5112 Background: Previously, we proposed novel risk group definitions for prostate cancer patients based on Prostate-Specific Membrane Antigen (PSMA) targeted positron emission tomography (PET). PSMA-PET pan-stage nomograms (PPP3) were developed using the international, multicentre PROMISE registry (NCT06320223) to prognosticate overall survival (OS). Here, we present an external validation of PPP3. Methods: Eligible patients enrolled into our PROMISE registry database after the PPP3 data cap were included into this external validation study. Included patients had histologically proven prostate cancer and underwent PSMA-PET at hospitals in Turkey, Cyprus, Italy, China, South Africa or Germany between 2015 and 2022. PSMA-PET was standardized by PROMISE version 2 (V2); total lesion count, total tumor volume, PSMA expression score and OS follow-up were obtained as per local site practice. PPP3 nomograms were applied to calculate risk groups and Harrell´s C-indices for the external validation cohort. Calibration curves were measured for 5-year OS. Head-to-head comparison between the visual PPP3 nomogram and the simplified risk stratification table was examined by area under the receiver operating characteristics curve (ROC-AUC). Results: 1855 male patients across all disease stages with 179 (9.6%) reported deaths and median OS follow-up of 4.8 years (IQR 3.7-6.1) were analysed. In the external validation cohort C-indices (95% CI) were 0.71 (0.67-0.76) for the visual nomogram and 0.73 (0.69-0.77) for the quantitative nomogram, respectively. By simplified risk stratification table, 77 of 1855 patients (4.2%) were underestimated and 16 (0.9%) were overestimated, when compared with visual nomograms. Prognostic accuracy was comparable using both methods (AUC Nomogram: 0.64 vs. AUC Table: 0.63, p = 0.02). Conclusions: PPP3 nomograms were validated in an external multi-site patient cohort. Prognostication was accurate (C-indices > 0.70) for both PPP3 nomograms. Clinical trial information: NCT06320223 .

Aim/Background Oligometastatic Prostate Cancer (omPC) spread ranges from localized to high-volume distant disease. PSMA PET has become the preferred diagnostic modality and is able to provide localization with unprecedented accuracy. It was hypothesized that number of metastases, site of metastases and PSMA derived volume of disease are associated with overall survival (OS). Methods A total of 1,689 omPC patients at biochemical recurrence with disease localization on PSMA PET were retrospectively analyzed. Data include the molecular imaging TNM system (miTNM), total tumor volume, and OS. Subgroups with 1 to 3 (any miN, miM1; OMPC3), 4 or 5 (any miN, miM1; OMPC5), and 6 or 7 (any miN, miM1; OMPC7) metastases or with up to 3 pelvic-only lymph node metastases (miN1/N2, miM0; ONPC3) were compared. A penalized hazard model for OS was applied. A subgroup analysis with complete cases was conducted to test the additive value of Gleason score in a combined model. Results Five-year OS for OMPC3/OMPC5/OMPC7/ONPC3 was 86/84/77/93%, respectively. Univariate Cox-regression findings present the prognostic value of visceral metastases (HR = 1.8 [1.2; 2.8]; P = 0.0040), bone metastases (HR = 1.6 [1.3; 1.9]; P < 0.001), extrapelvic lymph-node metastases (HR [95%CI] = 1.2 [0.98; 1.5]; P = 0.071), as well as total tumor volume (mL; HR = 1.01 [1.01; 1.02]; P < 0.001) and SUVmean (HR = 1.0 [1.0-1.0]; P = 0.001). Based on the penalized hazard model, total tumor volume was the selected independent predictor for OS. In the two largest subgroups ONPC3 and OMPC3, a volume of 3.1 ml significantly separated low vs. high volume for OS. Additive value of Gleason score to the penalized hazard model in a subgroup analysis was not confirmed. Conclusion PSMA PET number of metastases and tumor volume are highly prognostic for omPC. OS in men with ≥ 6 metastases or ≥ 3.1 mL tumor volume is significantly worse compared with less disease.

BACKGROUND:Prostate-specific membrane antigen (PSMA)-PET usage in patients with prostate cancer is growing rapidly. Thus, novel risk-group definitions based on PSMA-PET are urgently needed for guidelines, clinical use, and trial study design. We report improved risk classification based on PSMA-PET Prostate Cancer Molecular Imaging Standardized Evaluation (PROMISE; PPP) nomograms (PPP3) to prognosticate 3-year, 5-year, and 7-year overall survival. METHODS:In this international, retrospective, registry-based cohort study, we collected data from the PROMISE PET registry with ongoing overall survival follow-up. Male patients (aged ≥18 years) with histological proven prostate cancer at any disease stage and any performance status, who underwent any PSMA-PET between Dec 6, 2012, and June 26, 2024, were included in the registry. Patients with neuroendocrine pattern or metastasised or disseminated malignancy other than prostate cancer were excluded. 35 investigator sites in Europe, Asia, Australia, North America, and South America were split pairwise (2:1) into development and validation cohorts. Entire investigator sites were split pairwise according to their site characteristics (ie, number of patients per disease group, country, follow-up). The primary study objective was overall survival. PPP3 nomograms were created based on Cox regression models with least absolute shrinkage and selection operator penalty to prognosticate 3-year, 5-year, and 7-year overall survival. Calibration curves and Harrell's c indices were applied and head-to-head comparison with clinical risk scores separated for each disease subgroup was conducted. Based on the visual PPP3 nomogram, a simplified risk-stratification table was created. FINDINGS:We analysed 11 154 patients and 7253 were included in the development cohort and 3901 in the validation cohort. Median follow-up to censoring or death was 4·9 years (IQR 3·5-6·6). Clinical disease group and PROMISE metrics were combined into visual and quantitative PPP3 nomograms, respectively. C indices were 0·83 (95% CI 0·82-0·84) for the visual nomogram and 0·84 (0·82-0·85) for the quantitative nomogram. Both nomograms and the simplified risk stratification table were accurate and equal or superior compared with established clinical risk scores (International Staging Collaboration for Cancer of the Prostate, European Association of Urology, a nomogram defined by Gafita and colleagues, and National Comprehensive Cancer Network). INTERPRETATION:We present new risk nomograms by PROMISE along with a simple table to prognosticate 3-year, 5-year, and 7-year overall survival in prostate cancer. PROMISE and PPP3 assessments are freely available online for global implementation. FUNDING:German Research Foundation, Prostate Cancer Foundation, Innovative Health Initiative Joint Undertaking, Novartis, AstraZeneca, and Amgen.

BACKGROUND AND OBJECTIVE:Prostate-specific membrane-antigen positron emission tomography (PSMA-PET) detects distant metastases in more than half of patients with increasing prostate-specific antigen despite castrate levels of testosterone and high-risk nonmetastatic disease on conventional imaging. Here, we aim to evaluate prognostic implications of PSMA-PET staging in patients with nonmetastatic castration-resistant prostate cancer (nmCRPC). METHODS:Overall, 514 patients who underwent PSMA-PET for nmCRPC at investigator sites across the world between 2013 and 2022, were retrospectively evaluated in a large, international multi-center PROMISE-PET Registry study. PROMISE metrics and PSMA-PET reports were retrospectively analyzed in accordance with PROMISE V2 criteria. Total tumor volume, PSMA expression score, and molecular imaging metastatic disease (miM1) were analyzed to prognosticate overall survival (OS). RESULTS:Median follow-up was 4.4 yr (interquartile range 2.9-6.7). Overall, 294 patients (57%) were deceased at last follow-up. PSMA-PET detected metastatic disease in 340 patients (66%), and visceral metastases in 28 patients (5.4%). The optimal cutoff point for tumor volume was identified as 7.8 ml, which significantly stratified the cohort into low- versus high-volume groups. Patients with high-volume disease had worse OS than those with low-volume disease (hazard ratio [HR], 2.47; 95% confidence interval [CI], 2.22-2.71; p < 0.001). Patients with any distant metastases (miM1) on PSMA-PET had significantly shorter OS compared to those without detectable metastatic disease (HR, 1.74; 95% CI, 1.49-2.00; p < 0.001). CONCLUSION:Higher tumor volume on PSMA-PET and presence of distant metastases were strongly associated with OS in patients with nmCRPC. PSMA-PET stage and tumor volume should be included in future nmCRPC risk stratification.

Molecular imaging with positron emission tomography (PET) using tumour-targeting radiopharmaceuticals has gained widespread acceptance in oncology with numerous clinical applications. The hybrid imaging modality PET/CT (computed tomography) allows simultaneous assessment of both molecular and morphologic information. Therefore, PET/CT represents an efficient tool for comprehensive whole-body staging and restaging within single imaging session. In oncology, the glucose analogue 18-F-fluorodeoxyglucose (FDG) is the most widely used PET/CT radiopharmaceutical in clinical routine. FDG PET and FDG PET/CT have been used for staging and restaging of tumour patients in numerous studies. This chapter will discuss the applications and primary indications of FDG PET/CT in oncology with particular emphasis on lung cancer, lymphoma, head and neck cancer, melanoma and breast cancer, among other tumour entities. A review of the current literature is presented, focusing on primary diagnosis, staging and detection of recurrent disease. Besides its established role in diagnosis, staging and restaging of disease in oncology, there is growing evidence that FDG PET/CT is valuable in assessment of therapy response, potentially influencing treatment planning and therapeutic decision making by evaluating tumour control, which will also be discussed in this chapter.

We aimed to compare various imaging-based response criteria in men with metastatic castration-resistant prostate cancer (mCRPC) treated with [177Lu]Lu-Prostate-specific membrane antigen radioligand therapy (LuPSMA). This retrospective study included 84 men who received a median of 4 [177Lu]PSMA cycles (IQR 2–5) and median of 24.3 GBq (IQR 14.9–32.9 GBq) at the Department of Nuclear Medicine at University Hospital Essen between March 2019 and May 2022. Response assessments were conducted comparing baseline PET/CT and PET/CT at 6–8 weeks after second cycle of LuPSMA using multiple criteria: Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, the adapted Prostate Cancer Working Group Criteria 4 (aPCWG4) without follow-up confirmation, Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST), the PSMA PET Progression (PPP), and Response Evaluation Criteria in PSMA-Imaging 1.0 (RECIP) with visual assessment or different quantitative volumetry methods (qPSMA, SUV ≥ 4). Responses were categorized as progressive disease (PD) or non-PD. The primary endpoint was the prognostic significance of these response criteria for overall survival, evaluated via Cox regression analysis. Harrell`s C-index was used for concordance of different imaging-based criteria and survival. A total of 34 (40.5

The impact of salvage radiotherapy (SRT) on overall survival (OS) in patients experiencing biochemical recurrence (BCR) of prostate cancer remains an area of active investigation. The international multicenter PROMISE registry provides a valuable dataset to explore the association between SRT and long-term clinical outcomes in this patient population (NCT06320223). Methods: Comprehensive restaging at the time of BCR was performed by integrating both serologic markers and advanced molecular imaging (PET/CT or PET/MRI), offering an accurate assessment of molecular imaging (mi) TNM stage. Results: In total, 1410 patients experiencing BCR with prior prostatectomy were included. The median follow-up was 5.2 y (interquartile range, 3.8-6.9 y). SRT was administered after PET to 381 of 680 patients (56.0%) with PET-negative disease (miT0N0M0) and to 478 of 730 patients (65.0%) with PET-locoregional disease (miT/N+ M0). SRT was associated with longer OS in the entire cohort (hazard ratio, 0.66; 95% CI, 0.47-0.93; P = 0.019) with 5- and 7-y survival rates of 95.2% (95% CI, 93.6%-96.8%) and 90.8% (95% CI, 88.1%-93.6%), respectively. Without SRT, 5- and 7-y survival rates were 92.1% (95% CI, 89.6%-94.7%) and 83.8% (95% CI, 79.8%-88.1%), respectively. Subgroup analysis found significant benefit for patients with miT0N0M0 disease (hazard ratio, 0.42; 95% CI, 0.22-0.78; P = 0.0061), particularly those with a prostate-specific antigen level of 0.5 ng/mL or lower (P = 0.03, log-rank test). Conclusion: SRT improves OS for patients with BCR, especially those with a negative prostate-specific membrane antigen-targeted PET.

Concurrent enzalutamide may upregulate PSMA expression and enhance the efficacy of [177Lu]Lu-PSMA-617 radioligand therapy (PSMA-RLT). We evaluated outcomes of PSMA-RLT with and without concurrent enzalutamide in a real-world metastatic castration-resistant prostate cancer (mCRPC) cohort. We retrospectively evaluated 208 mCRPC patients treated with [177Lu]Lu-PSMA-617 at a single institution between June 2015 and January 2026. Among them, 106 received concurrent enzalutamide and 102 without any concurrent androgen receptor pathway inhibitor. The primary endpoint was overall survival (OS), and secondary endpoints were progression-free survival (PFS), PSA50 response, pain response, and toxicity. Median OS was 20.0 months in the concurrent enzalutamide group versus 12.4 months in the no-ARPI group (log-rank p = 0.082). In multivariable Cox analysis, concurrent enzalutamide was not independently associated with OS (hazard ratio 1.15, 95

The management of prostate cancer has posed challenges for clinicians in determining optimal treatment strategies. Over the years, various radiopharmaceuticals have been utilized for both the diagnosis and treatment of the prostate cancer. Recent advancements in prostate specific membrane antigen (PSMA) based imaging have enabled the early and precise detection of local recurrence, lymph nodes or distant metastases, resulting a paradigm shift, which significantly influenced clinical decision making. Moreover, PSMA targeted treatments, as a part of theranostic approach, have introduced novel treatment options for patients with castration resistant metastatic prostate cancer, who were previously limited to palliative treatment alternatives. The clinical integration of PSMA based imaging and treatment has led to the commencement of collaborative studies across multiple disciplines including radiation oncology. Radiopharmaceuticals led by PSMA have the potential to facilitate accurate treatment decision making through earlier and more precise lesion detection, as well as improve patient outcomes when combined with radiotherapy. We aimed to review the role of radiopharmaceuticals in diagnosis and treatment of prostate cancer, focusing on their utility in guiding radiotherapy and the potential benefits of combining these radiopharmaceuticals with radiotherapy.

The advent of prostate-specific membrane antigen (PSMA) positron emission tomography (PET) imaging has revolutionized the evaluation and management of prostate cancer, enabling superior lesion detection and characterization across various disease stages. In response to the growing need for standardized interpretation, the Prostate Cancer Molecular Imaging Standardized Evaluation (PROMISE) criteria were introduced in 2018, offering a structured approach to staging and risk assessment. As PSMA-targeted imaging becomes more central in response assessment and theranostics, updated PROMISE criteria have been proposed to reflect treatment-related changes and incorporate newer therapies like PSMA radioligand therapy (RLT). This review provides an in-depth overview of the updated PROMISE criteria, highlighting key changes, their rationale, and their application in assessing treatment response. Comparative discussion with other response criteria, including RECIST, PERCIST, and RECIP, is included. We also address practical challenges, potential pitfalls, and future directions for integrating PROMISE with emerging technologies such as artificial intelligence and radiomics. By refining response evaluation in prostate cancer, the updated PROMISE criteria represent a significant step toward precision imaging and personalized therapy.

The PRIMARY score was implemented in Prostate Cancer Molecular Imaging Standardized Evaluation (PROMISE) version 2 to improve accuracy for the diagnosis of clinically significant prostate cancer using prostate-specific membrane antigen (PSMA) positron emission tomography (PET). We reviewed overall survival (OS) for patients who underwent PSMA PET for initial staging to evaluate the prognostic value of PRIMARY in a large, international, multicenter cohort. The cohort comprised 1889 patients who underwent PSMA PET for initial staging of prostate cancer at investigator sites across Europe and Australia between 2012 and 2021. Hazard ratios (HRs) with 95% confidence interval (CI) were calculated for PRIMARY scores to identify predictors of OS. Complete-case head-to-head comparisons were conducted for Prostate Imaging-Reporting and Data System (PI-RADS) versus PRIMARY scores, and cT stage versus PRIMARY scores. We present preliminary findings up to January 31, 2025, when 231 deaths had occurred. PRIMARY score 5 (HR 1.5, 95% CI 1.0-2.3; p = 0.045) was associated with shorter OS. Improvements in C index values confirmed the added prognostic value of the PRIMARY score when combined with PI-RADS or cT stage. PRIMARY score 5 on initial PSMA PET is prognostic for shorter OS. There is ongoing long-term follow-up in the PROMISE registry (NCT06320223, promise-pet.org).

PSMA-PET has become a pivotal imaging method for staging and restaging of prostate cancer. Risk stratification of the disease is a crucial for the patients to receive most appropriate treatment, and for the clinicians to follow the patients more precisely. PSMA-PET provides non-invasive biomarkers for the risk assessment of prostate cancer, offering prediction of clinical outcomes. PROMISE criteria have been developed as comprehensive and integrated framework demonstrating association with overall survival. In this review, we aim to provide a brief update of the prognostic value of PSMA-PET for risk assessment in prostate cancer.

Purpose: The aim of this study was to evaluate the potential role of [18F]FDG positron emission tomography/computed tomography (PET/CT) in the characterization of thymic epithelial tumors (TETs). Materials and Methods: A total of 73 patients who underwent preoperative [18F]FDG PET/CT were included in this study. Visual total score (VTS), maximum standard uptake values (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and heterogeneity index (HI) parameters were analyzed to investigate the prediction of histopathologic grade and advanced stage. Results: The cohort included 26 patients with low-grade thymoma (LGT), 36 patients with high-grade thymoma (HGT), and 11 patients with thymic carcinoma (TC). Ninety-one percent of TC had VTS >2, whereas 31% of LGT and 75% of HGT had VTS >2. SUVmax, MTV, and TLG were statistically significantly higher in the TC group than in both thymoma and HGT. Using the cutoff value of 7.25 for SUVmax, TC was differentiated from thymomas with 91% sensitivity and 74% specificity. TC had significantly lower HI values than thymomas. HI parameters showed good diagnostic ability to differentiate TC from thymoma and TC from HGT. SUVmax, MTV, and TLG were significantly higher in advanced-stage disease than in early-stage disease. Conclusions: Visual and quantitative parameters can reliably predict both advanced disease and the grade of primary tumor in TETs. Therefore, as a promising metabolic imaging method, [18F]FDG PET/CT makes important contributions to preoperative evaluation in routine clinical practice.

Transarterial radioembolization (TARE) with Yttrium-90- microspheres is a well-tolerated and efficient treatment option in adult patients with unresectable primary and secondary liver malignancies. However, the use of TARE has been reported in limited pediatric cases. We present a twelve-year-old male with metastatic unresectable fibrolamellar hepatocellular carcinoma who received multidisciplinary treatments including chemotherapy, TARE, and transarterial chemoembolization with remarkable regression of the hepatic lesions. The patient is alive with the disease and a good quality of life for 33 months since diagnosis.

Objective To compare the incidence and natural course of reactive axillary lymph nodes (RAL) between mRNA and attenuated whole-virus vaccines using Deauville criteria. Methods In this multi-institutional PET-CT study comprising multiple vaccine types (Pfizer–BioNTech/Comirnaty, Moderna/Spikevax, Sinovac/CoronaVac and Janssen vaccines), we evaluated the incidence and natural course of RAL in a large cohort of oncological patients utilizing a standardized Deauville scaling system (n=522; 293 Female, Deauville 3-5 positive for RAL). Univariate and multivariate analyses were conducted to evaluate the predictive value of clinical parameters (absolute neutrophil count [ANC], platelets, age, sex, tumor type, and vaccine-to-PET interval) for PET positivity. Results Pfizer–BioNTech/Comirnaty and Moderna vaccines revealed similar RAL incidences for the first 20 days after the second dose of vaccine administration (44% for the first 10 days for both groups, 26% vs. 20% for 10–20 days, respectively for Moderna and Pfizer). However, Moderna recipients revealed significantly higher incidences of RAL after 20 days compared to Pfizer–BioNTech/Comirnaty, with nodal reactivity spanning up to the 9th week post-vaccination (15% vs. 4%, respectively P < 0.001). No RAL was observed in patients who received either a single dose of J&J vaccine or two doses of CroronaVac. Younger patients showed increased likelihood of RAL, otherwise, clinical/demographic parameters were not predictive of RAL ( P = 0.014 for age, P > 0.05 for additional clinical/demographic parameters). Conclusion RAL based on strict PET criteria was observed with mRNA but not with attenuated whole-virus vaccines, in line with higher immunogenicity and stronger protection offered by mRNA vaccines.

Purpose: The aim of this study was to evaluate the effect of an increase in the time interval between hepatic intra-arterial injection of 99mTc-macroaggregated albumin (MAA) and hepatic artery perfusion scintigraphy (HAPS) on the lung shunt fraction (LSF) and perfused volume (PV) calculations in the treatment planning of selective internal radiation therapy (SIRT).Methods: The authors enrolled 51 HAPS sessions from 40 patients diagnosed with primary or metastatic liver malignancy. All patients underwent scan at the first and fourth hour after hepatic arterial injection of 99mTc-MAA. Based on single-photon emission computed tomography images, LSF values were measured from each patient's first and fourth hour images. PV1 and PV4 were also calculated based on three-dimensional images using 5% and 10% cutoff threshold values and compared with each other.Results: The authors found that the median of LSF4 was statistically significantly higher than LSF1 (3.05 vs. 4.14, p <= 0.01). There was no statistically significant difference between PV1 and PV4 on the 10% (p = 0.72) thresholds.Conclusions: LSF values can be overestimated in case of delayed HAPS, potentially leading to treatment cancellation due to incorrectly high results in patients who could benefit from SIRT. Threshold-based PV values do not significantly change over time; nevertheless, keeping the short interval time would be safer.

Epithelial-myoepithelial carcinoma (EMC) is a rare low-grade salivary gland neoplasm.Distant metastasis is rare, and 18 F-fluorodeoxyglucose positron emission tomography/computed tomography ( 18 F-FDG PET/CT) has been used to determine the metastatic disease in EMC. 68Ga-fibroblast activation protein inhibitors (FAPI) PET/CT is a promising imaging modality for diagnostic and theognostic purposes in various malignancies.Comparison studies with 18 F-FDG have investigated the role of 68 Ga-FAPI PET/CT.Herein, we present 18 F-FDG and 68 Ga-FAPI-04 PET/CT findings of a 51-year-old woman with metastatic EMC arising from ex-pleomorphic adenoma of the parotid.