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Simple Summary: The review explores the critical role of prostate-specific membrane antigen (PSMA) PET/CT imaging in diagnosing, staging, and treating prostate cancer. PSMA PET/CT offers superior diagnostic capabilities for identifying prostate cancer's spread, with potential as a prognostic indicator for the disease's recurrence and survival. It highlights PSMA's variability in expression, impacting personalised treatment plans, notably in radioligand therapy with [177Lu] Lu-PSMA-617. This technology enhances treatment strategies, improves outcomes, and reduces unnecessary interventions, marking a significant advancement in personalised prostate cancer management. 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. [ABSTRACT FROM AUTHOR]

Active surveillance remains a treatment option for low- to intermediate-risk prostate cancer (PCa) patients. Prostate-specific membrane antigen positron emission tomography and computed tomography (PSMA PET/CT) has emerged as a useful modality to assess intraprostatic lesions. This systematic review aims to evaluate PSMA PET/CT in localized low- to intermediate-risk PCa to determine its role in active surveillance. Following PRISMA guidelines, a search was performed on Medline, Embase, and Scopus. Only studies evaluating PSMA PET/CT in localized low- to intermediate-risk PCa were included. Studies were excluded if patients received previous treatment, or if they included high-risk PCa. The search yielded 335 articles, of which only four publications were suitable for inclusion. One prospective study demonstrated that PSMA PET/CT-targeted biopsy has superior diagnostic accuracy when compared to mpMRI. One prospective and one retrospective study demonstrated MRI occult lesions in 12.3–29% of patients, of which up to 10% may harbor underlying unfavorable pathology. The last retrospective study demonstrated the ability of PSMA PET/CT to predict the volume of Gleason pattern 4 disease. Early evidence demonstrated the utility of PSMA PET/CT as a tool in making AS safer by detecting MRI occult lesions and patients at risk of upgrading of disease. [ABSTRACT FROM AUTHOR]

Objectives: To identify whether synchronous reading of multiparametric magnetic resonance imaging (mpMRI) and 68Ga‐PSMA‐11 positron emission tomography (PET)/computed tomography (prostate‐specific membrane antigen [PSMA‐PET]) images can improve diagnostic performance and certainty compared with mpMRI/PSMA‐PET reported independently and synthesized, while also assessing concordance between imaging modalities and agreement with histopathology. Methods: This was a retrospective analysis of 100 patients randomly selected from the PRIMARY trial, a prospective Phase II multicentre imaging trial. Three dual‐trained radiologist/nuclear medicine physicians re‐reported the mpMRI and PSMA‐PET both independently and synchronously for the same patients in random order, blinded to previous results. Diagnostic performance was assessed for mpMRI/PSMA‐PET images read synchronously or independently and then synthesized. Agreement between imaging results and histopathology was examined. 'Concordance' between imaging modalities was defined as overlapping lesions. Reporting certainty was evaluated by the individual reporters for each modality. Results: International Society of Urological Pathology Grade Group ≥2 cancer was present in 60% of patients on biopsy. Synchronous reading of mpMRI/PSMA‐PET increased sensitivity compared to mpMRI or PSMA‐PET alone (93% vs 80% vs 88%, respectively), although specificity was not improved (63% vs 58% vs 78%, respectively). No significant difference in diagnostic performance was noted between mpMRI/PSMA‐PET read synchronously and mpMRI or PSMA‐PET reported independently and then synthesized. Most patients had concordant imaging (60%), while others had discordant lesions only (28%) or a mixture (concordant and discordant lesions; 12%). When mpMRI/PSMA‐PET findings were concordant and positive, 95% of patients had clinically significant prostate cancer (csPCa). When PSMA‐PET alone was compared to synchronous PSMA‐PET/MRI reads, there was an improvement in reader certainty in 20% of scans. Conclusion: Synchronous mpMRI/PSMA‐PET reading improves reader certainty and sensitivity for csPCa compared to mpMRI or PSMA‐PET alone. However, synthesizing the results of independently read PSMA‐PET and mpMRI reports provided similar diagnostic performance to synchronous PSMA‐PET/MRI reads. This may provide greater flexibility for urologists in terms of referral patterns, reducing healthcare system costs and improving efficiencies in prostate cancer diagnosis. [ABSTRACT FROM AUTHOR]

1 Table Comparison of salvage radiation treatment and surveillance as management strategies for low-risk biochemical recurrence with negative prostate-specific membrane antigen positron emission tomography/CT. Abbreviations ADT androgen deprivation therapy EAU European Association of Urology PET positron emission tomography PSMA prostate-specific membrane antigen RT radiation therapy Biochemical recurrence, or first detection of measurable serum PSA after radical prostatectomy, occurs in approximately one-third of patients [[1]] and is often the first indicator of residual or relapsed prostate cancer. As most potential sources of biochemical recurrence are located in the pelvis, treatment of biochemical recurrence largely relies on salvage radiation therapy (RT), including prostate bed/fossa with or without pelvic lymph node RT, sometimes with androgen deprivation therapy (ADT). [Extracted from the article]

Summary: Early detection and management of prostate cancer has evolved over the past decade, with a focus now on harm minimisation and reducing overdiagnosis and overtreatment, given the proven improvements in survival from randomised controlled trials.Multiparametric magnetic resonance imaging (mpMRI) is now an important aspect of the diagnostic pathway in prostate cancer, improving the detection of clinically significant prostate cancer, enabling accurate localisation of appropriate sites to biopsy, and reducing unnecessary biopsies in most patients with normal magnetic resonance imaging scans.Biopsies are now performed transperineally, substantially reducing the risk of post‐procedure sepsis.Australian‐led research has shown that prostate‐specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) has superior accuracy in the staging of prostate cancer than conventional imaging (CT and whole‐body bone scan).Localised prostate cancer that is low risk (International Society for Urological Pathology [ISUP] grade 1, Gleason score 3 + 3 = 6; and ISUP grade group 2, Gleason score 3 + 4 = 7 with less than 10% pattern 4) can be offered active surveillance, reducing harms from overtreatment.Prostatectomy and definitive radiation remain the gold standard for localised intermediate and high risk disease. However, focal therapy is an emerging experimental treatment modality in Australia in carefully selected patients.The management of advanced prostate cancer treatment has evolved to now include several novel agents both in the metastatic hormone‐sensitive and castration‐resistant disease settings. Multimodal therapy with androgen deprivation therapy, additional systemic therapy and radiotherapy are often recommended.PSMA‐based radioligand therapy has emerged as a treatment option for metastatic castration‐resistant prostate cancer and is currently being evaluated in earlier disease states. [ABSTRACT FROM AUTHOR]

Simple Summary: Prostate-specific membrane antigen (PSMA) positron emission tomography-computed tomography (PET-CT) is an essential imaging tool that is used to locate prostate cancer when it recurs. The results of this scan are used to guide clinical decisions for the management of cancer. However, the long-term effect of these clinical decisions is yet to be determined. In this study, we followed men with recurrent prostate cancer for 3 years after they had a clinical decision made based on a PSMA PET-CT. Our results showed that 75% of men had no addition or change in their treatment plan 3 years after their initial clinical decision was made. In men with a PSMA PET-CT that showed no suspected cancer, 85% had no addition or change to their treatment plan. This indicates that clinical decisions made using PSMA PET-CT in this setting can have a medium- to long-lasting effect. Prostate-specific membrane antigen (PSMA) positron emission tomography-computed tomography (PET-CT) is a novel imaging modality used to stage recurrent prostate cancer. It has the potential to improve prognostication and ultimately guide the timing of treatment for men with recurrent prostate cancer. This study aims to assess the clinical impact of PSMA PET-CT by analyzing its predictive value of treatment progression after 3 years of follow-up. In this prospective cohort study of 100 men, patients received a PSMA PET-CT for restaging of their disease which was used by a multi-disciplinary team to make a treatment decision. The primary endpoint was treatment progression. This was defined as the addition or change of any treatment modalities such as androgen deprivation therapy (ADT), radiation therapy or chemotherapy. The median follow-up time was 36 months (IQR 24–40 months). No treatment progression was found in 72 (75%) men and therefore 24 (25%) patients were found to have treatment progression. In men with a negative PSMA PET-CT result, 5/33 (15.1%) had treatment progression and 28/33 (84.8%) had no treatment progression. In conclusion, clinical decisions made with PSMA PET-CT results led to 75% of men having no treatment progression at 3 years of follow-up. In men with negative PSMA PET-CT results, this increased to 85% of men. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate outcomes for men with biochemically recurrent prostate cancer who were selected for transponder-guided salvage radiotherapy (SRT) to the prostate bed alone by 68Ga-labelled prostate-specific membrane antigen positron emission tomography (68Ga-PSMA-PET). Methods: This is a single-arm, prospective study of men with a prostate-specific antigen (PSA) level rising to 0.1–2.5 ng/mL following radical prostatectomy. Patients were staged with 68Ga-PSMA-PET and those with a negative finding, or a positive finding localised to the prostate bed, continued to SRT only to the prostate bed alone with real-time target-tracking using electromagnetic transponders. The primary endpoint was freedom from biochemical relapse (FFBR, PSA > 0.2 ng/mL from the post-radiotherapy nadir). Secondary endpoints were time to biochemical relapse, toxicity and patient-reported quality of life (QoL). Results: Ninety-two patients (median PSA of 0.18 ng/ml, IQR 0.12–0.36), were screened with 68Ga-PSMA-PET and metastatic disease was found in 20 (21.7%) patients. Sixty-nine of 72 non-metastatic patients elected to proceed with SRT. At the interim (3-year) analysis, 32 (46.4%) patients (95% CI 34.3–58.8%) were FFBR. The median time to biochemical relapse was 16.1 months. The rate of FFBR was 82.4% for ISUP grade-group 2 patients. Rates of grade 2 or higher gastrointestinal and genitourinary toxicity were 0% and 15.2%, respectively. General health and disease-specific QoL remained stable. Conclusion: Pre-SRT 68Ga-PSMA-PET scans detect metastatic disease in a proportion of patients at low PSA levels but fail to improve FFBR. Transponder-guided SRT to the prostate bed alone is associated with a favourable toxicity profile and preserved QoL. Trial registration number: ACTRN12615001183572, 03/11/2015, retrospectively registered. [ABSTRACT FROM AUTHOR]

Introduction: There has been a growing body of evidence highlighting the improved sensitivity and specificity for prostate specific membrane antigen (PSMA) positron emission tomography (PET) in advanced prostate cancer imaging. We aimed to assess prostate cancer staging practice patterns in Australia using population‐based data. Subject and Methods: We extracted data on men diagnosed with prostate cancer between October 2016 and December 2018 from the Prostate Cancer Outcomes Registry‐Victoria (PCOR‐Vic). We evaluated trends and comparisons between patients receiving PET/CT (with or without conventional imaging (CImg)), and CImg alone, and analysed imaging modality as predictor of clinical regional node positive disease (cN1 vs cN0/X), metastatic disease (cM1 vs cM0/X), and treatment received. Results: In total, 6139 patients in the registry had either a staging PET scan (n = 889, 14%), CImg without PET scan (n = 2464, 40%), or no recorded PET or CImg (n = 2786, 45%). The proportion of allimaged patients who received staging PET increased from 19% to 36% from the first to last three‐month period, and in the high‐risk category the increase was 23–43%. After adjustment for grade group, PET vs CImg‐only patients were observed to have a higher proportion of cN1 disease (OR = 2.46, 95% CI: 1.90–3.20) but not cM1 disease (OR = 1.10, 95% CI: 0.84–1.44). Conclusions: Our registry data highlights the rapid uptake of PET imaging, particularly in high‐risk disease. Based on this data, we highlight the increased diagnosis of nodal disease, thus potentially optimizing patient selection prior to definitive treatment for prostate cancer. [ABSTRACT FROM AUTHOR]

Summary: Prostate cancer continues to be the most commonly diagnosed cancer, and the second leading cause of cancer death among Australian men.Prostate‐specific antigen testing is personalised (not dichotomous in nature) and its interpretation should take into account the patient's age, symptoms, previous results and medication (eg, 5‐α reductase inhibitors such as dutasteride).Multiparametric magnetic resonance imaging of the prostate has been proven to have a 93% sensitivity for detecting clinically significant prostate cancer. It has the potential to decrease unnecessary prostate biopsies by around 27%.International Society of Urological Pathology (ISUP) grade 1 (Gleason score 6) has been shown to have very little, if any, risk of metastasisISUP grade 1 (Gleason score 3 +3 = 6) and low percentage ISUP grade 2 (Gleason score 3 + 4 [< 10%] = 7) can be offered active surveillance. The goal of active surveillance is to defer treatment but is still curative when required.With better imaging (magnetic resonance imaging and emerging prostate‐specific membrane antigen positron emission tomography–computed tomography) and transperineal prostate biopsy, more men can be offered screening after discussion of risks and benefits, knowing that overdiagnosis has been minimised and radical treatment is reserved for only the most aggressive disease. [ABSTRACT FROM AUTHOR]

Objective: To compare the accuracy of 68gallium prostate‐specific membrane antigen positron emission tomography/computed tomography (68Ga‐PSMA PET/CT) with multiparametric MRI (mpMRI) in detecting and localising primary prostate cancer when compared with radical prostatectomy (RP) specimen pathology. Patients and methods: Retrospective review of men who underwent 68Ga‐PSMA PET/CT and mpMRI for primary prostate cancer before RP across four centres between 2015 and 2018. Patients undergoing imaging for recurrent disease or before non‐surgical treatment were excluded. We defined pathological index tumour as the lesion with highest International Society of Urological Pathology Grade Group (GG) on RP specimen pathology. Our primary outcomes were rates of accurate detection and localisation of RP specimen pathology index tumour using 68Ga‐PSMA PET/CT or mpMRI. We defined tumour detection as imaging lesion corresponding with RP specimen tumour on any imaging plane, and localisation as imaging lesion matching RP specimen index tumour in all sagittal, axial, and coronal planes. Secondary outcomes included localisation of clinically significant and transition zone (TZ) index tumours. We defined clinically significant disease as GG 3–5. We used descriptive statistics and the Mann–Whitney U‐test to define and compare demographic and pathological characteristics between detected, missed and localised tumours using either imaging modality. We used the McNemar test to compare detection and localisation rates using 68Ga‐PSMA PET/CT and mpMRI. Results: In all, 205 men were included in our analysis, including 133 with clinically significant disease. There was no significant difference between 68Ga‐PSMA PET/CT and mpMRI in the detection of any tumour (94% vs 95%, P > 0.9). There was also no significant difference between localisation of all index tumours (91% vs 89%, P = 0.47), clinically significant index tumours (96% vs 91%, P = 0.15) or TZ tumours (85% vs 80%, P > 0.9) using 68Ga‐PSMA PET/CT and mpMRI. Limitations include retrospective study design and non‐central review of imaging and pathology. Conclusion: We found no significant difference in the detection or localisation of primary prostate cancer between 68Ga‐PSMA PET/CT and mpMRI. Further prospective studies are required to evaluate a combined PET/MRI model in minimising tumours missed by either modality. [ABSTRACT FROM AUTHOR]

Objectives: To develop a registration framework for correlating positron emission tomography/computed tomography (PET/CT) images with multiparametric magnetic resonance imaging (mpMRI) and histology of the prostate, thereby enabling voxel‐wise analysis of imaging parameters. Patients and Methods: In this prospective proof‐of‐concept study, nine patients scheduled for radical prostatectomy underwent mpMRI and PET/CT imaging before surgery. One had PET imaging using 18F‐fluoromethylcholine, five using 68Ga‐labelled prostate‐specific membrane antigen (PSMA)‐HBED‐CC (PMSA‐11), and three using a trial 68Ga‐labelled THP‐PSMA tracer. PET/CT data were co‐registered with mpMRI via the CT scan and an in vivo three‐dimensional T2‐weighted (T2w) MRI, and then co‐registered with ground truth histology data using ex vivo MRI of the prostate specimen. Maximum and mean standardised uptake values (SUVmax and SUVmean) were extracted from PET data using tumour annotations from histology, and Kolmogorov–Smirnov tests were used to compare between tumour‐ and benign‐voxel values. Correlation analysis was performed between mpMRI and PET SUV tumour voxel values using Pearson's correlation coefficient and R2 statistics. Results: PET/CT data from all nine patients were successfully registered with mpMRI and histology data. SUVmax and SUVmean ranged from 2.21 to 12.11 and 1.08 to 4.21, respectively. All patients showed the PET SUV values in benign and tumour voxels were from statistically different distributions. Correlation analysis showed no consistent trend between the T2w or apparent diffusion coefficient values and PET SUV. However, parameters from dynamic contrast‐enhanced (DCE) MRI including the maximum enhancement, volume transfer constant (Ktrans), and the initial area under the contrast agent concentration curve for the first 60 s after injection (iAUGC60), showed consistent positive correlations with PET SUV. Furthermore, R2* values from blood oxygen level‐dependent (BOLD) MRI showed consistent negative correlations with PET SUV‐voxel values. Conclusion: We have developed a novel framework for registering and correlating PET/CT data at a voxel‐level with mpMRI and histology. Despite registration uncertainties, perfusion and oxygenation parameters from DCE MRI and BOLD imaging showed correlations with PET SUV. Further analysis will be performed on a larger patient cohort to quantify these proof‐of‐concept findings. Improved understanding of the correlation between mpMRI and PET will provide supportive information for focal therapy planning of the prostate. [ABSTRACT FROM AUTHOR]

The ability to accurately stage prostate cancer in both the primary and secondary staging setting can have a major impact on management. Until recently radiological staging has relied on computer tomography, magnetic resonance imaging, and nuclear bone scans to evaluate the extent of disease. However, the utility of these imaging technologies has been limited by their sensitivity and specificity especially in detecting early recurrence. Functional imaging using positron-emission tomography with a radiolabeled ligand targeted to prostate-specific membrane antigen has transformed the prostate cancer imaging landscape. Initial results suggest that it is a substantial improvement over conventional imaging in the setting of recurrence following primary therapy by having a superior ability to detect disease and to do so at an earlier stage. Additionally, it appears that the benefits seen in the secondary staging setting may also exist in the primary staging setting. [ABSTRACT FROM AUTHOR]

the article offers information on prostate-specific membrane antigen positron-emission tomography imaging radio-guided surgery helps in the treatment of prostate cancer. Topics discussed include use of radiotracer during salvage lymphadenectomy for recurrent prostate cancer; intra-operative c-probe measurements; and technology helps in the treatment of prostate cancer.

The article focuses on significance of positron-emission/computed tomography (PET/CT) associated with prostate-specific membrane antigen (PSMA) usage for prostate cancer diagnosis. Topics discussed include enhancement of conventional imaging services by small molecule ligands development that binds with PSMA molecule; prostate recurrence identification among biochemical recurrence (BCR) patients; and illustration of high risks for radical prostatectomy among patients.

Abstract Background Stereotactic ablative body radiotherapy (SABR) is an emerging treatment option for oligometastatic prostate cancer. However, limited prospective evidence is available. Objective To determine the safety and feasibility of single fraction SABR for patients with oligometastatic prostate cancer. Secondary endpoints were local and distant progression-free survival (LPFS and DPFS), toxicity, quality of life (QoL), and prostate-specific antigen response. Design, setting, and participants In a prospective clinical trial, patients were screened with computed tomography, bone scan, and sodium fluoride positron emission tomography scan and had one to three oligometastases. Kaplan-Meier methods were used to determine LPFS and DPFS. Toxicity was graded using Common Terminology Criteria for Adverse Event version 4.0. QoL was assessed using European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-BM22 at 1, 3,12, and 24 mo. Intervention A single fraction of 20-Gy SABR to each lesion. Results and limitations Between 2013 and 2014, 33 consecutive patients received SABR to a total of 50 oligometastases and were followed for 2 yr. The median age was 70 yr. The Gleason score was ≥8 in 15 patients (45%). Twenty patients had bone only, 12 had node only, and one had mixed disease. SABR was feasible and delivered as planned in 97% of cases. There was one grade 3 adverse event (3.0%, vertebral fracture). No patient died. The 1 and 2-yr LPFS was 97% (95% confidence interval [CI]: 91–100) and 93% (95% CI: 84–100), and DPFS was 58% (95% CI: 43–77) and 39% (95% CI: 25–60), respectively. In those not on androgen deprivation therapy (ADT; n = 22), the 2-yr freedom from ADT was 48%. There was no significant difference from baseline QoL observed. Limitations include small sample size, limited duration of follow-up, and lack of a control arm. Conclusions A single SABR session was feasible and associated with low morbidity in this cohort. Over one-third of patients did not progress and were free from ADT at 2-yr. QoL measures were maintained with this treatment strategy. Patient summary This clinical trial investigated single treatment stereotactic radiotherapy for low volume advanced prostate cancer. The approach was found to be safe with avoidance of hormone therapy in almost half of the participants at 2 yr. Take Home Message For patients with one to three oligometastases from prostate cancer, single fraction 20-Gy stereotactic ablative body radiotherapy was both safe and feasible. Local and distant progression-free survival at 2 yr were 93% and 39%, respectively. Quality of life was maintained at baseline levels using this treatment strategy. [ABSTRACT FROM AUTHOR]

We synthesised evidence from head-to-head comparisons of prostate-specific membrane antigen positron emission tomography (PSMA-PET) and conventional imaging modalities the same patient cohorts and found that PSMA-PET is significantly more sensitive and specific than computed tomography, multiparametric magnetic resonance imaging (mpMRI), and bone scans for staging of nodal and bone metastases staging, and more sensitive than mpMRI in local tumour staging when PSMA-PET/MRI was used. The results suggest that first-line PSMA-PET for imaging of primary prostate cancer would significantly improve diagnostic accuracy. Further studies are needed to identify how such an improvement can be translated into further oncological benefits. Whether prostate-specific membrane antigen positron emission tomography (PSMA-PET) should replace conventional imaging modalities (CIM) for initial staging of intermediate-high risk prostate cancer (PCa) requires definitive evidence on their relative diagnostic abilities. To perform head-to-head comparisons of PSMA-PET and CIM including multiparametric magnetic resonance imaging (mpMRI), computed tomography (CT) and bone scan (BS) for upfront staging of tumour, nodal, and bone metastasis. A search of the PubMed, EMBASE, CENTRAL, and Scopus databases was conducted from inception to December 2021. Only studies in which patients underwent both PSMA-PET and CIM and imaging was referenced against histopathology or composite reference standards were included. Quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) checklist and its extension for comparative reviews (QUADAS-C). Pairwise comparisons of the sensitivity and specificity of PSMA-PET versus CIM were performed by adding imaging modality as a covariate to bivariate mixed-effects meta-regression models. The likelihood ratio test was applied to determine whether statistically significant differences existed. A total of 31 studies (2431 patients) were included. PSMA-PET/MRI was more sensitive than mpMRI for detection of extra-prostatic extension (78.7% versus 52.9%) and seminal vesicle invasion (66.7% versus 51.0%). For nodal staging, PSMA-PET was more sensitive and specific than mpMRI (73.7% versus 38.9%, 97.5% versus 82.6%) and CT (73.2% versus 38.5%, 97.8% versus 83.6%). For bone metastasis staging, PSMA-PET was more sensitive and specific than BS with or without single-photon emission computerised tomography (98.0% versus 73.0%, 96.2% versus 79.1%). A time interval between imaging modalities >1 month was identified as a source of heterogeneity across all nodal staging analyses. Direct comparisons revealed that PSMA-PET significantly outperforms CIM, which suggests that PSMA-PET should be used as a first-line approach for the initial staging of PCa. We reviewed direct comparisons of the ability of a scan method called PSMA-PET (prostate-specific membrane antigen positron emission tomography) and current imaging methods to detect the spread of prostate cancer outside the prostate gland. We found that PSMA-PET is more accurate for detection of the spread of prostate cancer to adjacent tissue, nearby lymph nodes, and bones. [ABSTRACT FROM AUTHOR]

Studies suggest that prostate-specific membrane antigen (PSMA)-targeted imaging is superior to conventional imaging for detection of primary and recurrent prostate cancer, albeit with several clinically relevant limitations. PSMA-targeted imaging may have greater sensitivity and specificity for detection of oligometastatic disease. However, whether PSMA imaging alters disease progression despite treatment intensification is yet to be determined in prospective clinical trials. Prostate-specific membrane antigen (PSMA) is a promising molecular target for prostate cancer (PCa) that has allowed the development of a novel diagnostic approach to PCA in the primary and recurrent settings. To summarize available data and recommendations regarding the use of PSMA in newly diagnosed and recurrent PCa via a narrative review. A literature review was conducted using MEDLINE (via PubMed) and Scopus. The search strategy included meta-analyses, reviews, and original studies on staging and restaging with 68Ga-PSMA positron emission tomography (PET)/computed tomography (CT). Studies comparing PSMA-targeted imaging and conventional imaging suggest superior performance of PSMA-targeted imaging in primary and recurrent PCa, albeit with several clinically relevant limitations. Pretreatment 68Ga-PSMA PET/CT allowed more accurate PCa staging in compared to routine practice for high-risk cases, and identified a number of otherwise unknown metastatic lesions. In biochemically recurrent PCa, PSMA PET can reveal sites of recurrence with greater sensitivity and specificity than conventional imaging, potentially detecting a major proportion of occult disease. This review will help providers in applying the most up-to-date and relevant literature to (1) determine which patients truly have oligometastatic disease and (2) ascertain who is most likely to experience a meaningful response to local consolidation in the biochemical recurrence setting. Data on PSMA diagnostic studies in primary and recurrent PCa highlight the accuracy and clinical application of PSMA PET. While this review and the evidence to date might lead to a perception of superiority in metastasis directed therapy, fundamental lack of phase III clinical trials with clinically meaningful outcomes are yet to be determined. PSMA (prostate-specific membrane antigen) scans have shown great promise for initial evaluation of prostate cancer (PCa) and in detection of PCa recurrence. The benefits are more apparent for initial staging of PCa. There are more limited clinical trial results for PCa recurrence on how best to use this new technique to guide cancer treatment. [ABSTRACT FROM AUTHOR]

Prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) produces strikingly superior images compared to conventional imaging, raising the important question of whether conventional imaging is sufficiently accurate to guide patient management. Reducing false positive results with consequent improvement in accuracy is not stage migration and PSMA PET/CT can be a successor to conventional imaging in the staging of metastatic hormone-sensitive prostate cancer. [ABSTRACT FROM AUTHOR]

Accurate staging of high-risk localised, advanced, and metastatic prostate cancer is becoming increasingly more important in guiding local and systemic treatment. Gallium-68 prostate-specific membrane antigen (PSMA) positron emission tomography (PET) has increasingly been utilised globally to assess the local and metastatic burden of prostate cancer, typically in biochemically recurrent or advanced disease. Following our previous meta-analysis, a high-volume series has been reported highlighting the utility of 68Ga-PSMA PET in this setting. To perform a systematic review and meta-analysis to update reported predictors of positive 68Ga-PSMA PET according to prior therapy and proportion of positivity in various anatomical locations with sensitivity and specificity profiles. We performed critical reviews of MEDLINE, EMBASE, ScienceDirect, Cochrane Libraries, and Web of Science databases in July 2018 according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. Quality assessment was performed using Quality Assessment if Diagnostic Accuracy Studies-2 tool. Meta-analyses of proportions were performed using a random-effect model. Summary sensitivity and specificity values were obtained by fitting bivariate hierarchical regression models. A total of 37 articles including 4790 patients were analysed. For patients with biochemical recurrence, positive 68Ga-PSMA PET scans increased with higher pre-PET prostate-specific antigen (PSA) levels. For PSA categories 0–0.19, 0.2–0.49, 0.5–0.99, 1–1.99, and ≥2 ng/ml, the percentages of positive scans were 33%, 45%, 59%, 75%, and 95%, respectively. No significant differences in positivity were noted between Gleason sums ≤7 and ≥8. Significant differences in positivity after biochemical recurrence in the prostate bed were noted between radical prostatectomy (22%) and radiotherapy (52%) patients. On per-node analysis, high sensitivity (75%) and specificity (99%) were observed. Ga-68-PSMA PET improves detection of metastases with biochemical recurrence, particularly at low pre-PET PSA levels of >0.2 ng/ml (33%) and 0.2–0.5 ng/ml (45%). Ga-68-PSMA-PET produces favourable sensitivity and specificity profiles on meta-analysis of pooled data. This analysis highlights different anatomic patterns of metastatic spread according to PSMA PET in the primary and biochemically recurrent settings. Gallium-68 prostate-specific membrane antigen positron emission tomography is now an established imaging technique that has been developed in response to inadequacies in standard of care imaging modalities to improve the detection of metastatic disease in prostate cancer, particularly in the setting of disease recurrence. To date, this imaging modality in the setting of primary staging is controversial, given the paucity of data. In light of the growing body of evidence, we summarised the data to date to provide clinicians with an overview of this imaging modality. Gallium-68 prostate-specific membrane antigen positron emission tomography is now an established imaging technique that has been developed in response to inadequacies in standard-of-care imaging modalities to improve the detection of metastatic disease in prostate cancer. In light of the growing body of evidence, we summarised the data to date to provide clinicians with an overview of this imaging modality. [ABSTRACT FROM AUTHOR]

Context Positron emission tomography (PET) of 68 Ga-labelled prostate-specific membrane antigen ( 68 Ga-PSMA) is an emerging imaging modality introduced to assess the burden of prostate cancer, typically in biochemically recurrent or advanced disease. 68 Ga-PSMA PET provides the ability to selectively identify and localize metastatic prostate cancer cells and subsequently change patient management. Owing to its limited history, robust sensitivity and specificity data are not available for 68 Ga-PSMA PET–positive scans. Objective A systematic review and meta-analysis of reported predictors of positive 68 Ga-PSMA PET and corresponding sensitivity and specificity profiles. Evidence acquisition We performed critical reviews of MEDLINE, EMBASE, ScienceDirect, Cochrane Library, and Web of Science databases in April 2016 according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. Quality was assessed using the Quality Assessment if Diagnostic Accuracy Studies-2 tool. Meta-analysis and meta-regression of proportions were performed using a random-effects model with pre-PET prostate-specific antigen (PSA) levels as the dependent variable. Summary sensitivity and specificity values were obtained by fitting bivariate hierarchical regression models. Evidence synthesis Sixteen articles involving 1309 patients were analysed. The overall percentage of positive 68 Ga-PSMA PET among patients was 40% (95% confidence interval [CI] 19–64%) for primary staging and 76% (95% CI 66–85%) for biochemical recurrence (BCR). Positive 68 Ga-PSMA PET scans for BCR patients increased with pre-PET PSA. For the PSA categories 0–0.2, 0.2–1, 1–2, and >2 ng/ml, 42%, 58%, 76%, and 95% scans, respectively, were positive. Shorter PSA doubling time increased 68 Ga-PSMA PET positivity. On per-patient analysis, the summary sensitivity and specificity were both 86%. On per-lesion analysis, the summary sensitivity and specificity were 80% and 97%, respectively. Conclusions In the setting of BCR prostate cancer, pre-PET PSA predicts the risk of positive 68 Ga-PSMA PET. Pooled data indicate favourable sensitivity and specificity profiles compared to choline-based PET imaging techniques. Patient summary Positron emission tomography using 68 Ga-labelled prostate-specific membrane antigen is an emerging radiological technique developed to improve the characterisation of metastatic prostate cancer. We summarised the data available to date and found that this new test provides excellent rates of detection of cancer spread in late-stage prostate cancer. [ABSTRACT FROM AUTHOR]

Abstract: GABA (gamma-amino-butyric-acid) is the primary inhibitory neurotransmitter in the human brain. It has been proposed that the symptoms of autism spectrum disorders (ASDs) are the result of deficient GABA neurotransmission, possibly including reduced expression of GABAA receptors. However, this hypothesis has not been directly tested in living adults with ASD. In this preliminary investigation, we used Positron Emission Tomography (PET) with the benzodiazepine receptor PET ligand [11C]Ro15-4513 to measure α1 and α5 subtypes of the GABAA receptor levels in the brain of three adult males with well-characterized high-functioning ASD compared with three healthy matched volunteers. We found significantly lower [11C]Ro15-4513 binding throughout the brain of participants with ASD (p < 0.0001) compared with controls. Planned region of interest analyses also revealed significant reductions in two limbic brain regions, namely the amygdala and nucleus accumbens bilaterally. Further analysis suggested that these results were driven by lower levels of the GABAA α5 subtype. These results provide initial evidence of a GABAA α5 deficit in ASD and support further investigations of the GABA system in this disorder. This article is part of the Special Issue entitled ‘Neurodevelopmental Disorders’. [Copyright &y& Elsevier]