T-PET/CT and MpMRI in determining tumor location. Preoperative MpMRI and 68Ga PSMA I&T-PET/CT scans and pathology specimens of who underwent radical prostatectomy for PCa at our clinic between 2018-2021 were retrospectively evaluated. PSMA I&T-PET/CT, MpMRI, combined imaging were compared for tumor localization according to histopathological data. In terms of tumor localization, MpMRI demonstrated overall accuracy rates 75.9% (p kappa (κ) 0.0001* (0.525)). 68Ga PSMA I&T-PET/CT showed 71.5% (p κ 0.0001* (0.438)). For the combined imaging approach overall accuracy rate were calculated as 79.2% (p κ 0.0001* (0.576)). Additionally, high diagnostic accuracy was achieved for the combined imaging approach, particularly in the intermediate ISUP group. Moreover, SUVmax was calculated as 6.37. The combined use of 68Ga PSMA I&T-PET/CT and MpMRI has high diagnostic rates. However, the high cost is a significant disadvantage that limits their routine combined use.

PSMA PET/CT as a predictive tool for subregional importance estimates in the parotid gland

Objective. Xerostomia and radiation-induced salivary gland dysfunction remain a common side effect for head-and-neck radiotherapy patients, and attempts have been made to quantify the heterogeneity of the dose response within parotid glands. Prostate Specific Membrane Antigen (PSMA) ligands have demonstrated high uptake in salivary glands, which has been shown to correlate with gland functionality. Here we compare several models of parotid gland subregional relative importance with PSMA positron emission tomography (PET) uptake. We then develop a predictive model for Clark et al's relative importance estimates using PSMA PET and CT radiomic features, and demonstrate a methodology for predicting patient-specific importance deviations from the population. Approach. Intra-parotid gland uptake was compared with four regional importance models using 30 [18F]DCFPyL PSMA PET images. The correlation of uptake and importance was ascertained when numerous non-overlapping subregions were defined, while a paired t-test was used to compare binary region pairs. A radiomics-based predictive model of population importance was developed using a double cross-validation methodology. A model was then devised for supplementing population-level subregional importance estimates for each patient using patient-specific radiomic features. Main Results. Anticorrelative relationships were found to exist between PSMA PET uptake and four independent models of subregional parotid gland importance from the literature. Kernel Ridge Regression with principal component analysis feature selection performed best over test sets (Mean Absolute Error = 0.08), with gray level co-occurrence matrix (GLCM) features being particularly important. Deblurring PSMA PET images with neural blind deconvolution strengthened correlations and improved model performance. Significance. This study suggests that regions of relatively low PSMA PET uptake in parotid glands may exhibit relatively high dose-sensitivity. We’ve demonstrated the utility of PSMA PET radiomic features for predicting relative importance within subregions of parotid glands. PSMA PET appears to be a promising quantitative imaging modality for analyzing salivary gland functionality.

Temporal and regional patterns of prostate cancer positron emission tomography imaging among commercial insurance beneficiaries in the United States.

34 Background: Prostate specific membrane antigen positron emission tomography (PSMA-PET) imaging improves prostate cancer visualization and has been proposed as a tool to guide treatment decisions. As PSMA-PET imaging agents were not approved in the United States (US) until December 2020, little is known about national patterns of PET imaging utilization. Methods: We conducted a dynamic cohort study to evaluate use of PET imaging among insurance beneficiaries aged 40-89 years with a diagnosis of prostate cancer using deidentified administrative claims from Blue Cross Blue Shield Axis. We calculated the proportions of patients undergoing PET imaging in semiannual periods from January 1, 2016, through December 31, 2022, examining tracers specific to prostate cancer, including PSMA-targeted agents as well as fluciclovine, sodium fluoride, and choline tracers. Cochran-Armitage tests were used to evaluate trends in the proportion of individuals receiving PET imaging over time. We also assessed the association between regional [hospital referral region (HRR)] level contextual sociodemographic and healthcare characteristics and regional use of PSMA-PET imaging in 2022 using chi-square tests. Results: There were 410,505 beneficiaries with prostate cancer identified in the study period. The semiannual proportion of patients undergoing PET imaging increased from 4.5 [(95% confidence interval (CI) 4.1-5.0] per 1,000 in the first half of 2016 to 41.7 (95% CI 40.6-42.9) per 1,000 in the second half of 2022, p<0.001. Increases in PET imaging were driven by uptake of PSMA-PET imaging, which increased from 0.7 (95% CI 0.6-0.9) per 1000 in the second half of 2021 to 37.5 (95% CI 36.4-38.6) per 1,000 in the second half of 2022, p<0.001. Following approvals of PSMA-PET agents, other forms of PET imaging rapidly decreased – from 18.2 (95% CI 17.4-18.9) per 1000 in the second half of 2021 to 4.6 (95% CI 4.3-5.0) per 1,000 in the same period of 2022, p<0.001. Compared to HRRs in quartile 1 (Q1), HRRs in Q4 of PSMA-PET use in 2022 had higher levels of education (25.0% with college education or higher in Q1 versus 29.4% in Q4, p=0.005) and median household income ($50,200 in Q1 versus $60,900 in Q4, p<0.001). Conclusions: In this study from a large commercial US health insurer, PSMA-PET was rapidly incorporated into clinical practice and is now the dominant prostate cancer radiotracer. However, the initial uptake of PSMA-PET may be accompanied by disparity, as our data suggests less use in areas with lower income and education measures.

Massive pre-prostatic nodal metastasis from localized aggressive prostate cancer removed during robotic-assisted radical prostatectomy with extended pelvic lymph node dissection: a case report with brief literature review

BackgroundDuring robotic-assisted radical prostatectomy (RARP) for prostate cancer (PCa), few attention is given to pre-prostatic fat tissue (PPT) even during pelvic lymph node dissection (PLND). However, the rare potential involvement of PPT lymph nodes (LN) by PCa metastasis has already been reported by several authors and may influence therapeutic strategy in intermediate and high-risk patients. We present the case of a 69-year-old man who underwent RARP with extended PLND (ePLND) for aggressive PCa with massive pre-prostatic nodal metastasis, sampled during prostate biopsies. We sought to report this case for the particular preoperative images and reinforce benefits of resecting PPT during PLND for PCa.Please confirm if the author names are presented accurately and in the correct sequence (given name, middle name/initial, family name). Author 1 Given name: [Moncef] Last name [Al Barajraji].OkCase presentationA 69-year-old man consulted our department for high serum prostate specific antigen level (57 ng/mL). He had familial history of PCa only at first degree. On digital rectal evaluation, induration of left prostatic lobe was felt. Transrectal ultrasonography showed hypoechogenic lesion in left prostatic lobe with supra-centimetric nodule in PPT. Pelvic magnetic resonance revealed two lesions in the peripheral zone with a 19-mm nodule on right paramedian side of PPT (see Fig. 1). Transrectal ultrasound-guided prostate biopsies were performed, including the nodule. On left side, 2 biopsies out 6 showed Gleason 10 prostate cancer. On right side, all biopsies showed Gleason 9 prostate cancer. The PPT nodule showed Gleason 9 prostate cancer. Prostate specific membrane antigen (PSMA) positron emission tomography computed tomography scan showed hypermetabolic expression from left prostate lesions and PPT nodule. Transperitoneal RARP with ePLND was performed including PPT. Histopathological study revealed advanced prostate cancer with lymphovascular invasion and ECE (see Fig. 2). Evaluation of ePLND material showed metastasis in on pelvic LN and 23 mm nodal metastasis in PPT (see Fig. 2). Therefore, adjuvant therapy was initiated.Please check the edit made in the article title.OPkConclusionsPPT resection is not part of routine RARP with ePLND for PCa. However, this tissue might contain LN harbouring metastasis independently from pelvic LN, indicating adjuvant therapy in case of upstaging. Considering the low morbidity of resecting PPT and its facility, it should always been resected and sent for analysis in intermediate and high-risk PCa.

1787P Prostate specific membrane antigen positron emission tomography (PSMA PET)-directed clinical outcomes in metastatic hormone-sensitive prostate cancer (mHSPC): Implications for the STAMPEDE2 trial design

1787P Prostate specific membrane antigen positron emission tomography (PSMA PET)-directed clinical outcomes in metastatic hormone-sensitive prostate cancer (mHSPC): Implications for the STAMPEDE2 trial design

Towards simulation-free MR-linac treatment: utilizing male pelvis PSMA-PET/CT and population-based electron density assignments

Objective. This study aimed to investigate the dosimetric impact of using population-based relative electron density (RED) overrides in lieu of simulation computerized tomography (CT) in a magnetic resonance linear accelerator (MRL) workflow for male pelvis patients. Additionally, the feasibility of using prostate specific membrane antigen positron emission tomography/CT (PSMA-PET/CT) scans to assess patients’ eligibility for this proposed workflow was examined. Approach. In this study, 74 male pelvis patients treated on an Elekta Unity 1.5 T MRL were retrospectively selected. The patients’ individual RED values for 8 organs of interest were extracted from their simulation-CT images to establish population-based RED values. These values were used to generate individual (IndD) and population-based (PopD) RED dose plans, representing current and proposed MRL workflows, respectively. Lastly, this study compared RED values obtained from CT and PET-CT scanners in a phantom and a subset of patients. Results. Population-based RED values were mostly within two standard deviations of ICRU Report 46 values. PopD plans were comparable to IndD plans, with the average %difference magnitudes of 0.5%, 0.6%, and 0.6% for mean dose (all organs), D0.1cm 3 (non-target organs) and D95%/D98% (target organs), respectively. Both phantom and patient PET-CT derived RED values had high agreement with corresponding CT-derived values, with correlation coefficients ≥ 0.9. Significance. Population-based RED values were considered suitable in a simulation-free MRL treatment workflow. Utilizing these RED values resulted in similar dosimetric uncertainties as per the current workflow. Initial findings also suggested that PET-CT scans may be used to assess prospective patients’ eligibility for the proposed workflow. Future investigations will evaluate the clinical feasibility of implementing this workflow for prospective patients in the clinical setting. This is aimed to reduce patient burden during radiotherapy and increase department efficiencies.

18 F-prostate specific membrane antigen positron emission tomography/computerized tomography for lymph node staging in medium/high risk prostate cancer: A systematic review and meta-analysis.

Lymph node staging of prostate cancer (PCa) is important for planning and monitoring of treatment. 18 F-prostate specific membrane antigen positron emission tomography/computerized tomography ( 18 F-PSMA PET/CT) has several advantages over 68 Ga-PSMA PET/CT, but its diagnostic value requires further investigation. This meta-analysis focused on establishing the diagnostic utility of 18 F-PSMA PET/CT for lymph node staging in medium/high-risk PCa. We searched the EMBASE, PubMed, Cochrane library, and Web of Science databases from inception to October 1, 2022. Prostate cancer, 18 F, lymph node, PSMA, and PET/CT were used as search terms and the language was limited to English. We additionally performed a manual search using the reference lists of key articles. Patients and study characteristics were extracted and the QUADAS-2 tool was employed to evaluate the quality of included studies. Sensitivity, specificity, the positive and negative likelihood ratio (PLR and NLR), diagnostic odds ratio (DOR), area under the curve (AUC), and 95% confidence interval (CI) were used to evaluate the diagnostic value of 18 F-PSMA PET/CT. Stata 17 software was employed for calculation and statistical analyses. A total of eight diagnostic tests including 734 individual samples and 6346 lymph nodes were included in this meta-analysis. At the patient level, the results of each consolidated summary were as follows: sensitivity of 0.57 (95% CI 0.39-0.73), specificity of 0.95 (95% CI 0.92-0.97), PLR of 11.2 (95% CI 6.6-19.0), NLR of 0.46 (95% CI 0.31-0.68), DOR of 25 (95% CI 11-54), and AUC of 0.94 (95% CI 0.92-0.96). At the lesion level, the results of each consolidated summary were as follows: sensitivity of 0.40 (95% CI 0.21-0.62), specificity of 0.99 (95% CI 0.95-1.00), PLR of 40.0 (95% CI 9.1-176.3), NLR of 0.61 (95% CI 0.42-0.87), DOR of 66 (95% CI 14-311), and AUC of 0.86 (95% CI 0.83-0.89). 18 F-PSMA PET/CT showed moderate sensitivity but high specificity in lymph node staging of medium/high-risk PCa. The diagnostic efficacy was almost equivalent to that reported for 68 Ga-PSMA PET/CT. International Prospective Register of Systematic Reviews (PROSPERO), No. CRD42023391101.

Complex implementation factors demonstrated when evaluating cost-effectiveness and monitoring racial disparities associated with [18F]DCFPyL PET/CT in prostate cancer men

Prostate cancer (PC) staging with conventional imaging often includes multiparametric magnetic resonance (MR) of the prostate, computed tomography (CT) of the chest, abdomen, and pelvis, and whole-body bone scintigraphy. The recent development of highly sensitive and specific prostate specific membrane antigen (PSMA) positron emission tomography (PET) has suggested that prior imaging techniques may be insufficiently sensitive or specific, particularly when evaluating small pathologic lesions. As PSMA PET/CT is considered to be superior for multiple clinical indications, it is being deployed as the new multidisciplinary standard-of-care. Given this, we performed a cost-effectiveness analysis of [18F]DCFPyL PSMA PET/CT imaging in the evaluation of PC relative to conventional imaging and anti-3-[18F]FACBC (18F-Fluciclovine) PET/CT. We also conducted a single institution review of PSMA PET/CT scans performed primarily for research indications from January 2018 to October 2021. Our snapshot of this period of time in our catchment demonstrated that PSMA PET/CT imaging was disproportionately accessed by men of European ancestry (EA) and those residing in zip codes associated with a higher median household income. The cost-effectiveness analysis demonstrated that [18F]DCFPyL PET/CT should be considered as an alternative to anti-3-[18F]FACBC PET/CT and standard of care imaging for prostate cancer staging. [18F]DCFPyL PET/CT is a new imaging modality to evaluate PC patients with higher sensitivity and specificity in detecting disease than other prostate specific imaging studies. Despite this, access may be inequitable. This discrepancy will need to be addressed proactively as the distribution network of the radiotracer includes both academic and non-academic sites nationwide.

68Ga-PSMA PET/CT evaluation in men enrolled in prostate cancer Active Surveillance

To evaluate the accuracy of 68Ga-prostate specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) in the diagnosis of clinically significant prostate cancer (csPCa: Grade Group ≥ 2) in men enrolled in Active Surveillance (AS) protocol. From May 2013 to December 2021 200 men aged between 52 and 74 years (median age 63) with very low risk PCa were enrolled in an AS protocol study. During the follow up 48/200 (24%) men were upgraded and 10/200 (5%) decided to leave the AS protocol. After five years from confirmatory biopsy (range: 48-60 months) 40/142 (28.2%) consecutive patients were submitted to mpMRI and 68Ga-PSMA PET/CT imaging examinations before scheduled repeated biopsy. All the mpMRI (PI-RADS ≥ 3) and 68Ga-PET/TC standardized uptake value (SUVmax) ≥ 5 index lesions underwent targeted cores (mpMRI-TPBx and PSMA-TPBx) combined with transperineal saturation prostate biopsy (SPBx: median 20 cores). Multiparametric MRI and 68Ga-PSMA PET/CT showed 18/40 (45%) and 9/40 (22.5%) lesions suspicious for PCa. In 3/40 (7.5%) men a csPCa (GG2) was found; 68Ga-PSMA-TPBx vs. mpMRI-TPBx vs. SPBx diagnosed 2/3 (66.6%) vs. 2/3 (66.6%) vs. 3/3 (100%) csPCa, respectively. In detail, mpMRI and 68Ga-PSMA PET/TC demonstrated 16/40 (40%) vs. 7/40 (17.5%) false positive and 1 (33.3%) vs. 1 (33.3%) false negative results. Although 68PSMA PET/CT did not improve the detection for csPCa of SPBx (1 false negative result equal to 33.3% of the cases), at the same time, would have spared 31/40 (77.5%) scheduled biopsies showing a better diagnostic accuracy in comparison with mpMRI (83.3% vs. 70.2%).

The use of Lutetium-177 PSMA radioligand therapy with high dose rate brachytherapy for locally recurrent prostate cancer after previous definitive radiation therapy: a randomized, single-institution, phase I/II study (ROADSTER).

BackgroundIsolated local failure (ILF) can occur in patients who initially receive definitive radiation therapy for prostate cancer. Salvage therapy for ILF includes high dose rate (HDR) brachytherapy. Prostate Specific Membrane Antigen (PSMA) Positron Emission Tomography (PET) can accurately detect ILF and can exclude extraprostatic disease. Lutetium-177 PSMA Radioligand Therapy (RLT) is a novel treatment for prostate cancer that can target prostate cancer accurately, while sparing radiation dose to normal tissues.MethodsROADSTER is a phase I/II randomized, single-institution study. Patients with an ILF of prostate cancer after definitive initial radiation therapy are eligible. The ILF will be confirmed with biopsy, magnetic resonance imaging (MRI) and PSMA PET. Patients will be randomized between HDR brachytherapy in two fractions (a standard of care salvage treatment at our institution) (cohort 1) or one treatment of intravenous Lutetium-177 PSMA RLT, followed by one fraction of HDR brachytherapy (cohort 2). The primary endpoints for the phase I portion of the study (n = 12) will be feasibility, defined as 10 or more patients completing the study protocol within 24 months of study activation; and safety, defined as zero or one patients in cohort 2 experiencing grade 3 or higher toxicity in the first 6 months post-treatment. If feasibility and safety are achieved, the study will expand to a phase II study (n = 30 total) where preliminary efficacy data will be evaluated. Secondary endpoints include changes in prostate specific antigen levels, acute toxicity, changes in quality of life, and changes in translational biomarkers. Translational endpoints will include interrogation of blood, urine, and tissue for markers of DNA damage and immune activation with each treatment.DiscussionROADSTER explores a novel salvage therapy for ILF after primary radiotherapy with combined Lutetium-177 PSMA RLT and HDR brachytherapy. The randomized phase I/II design will provide a contemporaneous patient population treated with HDR alone to facilitate assessment of feasibility, tolerability, and biologic effects of this novel therapy.Trial registrationNCT05230251 (ClinicalTrials.gov).

Using of 18 fluorine labeled prostatic specific membrane antigen positron emission tomography-computed tomography in staging of prostatic cancer in correlation with prostate specific antigen level

Using of 18 fluorine labeled prostatic specific membrane antigen positron emission tomography-computed tomography in staging of prostatic cancer in correlation with prostate specific antigen level

PSMA-PET Guided Treatment in Prostate Cancer Patients with Oligorecurrent Progression after Previous Salvage Treatment

Prostate Specific Membrane Antigen-Positron Emission Tomography (PSMA-PET) is used to select recurrent prostate cancer (PCa) patients for metastases-directed therapy (MDT). We aimed to evaluate the oncologic outcomes of second-line PSMA-guided MDT in oligo-recurrent PCa patients. we performed a retrospective analysis of 113 recurrent PCa after previous radical prostatectomy and salvage therapies with oligorecurrent disease at PSMA-PET (≤3 lesions in N1/M1a-b) in three high-volume European centres. Patients underwent second-line salvage treatments: MDT targeted to PSMA (including surgery and/or radiotherapy), and the conventional approach (observation or Androgen Deprivation Therapy [ADT]). Patients were stratified according to treatments (MDT vs. conventional approach). Patients who underwent MDT were stratified according to stage in PSMA-PET (N1 vs. M1a-b). The primary outcome of the study was Progression-free survival (PFS). Secondary outcomes were Metastases-free survival (MFS) and Castration Resistant PCa free survival (CRPC-FS). Kaplan-Meier analyses assessed PFS, MFS and CRPC-FS. Multivariable Cox regression models identified predictors of progression and metastatic disease. Overall, 91 (80%) and 22 (20%) patients were treated with MDT and the conventional approach, respectively. The median follow-up after PSMA-PET was 31 months. Patients who underwent MDT had a similar PFS compared to the conventional approach (p = 0.3). Individuals referred to MDT had significantly higher MFS and CRPC-FS compared to those who were treated with the conventional approach (73.5% and 94.7% vs. 30.5% and 79.5%; all p ≤ 0.001). In patients undergoing MDT, no significant differences were found for PFS and MFS according to N1 vs. M1a-b disease, while CRPC-FS estimates were significantly higher in patients with N1 vs. M1a-b (100% vs. 86.1%; p = 0.02). At multivariable analyses, age (HR = 0.96) and ADT during second line salvage treatment (HR = 0.5) were independent predictors of PFS; MDT (HR 0.27) was the only independent predictor of MFS (all p ≤ 0.04) Conclusion: Patients who underwent second-line PSMA-guided MDT experienced higher MFS and CRPC-FS compared to men who received conventional management.

Patterns of Failure in Men With Radiorecurrent Prostate Cancer: A Post Hoc Analysis of 3 Prospective Gallium 68 Prostate-Specific Membrane Antigen Positron Emission Tomography/Computed Tomography Imaging Trials

Men with radiorecurrent prostate cancer (PCa) are often not offered curative treatment due to concerns regarding occult extraprostatic disease. Prostate specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) has significantly improved sensitivity for detecting extraprostatic disease compared with conventional imaging. We evaluated the patterns of PSMA-positivity in a cohort of men presenting for PSMA PET/CT to evaluate radiorecurrence. This was a post-hoc analysis of men from 3 prospective studies of PSMA PET/CT for radiorecurrent prostate cancer who had detailed clinicopathologic and treatment characteristics available and at least one positive PSMA PET/CT finding. Patterns of failure were defined as intraprostatic (including seminal vesicles) or extraprostatic (regional lymph node or distant metastatic disease with or without intraprostatic disease). Multivariable analyses (MVAs) were performed to evaluate for predictors of extraprostatic vs intraprostatic recurrence. Of the 128 patients included in this study, 17 (13%) were initially diagnosed with low-risk, 69 (54%) with intermediate-risk, and 42 (33%) with high-risk PCa. Median time since radiotherapy (RT) was 4.3 years (interquartile range [IQR], 2.7 - 7.2 years), and median PSA at time of PSMA PET/CT was 4.8 ng/mL (IQR, 2.8-10). Intraprostatic only failures were seen in 46 patients (36%), while extraprostatic failures were seen in 82 patients (64%). On MVA, greater years since RT was associated with decreased likelihood of extraprostatic recurrence (OR 0.89 [0.8 - 1.0], p=0.04) p=0.04) while increased PSA at PSMA PET/CT (OR 1.17 [1.05 - 1.29], p=0.003) and ADT use during initial treatment (OR 3.44 [1.0 - 11.85], p=0.05) were associated with extraprostatic recurrence. Nearly 1/3rd of patients with radiorecurrent disease who have identifiable disease on a PSMA PET/CT scan have intraprostatic recurrences only. Prospective studies evaluating salvage treatment approaches that integrate PSMA PET/CT imaging data are warranted.

Impact of 68Ga-PSMA PET/CT in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with enzalutamide.

48 Background: 68Ga prostate specific membrane antigen positron emission tomography/computed tomography (68Ga-PSMA PET/CT) is a highly sensitive diagnostic tool to detect prostate metastatic sites even at low levels of Prostate Specific Antigen (PSA). We evaluated the impact of 68Ga-PSMA PET/CT in patients treated with enzalutamide as first-line therapy for mCRPC. Methods: In an observational prospective study, 67 consecutive mCRPC patients were treated with enzalutamide 160 mg once daily in first-line for mCRPC. 68Ga-PSMA PET/CT was performed at baseline, after 3 months, during follow-up and at PSA/clinical progression. Patients were evaluated on a monthly basis for serological PSA response and safety. We measured at baseline the sum of metabolic total volume (SMTV), mean standardized uptake volume (SSUVmean), maximum standardized uptake volume (SSUVmax) and total lesion activity (STLA), which is the product of SMTV and SSUVmean, for a maximum of 20 lesions. These parameters together with baseline PSA level, Eastern Cooperative Oncology Group performance status (ECOG PS), Gleason Score (GS) and age were analyzed by univariate and multivariate Cox regression models as potential predictors of progression-free survival (PFS) and overall survival (OS). Results: At the moment of the present analysis, 58 mCRPC patients were considered fully evaluable. The median age was 75 years (range, 47-91), ECOG PS was 0 in 47 cases (81%), 1-2 in 11 (19%), GS was <8 in 22 (38%), 8-10 in 36 (62%), the median baseline PSA was 2.66 µg/L (range 0.09-197). We observed a median SMTV of 5.73 cm3, median SSUVmax of 44.85, median SSUVmean of 25.80 and median STLA of 59.66. At the median follow-up of 52 months, median PFS was 28.9 months (95% CI 16.3-43.6), median OS was not reached (95% CI 36.8-not reached). In univariate analysis, SSUVmax and STLA were significant for PFS (p=0.015 and p=0.001, respectively) and OS (p=0.026 and p=0.019, respectively), while SSUVmean was significant only for OS (p=0.028). On multivariate analysis, STLA only remained significant for PFS (p<0.001) and OS (p=0.026). Conclusions: The assessment of mCRPC by 68Ga-PSMA PET/CT before starting enzalutamide was associated with longer median PFS and OS compared to prior studies using standard imaging only. STLA, expression of both volume and intensity of 68Ga-PSMA uptake, appeared the strongest parameter able to predict PFS and OS.

The Impact of PSMA-PET on Oncologic Control in Prostate Cancer Patients Who Experienced PSA Persistence or Recurrence.

Background: Prostate Specific Membrane Antigen-Positron Emission Tomography (PSMA-PET) is currently recommended to restage prostate cancer (PCa) and to guide the delivery of salvage treatments. We aim to evaluate the oncologic outcomes of patients with recurrent PCa who received PSMA-PET. Methods: 324 hormone-sensitive PCa with PSA relapse after radical prostatectomy who underwent PSMA-PET in three high-volume European Centres. Patients have been stratified as pre-salvage who never received salvage treatments (n = 134), and post-salvage, including patients who received previous salvage therapies (n = 190). Patients with oligorecurrent (≤3 lesions), PSMA-positive disease underwent PSMA-directed treatments: salvage radiotherapy (sRT) or Metastases-directed therapy (MDT). Patients with polirecurrent (>3 lesions) PSMA-positive disease were treated with systemic therapy. Patients with negative PSMA-PET were treated with sRT or systemic therapies or observation. The primary outcome of the study was Progression-free survival (PFS). Secondary outcomes were: Metastases-free survival (MFS) and Castration Resistant Pca free survival (CRPC-FS). Results: median follow up was 23 months. In the pre-salvage setting, the PFS, MFS and CRPC-FS estimates at 3 years were 66.2% vs. 38.9%, 95.2% vs. 73.7% and 94.9% vs. 93.1% in patients with negative vs. positive PSMA-PET, respectively (all p ≥ 0.2). In the post-salvage setting, the PFS, MFS and CRPC-FS estimates at 3 years were 59.5% vs. 29.1%, 92.7% vs. 65.1% and 98.8% vs. 88.8% in patients with negative vs. positive PSMA-PET, respectively (all p ≤ 0.01). At multivariable analyses, a positive PSMA-PET was an independent predictor of progression (HR = 2.15) and metastatic disease (HR 2.37; all p ≤ 0.03). Conclusion: PSMA-PET in recurrent PCa detects the site of recurrence guiding salvage treatments and has a prognostic role in patients who received previous salvage treatments.

68Ga-PSMA PET/CT for the evaluation of metastasis in patients with prostate cancer: A systematic review and meta-analysis.

The aim of this study was to assess the diagnostic value of gallium-68-prostate specific membrane antigen (68Ga-PSMA) positron emission tomography/computed tomography (PET/CT) in detecting metastases in prostate cancer (PCa) patients. A comprehensive literature search of studies published before August 2021 in PubMed, Embase and Cochrane Library databases was conducted.The methodological quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. Studies investigating the diagnostic value of 68Ga-PSMA PET/CT were selected for qualitative and quantitative analysis. Twenty-five articles using 68Ga-PSMA PET/CT for detecting metastases in PCa patients were selected for qualitative analysis, 16 of which were selected for meta-analysis. The sensitivities of 68Ga-PSMA PET/CT in detecting lymph node metastases ranged from 33.3% to 96.08%, with high specificities ranged from 82% to 100%. Gallium-68-PSMA PET/CT demonstrated outstanding diagnostic performance in PCa patients with bone metastases. Only two articles about 68Ga-PSMA PET/CT for lung metastases showed that the detection value was limited. It was difficult to distinguish lung metastases in PCa patients from benign lesions or primary lung cancer. There was only one article about 68Ga-PSMA PET/CT for liver metastases, which showed that about 77.7% of metastatic lesions will be 68Ga-PSMA-positive and 22.3% will be false negatives. Due to the lack of articles on PCa visceral metastases, we only conducted a meta-analysis on lymph node metastases and bone metastases. In our meta-analysis, the per-patient pooled sensitivity, specificity, positive likelihood ratio (LR+), negative likelihood ratio (LR-), diagnostic odds ratio (DOR), and the area under the ROC curve (AUC) of lymph node metastases were 0.61, 0.96, 14.4, 0.41, 35, and 0.95, respectively. The per-lesion pooled sensitivity, specificity, LR+, LR-, DOR, and AUC of V were 0.74, 0.99, 76.0, 0.26, 289 and 0.99, respectively. The per-patient pooled sensitivity, specificity, LR+, LR-, DOR, and AUC of bone metastases were 0.97, 1.00, 1100.1, 0.03, 37490 and 0.98, respectively. Gallium-68-PSMA PET/CT demonstrated outstanding diagnostic performance for bone metastases in PCa patients. The majority of lymph node metastases, lung metastases, and liver metastases overexpressed PSMA, which could be directly detected. However, a considerable number of lesions were false negatives.