BACKGROUND:For over a decade the Advanced Prostate Cancer Consensus Conference (APCCC) covers a variety of topics that greatly impact daily practice. In 2025, a dedicated event was organised to discuss key questions in clinical management of patients with prostate cancer (PC) related to diagnostic tools (APCCC Diagnostics). Here we present the voting results of the APCCC Diagnostics questions. OBJECTIVE; DESIGN, SETTING, AND PARTECIPANTS: APCCC Diagnostics 2025 is a pilot project. The scientific committee for APCCC Diagnostics 2025 developed 88 multiple-choice consensus questions on six different topics. Prior to the conference, the panel members (''panellists'') voted on these questions via a web-based survey. Consensus was defined as ≥75% agreement, with strong consensus defined as ≥90% agreement. OUTCOMES MEASUREMENTS AND STATISTICAL ANALYSIS:Consensus was only reached on 17 of 88 questions (19%), of which six (7%) received a strong consensus. Specifically, consensus was reached for two of 17 questions (14%) in "how to diagnose PC"; seven of 16 (44%) in "how to stage PC"; three of 14 (21%) in "Biochemical Recurrence Scenario"; two of 11 (18%) in "metastatic disease: what to do?"; zero of 18 (0%) in "monitoring metastatic PC"; and three of 12 (25%) in "radioligand therapy and imaging." CONCLUSIONS:The voting results and their discussion may assist physicians in navigating controversial areas of clinical management related to diagnosis, staging, and restaging in the different clinical settings for PC, particularly where high-level evidence is scarce or conflicting. The findings can also help funders and policymakers in prioritising areas for future research.

Background Beyond its oncological role, [18F]-FDG PET is increasingly used to quantify adipose tissue (AT) metabolism. Technical and clinical parameters may impact [18F]-FDG accumulation and should be accounted for. We aimed to model how these parameters impact [18F]-FDG activity in AT using a large retrospective cohort. Methods 3230 [18F]-FDG PET-CT scans (2011-2014) from 2694 patients were semi-automatically segmented for subcutaneous AT (SAT) and visceral AT (VAT). A generalized additive mixed model (GAMM) was fitted on log-transformed [18F]-FDG activity per volume (kBq/cm3), decoupled from weight and dose. Fixed effects included AT type, sex, and cancer stage; non-linear smooth terms modeled blood glucose, blood volume, and dose; and a tensor product smooth of age and BMI was allowed to differ by sex and AT type. Results SAT had significantly lower [18F]-FDG activity than VAT (β = -0.48, p < .001). A sex effect (female β = 0.11, p < .001) was reversed in SAT by a significant interaction (β = -0.15, p < .001). Higher cancer stages reduced activity in SAT but not VAT. Blood glucose showed a U-shaped relationship with activity, minimum near 6 mmol/l. In females, SAT activity was U-shaped with age, inflecting at 50-60 years, while VAT showed a linear positive association. Conclusion VAT exhibited higher [18F]-FDG uptake than SAT during fasting, significantly modulated by sex. SAT activity increased with age in women after the age of about 50 years, possibly related to the menopausal transition; menopausal status itself was not recorded. A novel U-shaped blood glucose relationship suggests competitive uptake at euglycemic states, while increased glucose carrier levels at dysglycemic states may increase activity.

Abstract Background Cardiopulmonary transit time (CPTT), the time for blood to circulate from the right to the left ventricle, can be assessed on dynamic Rubidium-82 ([ 82 Rb]) cardiac PET/CT. Given its association with cardiac and pulmonary function, CPTT holds potential as a screening marker for pulmonary hypertension. This study investigated the relationship between CPTT and echocardiographic markers of cardiac function, as well as its association with pulmonary hypertension. In this retrospective single-center study, 111 patients (72 male, 39 female) referred for [ 82 Rb]RbCl-PET/CT and echocardiography within 31 days were included. CPTT, normalized to heart rate (NCPTT), was calculated from peak right and left ventricular [ 82 Rb] activity and examined in relation to patient characteristics and echocardiographic parameters, which were further used to categorize left and right ventricular systolic dysfunction, left ventricular diastolic dysfunction, and signs of elevated pulmonary arterial pressure. Results Prolonged NCPTT was significantly associated with lower left ventricular ejection fraction and increased body weight ( p < 0.05). NCPTT was significantly associated with left and right ventricular systolic dysfunction (OR = 1.21, 95%CI:1.04–1.42, p < 0.05; OR = 1.18, 95%CI:1.04–1.34, p < 0.01), elevated pulmonary arterial pressure (OR = 1.21, 95%CI:1.02–1.44, p < 0.05), and possible pulmonary hypertension ( p < 0.05), but not with left ventricular diastolic dysfunction. Conclusion Our findings suggest that NCPTT may serve as a useful additional marker for assessing cardiac function, particularly ejection fraction, and could help in the evaluation of patients with suspected cardiac systolic dysfunction, as well as the detection of pulmonary hypertension.

The sensitivity of PSMA-PET/CT for the detection of recurrent prostate cancer (rPC) is good at low PSA values and rapidly rises to > 80

BackgroundProstate-specific membrane antigen (PSMA)-based imaging has become an increasingly important diagnostic tool in prostate cancer, though limited by low surface expression of PSMA in some patients. Previous studies have demonstrated that dutasteride can induce PSMA expression in vitro and in vivo. This pilot study aimed to evaluate the impact of short-term dutasteride treatment on standardized uptake values (SUVmax) in PSMA PET imaging and the immunohistochemical expression of PSMA for the first time in humans.MethodsFour prostate cancer (PCa) patients underwent an initial PSMA PET/MRI of the prostate. Afterwards, all patients received 0.5 mg of oral dutasteride once daily for seven days. Subsequently, a second PSMA PET/MRI of the prostate and a template biopsy were performed. We compared the maximum standardized uptake value (SUVmax) of PSMA-positive lesions before and after dutasteride treatment. Additionally, histopathological specimens from PSMA-positive lesions and negative controls were analyzed for Gleason score and PSMA expression.ResultsAn increase in SUVmax was observed in all patients following short-term dutasteride treatment. Histological analysis confirmed prostate cancer with an ISUP grade of ≥ 2 in PSMA-positive lesions that exhibited increased SUVmax following short-term stimulation. One PSMA-positive lesion, which showed a decrease in SUVmax after stimulation, was negative for prostate cancer on biopsy.ConclusionThis pilot study demonstrated an increase in SUVmax in PSMA-positive prostate cancer lesions following a short-term seven-day course of dutasteride. Short-term dutasteride treatment prior to PSMA-PET imaging may have the potential to enhance detection rates in patients with prostate cancer. Further studies are needed to investigate this effect in larger patient populations.

Aim PSMA-based radioligand therapy (PSMA-RLT) for metastatic castration-resistant prostate cancer (mCRPC) is associated with nausea, vomiting, and fatigue. We evaluated whether standardized premedication with glucocorticoids and antiemetics reduces these side effects. Methods In this retrospective multicentre study, 67 mCRPC patients received 322 cycles of 177 Lu-PSMA-617 at three Swiss centres. All patients received 8 mg dexamethasone and 8 mg ondansetron intravenously 30 minutes before therapy. Side effects were assessed using study-specific questionnaires (195/322 returned; 61%). Baseline symptoms were documented using EORTC questionnaires in 30 patients. Biochemical response was evaluated in 36 patients using PCWG3 criteria. Results Absolute side effect rates were: nausea within 3 days 20.9%, inter-cycle nausea 35.8%, vomiting 10.4%, and fatigue 67.2%. After correction for baseline symptoms, estimated new-onset rates were lower: 16.3%, 26.1%, 7.0%, and 6.7%, respectively. Early nausea significantly predicted inter-cycle nausea (p=0.02). Side effects followed a U-shaped pattern across cycles. No significant association was observed between side effects and PCWG3 biochemical response, though statistical power was limited. Conclusions Absolute rates of nausea and fatigue were comparable to the VISION trial. However, new-onset rates of these two side effects were substantially lower after accounting for baseline symptoms. A protective effect of premedication with glucocorticoids and antiemetics could be the reason for this, but requires confirmation in prospective controlled studies.

Abstract Background Lobular breast cancer often shows only low [ 18 F]FDG uptake, limiting the sensitivity to detect metastases. Alternative tracers, targeting tumor activated fibroblasts or estrogen receptors, can offer higher accuracy. Also, Somatostatin Receptor 2 (SSTR2) is significantly expressed in some breast cancers, particularly in estrogen receptor rich tumors. Typical pulmonary carcinoids also have low [ 18 F]FDG accumulation, but approximately 63% of well-differentiated lesions express SSTR2. Case presentation We report the case of a 66-year-old female patient with lobular breast cancer and a coincidentally discovered typical carcinoid of the lung. On subsequent [ 68 Ga]Ga-DOTATATE PET/CT to stage the carcinoid tumor, two SSTR2 positive focal lesions in the bones were present, without [ 18 F]FDG uptake but with mild sclerosis, atypical for metastasis of carcinoids. Biopsy confirmed osseous breast cancer metastases. Conclusion SSTR2 expression in normal breast tissue and breast carcinoma has been described previously. However, the case underscores the importance of awareness of atypical presentations of cancer within a multi-tracer approach, whereby receptor profile and morphology must be carefully integrated.

Peptide receptor radionuclide therapy (PRRT) with radiolabelled somatostatin analogues, such as [¹⁷⁷Lu]Lu-DOTATATE, is approved as a second-line treatment for progressive, gastroenteropancreatic neuroendocrine tumors (GEP-NETs). However, emerging evidence suggests potential earlier roles for PRRT. A systematic review was conducted in accordance with the PRISMA guidelines, including case reports, original papers, and clinical trial protocols evaluating neoadjuvant, adjuvant, or first-line PRRT in GEP-NETs. A systematic search of PubMed and clinicaltrials.gov (up to May 31, 2025) finally identified 25 eligible papers. For each paper, data were extracted regarding clinical setting, patient characteristics, treatment regimen, and oncologic and surgical outcomes. The available preliminary data, comprising case reports, retrospective and prospective cohorts, show that neoadjuvant PRRT can induce tumor shrinkage, regression of vascular involvement, and conversion from unresectable to resectable disease in up to 45

Impaired renal function after [177Lu]Lu-PSMA radioligand therapy (RLT) is a growing concern as the field moves toward earlier applications. Little is known how renal function could be protected. This study evaluates the impact of furosemide administered shortly after [177Lu]Lu-PSMA RLT, based on long-term follow-up of renal function and quantitative assessment of renal uptake. Retrospective analysis of patients treated with a least 4 cycles of [177Lu]Lu-PSMA at two Swiss RLT centers with 40 mg furosemide 30 min after injection (CenA) and without (CenB). CenA used [177Lu]Lu-PSMA-I T and [177Lu]Lu-PSMA-617, while CenB used only [177Lu]Lu-PSMA-I T. A mixed-effects model was used to evaluate eGFR and PSA change per cycle in the first cohort. To increase the number for renal uptake of [177Lu]Lu-PSMA-I T in CenA, supplementary patients with less than 4 cycles were included for quantitative SPECT assessment. In CenA, 24 patients with 5.4±0.8 doses (17 [177Lu]Lu-PSMA-617 / 7 [177Lu]Lu-PSMA-I T) were followed over 202.0±58 days. In center CenB 20 patients with 5.4±0.9 doses were followed over 210.6±48 days. CenB showed a significant drop in eGFR per cycle of -2 ml/min/1.73m2 (CI − 2.8/−1.1), p < 0.001, while CenA showed no significant decrease per cycle, with 0.3 ml/min/1.73m2 (CI − 0.6/1.1), p = 0.587. For quantitative analysis 20 patients with [177Lu]Lu-PSMA-I T in CenB had a mean SUVpeak of 7.7±3.1, while 16 patients in CenA with [177Lu]Lu-PSMA-I T had a mean SUVpeak of 7.1±3.0 and 17 patients with [177Lu]Lu-PSMA-617 had a mean of 6.2±1.8. Furosemide may reduce tracer accumulation in the kidneys after [177Lu]Lu-PSMA RLT. This might explain the mostly stable eGFR values observed in CenA, while there was a significant drop in CenB, without furosemide. If diuretics could reduce renal toxicity without impairing efficacy warrants further prospective evaluation.

High-intensity focused ultrasound (HIFU) is an increasingly used, locally ablative therapy option in localized prostate cancer (PCa). Multiparametric MRI (mpMRI) is currently used for tumor delineation. However, up to 56% of patients will have recurrent disease, defined as International Society of Urological Pathology (ISUP) grade of 2 or greater on follow-up biopsies within 3 y. The objectives of this study were to evaluate recurrence and failure-free survival (FFS) rates in patients treated with HIFU after undergoing prostate-specific membrane antigen (PSMA) PET and to compare delineation and scoring for biopsy-proven lesions between imaging techniques (PSMA PET vs. mpMRI). Methods: This single-center retrospective cohort study included all patients who were scheduled for HIFU between June 2017 and May 2022 and underwent a PSMA PET scan within 6 mo before planned HIFU for initial therapy of low-risk or intermediate-risk PCa (primary HIFU) or local recurrence after radiotherapy (salvage HIFU). Outcomes assessed included FFS, defined as the absence of ISUP grade 2 or greater on follow-up biopsies, progression on imaging, or biochemical recurrence. Tumor detection on mpMRI and PSMA PET was compared using PRIMARY and Prostate Imaging Reporting and Data System (PI-RADS) 2.1 scores for patients with adequate mpMRI and PSMA PET within 6 mo of HIFU. Results: Of the 26 patients included in the cohort, 3 (12%) did not undergo HIFU after the PSMA PET scan because of PCa upstaging. Of the remaining 23 patients, 9 (39%) were treated for recurrent disease and 14 (61%) for primary disease. Over a mean follow-up time of 3.2 y, 15 patients (65%; 95% CI, 42.7%-83.6%) were free of disease at the last follow-up. Eight patients (35%) experienced recurrent or residual disease within 3 y. Image analysis was performed for 18 patients, for a total of 23 lesions, with mean PRIMARY and PI-RADS 2.1 scores of 4.1 (range, 2-5), and 3.3 (range, 2-5), respectively. Lesion detection was rated superior on PET over mpMRI for 12 lesions, whereas mpMRI was superior for 1 lesion. Conclusion: PSMA PET scans performed before HIFU identified 12% of patients who were unsuitable for treatment. The overall improved FFS rate and higher PRIMARY score, when compared with the existing literature, suggest a potential benefit of PSMA PET for tumor delineation.

[¹⁷⁷Lu]Lu-PSMA RLT represents an effective option for advanced mCRPC. SPECT/CT allows the assessment of biodistribution and lesion-level tracer accumulation. We aimed to determine whether semiquantitative RLT SPECT/CT parameters could predict response on a lesion level. We retrospectively considered consecutive mCRPC patients who, between February 2022 and January 2026, received minimum two [¹⁷⁷Lu]Lu-PSMA-617 cycles at Messina and Genova Universities, with SPECT/CT at the 1st RLT, including whole PSMA-positive disease. Each [¹⁷⁷Lu]Lu-PSMA-617-positive lesion was semiautomatically segmented using MIM through a 40

Aim:PSMA-based radioligand therapy (PSMA-RLT) for metastatic castration-resistant prostate cancer (mCRPC) is associated with nausea, vomiting, and fatigue. We evaluated whether standardized premedication with glucocorticoids and antiemetics reduces these side effects. Methods:In this retrospective multicentre study, 67 mCRPC patients received 322 cycles of 177Lu-PSMA-617 at three Swiss centres. All patients received 8 mg dexamethasone and 8 mg ondansetron intravenously 30 minutes before therapy. Side effects were assessed using study-specific questionnaires (195/322 returned; 61%). Baseline symptoms were documented using EORTC questionnaires in 30 patients. Biochemical response was evaluated in 36 patients using PCWG3 criteria. Results:Absolute side effect rates were: nausea within 3 days 20.9%, inter-cycle nausea 35.8%, vomiting 10.4%, and fatigue 67.2%. After correction for baseline symptoms, estimated new-onset rates were lower: 16.3%, 26.1%, 7.0%, and 6.7%, respectively. Early nausea significantly predicted inter-cycle nausea (p=0.02). Side effects followed a U-shaped pattern across cycles. No significant association was observed between side effects and PCWG3 biochemical response, though statistical power was limited. Conclusions:Absolute rates of nausea and fatigue were comparable to the VISION trial. However, new-onset rates of these two side effects were substantially lower after accounting for baseline symptoms. A protective effect of premedication with glucocorticoids and antiemetics could be the reason for this, but requires confirmation in prospective controlled studies.

The Pelvic Rosetta Classification (PRC) project aimed to develop an interdisciplinary, landmark-based pelvic lymph node map for patients with prostate cancer to improve communication between imaging specialists and urologists. Methods: After an intense development phase, we conducted 3 evaluation rounds including 19 clinical experts having consensus meetings after each evaluation round. Experts contoured lymph node areas (LNA) for 2 patients with prostate cancer. Contours were assessed qualitatively and quantitatively. The PRC was further validated by assignment of 30 prostate-specific membrane antigen PET/CT-positive lesions to LNAs. The interrater reliability was calculated using Fleiss κ. Based on the final PRC, a complete contour and a 3-dimensional model were created. Results: Eight pelvic (external iliac, cranial/caudal obturator fossa, dorsal internal iliac, vesico-prostatic pedicle, mesorectal/perirectal, presacral, preprostatic/retropubic) and 4 extrapelvic (common iliac, intercommon, sigmoid, inguinal) LNAs were defined using anatomic landmarks which are consistently recognizable on imaging and intraoperatively. Strong consensus between experts existed for smaller, well-defined LNAs (e.g., preprostatic/retropubic, mesorectal/perirectal LNAs) compared with regions with proportionally large borders (e.g., obturator fossa, vesico-prostatic pedicle LNAs). Overall, moderate agreement (κ = 0.53) was observed during validation. Discrepancies were mostly encountered for lesions adjacent to borders between LNAs. The final contour and 3-dimensional model were approved by all experts. Conclusion: The PRC project showed fair reproducibility and validity. Further external validation is needed to assess its influence on interdisciplinary communication and treatment outcomes.

Aggressive-variant prostate cancer (AVPC) is characterized by several high-risk features and is typically treated with chemotherapy. In this study, we evaluated the outcomes of patients with AVPC who received prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT). Methods: This retrospective study included patients with AVPC with metastatic castration-resistant prostate cancer who received PSMA RLT at 3 academic centers. Patients with AVPC were further stratified into 2 subcategories: AVPC-C (clinicopathologic), referring to patients who met AVPC on the basis of clinical or pathologic features, and AVPC-MS (molecular signature), referring to patients who met AVPC criteria on the basis of genomic alterations. Prostate-specific antigen (PSA) response was calculated in the overall cohort, and PSA progression-free survival and overall survival (OS) were calculated in the paired cohort. In the segmentation cohort, SUVmean and total tumor volume were quantified using MIM software. Results: In total, 82 patients were classified as having AVPC, of whom 47 (57%) had AVPC-C and 35 (43%) had AVPC-MS. In the overall cohort, the percentage of patients who had a reduction in PSA of at least 50% or more from baseline was similar between the AVPC and non-AVPC groups (62.1% vs. 60.7%, respectively). In the paired cohort, the median PSA progression-free survival in the AVPC group was 3.2 mo (95% CI, 2.5-5.7 mo), compared with 4.2 mo (95% CI, 3.5-5.1 mo) in the non-AVPC group (P = 0.10). The median OS was shorter in the AVPC group (11.8 mo; 95% CI, 9.7-14.9 mo) compared with the non-AVPC group (13.3 mo; 95% CI, 12.1-15.0 mo; P = 0.04). There was no difference in median OS between AVPC-MS and AVPC-C subgroups (11.9 mo vs. 10.9 mo, respectively; P = 0.8). In the segmentation cohort, there was a trend toward lower SUVmean in patients with AVPC (5.9 vs. 6.6 in patients without AVPC, P = 0.07); however, there was no difference in median total tumor volume between the groups (253.4 mL vs. 298.6 mL, respectively; P = 0.6). Conclusion: Although patients with AVPC exhibited significantly worse OS after PSMA RLT, the percentage of patients treated with PSMA RLT who had a reduction in PSA of at least 50% or more from baseline was similar between the AVPC and non-AVPC groups. These findings support the consideration of PSMA RLT as a treatment option in patients with AVPC who have adequate PSMA expression.

INTRODUCTION:The landscape of diagnosis and treatment of locally advanced and metastatic prostate cancer has seen an unprecedented evolution in recent years. Incorporation of results from pivotal studies is crucial for state-of-the-art counselling of patients and to inform treatment recommendations. However, in daily practice ambiguous situations may occur or various options may seem adequate. Furthermore, specific national regulations, e.g. availability of diagnostic tools and drug approvals, may influence treatment choices. This paper presents the voting results of a Swiss expert panel that convened in August 2024 and discussed selected questions addressed by an international panel of experts during the Advanced Prostate Cancer Conference held in Lugano in April 2024. The objective is to facilitate national harmonization of diagnosis and treatment of locally advanced and metastatic prostate cancer and thereby providing a basis for discussion with individuals with prostate cancer.

A 65-year-old woman with a history of ductal mammary carcinoma and recent autonomic dysfunction underwent a Rb-82 chloride (RbCl) cardiac PET/CT scan that showed no ischemia or scarring, but significantly reduced myocardial flow reserve (MFR) (global: 1.5) and a CAC-Score of 0. The patient’s chemotherapy history (paclitaxel, carboplatin, epirubicin, pembrolizumab 2 years before) with elevated Troponin T and NT-pro-BNP levels at that time, and now reduced MFR with 0 CAC suggests cancer-therapy-related cardiotoxicity. An important differential diagnosis to the more common CAD-associated microvascular disease. Furthermore, tumor recurrence with a PET-avid lymph node metastasis was found additionally.

Prostate-specific membrane antigen (PSMA) PET is a powerful tool for prostate cancer staging and restaging, providing higher sensitivity and specificity than conventional imaging. The recognition of interpretive pitfalls led to the development of various scoring systems and frameworks, which in turn created challenges for consistent interpretation. The Prostate Cancer Molecular Imaging Standardized Evaluation (PROMISE) version 2 classification integrates the five-point PRIMARY score for assessing local disease, the molecular imaging TNM stage for disease extent, and the PSMA expression score to assess eligibility for PSMA-targeted radioligand therapy. The PSMA Reporting and Data System (PSMA-RADS) classifies PSMA PET/CT findings on the basis of the likelihood of presence of prostate cancer. For assessing therapy response, PSMA PET Progression (PPP) criteria focus on new lesions and clinical or biochemical progression, whereas Response Evaluation Criteria in PSMA PET/CT (RECIP 1.0) assess new lesions and changes in total PSMA-positive total tumor volume. The European Association of Nuclear Medicine (EANM) E-PSMA guideline and EANM-Society of Nuclear Medicine and Molecular Imaging procedure guidelines provide standardized reporting recommendations, incorporating elements from existing systems such as PROMISE, PSMA-RADS, and PPP. Nevertheless, such systems can be essential for optimizing prostate cancer management and facilitating communication among imaging professionals, clinicians, and patients. This article outlines these systems and discusses potential strengths and weaknesses.

5091 Background: CHAARTED criteria using CT and bone scan are widely recognized as prognostic in metastatic, hormone-sensitive prostate cancer (mHSPC) and can guide decisions about treatment, including intensification. However, clinicians are increasingly using PSMA PET/CT (PSMA-PET) instead of conventional imaging. Currently, PSMA-PET criteria for identifying poor prognostic mHSPC has limited evidence. The aim of this study is to identify features on PSMA PET/CT that correlate to progression free survival (PFS) and overall survival (OS) in the context of CHAARTED criteria in an ENZAMET sub-cohort. Methods: ENZAMET (ANZUP 1304, NCT02446405) is an international, open-label, randomized, phase 3 trial. Eligible participants had mHSPC evident on CT and/or bone scan. Participants (pts) were randomly assigned (1:1) to receive testosterone suppression plus enzalutamide or a non-steroidal antiandrogen (NSAA). Pts who underwent PSMA-PET prior to study enrolment were identified for this sub-study. Imaging (PSMA-PET, CT, bone scan) were de-identified, and centrally evaluated by three imaging experts blinded to clinical outcomes for number, site, and intensity of metastatic deposits. Additional correlative findings on bone scan and PSMA-PET/CT were determined. A semi-automated quantitative imaging analysis was undertaken to derive PSMA-total tumor volume (PSMA-TTV). The analysis evaluated the association between PSMA-TTV (analysed continuously and as quartiles Q1-3 vs Q4), site (lymph node, bone, viscera) with PFS, OS, and CHAARTED criteria. Kaplan-Meier survival estimates, log-rank tests, and Cox regression after adjusting for treatment arm were used for analysis. Results: 100 pts (51 enzalutamide, 49 control NSAA) had a PSMA-PET/CT prior to enrolment. In this sub-cohort, median age was 69 years, 36 were synchronous, 74 patients were low volume on CHAARTED criteria. On PSMA-PET 19 pts had bone only disease, 37 had lymph node (LN) only, 33 bone and LN and 9 visceral involvement. In 54 pts with bone involvement on PSMA-PET, 53 had concordant findings on bone scan. Median PSMA TTV in the study cohort was 28 mL (61 mL vs 22 mL in CHAARTED high vs low volume) with the highest PSMA TTV quartile (Q4) >71mL. 5-year PFS for PSMA TTV Q4 vs Q1-3 was 36% vs 61% (p=0.011), with HR per doubling of TTV = 1.19 (95%CI: 1.03 – 1.38). In the pts with CHAARTED criteria low volume mHSPC, 5-year PFS for PSMA TTV Q4 vs Q1-3 was 21% vs 57% (p<0.001). 5-year OS for PSMA TTV Q4 vs Q1-3 was 60% vs 74% (p=0.18) with HR per doubling of TTV = 1.10 (95%CI: 0.91 – 1.32). Conclusions: PSMA-TTV is associated with PFS in mHSPC in this ENZAMET sub-cohort with the highest volume quartile (>71mls) showing significantly shorter PFS, including within the CHAARTED criteria low volume cohort. Further validation of PSMA-TTV as a prognostic biomarker with potential to identify patients for intensification is warranted in larger mHSPC cohorts. Clinical trial information: NCT02446405 .

Clinically accurate detection of prostate cancer (PCa) metastases is crucial for management of high-risk PCa patients scheduled for radical prostatectomy. We determine the safety and diagnostic accuracy of pre-operative 68Ga-PSMA-11 PET/CT imaging in newly diagnosed high-risk PCa and assess its impact on patient management. Investigator-initiated prospective multi-center multinational single-arm open-label phase 1/2 imaging trial (EuRadCT 2016–001815-19). Patients with high-risk PCa scheduled for prostatectomy were enrolled at 9 institutions in Germany, Austria, and Switzerland to undergo 68Ga-PSMA-11 PET/CT for primary staging. The primary objectives were the evaluation of 68Ga-PSMA-11 PET/CT imaging to detect the primary tumor and lymph node disease and safety assessment. Secondary objectives included detection of distant metastases, correlation of 68Ga-PSMA-11 uptake with Gleason Score, and determining the impact on clinical management. Impact of pre-operative 68Ga-PSMA-11 PET/CT imaging on target volume definition for radiation therapy was assessed. 173 patients underwent 68Ga-PSMA-11 PET/CT for primary staging. Histopathologic correlation was available in 139 patients (imaging dataset), with lymph node metastases in 55 patients (39.6