Prostate-specific Membrane Antigen Positron Emission Tomography Research Articles

Management of bone metastasis in prostate cancer.

Progression of bone metastases is the primary cause of death in prostate cancer, and skeletal-related events (SREs), including pathologic fractures, spinal cord compression, radiation, or surgery to bone can impair patients' quality of life. Over the past decade, the development of cytotoxic agents, androgen-receptor-axis-targeted therapies (ARATs), and radioligand therapies has prolonged overall survival of prostate cancer patients with bone metastases and reduced the risk of SREs. The use of bone-modifying agents has also contributed to the reduced risk of SREs. Initial use of a cytotoxic agent, docetaxel, or an ARAT agent with androgen deprivation therapy (ADT) is the current approach to metastatic castration-sensitive prostate cancer. However, there is no consensus on the optimal medication for upfront use in combination with ADT, or on specific patient selection. Recently, next-generation imaging modalities, such as whole-body magnetic resonance imaging and prostate-specific membrane antigen-positron emission tomography have been utilized to detect bone metastases at an early stage. In addition, metastasis-directed therapy, such as stereotactic body radiation therapy, has been attempted. In the future, patients with bone metastatic prostate cancer will be divided into subgroups and their treatment options will be tailored to their specific characteristics.

Expanding the role of PSMA PET in active surveillance

IntroductionAccurate grading at the time of diagnosis is fundamental to risk stratification and treatment decision making, particularly for men being considered for Active Surveillance (AS). With the introduction of prostate-specific membrane antigen (PSMA) positron emission tomography (PET) there has been considerable improvement in sensitivity and specificity for the detection and staging of clinically significant prostate cancer. Our study aims to determine the role of PSMA PET/CT in men with newly diagnosed low or favourable intermediate risk prostate cancer to better select men for AS.MethodThis is a retrospective single centre study performed from January 2019 and October 2022. This study includes men identified from electronic medical record system who had undergone a PSMA PET/CT following newly diagnosed low or favourable-intermediate risk prostate cancer. Primary outcome was to assess the change in management for men being considered for AS following PSMA PET/CT results on the basis of PSMA PET characteristics.ResultsIn total, there were 11 of 30 men (36.67%) who were assigned management by AS and 19 of 30 men (63.33%) who had definitive treatment. 15 of the 19 men that needed treatment had concerning features on PSMA PET/CT results. Of the 15 men with concerning features on PSMA PET, 9 (60%) men were found to have adverse pathological features on final prostatectomy features.ConclusionThis retrospective study suggests that PSMA PET/CT has potential to influence the management of men with newly diagnosed prostate cancer that would otherwise be appropriate for active surveillance.

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).

Multiparametric dynamic whole-body PSMA PET/CT using [68Ga]Ga-PSMA-11 and [18F]PSMA-1007

BackgroundRoutine prostate-specific membrane antigen (PSMA) positron emission tomography (PET) performed for primary staging or restaging of prostate cancer patients is usually done as a single static image acquisition 60 min after tracer administration. In this study, we employ dynamic whole-body (D-WB) PET imaging to compare the pharmacokinetics of [68Ga]Ga-PSMA-11 and [18F]PSMA-1007 in various tissues and lesions, and to assess whether Patlak parametric images are quantitative and improve lesion detection and image readability.MethodsTwenty male patients with prostate cancer were examined using a D-WB PSMA PET protocol. Ten patients were scanned with [68Ga]Ga-PSMA-11 and ten with [18F]PSMA-1007. Kinetic analyses were made using time-activity curves (TACs) extracted from organs (liver, spleen, bone, and muscle) and lesions. For each patient, three images were produced: SUV + Patlak parametric images (Ki and DV). All images were reviewed visually to compare lesion detection, image readability was quantified using target-to-background ratios (TBR), and Ki and DV values were compared.ResultsThe two PSMA tracers exhibited markedly different pharmacokinetics in organs: reversible for [68Ga]Ga-PSMA-11 and irreversible for [18F]PSMA-1007. For both tracers, lesions kinetics were best described by an irreversible model. All parametric images were of good visual quality using both radiotracers. In general, Ki images were characterized by reduced vascular signal and increased lesion TBR compared with SUV images. No additional malignant lesions were identified on the parametric images.ConclusionD-WB PET/CT is feasible for both PSMA tracers allowing for direct reconstruction of parametric Ki images. The use of multiparametric PSMA images increased TBR but did not lead to the detection of more lesions. For quantitative whole-body Ki imaging, [18F]PSMA-1007 should be preferred over [68Ga]Ga-PSMA-11 due to its irreversible kinetics in organs and lesions.

An Australian experience using Tc-PSMA SPECT/CT in the primary diagnosis of prostate cancer and for staging at biochemical recurrence after local therapy.

Technetium 99 prostate-specific membrane antigen(Tc-PSMA) single-photon emission computed tomography/computed tomography (SPECT/CT) has the potential to provide greater accessibility globally thangallium 68(Ga)-PSMA positron emission tomography (PET)/CT but has not been studied as extensively in primary diagnosis, staging, or relapse of prostate cancer (PC). We instituted a novel SPECT/CT reconstruction algorithm using Tc-PSMA and established a database to prospectively accumulate data on all patients referred with PC. This study extracts data on all patients referred over a 3.5-year period with the primary aim of comparing the diagnostic accuracy of Tc-PSMA and multiparametric magnetic resonance imaging (mpMRI) in the primary diagnosis of PC. The secondary aim was to assess the sensitivity of Tc-PSMA in detecting disease with relapse after either radical prostatectomy or primary radiotherapy. A total of 425 men referred for primary staging (PS) of PC and 172 men referred with biochemical relapse (BCR) were evaluated. We evaluated diagnostic accuracy and correlations between Tc-PSMA SPECT/CT, magnetic resonance imaging(MRI), prostate biopsy, prostate-specific antigen (PSA), and age in the PS group and positivity rates at different PSA levels in the BCR group. Taking the biopsy's grade according to the International Society of Urological Pathologyprotocol as a reference, the sensitivity (true positive rate), specificity (true negative rate), accuracy (positive and negative predictive value), and precision (positive predictive value) for Tc-PSMA in the PS group were 99.7%, 83.3%, 99.4%, and 99.7%, respectively. Comparison rates for MRI in this group were 96.4%, 71.4%, 95.7%, and 99.1%. We found moderate correlations between Tc-PSMA uptake in the prostate and biopsy grade, the presence of metastases, and PSA. In BCR, the Tc-PSMA positive rates were 38.9%, 53.2%, 62.5%, and 84.6% at PSA levels of <0.2, 0.2 to <0.5, 0.5 to <1.0, and > 1.0 ng/mL respectively. We have shown that Tc-PSMA SPECT/CT using an enhanced reconstruction algorithm has a diagnostic performance similar to Ga-PSMA PET/CT and mpMRI in an everyday clinical setting. It may have some advantages in cost, sensitivity for primary lesion detection, and the ability for intraoperative localization of lymph nodes.

Using 18F-DCFPyL Prostate-Specific Membrane Antigen–Directed Positron Emission Tomography/Magnetic Resonance Imaging to Define Intraprostatic Boosts for Prostate Stereotactic Body Radiation Therapy

The recently reported FLAME trial demonstrated a biochemical disease-free survival benefit to using a focal intraprostatic boost to multiparametric magnetic resonance imaging (mpMRI)-identified lesions in men with localized prostate cancer treated with definitive radiation therapy. Prostate-specific membrane antigen (PSMA)-directed positron emission tomography (PET) may identify additional areas of disease. In this work, we investigated using both PSMA PET and mpMRI in planning focal intraprostatic boosts using stereotactic body radiation therapy (SBRT). We evaluated a cohort of patients (n=13) with localized prostate cancer who were imaged with 2-(3-(1-carboxy-5-[(6-[18F]fluoro-pyridine-2-carbonyl)-amino]-pentyl)-ureido)-pentanedioic acid (18F-DCFPyL) PET/MRI on a prospective imaging trial before undergoing definitive therapy. The number of lesions concordant (overlapping) and discordant (no overlap) on PET and MRI was assessed. Overlap between concordant lesions was evaluated using the Dice and Jaccard similarity coefficients. Prostate SBRT plans were created fusing the PET/MRI imaging to computed tomography scans acquired the same day. Plans were created using only MRI-identified lesions, only PET-identified lesions, and the combined PET/MRI lesions. Coverage of the intraprostatic lesions and doses to the rectum and urethra were assessed for each of these plans. The majority of lesions (21/39, 53.8%) were discordant between MRI and PET, with more lesions seen by PET alone (12) than MRI alone (9). Of lesions that were concordant between PET and MRI, there were still areas that did not overlap between scans (average Dice coefficient, 0.34). Prostate SBRT planning using all lesions to define a focal intraprostatic boost provided the best coverage of all lesions without compromising constraints on the rectum and urethra. Using both mpMRI and PSMA-directed PET may better identify all areas of gross disease within the prostate. Using both imaging modalities could improve the planning of focal intraprostatic boosts.

Diagnostic Performance of 68Ga-PSMA-11 Positron Emission Tomography/Computed Tomography to Monitor Treatment Response in Patients with Metastatic Prostate Cancer: The Concordance Between Biochemical Response and Prostate-specific Membrane Antigen Results

BackgroundTreatment response is traditionally monitored using prostate-specific antigen (PSA) and conventional imaging in patients with metastatic prostate cancer (mPCa). ObjectiveTo assess the diagnostic performance of prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT) when monitoring mPCa patients receiving systemic treatment and also to investigate the concordance between PSMA PET response according to the PSMA PET progression (PPP) criteria and biochemical response. Design, setting, and participantsA total of 96 patients with 68Ga-PSMA-11 PET/CT-detected mPCa at baseline PSMA PET/CT (bPSMA) who underwent at least one follow-up scan after receiving systemic treatment were included in the study. PSA levels at bPSMA and follow-up PSMA PET (fPSMA) scans were recorded. The PPP criteria were used to define PSMA progression. Biochemical progression was defined as ≥25% increase in PSA. PSMA PET and PSA responses were dichotomized into progressive disease (PD) versus non-PD, and the concordance between PSA and PSMA responses was evaluated. Outcome measurements and statistical analysisThe concordance between PSA and PSMA PET responses was presented using frequencies, percentages, and Cohen’s kappa test. Results and limitationsA total of 345 serial PSMA PET/CT (96 bPSMA and 249 fPSMA) scans were evaluated. The positivity rates of PSMA PET scans for PSA levels of <0.01, 0.01–0.2, 0.2–4, and >4 ng/ml were 55.6%, 75.0%, 100%, and 98.8%, respectively. PSA and PSMA responses showed moderate-to-high concordance (Cohen’s κ = 0.623, p < 0.001). PSA-PSMA discordance was detected in 39 scans (17%). The most common cause of discordance was the discordant results between different metastatic lesions (16/28, 57.1%) in patients with PPP without PSA progression and local progression in prostate (n = 7/11, 63.6%) in patients with PSA progression without PPP. ConclusionsPSMA PET/CT showed very high detection rates of malignant lesions even at very low PSA values and showed significant concordance with PSA response when monitoring treatment response in patients receiving systemic treatment for mPCa. Patient summaryThis study describes that prostate-specific membrane antigen positron emission tomography (PSMA PET), a new sensitive imaging tool, can detect malignant lesions even at very low prostate-specific antigen values when monitoring metastatic prostate cancer. The PSMA PET response and biochemical response showed significant concordance, and the reason for discordant results seems to be the different responses of metastatic lesions and prostatic lesions to systemic treatment.

Biochemically recurrent prostate cancer: rationalisation of the approach to imaging

To assess the utility of magnetic resonance imaging (MRI) in addition to the additive benefit of the conventional imaging techniques, computed tomography (CT) and nuclear medicine (NM) bone scintigraphy, for investigation of biochemical recurrence (BCR) post-prostatectomy where access to prostate specific membrane antigen (PSMA) positron-emission tomography (PET)-CT is challenging. Relevant imaging over a 5-year period was reviewed. Ethical approval was granted by the internal review board. All patients with suspected BCR, defined as a PSA ≥0.2 ng/ml on two separate occasions, underwent a retrospective imaging review. This was performed on PACS archive search database in a single centre using search terms "PSA" and "prostatectomy" in the three imaging methods; MRI, CT, and NM bone scintigraphy. All PSMA PET CT performed were recorded. One hundred and eighty-five patients were identified. Patients with an MRI pelvis that demonstrated distant metastases (i.e., pelvic bone metastases or lymph node involvement more cranial to the bifurcation of the common iliac arteries) were more likely to have a positive CT and/or NM bone scintigraphy. The Pearson correlation coefficient between the findings of M1 disease at MRI pelvis and the presence of distant metastases at CT thorax, abdomen, pelvis and NM bone scintigraphy was calculated at 0.81 (p<0.01) and 0.91 (p<0.01) respectively. An imaging strategy based on risk stratification and technique-specific selection criteria leads to more appropriate use of resources, and in turn, increases the yield of conventional imaging methods. MRI prostate findings can be used to predict the additive value of CT/NM bone scintigraphy allowing a more streamlined approach to their use.

ASO Author Reflections: PSMA PET in the Prostate Cancer Primary Staging Scenario-A Reliable Method with a Remarkable Decision-Making Impact.

Prostate cancer (PCa) is the second most common malignant tumor in men in Brazil and worldwide. Although positron emission tomography (PET) prostate-specific membrane antigen (PSMA) has been used for over 10years and several studies have been published regarding its superior performance in PCa primary staging and other scenarios, the management decision is often still based on conventional imaging information. A retrospective analysis was performed in 35 patients with PCa in the primary staging scenario with conventional exams as well as with PET PSMA. The findings of our study showed changes on the staging classification and significant impact on the therapeutic choice. PET PSMA is a dependable imaging exam and has already proved its worth and superiority when compared with conventional methods to evaluate PCa patients in primary staging and biochemical relapse, in addition to other potential roles. Prospective studies are needed to assess the outcome of patients whose management was guided by PSMA.

PD10-02 USING THE NEGATIVE PREDICTIVE VALUE AND SUVMAX OF PSMA PET/CT FOR AVOIDING PELVIC LYMPH NODE DISSECTION WITH RADICAL PROSTATECTOMY

You have accessJournal of UrologyCME1 Apr 2023PD10-02 USING THE NEGATIVE PREDICTIVE VALUE AND SUVMAX OF PSMA PET/CT FOR AVOIDING PELVIC LYMPH NODE DISSECTION WITH RADICAL PROSTATECTOMY Amandeep Arora, Archi Agarwal, Mahendra Pal, Ganesh Bakshi, Santosh Menon, Gujela Ajit, and Gagan Prakash Amandeep AroraAmandeep Arora More articles by this author , Archi AgarwalArchi Agarwal More articles by this author , Mahendra PalMahendra Pal More articles by this author , Ganesh BakshiGanesh Bakshi More articles by this author , Santosh MenonSantosh Menon More articles by this author , Gujela AjitGujela Ajit More articles by this author , and Gagan PrakashGagan Prakash More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003250.02AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The prostate-specific membrane antigen positron-emission-tomography (PSMA-PET) scan is increasingly being utilized for staging prostate cancer (PCa). Here, we sought to evaluate the accuracy of the PSMA-PET scan with the aim of identifying patients who could be spared a pelvic lymph node dissection (PLND) at the time of radical prostatectomy (RP) based on the results of the PSMA-PET scan. METHODS: We retrospectively reviewed records of patients who underwent a PSMA-PET scan followed by an RP with extended PLND (external iliac, obturator and common iliac nodes) at our tertiary cancer care centre from Aug 2015 - September 2022. Patients were classified as clinically node negative or positive (cN0 or cN+) based on the PSMA PET scan. The nodal status in the PSMA-PET scan was compared with the final histopathology of the PLND (pN0 or pN+). RESULTS: A total of 205 patients were included and were stratified as follows based on MRI and PSMA-PET scans: 6 (2.9%) low-risk, 49 (23.9%) intermediate-risk, 46 (22.4%) high-risk localized, 89 (43.4%) locally-advanced node-negative and 15 (7.3%) node-positive patients. The sensitivity, specificity, positive predictive value, and negative predictive value of the PSMA PET scan for nodal status were 37.5%, 98.2%, 80% and 89.4% respectively. The NPV was 89.4%, 93.8%, 87% and 86.6% for overall, intermediate-risk, high-risk localized and locally-advanced node-negative patients respectively. The median SUVmax of the primary prostate lesion in patients who were true negatives for nodes, as identified by the PSMA-PET scan, was significantly lower (12.8 vs 26.4, p<0.001) than that in patients who were false negative (cN0 on PSMA but pN+ in final pathology). Of the 190 cN0 patients, 20 had a false negative PSMA PET scan. Three of the 49 intermediate-risk patients had a false negative PSMA PET scan for nodes; the SUVmax scores of their prostate lesions were 26.59, 40.06 and 54.55 which were much higher than the median SUVmax score (12.8) in patients with a true negative scan. For the 135 high-risk cN0 patients, the 17 false negative patients had a median SUVmax of 24.37 compared to those with a true negative scan (13.57), p<0.001. CONCLUSIONS: The high NPV of PSMA-PET scan coupled with the SUVmax of the primary prostatic lesion can help avoid a PLND in intermediate and high-risk patients with a ‘negative’ PSMA-PET scan. The results can be considered as hypothesis generating and indicate the use of PSMA as a biomarker for predicting nodal disease. Further larger studies can help determine the ideal cut-off values for the SUVmax of the primary lesion. Source of Funding: No © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e326 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Amandeep Arora More articles by this author Archi Agarwal More articles by this author Mahendra Pal More articles by this author Ganesh Bakshi More articles by this author Santosh Menon More articles by this author Gujela Ajit More articles by this author Gagan Prakash More articles by this author Expand All Advertisement PDF downloadLoading ...

Impact of piflufolastat F-18 PSMA PET imaging on clinical decision-making in prostate cancer across disease states: A retrospective review.

Piflufolastat F-18 (18F-DCFPyL) prostate-specific membrane antigen (PSMA) positron emission tomography (PET) imaging is approved by the US food and drug administration for initial staging of high-risk prostate cancer, biochemical recurrence (BCR), and restaging of metastatic prostate cancer. Here, we sought to assess how its integration into clinical care may have impacted the management of patients. We identified 235 consecutive patients who underwent an 18F-DCFPyL PET scan from August 2021 to June 2022. The median prostate-specific antigen at the time of imaging was 1.8 ng/mL (Range: 0-3740 ng/mL). Descriptive statistics were used to analyze its impact on clinical care for a subset of 157 patients with available treatment information: 22 for initial staging, 109 with BCR, and 26 patients with known metastatic disease. PSMA-avid lesions were detected in 154/235 (65.5% of) patients. In patients undergoing initial staging, 18/39 (46.2% of) patients had extra-prostatic metastatic lesions; 15/39 (38.5% of) scans were negative and 6/39 (15.4%) had equivocal results. 12/22 (54.5% of) patients had a change in their treatment plan post-PSMA PET scan while 10/22 (45.5%) had no change in their treatment plan. In the BCR cohort, 93/150 (62.0%) had a local recurrence or metastatic lesions. Equivocal and negative scans accounted for 11/150 (7.3%) and 46/150 (30.7%) of scans, respectively. 37/109 (33.9% of) patients had a change in their treatment plan, while treatment was not altered in 72/109 (66.1% of) cases. In patients with metastatic disease, 43/46 (93.5%) had PSMA-avid lesions identified; equivocal and negative scans accounted for 2/46 (4.3%) and 1/46 (2.2%) of scan results, respectively. 6/26 (23.1%) had their tentative treatment plan adjusted after the PSMA PET scan. No change in the treatment plan was observed in 20/26 (76.9% of) cases. Integration of F-18 PSMA PET imaging impacted clinical decision-making and subsequent management across all stages of prostate cancer. It remains to be seen whether this translates into superior survival outcomes.

Impact of Prostate-Specific Membrane Antigen Positron Emission Tomography/Computed Tomography on the Therapeutic Decision of Prostate Carcinoma Primary Staging: A Retrospective Analysis at the Brazilian National Public Health System.

Prostate cancer (PCa) is the most common malignant tumor in males and conventional imaging does not provide accurate primary staging. Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) presents superior performance and strongly affects therapeutic choice. The aim of this study was to evaluate the impact of PSMA PET, compared with conventional imaging methods, on the therapeutic approach in primary staging scenarios in patients with PCa treated at the Brazilian National Public Health System. Overall, 35 patients diagnosed with PCa were evaluated using PSMA after conventional staging imaging with multiparametric magnetic resonance (MMR) and/or total abdominal computed tomography (CT) scan and bone scintigraphy (BS). The PCa extension identified by PET was compared with conventional imaging; staging changes and the management impact were then determined. PET comparison with conventional imaging, staging, and decision-making changes was analyzed using descriptive statistics. PET revealed local disease (LD) in 15 (42.9%) patients, seminal vesicle invasion (SVI) in 5 (14.3%) patients, pelvic nodal impairment (PNI) in 7 (20%) patients, pelvic and distant nodes in 3 (8.6%) patients, pelvic nodes and bone metastasis in 4 (11.4%) patients, and pelvic and distant nodes and bone metastasis in 1 (2.8%) patient. Staging changes were observed in 60% of patients, with downstaging predominance (76.2%). Volume increase was identified in 11 (31.4%) patients (only 4 related to upstaging, 36.4%). The board changed management decisions for 60% of the patients. The main limitations of this study were the sample size and its retrospective nature. PSMA findings changed the management decisions in more than half of the patients, which made the majority eligible for locoregional treatment and avoided unnecessary procedures in the systemic disease scenario.

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.

A Systematic Review of the Variability in Performing and Reporting Intraprostatic Prostate-specific Membrane Antigen Positron Emission Tomography in Primary Staging Studies

ContextProstate cancer (PCa) remains one of the leading causes of cancer-related deaths in men worldwide. Men at risk are typically offered multiparametric magnetic resonance imaging and, if suspicious, a targeted biopsy. However, false-negative rates of magnetic resonance imaging are consistently 18%; therefore, there is growing interest in improving the diagnostic performance of imaging through novel technologies. Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) is being utilised for PCa staging and, more recently, for intraprostatic tumour localisation. However, significant variability has been observed in how PSMA PET is performed and reported. ObjectiveIn this review, we aim to evaluate how pervasive this variability is in trials investigating the performance of PSMA PET in primary PCa workup. Evidence acquisitionFollowing the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, we performed an optimal search in five different databases. After removing duplicates, 65 studies were included in our review. Evidence synthesisStudies dated back as early as 2016, with numerous different source countries. There was variation in the reference standard for PSMA PET, with some using biopsy specimens or surgical specimens, and in some cases, a combination of the two. Similar inconsistencies were noted when studies selected histological definitions of clinically significant PCa, while some omitted their definition altogether. The most significant variations in performing PSMA PET were the radiotracer type, dose, acquisition time after injection, and the PET camera being utilised. Substantial variation in the reporting of PSMA PET was noted, with no consistency in defining what constitutes a positive intraprostatic lesion. Across 65 studies, four different definitions were used. ConclusionsThis systematic review has highlighted considerable variation in obtaining and performing a PSMA PET study in the context of primary PCa diagnosis. Given the discrepancy in how PSMA PET was performed and reported, it questions the homogony of studies from centre to centre. Standardisation of PSMA PET is required for this to become a consistently useful and reproducible modality in the diagnosis of PCa. Patient summaryProstate-specific membrane antigen (PSMA) positron emission tomography (PET) is being utilised for staging and localisation of prostate cancer (PCa); however, there is significant variability in performing and reporting PSMA PET. Standardisation of PSMA PET is required for results to be consistently useful and reproducible for the diagnosis of PCa.

Transcriptomic Heterogeneity in High-risk Prostate Cancer and Implications for Extraprostatic Disease at Presentation on Prostate-specific Membrane Antigen Positron Emission Tomography

Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) has greater specificity and sensitivity for detection of extraprostatic prostate cancer (PCa) at presentation than conventional imaging. Although the long-term clinical significance of acting on these findings is unknown, it has been shown that the risk of upstaging is prognostic for long-term outcomes in men with high-risk (HR) or very high-risk (VHR) PCa. We evaluated the association between the risk of upstaging on PSMA PET and the Decipher genomic classifier score, a known prognostic biomarker in localized PCa that is being evaluated for its predictive ability to direct systemic therapy intensification. In a cohort of 4625 patients with HR or VHR PCa, the risk of upstaging on PSMA PET was significantly correlated with the Decipher score (p < 0.001). These results should be seen as hypothesis-generating and warrant further studies on the causal pathways linking PSMA findings, Decipher scores, extraprostatic disease, and long-term clinical outcomes. Patient summaryWe found significant correlation between the risk of having prostate cancer outside the prostate gland on a sensitive scan (based on prostate-specific membrane antigen [PSMA]) at initial staging and the Decipher genetic score. The results warrant further studies on the causal pathways between PSMA scan findings, Decipher scores, disease outside the prostate, and long-term outcomes.

Feasibility of biology-guided radiotherapy for metastatic renal cell carcinoma driven by PSMA PET imaging

BackgroundBiology-guided radiotherapy (BgRT) is a novel treatment where the detection of positron emission originating from a volume called the biological tracking zone (BTZ) initiates dose delivery. Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) is a novel imaging technique that may improve patient selection for metastasis-directed therapy in renal cell carcinoma (RCC). This study aims to determine the feasibility of BgRT treatment for RCC. Material and methodsAll consecutive patients that underwent PSMA PET/CT scan for RCC staging at our institution between 2014 and 2020 were retrospectively considered for inclusion. GTVs were contoured on the CT component of the PET/CT scan. The tumor-to-background ratio was quantified from the normalized standardized uptake value (nSUV), defined as the ratio between SUVmax inside the GTV and SUVmean inside the margin expansion. Tumors were classified suitable for BgRT if (1) nSUV was greater or equal to an nSUV threshold and (2) if the BTZ was free of any PET-avid region other than the tumor. ResultsOut of this cohort of 83 patients, 47 had metastatic RCC and were included in this study. In total, 136 tumors were delineated, 1 to 22 tumors per patient, mostly in lung (40%). Using a margin expansion of 5 mm/10 mm/20 mm and nSUV threshold = 3, 66%/63%/41% of tumors were suitable for BgRT treatment. Uptake originating from another tumor, the kidney, or the liver was typically inside the BTZ in tumors judged unsuitable for BgRT. ConclusionsMore than 60% of tumors were found to be suitable for BgRT in this cohort of patients with RCC. However, the proximity of PET-avid organs such as the liver or the kidney may affect BgRT delivery.

Clinical outcomes after utilization of PSMA PET scans in patients with biochemical recurrent prostate cancer.

57 Background: The optimal management of biochemical recurrent prostate cancer (BCR) remains unknown. Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) scans can visualize micrometastatic disease, thus expanding treatment options for BCR from observation or androgen deprivation therapy (ADT) to potentially include metastasis-directed radiation (XRT) or next-generation hormonal agents (NHA). We aimed to describe how BCR patients were managed after PSMA PET scans and their clinical outcomes. Methods: We performed a retrospective chart review of 262 patients from the University of Michigan’s PSMA PET scan database (825 patients with scans 2017–2021). Patients who received maximal local therapy (defined as XRT alone n=199 or surgery + XRT n=63) are presented. Only patients with BCR and a minimum of 1 year follow-up after scans were included. Baseline patient and tumor characteristics, PSMA PET scan results, first and subsequent therapy delivered after PSMA PET, and prostate-specific antigen (PSA) and standard imaging results post PSMA PET were annotated. Primary endpoint is time from first post-scan therapy (within 6 months of scan) to subsequent therapy. Secondary outcomes include probability of no subsequent therapy in 1 year based on first post-scan therapy and PSMA scan findings and PSMA PET findings and association with Gleason score, PSA at BCR, and time from diagnosis to PSMA scan. Results: Of 262 patients with maximal local therapy, 115 met inclusion criteria. Primary definitive treatment was XRT alone in 58% and surgery + XRT in 42%. Median PSA at time of scan was 4.4 ng/mL, and PSMA PET was positive in 87%. First therapy rendered after PSMA PET included 15% no therapy, 26% XRT only, 28% systemic therapy only (ADT +/- NHA), 27% combination therapy (XRT +/- systemic), and 4% other. Subsequent therapy was given in 26%. The median time from first to subsequent therapy was 41 months in patients who received XRT alone as first therapy and not reached for those with combination XRT + ADT. None of the 33 treated with combination therapy required subsequent therapy in 1 year. Remainder of analyses incomplete due to small sample sizes. Results to be updated by time of symposium. Conclusions: This observational study characterizes longer term clinical outcomes in patients with BCR who undergo various therapies after PSMA PET scans. Data may inform current decision making while prospective clinical trial data is awaited.

Prostate-specific Membrane Antigen–radioguided Surgery Facilitates Pelvic Lymph Node Dissection During Radical Prostatectomy for the Treatment of Locally Advanced Prostate Cancer with Regional Lymph Node Metastases

Lymph node metastases (LNMs) are common in intermediate- to high-risk prostate cancer (PC) and may be missed during extended pelvic lymph node dissection (ePLND). Here we report on the use of prostate-specific membrane antigen (PSMA)-radioguided surgery (RGS) during open radical prostatectomy (RP) with ePLND to resect locoregional LNMs identified on preoperative PSMA positron emission tomography (PET). Preoperative PSMA PET showed 78 LNMs in 35 patients undergoing RP with ePLND and RGS between January 2018 and June 2020. In 14 patients (40%), LNMs were located outside the ePLND template. RGS achieved resection of PSMA-positive LNMs in 33/35 patients (94%). On univariable analysis, lower metastatic burden with up to two PSMA-positive LNMs on preoperative PET was associated with better postoperative outcomes. Limitations include the retrospective analysis and the small sample size. RGS facilitates resection of PSMA-positive LNs in patients treated with RP. Our data indicate a favorable treatment outcome in patients with low metastatic LN burden on preoperative PSMA PET. Patient summaryWe investigated the use of radioactive guidance to remove lymph nodes affected by prostate cancer during surgical removal of the prostate. This approach can help to identify cancerous lymph nodes that might otherwise be missed and could lead to better survival outcomes.

The current status of prostate cancer treatment and PSMA theranostics

In the treatment of cancer, understanding the disease status, or accurate staging, is extremely important, and various imaging techniques are used. Computed tomography (CT), magnetic resonance imaging, and scintigrams are commonly used for solid tumors, and advances in these technologies have improved the accuracy of diagnosis. In the clinical practice of prostate cancer, CT and bone scans have been considered especially important for detecting metastases. Nowadays, CT and bone scans are called conventional methods because positron emission tomography (PET), especially prostate-specific membrane antigen (PSMA)/PET, is extremely sensitive in detecting metastases. Advances in functional imaging, such as PET, are advancing the diagnosis of cancer by allowing information to be added to the morphological diagnosis. Furthermore, PSMA is known to be upregulated depending on the malignancy of the prostate cancer grade and resistance to therapy. Therefore, it is often highly expressed in castration-resistant prostate cancer (CRPC) with poor prognosis, and its therapeutic application has been attempted for around two decades. PSMA theranostics refers to a type of cancer treatment that combines both diagnosis and therapy using a PSMA. The theranostic approach uses a radioactive substance attached to a molecule that targets PSMA protein on cancer cells. This molecule is injected into the patient’s bloodstream and can be used for both imaging the cancer cells with a PET scan (PSMA PET imaging) and delivering radiation directly to the cancer cells (PSMA-targeted radioligand therapy), with the aim of minimizing damage to healthy tissue. Recently, in an international phase III trial, the impact of 177Lu-PSMA-617 therapy was studied in patients with advanced PSMA-positive metastatic CRPC who had previously been treated with specific inhibitors and regimens. The trial revealed that 177Lu-PSMA-617 significantly extended both progression-free survival and overall survival compared to standard care alone. Although there was a higher incidence of grade 3 or above adverse events with 177Lu-PSMA-617, it did not negatively impact the patients’ quality of life. PSMA theranostics is currently being studied and used primarily for the treatment of prostate cancer, but it has the potential to be applied to other types of cancers as well.

Can 18F-PSMA-7Q PET/CT replace prostate biopsy for the diagnosis of prostate cancer?-A single-center retrospective study.

Of the currently available prostate-specific membrane antigen (PSMA) positron emission tomography (PET) tracers, although 68Ga-PSMA-11 and 18F-DCFPyL have been approved by the US Food and Drug Administration (FDA), both tracers are excreted rapidly through the urinary tract, resulting in strong accumulation in the bladder and blurring the prostate.18F-PSMA-7Q is a novel quinoline-containing PSMA PET tracer developed by our team, which is primarily excreted through the liver. It can reduce the incidence of urine-induced false-positives in the prostate. We aimed to explore the diagnostic efficacy of 18F-PSMA-7Q PET/computed tomography (CT), and when 18F-PSMA-7Q PET/CT can be used instead of prostate biopsy to diagnose prostate cancer. Patients who underwent 18F-PSMA-7Q PET/CT for prostate cancer staging or prostate biopsy guidance at our institution between July 2020 and December 2021 were retrospectively enrolled. Molecular imaging PSMA (miPSMA) scores were assigned for intra-prostatic lesions according to the Prostate Cancer Molecular Imaging Standardized Evaluation (PROMISE) criteria, and the diagnostic efficacy of 18F-PSMA-7Q PET/CT for different miPSMA scores was evaluated using pathological diagnosis as the gold standard. Of the 125 enrolled patients, 101 had prostate cancer, and 24 had prostatic hyperplasia or prostatitis. miPSMA ≥2 was the optimal diagnostic threshold, and area under curve (AUC) was 0.948, the sensitivity and specificity were 91.1% and 83.0%. The prostate cancer detection rates of 18F-PSMA-7Q PET/CT were 14.3% (3/21), 60.0% (6/10), 96.7% (58/60), and 100% (34/34) for patients with miPSMA scores of 0, 1, 2, and 3, respectively. There was no significant difference in the detection rate of prostate cancer between groups with miPSMA scores of 2 and 3, but there were significant differences between any other 2 groups. The prostate cancer detection rate of 18F-PSMA-7Q PET/CT was high for lesions with greater miPSMA scores of 2 and 3. For patients with a high miPSMA score, particularly those with a miPSMA score of 3, prostate biopsy can be omitted and prostate cancer-related treatment can be considered.