Role Of Prostate-specific Membrane Antigen Research Articles

The role of PSMA PET/CT in predicting downgrading in patients with Gleason score 4+4 prostate cancer in prostate biopsy

BackgroundTo investigate the predictable parameters associated with downgrading in patients with a Gleason score (GS) 8 (4+4) in prostate biopsy after radical prostatectomy.MethodsWe retrospectively analyzed 62 patients with a GS of 4+4 on prostate biopsy who underwent robotic radical prostatectomy between 2017 and 2022.Results38 of 62 (61.2%) were downgraded. In multivariable logistic regression model, Ga-68 prostate-specific membrane antigen (PSMA) positron-emission tomography (PET)/computed tomography (CT) SUV max was independent predictor of downgrading (OR 0.904; p = 0.011) and a Logistic Regression model was constructed using the following formula: Y = 1.465–0.95 (PSMA PET/CT SUV max). The model using this variable correctly predicted the downgrading in 72.6% of patients. The AUC for PSMA PET/CT SUV max was 0.709 the cut off being 8.8.A subgroup analysis was performed in 37 patients who had no other European Association of Urology (EAU) high risk features. 25 out of 37 (67.5%) were downgraded, and 21 of these 25 had organ confined disease. Low PSMA SUV max (<8.1) and percentage of GS 4+4 biopsy cores to cancer bearing cores (45.0%) were independently associated with downgrading to GS 7.ConclusionPSMA PET/CT can be used to predict downgrading in patients with GS 4+4 PCa. Patients with GS 4+4 disease, but no other EAU high risk features, low percentage of GS 4+4 biopsy cores to cancer bearing cores, and a low PSMA PET/CT SUV max are associated with a high likelihood of the cancer reclassification to intermediate risk group.

The Current Landscape of Prostate-Specific Membrane Antigen (PSMA) Imaging Biomarkers for Aggressive Prostate Cancer.

The review examines the vital role of prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) in the diagnosis, staging, and treatment of prostate cancer (PCa). It focuses on the superior diagnostic abilities of PSMA PET/CT for identifying both nodal and distant PCa, and its potential as a prognostic indicator for biochemical recurrence and overall survival. Additionally, we focused on the variability of PSMA's expression and its impact on personalised treatment, particularly the use of [177Lu] Lu-PSMA-617 radioligand therapy. This review emphasises the essential role of PSMA PET/CT in enhancing treatment approaches, improving patient outcomes, and reducing unnecessary interventions, positioning it as a key element in personalised PCa management.

PSMA PET/CT for Response Assessment and Overall Survival Prediction in Patients with Metastatic Castration-Resistant Prostate Cancer Treated with Androgen Receptor Pathway Inhibitors.

We aimed to evaluate the role of prostate-specific membrane antigen (PSMA) PET/CT for response assessment and outcome prediction in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with androgen receptor pathway inhibitors (ARPIs), including abiraterone acetate or enzalutamide. Methods: We retrospectively analyzed 30 ARPI-treated mCRPC patients who underwent 68Ga-PSMA-11 PET/CT within 8 wk before (baseline) and 12 ± 4 wk after treatment initiation. Total PSMA tumor volume was calculated using the fixed threshold method (SUV ≥ 3). Patients were categorized as PSMA responders (PSMA-Rs) or PSMA nonresponders (PSMA-NRs) on the basis of both European Association of Urology/European Association of Nuclear Medicine (EAU/EANM) criteria and Response Evaluation Criteria in PSMA PET/CT (RECIP) 1.0. PSMA-R included patients with a complete response, a partial response, or stable disease, and PSMA-NR included those with progressive disease. On the basis of prostate-specific antigen (PSA), patients were classified as biochemical responders if PSA decreased by at least 50% and as nonresponders if it did not. The Φ-coefficient was used to evaluate the correlation of PSMA- and PSA-based responses. Survival analysis was performed using the Cox regression hazard model and the Kaplan-Meier method. Predictive accuracy was tested for both response criteria. Results: On the basis of PSMA PET/CT, 13 (43%) patients were PSMA-NR according to the EAU/EANM criteria and 11 (37%) patients were PSMA-NR according to RECIP 1.0. Significant correlations were observed between PSMA- and PSA-based responses for both criteria (Φ = 0.79 and 0.66, respectively). After a median follow-up of 25 mo (interquartile range, 21-43 mo), the median overall survival was significantly longer for PSMA-R than PSMA-NR (54 vs. 22 mo) for both the EAU/EANM criteria and RECIP 1.0, with hazard ratios of 6.9 (95% CI, 1.9-26; P = 0.004) and 5.6 (95% CI, 1.69-18.26, P = 0.005), respectively. No significant difference in predictive accuracy was found between the 2 criteria (C-index, 0.79 vs. 0.76, respectively, P = 0.54). Flare phenomena at the second PSMA PET study were not observed in our cohort. Conclusion: Our results demonstrate that PSMA PET/CT is a valuable imaging biomarker for response assessment and overall survival prediction when performed at 3 mo after ARPI treatment initiation in mCRPC patients. Both proposed PSMA response criteria (EAU/EANM and RECIP 1.0) seem to perform equally well. No PSMA flare was observed. Prospective validation of these findings is strongly needed.

The role of PSMA PET/CT to predict upgrading in patients undergoing radical prostatectomy for ISUP grade group 1 prostate cancer.

To investigate the additive role of prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) independent from multiparametric magnetic resonance imaging (mpMRI) and clinical-pathological parameters to predict pathological upgrading in patients with ISUP grade group (GG) 1 prostate cancer (PCa) at prostate biopsy. A total of 41 patients who underwent robotic radical prostatectomy (RP) for GG1 disease at prostate biopsy with preoperative PSMA PET/CT and mpMRI images available for central review were included in the study. Univariate and multivariate logistic regression analyses were performed to determine the independent predictors of pathological upgrading (GG ≥ 2). Final RP pathology revealed upgrading in 26 patients (65.9%); to GG 2 disease in 25 cases and GG 4 disease in one case. International Society of Urological Pathology (ISUP) upgrading rates for prostate imaging-reporting and data system (PIRADS)-5, PIRADS-4, and PIRADS ≤ 3 lesions were 78%, 74%, and 38%, respectively. Fourteen out of 15 (93.3%) patients with an SUVmax ≥ 5.6 and all patients with an SUVmax ≥ 6.5 (n = 10) had pathological upgrading. The upgrading rate in patients with SUV < 5.6 was 46.2% (12/26). Intraprostatic SUVmax ≥ 5.6 was found as the only independent predictor of pathological upgrading in multivariate analysis. High prostatic PSMA uptake was found to be a very reliable predictor of pathological upgrading, but low PSMA uptake cannot exclude pathological upgrading. Intraprostatic PSMA uptake along with previously known mpMRI and biopsy-related parameters should be considered when making a treatment decision in patients with GG1 PCa at prostate biopsy.

A Novel Role of Prostate-Specific Membrane Antigen in Telomere Stability in Prostate Cancer Cells.

Role of PSMA in telomere stability suggests a strong correlation between PSMA expression and prostate cancer progression.

Rapid Tumor Washout of 177 Lu-PSMA Radioligand in Renal Cell Carcinoma.

The role of prostate-specific membrane antigen (PSMA) targeted molecular imaging and radionuclide therapy in prostate cancer is well known. PSMA is also overexpressed in the neovasculature of a number of solid tumors, including renal cell carcinoma (RCC). Several studies have demonstrated the diagnostic utility of PSMA PET imaging in the setting of RCC. To date, no PSMA radioligand therapy of RCC patient has been reported according to literature. Here, we report our experience treating a patient with metastatic RCC with 177 Lu-PSMA I&T radioligand therapy, but unexpected imaging findings with rapid washout of 177 Lu-PSMA from the tumor.

Preferential expression of prostate specific membrane in CD34 labeled Neo-vasculature of Hepatocellular carcinoma: Prognostic and therapeutic potentials

Abstract Background Hepatocellular carcinoma (HCC) is highly prevalent and lethal worldwide. Viral hepatitis related HCC represents 80% of all HCC cases. Eventually, angiogenesis becomes a crucial step in all HCCs. Angiogenetic markers are shared by non-malignant conditions. Finding a marker specifically expressed in tumor-vasculature and predict prognosis can provide optimal guide for decision making and involvement of new therapeutic options. prostate specific membrane antigen (PSMA) is a type II transmembrane protein upgraded in many tumours with promising role in prostate cancer as a potential prognostic and therapeutic indicator. However, the role of PSMA in HCC is not widely studied yet. This work aimed at evaluating PSMA expression in HCC. Methodology PSMA immunohistochemical staining was performed on 73 HCC cases to evaluate its expression. Relationship to different clinico-pathologic parameters was assessed statistically. Results PSMA was expressed in tumor-vasculature of HCC with 32% showed high expression. Adjacent non-tumoral tissue showed negative expression for PSMA. PSMA expression was significantly correlated with viral hepatitis related HCC (P=0.03), tumor grade (P=0.07), stage, node and distant metastasis (P=0.001 each). PSMA is the most independent predictor for OS and PFS. Conclusion PSMA is expressed preferentially in tumor-vasculature of HCC with higher expression in viral hepatitis related HCC and correlation with poor prognostic parameters, short OS and PFS. PSMA is considered a promising prognostic and therapeutic marker in HCC especially viral hepatitis related.

EAU-EANM Consensus Statements on the Role of Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography in Patients with Prostate Cancer and with Respect to [177Lu]Lu-PSMA Radioligand Therapy

BackgroundProstate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT) is useful for selected clinical indications in patients with prostate cancer (PCa) but it may have broader clinical utility owing to the emergence of lutetium-177-PSMA-617 ([177Lu]Lu-PSMA) therapy. However, robust data regarding the impact of PSMA PET/CT on patient management and treatment are lacking, and in many areas, the role of next-generation imaging has not been defined. ObjectiveTo assess expert opinion on the use of PSMA-based imaging and therapy to develop interim guidance. Design, setting, and participantsA panel of 21 PCa experts from various disciplines received thematic topics and relevant literature. A questionnaire to assess proposed guidance statements regarding PSMA PET/CT and [177Lu]Lu-PSMA therapy was developed for completion remotely in a first e-Delphi round. A subsequent panel discussion was conducted during a 1-d meeting, which included a second Delphi round. Outcome measurements and statistical analysisPanellists voted anonymously on statements using a nine-point Likert scale from 1 = strongly disagree to 9 = strongly agree. Median scores were calculated and consensus was assessed using methods proposed by the Research and Development (RAND) corporation. Results and limitationsStatements were developed to cover the following topics: PSMA PET/CT utility, clinical use, and choice of tracer; patient selection; and management of patients receiving [177Lu]Lu-PSMA for metastatic PCa. Consensus was reached for 33/36 statements. In-group bias is a potential limitation, as some statements were rephrased during discussions at the 1-d meeting. ConclusionsAdoption of PSMA PET/CT as an imaging tool to guide [177Lu]Lu-PSMA therapy should be supported by indications for appropriate use. Patient summaryA panel of experts in prostate cancer reached a consensus for the majority of statements proposed regarding the role of prostate-specific membrane antigen (PSMA)-based imaging and therapy, particularly the use of PSMA-based imaging in patients suitable for [177Lu]Lu-PSMA therapy and the need to perform PSMA-based imaging before considering patients as candidates for this therapy.

The role of prostate-specific membrane antigen PET/computed tomography in the management of prostate cancer patients: could we ask for more?

Thanks to the development of novel PSMA-based peptides, molecular imaging, such as PET/CT paired with theranostic-based approaches have recently been proposed for treatment of prostate cancer. Patient selection, however, remains challenging because of the absence of strong prospective data to interpret and translate imaging scans into effective and well tolerated treatment regimens. In this review, we discuss the latest findings in PSMA imaging in prostate cancer patients. Particularly, we go into detail into the impact of PSMA imaging on the treatment management in primary staging, biochemical recurrence and in advanced prostate cancer. For primary prostate cancer staging, PSMA PET/CT seems crucial for primary therapy assessment, being able in some cases to detect lesions outside the surgical template, thus permitting a change in management. Moreover, N+ condition at PSMA has been correlated with a worse biochemical recurrence-free and therapy-free survival. The early detection of PSMA-positive findings in recurrent prostate cancer is associated with a better time to relapse survival. Similarly, for advanced prostate cancer patients, accurate restaging with PSMA imaging is gaining importance for early prediction of response to systemic therapies and to assure the best outcome possible. With regards to theranostics, appropriate selection of patients eligible for 177Lu-PSMA requires PSMA imaging, whereas the role of added FDG-PET for discriminating those with PSMA/FDG discordance needs to be further evaluated.

Evolving Castration Resistance and Prostate Specific Membrane Antigen Expression: Implications for Patient Management

Simple SummaryThis review is a summary of recent findings on the role of prostate-specific membrane antigen (PSMA) in metastatic castration-resistant prostate cancer (mCRPC) and how they can be implemented into patient management. The multiple aspects, interactions and functions of PSMA expression should be considered with regard to diagnosis and treatment. Approval of 177Lu-PSMA radioligand therapy (PSMA-RLT) by the FDA is impending and might lead to broader indications for application than third-line therapy of mCRPC. Earlier use of PSMA-RLT and combinatorial approaches with other novel agents are the promising future of mCRPC management.Metastatic castration-resistant prostate cancer (mCRPC) remains an incurable disease, despite multiple novel treatment options. The role of prostate-specific membrane antigen (PSMA) in the process of mCRPC development has long been underestimated. During the last years, a new understanding of the underlying molecular mechanisms of rising PSMA expression and its association with disease progression has emerged. Accurate understanding of these complex interactions is indispensable for a precise diagnostic process and ultimately successful treatment of advanced prostate cancer. The combination of different novel therapeutics such as androgen deprivation agents, 177LU-PSMA radioligand therapy and PARP inhibitors promises a new kind of efficacy. In this review, we summarize the current knowledge about the most relevant molecular mechanisms around PSMA in mCRPC development and how they can be implemented in mCRPC management.

More Than Meets the Eye: Scientific Rationale behind Molecular Imaging and Therapeutic Targeting of Prostate-Specific Membrane Antigen (PSMA) in Metastatic Prostate Cancer and Beyond.

Simple SummaryProstate-specific membrane antigen (PSMA) is a transmembrane protein that is overexpressed in prostate cancer and correlates with the aggressiveness of the disease. PSMA is a promising target for imaging and therapeutics in prostate cancer patients validated in prospective trials. However, the role of PSMA in prostate cancer progression is poorly understood. In this review, we discuss the biology and scientific rationale behind the use of PSMA and other targets in the detection and theranostics of metastatic prostate cancer.Prostate cancer is the second most common cancer type in men globally. Although the prognosis for localized prostate cancer is good, no curative treatments are available for metastatic disease. Better diagnostic methods could help target therapies and improve the outcome. Prostate-specific membrane antigen (PSMA) is a transmembrane glycoprotein that is overexpressed on malignant prostate tumor cells and correlates with the aggressiveness of the disease. PSMA is a clinically validated target for positron emission tomography (PET) imaging-based diagnostics in prostate cancer, and during recent years several therapeutics have been developed based on PSMA expression and activity. The expression of PSMA in prostate cancer can be very heterogeneous and some metastases are negative for PSMA. Determinants that dictate clinical responses to PSMA-targeting therapeutics are not well known. Moreover, it is not clear how to manipulate PSMA expression for therapeutic purposes and develop rational treatment combinations. A deeper understanding of the biology behind the use of PSMA would help the development of theranostics with radiolabeled compounds and other PSMA-based therapeutic approaches. Along with PSMA several other targets have also been evaluated or are currently under investigation in preclinical or clinical settings in prostate cancer. Here we critically elaborate the biology and scientific rationale behind the use of PSMA and other targets in the detection and therapeutic targeting of metastatic prostate cancer.

PSMA Theranostics: A "Must Have" in Every Prostate Cancer Center. Illustration of Two Clinical Cases and Review of the Literature.

This manuscript describes the history of 2 patients with prostate cancer (PCa) and the role of prostate-specific membrane antigen (PSMA) theranostics in their clinical management. In the first patient, PSMA-directed positron emission tomography (PET)/computed tomography (CT) imaging was used for primary staging of high-risk PCa before initial therapy. Then after biochemical relapse it was used to plan the scope of further treatment, in which it allowed among others to perform precise target volume delineation for salvage radiotherapy for pathologic lymph nodes. In the second patient with metastatic castration-resistant prostate cancer (mCRPC), PSMA-guided imaging played a key role in the qualification for PSMA-directed radioligand therapy (RLT) with lutetium-177. We also present a review of the current literature concerning PSMA theranostics in the 2 clinical settings, ie, primary staging of PCa and PSMA RLT of mCRPC. In the first part of the review, we report on the diagnostic efficacy of various PSMA imaging radiotracers labeled with gallium-68, fluorine-18, and technetium-99m. In the second part, we describe the limitations and future perspectives of PSMA therapeutic radiopharmaceuticals, including various beta(-) and alpha emitters.

Role of PSMA PET/CT imaging in the diagnosis, staging and restaging of prostate cancer.

Prostate-specific membrane antigen (PSMA) PET/CT is a novel imaging technique for the detection and staging of either primary or recurrent prostate cancer. Early studies demonstrated its improved sensitivity and specificity over and in combination with other currently employed imaging techniques, such as multiparametricMRI, bone scan, PET and CT. However, the lack of strength and confidence in these studies has meant incorporation of PSMA PET/CT into clinical guidelines and practice has been limited to date. In response, a number of high-quality prospective studies have recently emerged and reflect exciting results seen in preceding publications. Here we recount some of the key earlier publications, report results from the latest studies and look to the future discussing some of the eagerly awaited ongoing clinical trials.

Prostate-Specific Membrane Antigen (PSMA) Promotes Angiogenesis of Glioblastoma Through Interacting With ITGB4 and Regulating NF-κB Signaling Pathway.

BackgroundGlioblastoma multiforme (GBM) is the most common primary malignant tumor in the central nervous system (CNS), causing the extremely poor prognosis. Combining the role of angiogenesis in tumor progression and the role of prostate-specific membrane antigen (PSMA) in angiogenesis, this study aims to explore the functions of PSMA in GBM.MethodsClinical GBM specimens were collected from 60 patients who accepted surgical treatment in Fudan University Shanghai Cancer Center between January 2018 and June 2019. Immunohistochemical staining was used to detect PSMA and CD31 expression in GBM tissues. Prognostic significance of PSMA was evaluated by bioinformatics. Human umbilical vein endothelial cells (HUVECs) transfected with PSMA overexpression plasmids or cultured with conditioned medium collected based on GBM cells, were used for CCK8, Transwell and tube formation assays. High-throughput sequencing and immunoprecipitation were used to explore the underlying mechanism. Furthermore, the in vivo experiment had been also conducted.ResultsWe demonstrated that PSMA was abundantly expressed in endothelium of vessels of GBM tissues but not in vessels of normal tissues, which was significantly correlated with poor prognosis. Overexpression of PSMA could promotes proliferation, invasion and tube formation ability of human umbilical vein endothelial cells (HUVECs). Moreover, U87 or U251 conditioned medium could upregulated PSMA expression and induce similar effects on phenotypes of HUVECs, all of which could be partially attenuated by 2-PMPA treatment. The mechanistic study revealed that PSMA might promote angiogenesis of GBM through interacting with Integrin β4 (ITGB4) and activating NF-κB signaling pathway. The in vivo growth of GBM could be alleviated by the treatment of 2-PMPA.ConclusionThis study identified PSMA as a critical regulator in angiogenesis and progression of GBM, which might be a promising therapeutic target for GBM treatment.

Head-to-head comparison of 68Ga-PSMA-11 PET/CT and mpMRI in the detection, intra-prostatic localization, and local extension of primary prostate cancer: A single-center imaging study with histopathology gold-standard.

193 Background: The local staging of prostate cancer relies on systematic or targeted biopsies and multiparametric magnetic resonance imaging (mpMRI). The role of prostate-specific membrane antigen (PSMA)-targeted PET in the evaluation of intraprostatic cancer foci and T-staging assessment is not well defined. The goal of this analysis was to compare the diagnostic performance of PSMA PET/CT, mpMRI and the combination of the two (PSMA PET/CT+mpMRI) in the detection, intra-prostatic localization and local extension of primary prostate cancer with histopathology as the gold standard.Methods: Patients with intermediate- or high-risk prostate cancer underwent a PSMA PET/CT scan and mpMRI prior to intended radical prostatectomy. Each imaging modality was interpreted by 3 blinded independent readers. A majority rule was applied (2:1). A standardized approach was used to assess presence, location and size of prostate cancer foci within the prostate. The analysis was conducted on a lesion- and segment-level. Whole mount pathology was interpreted by a Genito-Urinary pathologist using the same standardized method described above. Accuracy in determining the location, extra-capsular extension (ECE) and seminal vesicle invasion (SVI) of prostate cancer foci were assessed using receiver operating characteristic (ROC) analysis. A “raw-stringent” and “neighboring” approach were used to define imaging/pathology correlation for the detection of individual prostate cancer foci. Results: The final analysis included 74 patients. Detection rate was 75%, 79% and 82% using the “raw-stringent” approach, 86%, 83% and 87% using the “neighboring” approach for PSMA PET/CT, mpMRI and PSMA PET/CT+mpMRI, respectively. Differences in detection rates between PSMA PET/CT, mpMRI and PSMA PET/CT+mpMRI were not statistically significant. The two imaging modalities performed similarly (AUC = 0.70 vs 0.73, p = 0.09; AUC = 0.77 for the two together) in localizing prostate cancer. ΔAUC between PSMA PET/CT+mpMRI and the two imaging modalities alone was statistically significant (p &lt; 0.001), but not between PSMA PET/CT and mpMRI (p = 0.093). mpMRI performed better than PSMA PET/CT in the T-staging assessment: ECE (AUC = 0.79 vs 0.59, p = 0.002) and SVI (AUC = 0.84 vs 0.63, p = 0.001). Conclusions: PSMA PET/CT and mpMRI have similar diagnostic accuracy in the detection and intra-prostatic localization of prostate cancer foci while mpMRI performs better in the assessment of ECE and SVI. The combination of the two imaging modalities improves performance of the two modalities alone, but this does not reach statistically significant levels on a lesion-level and might not justify changes in the current practices for local staging of prostate cancer.

Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography Compared with Conventional Imaging for Initial Staging of Treatment-naïve Intermediate- and High-risk Prostate Cancer: A Retrospective Single-center Study

BackgroundThe role of prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) imaging in the initial staging of men with prostate cancer (PCa) has yet to be evaluated adequately. ObjectiveTo investigate the concordance of PSMA PET/CT with conventional imaging (CI) with cross-sectional abdominopelvic and/or radionuclide bone imaging in the initial staging of patients with treatment-naïve PCa. Design, setting, and participantsWe performed a post hoc retrospective cohort study of patients enrolled in a prospective single-arm trial (NCT03368547). We included patients with intermediate-risk (IR) and high-risk (HR) PCa who underwent PSMA PET/CT within 6 mo of CI. Patients with any treatment prior to PSMA PET/CT were excluded. Patient- and tumor-specific data, and imaging findings were obtained. Outcome measurements and statistical analysisOur primary outcome measurement was the concordance rate of PSMA PET/CT with CI for the identification of N, M1a, M1b, and M1c disease. Descriptive statistics were used. Results and limitationsA total of 168 patients with treatment-naïve IR and HR PCa met the inclusion criteria. HR disease accounted for 124/168 (73.8%) patients. The median prostate-specific antigen was 11.4 (6.8–24.6)ng/ml. The rates of nonconcordance between PSMA PET/CT and CI were 34/162 (21.0%), 5/70 (7.1%), 8/92 (8.7%), and 1/71 (1.4%) for N, M1a, M1b, and M1c disease, respectively. PSMA PET/CT assigned a higher stage in 37/168 (22.0%) patients and a lower stage in 12/170 (7.1%) patients. In a subset of 50 patients treated with radical prostatectomy and pelvic lymph node dissection, the prevalence of PSMA PET/CT–positive and that of CI-positive nodal disease were 14% and 4%, and the false negative rates were 30% and 32%, respectively. The principal limitations of this study include the heterogeneity in CI modalities and the 6-mo time frame between CI and PSMA PET. ConclusionsPSMA PET/CT imaging may serve as a valuable tool in the initial staging of treatment-naïve IR and HR PCa. Patient summaryWe evaluated how prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) compared with standard imaging (such as computed tomography, bone scan, and prostate magnetic resonance imaging) for initial staging of patients with prostate cancer. Our findings suggest that PSMA PET/CT may detect and rule out more metastatic lesions, which could prove valuable in guiding treatment.

The potential of PSMA-targeted alpha therapy in the management of prostate cancer

ABSTRACT Introduction Alpha emitters present several advantages for cancer therapy. The radiopharmaceutical 223Ra-dichloride has been recently introduced for the targeted alpha therapy (TAT) of metastastic castration-resistant prostate cancer (mCRPC). However, since 223Ra-dichloride targets only skeletal lesions, its use in clinical practice is recommended only in subjects without visceral metastases. To overcome this, several efforts have been made to develop radiopharmaceuticals suitable for TAT and specifically directed toward the biomarker prostate specific membrane antigen (PSMA), overexpressed by both skeletal and visceral metastases from mCRPC. Areas covered The radiobiological principles concerning TAT applications are covered, with particular emphasis on its pros and cons, especially in comparison with beta-emitter radionuclide therapy. Furthermore, the role of PSMA as a theranostic target for imaging and therapy is reviewed. Lastly, the pre-clinical and clinical applications of TAT through 225Actinium (225AC) and 213Bismuth (213Bi) are discussed. Expert opinion PSMA-based TAT holds the promise of becoming a powerful tool for the management of mCRPC. Nevertheless, several issues have still to be addressed, especially concerning TAT toxicity. Furthermore, several efforts have to be made for identifying the more adequate alpha-emitter (225Ac vs 213Bi) with a view to the patient’s tailored therapeutic approach.

Use of prostate-specific membrane antigen positron-emission tomography/CT in response assessment following upfront chemohormonal therapy in metastatic prostate cancer.

Prostate-specific membrane antigen (PSMA) PET/CT imaging is increasingly being utilised in clinical practice, demonstrating greater sensitivity in the detection of metastatic prostate cancer (mPC) compared to conventional imaging [1]. Prior studies have primarily focussed on its use following biochemical recurrence to detect oligometastatic disease potentially amenable to salvage therapies [2-4]. However, the role of PSMA PET/CT in assessing treatment response remains unclear. Standardised criteria for metabolic response have not been established, particularly to account for whole body tumour burden and the effects of systemic therapies on PSMA expression.

The emerging role of prostate-specific membrane antigen (PSMA) PET-CT in patients with high-risk prostate cancer: moving the bar in high-risk prostate cancer.

The emerging role of prostate-specific membrane antigen (PSMA) PET-CT in patients with high-risk prostate cancer: moving the bar in high-risk prostate cancer.

The role of prostate-specific membrane antigen PET/computed tomography in primary staging of prostate cancer.

Functional imaging with PET combined with computed tomography (CT) is of emerging interest in prostate cancer (PCa). Development of prostate-specific membrane antigen (PSMA) radiolabelled ligands has thrust PET/CT into the limelight as an alternative to conventional imaging techniques, and the evidence base to support its utility in primary staging of newly diagnosed PCa is rapidly growing. This review focuses on the most recent and important publications evaluating PSMA PET/CT in primary staging of PCa. Three recent meta-analyses have reported Ga-PSMA PET/CT to demonstrate superior sensitivity and specificity for pelvic lymph node detection than conventional imaging. A recent systematic review also suggests Ga-PSMA PET/CT to be superior to bone scan for identifying bone metastases. However, the majority of studies are of a retrospective nature, and few provide histopathological correlation of PSMA PET/CT findings. Data from prospective studies are awaited to determine accuracy and management impact of PSMA PET/CT in primary staging. PSMA PET/CT is rapidly altering the landscape of primary staging in PCa. It appears to be superior to conventional imaging for detecting regional and distant metastasis, though caution should be applied given the lack of prospective studies assessing how significant findings should be integrated into patient management. PSMA PET/CT could potentially become the gold standard for primary staging of high-risk PCa if future prospective data can prove its validity in this space.