BACKGROUND AND OBJECTIVE:Biochemical recurrence (BCR) of prostate cancer (PCa) after curative radiotherapy (RT) is defined according to the Phoenix criteria, which is a prostate-specific antigen (PSA) rise of ≥2.0 ng/ml above the PSA nadir. Prostate-specific membrane antigen (PSMA)-based positron emission tomography/computed tomography (PET/CT) can identify PCa recurrences at very low PSA values. Our aim was to investigate the detection rate and extent of PCa recurrences using PSMA PET/CT after curative RT among patients with a PSA rise of ≥2.0 ng/ml above the nadir (Phoenix positive, Ph+) and patients not reaching this threshold (Phoenix negative, Ph-) and to compare therapeutic management and clinical outcomes in terms of time to androgen deprivation therapy (ADT) and castration-resistance PCa (CRPC), as well as overall survival. METHODS:We conducted a retrospective analysis of the Prostate Cancer Network Amsterdam (2015-2023) cohort of 568 patients who received curative-intent RT for PCa. Data on PSMA PET/CT outcomes, therapeutic management, and clinical follow-up were collected, including (re)initiation of ADT, progression to CRPC, and survival. Results were compared between groups using logistic regression and survival analyses. KEY FINDINGS AND LIMITATIONS:The study cohort comprised 222 patients (39.1%) classified as Ph- and 346 (60.9%) classified as Ph+. PSMA-avid lesions were detected in 170 Ph- patients (76.6%) and 322 (93.1%) Ph+ patients. In these groups, 75.9% of Ph- patients and 45.0% of Ph+ patients were eligible for local salvage therapy (odds ratio [OR 3.84]; p < 0.001). Distant metastases were less frequent in the Ph- group (n = 37, 21.8%) than in the Ph+ group (n = 157, 48.8%; OR 0.29; p < 0.001). Survival analyses revealed longer times to ADT (re)initiation and progression to CRPC, as well as lower overall mortality, in the Ph- group (log-rank p < 0.001). The retrospective study design is the main limitation. CONCLUSIONS AND CLINICAL IMPLICATIONS:For patients with PCa recurrence, PSMA PET/CT can detect this recurrence in the majority of cases not meeting the Phoenix criteria for BCR. Early imaging detects recurrences at a less advanced disease stage, allowing potential salvage treatments. In addition, early PSMA PET/CT is associated with longer times to ADT (re)initiation and progression to CRPC, as well as longer overall survival. These positive clinical implications warrant confirmation of our results in prospective studies to reduce potential leadtime bias. PATIENT SUMMARY:We investigated early use of a special type of scan called PSMA PET (prostate-specific membrane antigen positron emission tomography) in patients with suspicion of recurrence of their prostate cancer after radiotherapy. Early scans can detect recurrence before the cancer progresses to a more advanced stage.

Background and objectiveA combined approach of magnetic resonance imaging (MRI)-targeted biopsy (TBx) and bilateral systematic biopsy (SBx) is advised in patients who have an increased risk of prostate cancer (PCa). The diagnostic gain of SBx in detecting PCa for treatment planning of patients undergoing robot-assisted radical prostatectomy (RARP) is unknown. This study aims to determine the impact of omitting contralateral SBx on the surgical planning of patients undergoing RARP in terms of nerve-sparing surgery (NSS) and extended pelvic lymph node dissection (ePLND).MethodsCase files from 80 men with biopsy-proven PCa were studied. All men had a unilateral suspicious lesion on MRI, and underwent TBx and bilateral SBx. Case files were presented to five urologists for the surgical planning of RARP. Each case file was presented randomly using two different sets of information: (1) results of TBx + bilateral SBx, and (2) results of TBx + ipsilateral SBx. The urologists assessed whether they would perform NSS and/or ePLND.Key findings and limitationsA change in the surgical plan concerning NSS on the contralateral side was observed in 9.0% (95% confidence interval [CI] 6.4-12.2) of cases. Additionally, the indication for ePLND changed in 5.3% (95% CI 3.3-7.9) of cases. Interobserver agreement based on Fleiss’ kappa changed from 0.44 to 0.15 for the indication of NSS and from 0.84 to 0.83 for the indication of ePLND.Conclusions and clinical implicationsIn our series, the diagnostic information obtained from contralateral SBx has limited impact on the surgical planning of patients with a unilateral suspicious lesion on MRI scheduled to undergo RARP.Patient summaryIn patients with one-sided prostate cancer on magnetic resonance imaging, omitting biopsies on the other side rarely changed the surgical plan with respect to nerve-sparing surgery and the indication to perform extended lymph node dissection.

Purpose: Prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) is an emerging staging tool for patients with primary high-risk prostate cancer (PCa). Patients with primary metastatic disease are staged using PSMA-PET/CT imaging, while previously published randomized clinical trials relied on conventional imaging (i.e., bone scintigraphy (BS) results. The aim of this study was to compare the ability of bone metastatic lesion detection and changes in staging for 18F-PSMA-PET/CT versus BS in high-risk PCa patients. Methods: 79 patients with high-risk PCa were prospectively staged using BS and subsequent 18F-PSMA-PET/CT before initial therapy. Patients who presented with a BS showing no metastases represented Group 1, and patients with a BS showing low-volume disease accord-ing to the CHAARTED criteria (<4 bone metastases, no metastases outside vertebral column or pelvis and no visceral metastases) repre-sented Group 2. Metastatic risk group according to CHAARTED and treatment strategies based on both imaging modalities were assessed. Results: A change of CHAARTED risk group was observed in 9/70 (12.8%) of patients in Group 1. In Group 2, a change of risk group was found in 66.7% of patients, due to either upstaging (4/9 patients (44.4%)) and downstaging (2/9 patients (22.2%)). Treatment changes due to use of a different imaging modality occurred in almost 20% of patients. Conclusion: In patients with negative for cancer results on BS, upstaging on 18F-PSMA-PET/CT occurred only infrequently. Moreover, 18F-PSMA-PET/CT resulted in both upstaging and downstaging in a substantial subset of patients with low-volume metastatic disease on BS. Treatment changes occurred in almost 20% of cases depending on imaging results. (c) 2022 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

5009 Background: [ 177 Lu]Lu-PSMA-617 (Pluvicto) is a novel treatment for patients with metastatic castration resistant prostate cancer. In a phase 1 dosimetry study, we previously showed that [ 177 Lu]Lu-PSMA-617 could be offered to patients with PSMA-expressing, recurrent, oligometastatic hormone-sensitive prostate cancer (oHSPC) with encouraging outcomes (Privé et al, CCR 2021). We here report the results of the following randomized phase 2 trial. Methods: This was an investigator initiated, international, multicenter, open-label, randomized phase 2 trial (NCT04443062). Fifty-eight oHSPC patients ineligible for salvage treatments, were randomized in a 1:1 fashion to [ 177 Lu]Lu-PSMA-617 vs. the standard of care (SoC) of deferred androgen deprivation therapy (ADT). Eligibility consisted of fast-progressing oHSPC (prostate specific antigen [PSA] doubling time <6 months) following radical prostatectomy or radiotherapy, with a maximum of 5 metastases on PSMA-PET/CT. Patients received 2 (+2 optional) cycles of 7.4 GBq [ 177 Lu]Lu-PSMA-617. The primary outcome was progression-free survival (i.e. time without ADT). Progressive disease (PD) was defined as a 100% increase in PSA since randomization, radiographic or clinical progression or earlier necessitation of subsequent therapy (e.g. ADT). Secondary outcomes were PSA response, adverse events and quality of life. Results: Between April 20, 2020 and July 29 2024, 58 of 78 screened men were eligible. Data cut-off was set on December 24 th 2024. Median age was 72 years (range 51-82) with a median baseline PSA of 3.6 (1.2-29). Two patients received 2 cycles whereas 27 patients underwent 4 cycles of [ 177 Lu]Lu-PSMA-617. At a median follow-up time of 7 months (range 1-31), 93% (27/29) and 38% (11/29) of the SoC and arm, respectively, reached the definition for PD. The median progression free survival was 5 months (95% CI 4-6 months) for the SoC group whereas the median progression free survival was not reached for the [ 177 Lu]Lu-PSMA-617 group (HR, 0.07 [95% CI, 0.02 to 0.19]; P <.001). The median percentage PSA change was +125% vs. -91% in the SoC vs. [ 177 Lu]Lu-PSMA-617 arm, respectively. Twenty-one percent (6/29) of [ 177 Lu]Lu-PSMA-617 arm patients had a complete remission. The most common treatment-related adverse events were grade (G) 1 dry mouth (59%), G 1 fatigue (55%), G 1 nausea (48%), G 1 bone marrow toxicity (24-30%) which generally normalized during follow-up. G ≥2 adverse events were seldom observed (<15%) and not clinically relevant. Conclusions: [ 177 Lu]Lu-PSMA-617 showed promising efficacy as monotherapy in oligometastatic hormone sensitive prostate cancer patients to defer from androgen deprivation therapy, with minimal and mostly transient side effects. Following surgery and external beam radiotherapy, could become a third metastases-directed therapeutic option for oligometastatic prostate cancer patients to prolong ADT-free interval. Clinical trial information: NCT04443062 .

Purpose: Due to advancing neoadjuvant treatment strategies, accurate diagnosis of pancreatic ductal adenocarcinoma (PDAC) has become even more crucial. Current imaging modalities lack diagnostic accuracy to differentiate between PDAC and other pancreatobiliary diseases. For diagnosis of PDAC, a highly potential imaging modality has recently been proposed: Prostate-Specific Membrane Antigen (PSMA) PET/CT. PSMA has been translated to the clinic successfully for prostate cancer, both for staging and diagnosis of recurrent disease. Moreover, PSMA-based radioligand therapy offers therapeutic options. This phase I/II study aims to assess the feasibility of 18F-PSMA PET/CT to detect PDAC and unravel its theragnostic potential. Method: Patients with clinically suspected resectable PDAC were prospectively enrolled. 18F-PSMA PET/CT was performed prior to surgical resection. Images were both visually and semi-quantitatively interpreted. Relative PSMA-ligand concentrations were measured using standardized uptake value (SUV). For all PSMA-positive lesions, target-to-background ratio (TBR) was calculated as maximum intensity (SUVmax) of the primary tumor divided by mean intensity (SUVmean) of the aortic blood pool. Tracer uptake will be correlated to immunohistochemical PSMA expression in resected specimens. Results: Preliminary results demonstrate PSMA uptake in 12 out of 15 patients. Mean TBR was 4.3 (SD = 1.7) and correlated with mean SUVmax 4.6 (SD = 1.6). No lymph nodes or distant metastases were detected. Physiological duodenal uptake challenged but did not hamper visual interpretation. Conclusion: Detection of pancreatic cancers, including PDAC, is feasible using novel 18F-PSMA PET/CT. Based on semi-quantitative data, PSMA theragnostic applicability may be considered, but distinction of primary tumours is challenging.

You have accessJournal of UrologyCME1 May 2022MP51-03 DEVELOPMENT OF A NOVEL NOMOGRAM TO IDENTIFY CANDIDATES FOR EXTENDED PELVIC LYMPH-NODE DISSECTION IN PROSTATE CANCER USING MRI AND PSMA PET Dennie Meijer, André Vis, Matthew Roberts, Amila Siriwardana, Andrew Morton, John Yaxley, Hemamali Samaratunga, Louise Emmett, Peter van de Ven, Martijn Heijmans, Henk Van der Poel, Maarten Donswijk, Thierry Boellaard, Ivo Schoots, Daniela Oprea-Lager, Geoffrey Coughlin, and Pim van Leeuwen Dennie MeijerDennie Meijer , André VisAndré Vis , Matthew RobertsMatthew Roberts , Amila SiriwardanaAmila Siriwardana , Andrew MortonAndrew Morton , John YaxleyJohn Yaxley , Hemamali SamaratungaHemamali Samaratunga , Louise EmmettLouise Emmett , Peter van de VenPeter van de Ven , Martijn HeijmansMartijn Heijmans , Henk Van der PoelHenk Van der Poel , Maarten DonswijkMaarten Donswijk , Thierry BoellaardThierry Boellaard , Ivo SchootsIvo Schoots , Daniela Oprea-LagerDaniela Oprea-Lager , Geoffrey CoughlinGeoffrey Coughlin , and Pim van LeeuwenPim van Leeuwen View All Author Informationhttps://doi.org/10.1097/JU.0000000000002626.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Preoperative assessment of the probability of pelvic lymph-node metastatic (pN1) disease is required to identify patients with prostate cancer (PCa) who are candidates for extended pelvic lymph-node dissection (ePLND). METHODS: The aim of this study was to develop a novel prognostic model for predicting pathological lymph-node (pN)-status in contemporary patients with localized PCa, using preoperative clinical and histopathological parameters and imaging modalities such as magnetic resonance imaging (MRI) and prostate-specific membrane antigen (PSMA)-positron emission tomography (PET). Logistic regression with backward elimination was used to select variables for the prognostic model. Performance of the final model was evaluated using the area under the receiver operating characteristic curve (AUC) and decision-curve analyses (DCAs). RESULTS: Overall, 700 consecutive patients who underwent robot-assisted radical prostatectomy (RARP) and ePLND were included in the original cohort. Of these, 185/700 patients (26%) were found to have pN1-disease. The final model included initial prostate-specific antigen (PSA)-value, radiological T-stage on MRI, highest biopsy Grade Group (GG), biopsy technique (MRI-targeted versus systematic), percentage of systematic cores with clinically significant PCa (≥GG2) and PSMA-PET findings. AUC for predicting pN-status was found to be 0·82 (95%CI 0·78-0·85) for the final model. The DCA demonstrated an increased net-benefit in the threshold probability ≥3%. Using a cut-off of 7% above which to perform ePLND, 16% of ePLNDs could have been correctly avoided. Using 10% as a cut-off to prompt ePLND, 34% of ePLNDs would be spared, in exchange of 5·5% of patients with pelvic lymph-node metastatic disease. CONCLUSIONS: The novel nomogram to predict pelvic lymph-node metastatic disease was developed in patients with clinically localized PCa based on clinical and histopathological parameters, and parameters assessed on MRI and PSMA-PET imaging. The novel nomogram performed superior to presently available nomograms and was able to avoid ePLND in a substantial proportion of patients. Source of Funding: None © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e875 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.Metrics Author Information Dennie Meijer More articles by this author André Vis More articles by this author Matthew Roberts More articles by this author Amila Siriwardana More articles by this author Andrew Morton More articles by this author John Yaxley More articles by this author Hemamali Samaratunga More articles by this author Louise Emmett More articles by this author Peter van de Ven More articles by this author Martijn Heijmans More articles by this author Henk Van der Poel More articles by this author Maarten Donswijk More articles by this author Thierry Boellaard More articles by this author Ivo Schoots More articles by this author Daniela Oprea-Lager More articles by this author Geoffrey Coughlin More articles by this author Pim van Leeuwen More articles by this author Expand All Advertisement PDF downloadLoading ...

Purpose: To assess the diagnostic performance of prostate specific membranous antigen (PSMA) positron emission tomography/computed tomography (PET/CT) imaging to localize primary prostate cancer (PCa) in men with persistent elevated prostate-specific antigen (PSA) levels and previous prostate biopsies that were negative for PCa. Methods: In this study, 34 men with persistently elevated PSA-levels, previous negative for PCa biopsies and who subsequently underwent diagnostic PSMA-PET/CT imaging were retrospectively evaluated. Men were divided into 3 groups: 1. 12 men with a previous negative mpMRI scan (PI-RADS 1-2) 2. 17 men with a positive mpMRI scan (PI-RADS 3-5), but negative MRI-targeted biopsies and 3. Four men in whom mpMRI was contraindicated. If PSMA-avid lesions were seen, patients underwent 2-4 cognitive targeted biopsies in combination with systematic biopsies. The detection rate of PSMA-PET/CT for PCa, and the accuracy of (possible) targeted biopsies were calculated. Results: Included men had a median PSA-level of 22.8 ng/mL (Interquartile Range 15.6-30.0) at the time of PSMA-PET/CT. Elevated PSMA-ligand uptake in the prostate suspicious for PCa was observed in 22/34 patients (64.7%). In 18/22 patients (54.5%), PSMA-targeted prostate biopsies were performed. In 3/18 patients (16.6%), the targeted biopsies showed International Society of Urological Pathology (ISUP) score 1-2 PCa. The other men had inflammation or benign findings after histopathological examination of the biopsy cores. Conclusion: In this study, the clinical value of PSMA-PET/CT for patients with an elevated PSA-level, and negative for PCa biopsies was low. Only very few men were diagnosed with PCa, and no clinically significant PCa was found. (C) 2021 The Author(s). Published by Elsevier Inc.

You have accessJournal of UrologyProstate Cancer: Localized: Surgical Therapy IV (PD57)1 Sep 2021PD57-01 PREDICTING EARLY BIOCHEMICAL PROGRESSION IN PROSTATE CANCER PATIENTS STAGED WITH PSMA PET AND MULTIPARAMETRIC MAGNETIC RESONANCE IMAGING Dennie Meijer, Pim van Leeuwen, Maarten Donswijk, Thierry Boellaard, Ivo Schoots, Henk van der Poel, Harry Hendrikse, Daniela Oprea-Lager, and André Vis Dennie MeijerDennie Meijer More articles by this author , Pim van LeeuwenPim van Leeuwen More articles by this author , Maarten DonswijkMaarten Donswijk More articles by this author , Thierry BoellaardThierry Boellaard More articles by this author , Ivo SchootsIvo Schoots More articles by this author , Henk van der PoelHenk van der Poel More articles by this author , Harry HendrikseHarry Hendrikse More articles by this author , Daniela Oprea-LagerDaniela Oprea-Lager More articles by this author , and André VisAndré Vis More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002091.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The aim of this study was to point out predictors for early oncological outcome in patients who opt for robot-assisted laparoscopic radical prostatectomy (RARP) for localized prostate cancer (PCa) including conventional prognostic variables as well as multiparametric magnetic resonance imaging (mpMRI) and prostate-specific membrane antigen (PSMA) positron emission tomography (PET) imaging. METHODS: This observational study included 500 patients who underwent RARP and extended pelvic lymph node dissection (ePLND). Outcome measurement was biochemical progression of disease, defined as any post-operative PSA ≥0.2 ng/mL. A Cox-regression analysis was performed to assess predictors for biochemical progression, including initial prostate-specific antigen (PSA)-value, biopsy Grade Group (GG), T-stage on mpMRI, and lymph node status on PSMA PET imaging (miN0 vs. miN1). RESULTS: The median total follow-up of all included patients was 12.8 months (IQR 6.6-22.3). When assessing biochemical progression after surgery, initial PSA-value (per doubling; OR 1.24 (95%CI 1.08-1.43), p=0.003), biopsy GG ≥4 vs. GG 1-2 (OR 2.33 (95%CI 1.47-3.69), p<0.001), T-stage on mpMRI (rT3a vs. rT2: OR 2.04 (95%CI 1.30-3.20), p=0.002; ≥rT3b vs. rT2: OR 4.87 (95%CI 3.24-7.32), p<0.001) and miN1 on PSMA PET imaging (OR 2.16 (95%CI 1.46-3.20), p<0.001) were independent predictors of biochemical progression of disease. Moreover, the number of pelvic lymph node metastases on PSMA PET was significantly associated with biochemical progression: one pelvic lymph node metastasis vs. no metastatic disease resulted in an OR 2.60 (95%CI 1.57-4.31), p<0.001; two pelvic lymph node metastases or more on PSMA PET vs. no metastatic disease resulted in an OR 4.61 (95%CI 2.84-7.48), p<0.001. CONCLUSIONS: Initial PSA-value, biopsy GG ≥4, ≥rT3 disease on mpMRI and miN1 disease on PSMA PET were predictors for early biochemical progression after RARP. Furthermore, the number of pelvic lymph node metastases on staging PSMA PET was associated with biochemical progression. Identifying patients with an increased risk of biochemical progression after surgery may have implications for patient counseling in radical treatment decisions and on patient selection for modern (neo-)adjuvant and systematic treatments. Source of Funding: No funding was received for conducting this study. © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e1009-e1009 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Dennie Meijer More articles by this author Pim van Leeuwen More articles by this author Maarten Donswijk More articles by this author Thierry Boellaard More articles by this author Ivo Schoots More articles by this author Henk van der Poel More articles by this author Harry Hendrikse More articles by this author Daniela Oprea-Lager More articles by this author André Vis More articles by this author Expand All Advertisement PDF downloadLoading ...

BACKGROUND:Different nomograms exist for the preoperative prediction of pelvic lymph-node metastatic disease in individual patients with prostate cancer (PCa). These nomograms do not incorporate modern imaging techniques such as prostate-specific membrane antigen (PSMA) positron emission tomography (PET). OBJECTIVE:To determine the predictive performance of the Briganti 2017, Memorial Sloan Kettering Cancer Center (MSKCC), and Briganti 2019 nomograms with the addition of PSMA-PET in an international, multicenter, present-day cohort of patients undergoing robot-assisted radical prostatectomy (RARP) and extended pelvic lymph-node dissection (ePLND) for localized PCa. DESIGN, SETTING, AND PARTICIPANTS:All 757 eligible patients who underwent a PSMA-PET prior to RARP and ePLND in three reference centers for PCa surgery between January 2016 and November 2020 were included. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:Performance of the three nomograms was assessed using the receiver operating characteristic curve-derived area under the curve (AUC), calibration plots, and decision curve analyses. Subsequently, recalibration and addition of PSMA-PET to the nomograms were performed. RESULTS AND LIMITATIONS:Overall, 186/757 patients (25%) had pelvic lymph-node metastatic (pN1) disease on histopathological examination. AUCs of the Briganti 2017, MSKCC, and Briganti 2019 nomograms were 0.70 (95% confidence interval [95% CI]: 0.64-0.77), 0.71 (95% CI: 0.65-0.77), and 0.76 (95% CI: 0.71-0.82), respectively. PSMA-PET findings showed a significant association with pN1 disease when added to the nomograms (p < 0.001). Addition of PSMA-PET substantially improved the discriminative ability of the models yielding cross-validated AUCs of 0.76 (95% CI: 0.70-0.82), 0.77 (95% CI: 0.72-0.83), and 0.82 (95% CI: 0.76-0.87), respectively. In decision curve analyses, the addition of PSMA-PET to the three nomograms resulted in increased net benefits. CONCLUSIONS:The addition of PSMA-PET to the previously developed nomograms showed substantially improved predictive performance, which suggests that PSMA-PET is a likely future candidate for a modern predictive nomogram. PATIENT SUMMARY:Different tools have been developed to individualize the prediction of prostate cancer spread to lymph nodes before surgery. We found that the inclusion of modern imaging (prostate-specific membrane antigen positron emission tomography) improved substantially the overall performance of these prediction tools.