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BACKGROUND: Prostate-specific membrane antigen (PSMA)-PET was introduced into clinical practice in 2012 and has since transformed the staging of prostate cancer. Prostate Cancer Molecular Imaging Standardized Evaluation (PROMISE) criteria were proposed to standardise PSMA-PET reporting. We aimed to compare the prognostic value of PSMA-PET by PROMISE (PPP) stage with established clinical nomograms in a large prostate cancer dataset with follow-up data for overall survival. METHODS: In this multicentre retrospective study, we used data from patients of any age with histologically proven prostate cancer who underwent PSMA-PET at the University Hospitals in Essen, Münster, Freiburg, and Dresden, Germany, between Oct 30, 2014, and Dec 27, 2021. We linked a subset of patient hospital records with patient data, including mortality data, from the Cancer Registry North-Rhine Westphalia, Germany. Patients from Essen University Hospital were randomly assigned to the development or internal validation cohorts (2:1). Patients from Münster, Freiburg, and Dresden University Hospitals were included in an external validation cohort. Using the development cohort, we created quantitative and visual PPP nomograms based on Cox regression models, assessing potential PPP predictors for overall survival, with least absolute shrinkage and selection operator penalty for overall survival as the primary endpoint. Performance was measured using Harrell's C-index in the internal and external validation cohorts and compared with established clinical risk scores (International Staging Collaboration for Cancer of the Prostate [STARCAP], European Association of Urology [EAU], and National Comprehensive Cancer Network [NCCN] risk scores) and a previous nomogram defined by Gafita et al (hereafter referred to as GAFITA) using receiver operating characteristic (ROC) curves and area under the ROC curve (AUC) estimates. FINDINGS: We analysed 2414 male patients (1110 included in the development cohort, 502 in the internal cohort, and 802 in the external validation cohort), among whom 901 (37%) had died as of data cutoff (June 30, 2023; median follow-up of 52·9 months [IQR 33·9-79·0]). Predictors in the quantitative PPP nomogram were locoregional lymph node metastases (molecular imaging N2), distant metastases (extrapelvic nodal metastases, bone metastases [disseminated or diffuse marrow involvement], and organ metastases), tumour volume (in L), and tumour mean standardised uptake value. Predictors in the visual PPP nomogram were distant metastases (extrapelvic nodal metastases, bone metastases [disseminated or diffuse marrow involvement], and organ metastases) and total tumour lesion count. In the internal and external validation cohorts, C-indices were 0·80 (95% CI 0·77-0·84) and 0·77 (0·75-0·78) for the quantitative nomogram, respectively, and 0·78 (0·75-0·82) and 0·77 (0·75-0·78) for the visual nomogram, respectively. In the combined development and internal validation cohort, the quantitative PPP nomogram was superior to STARCAP risk score for patients at initial staging (n=139 with available staging data; AUC 0·73 vs 0·54; p=0·018), EAU risk score at biochemical recurrence (n=412; 0·69 vs 0·52; p<0·0001), and NCCN pan-stage risk score (n=1534; 0·81 vs 0·74; p<0·0001) for the prediction of overall survival, but was similar to GAFITA nomogram for metastatic hormone-sensitive prostate cancer (mHSPC; n=122; 0·76 vs 0·72; p=0·49) and metastatic castration-resistant prostate cancer (mCRPC; n=270; 0·67 vs 0·75; p=0·20). The visual PPP nomogram was superior to EAU at biochemical recurrence (n=414; 0·64 vs 0·52; p=0·0004) and NCCN across all stages (n=1544; 0·79 vs 0·73; p<0·0001), but similar to STARCAP for initial staging (n=140; 0·56 vs 0·53; p=0·74) and GAFITA for mHSPC (n=122; 0·74 vs 0·72; p=0·66) and mCRPC (n=270; 0·71 vs 0·75; p=0·23). INTERPRETATION: Our PPP nomograms accurately stratify high-risk and low-risk groups for overall survival in early and late stages of prostate cancer and yield equal or superior prediction accuracy compared with established clinical risk tools. Validation and improvement of the nomograms with long-term follow-up is ongoing (NCT06320223). FUNDING: Cancer Registry North-Rhine Westphalia.
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INTRODUCTION: We describe the development of a molecular assay from publicly available tumor tissue mRNA databases using machine learning and present preliminary evidence of functionality as a diagnostic and monitoring tool for prostate cancer (PCa) in whole blood. MATERIALS AND METHODS: We assessed 1055 PCas (public microarray data sets) to identify putative mRNA biomarkers. Specificity was confirmed against 32 different solid and hematological cancers from The Cancer Genome Atlas (n = 10,990). This defined a 27-gene panel which was validated by qPCR in 50 histologically confirmed PCa surgical specimens and matched blood. An ensemble classifier (Random Forest, Support Vector Machines, XGBoost) was trained in age-matched PCas (n = 294), and in 72 controls and 64 BPH. Classifier performance was validated in two independent sets (n = 263 PCas; n = 99 controls). We assessed the panel as a postoperative disease monitor in a radical prostatectomy cohort (RPC: n = 47). RESULTS: A PCa-specific 27-gene panel was identified. Matched blood and tumor gene expression levels were concordant (r = 0.72, p < 0.0001). The ensemble classifier ("PROSTest") was scaled 0%-100% and the industry-standard operating point of ≥50% used to define a PCa. Using this, the PROSTest exhibited an 85% sensitivity and 95% specificity for PCa versus controls. In two independent sets, the metrics were 92%-95% sensitivity and 100% specificity. In the RPCs (n = 47), PROSTest scores decreased from 72% ± 7% to 33% ± 16% (p < 0.0001, Mann-Whitney test). PROSTest was 26% ± 8% in 37 with normal postoperative PSA levels (<0.1 ng/mL). In 10 with elevated postoperative PSA, PROSTest was 60% ± 4%. CONCLUSION: A 27-gene whole blood signature for PCa is concordant with tissue mRNA levels. Measuring blood expression provides a minimally invasive genomic tool that may facilitate prostate cancer management.
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Biomarcadores de Tumor , Neoplasias de la Próstata , Humanos , Masculino , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/cirugía , Biopsia Líquida/métodos , Biomarcadores de Tumor/sangre , Biomarcadores de Tumor/genética , Anciano , Persona de Mediana Edad , Aprendizaje Automático , ARN Mensajero/sangre , ARN Mensajero/genética , Prostatectomía , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: [177Lu]Lu-PSMA-617 (177Lu-PSMA-617) plus protocol-permitted standard of care (SOC) prolonged overall survival (OS) and radiographic progression-free survival (rPFS) versus SOC in patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC) in the phase 3 VISION study, in addition to beneficial effects on symptomatic skeletal events (SSEs) and health-related quality of life (HRQOL). METHODS: Post hoc analyses used the full analysis set from the VISION study (N = 831) overall and by randomized treatment arm (177Lu-PSMA-617 plus SOC, n = 551; SOC, n = 280). Correlations were determined between OS and rPFS and between rPFS or OS and time to SSE or to worsening HRQOL (Functional Assessment of Cancer Therapy-Prostate [FACT-P] and 5-level EQ-5D [EQ-5D-5L]). Correlation analyses used an iterative multiple imputation copula-based approach (correlation coefficients [rho] of <0.3 were defined as weak, ≥0.3 and <0.5 as mild, ≥0.5 and <0.7 as moderate, and ≥0.7 as strong). RESULTS: In the overall population, rPFS correlated strongly with OS (rho, ≥0.7). Correlations between rPFS or OS and time to SSE without death were weak or mild. Time to worsening in the FACT-P total score and emotional and physical well-being domains correlated mildly or moderately with rPFS and moderately with OS. Correlation coefficients for time-to-worsening EQ-5D-5L scores were mild to moderate for both rPFS and OS. Correlation coefficients were similar between treatment arms. CONCLUSIONS: In this analysis of the VISION study, rPFS correlated strongly with OS but not with time to SSE or worsening HRQOL. These findings require further investigation.
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BACKGROUND: Metastatic castration-resistant prostate cancer remains fatal despite recent advances. Prostate-specific membrane antigen (PSMA) is highly expressed in metastatic castration-resistant prostate cancer. Lutetium-177 (177Lu)-PSMA-617 is a radioligand therapy that delivers beta-particle radiation to PSMA-expressing cells and the surrounding microenvironment. METHODS: We conducted an international, open-label, phase 3 trial evaluating 177Lu-PSMA-617 in patients who had metastatic castration-resistant prostate cancer previously treated with at least one androgen-receptor-pathway inhibitor and one or two taxane regimens and who had PSMA-positive gallium-68 (68Ga)-labeled PSMA-11 positron-emission tomographic-computed tomographic scans. Patients were randomly assigned in a 2:1 ratio to receive either 177Lu-PSMA-617 (7.4 GBq every 6 weeks for four to six cycles) plus protocol-permitted standard care or standard care alone. Protocol-permitted standard care excluded chemotherapy, immunotherapy, radium-223 (223Ra), and investigational drugs. The alternate primary end points were imaging-based progression-free survival and overall survival, which were powered for hazard ratios of 0.67 and 0.73, respectively. Key secondary end points were objective response, disease control, and time to symptomatic skeletal events. Adverse events during treatment were those occurring no more than 30 days after the last dose and before subsequent anticancer treatment. RESULTS: From June 2018 to mid-October 2019, a total of 831 of 1179 screened patients underwent randomization. The baseline characteristics of the patients were balanced between the groups. The median follow-up was 20.9 months. 177Lu-PSMA-617 plus standard care significantly prolonged, as compared with standard care, both imaging-based progression-free survival (median, 8.7 vs. 3.4 months; hazard ratio for progression or death, 0.40; 99.2% confidence interval [CI], 0.29 to 0.57; P<0.001) and overall survival (median, 15.3 vs. 11.3 months; hazard ratio for death, 0.62; 95% CI, 0.52 to 0.74; P<0.001). All the key secondary end points significantly favored 177Lu-PSMA-617. The incidence of adverse events of grade 3 or above was higher with 177Lu-PSMA-617 than without (52.7% vs. 38.0%), but quality of life was not adversely affected. CONCLUSIONS: Radioligand therapy with 177Lu-PSMA-617 prolonged imaging-based progression-free survival and overall survival when added to standard care in patients with advanced PSMA-positive metastatic castration-resistant prostate cancer. (Funded by Endocyte, a Novartis company; VISION ClinicalTrials.gov number, NCT03511664.).
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Dipéptidos/uso terapéutico , Compuestos Heterocíclicos con 1 Anillo/uso terapéutico , Calicreínas/antagonistas & inhibidores , Lutecio/uso terapéutico , Antígeno Prostático Específico/antagonistas & inhibidores , Antígeno Prostático Específico/uso terapéutico , Neoplasias de la Próstata Resistentes a la Castración/radioterapia , Radioisótopos/uso terapéutico , Anciano , Anciano de 80 o más Años , Terapia Combinada , Humanos , Lutecio/efectos adversos , Masculino , Persona de Mediana Edad , Tomografía de Emisión de Positrones , Próstata/diagnóstico por imagen , Neoplasias de la Próstata Resistentes a la Castración/diagnóstico por imagen , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/mortalidad , Radioisótopos/efectos adversos , Análisis de SupervivenciaRESUMEN
PURPOSE: The emergence of chimeric antigen receptor (CAR) T-cell therapy fundamentally changed the management of individuals with relapsed and refractory large B-cell lymphoma (LBCL). However, real-world data have shown divergent outcomes for the approved products. The present study therefore set out to evaluate potential risk factors in a larger cohort. METHODS: Our analysis set included 88 patients, treated in four German university hospitals and one Italian center, who had undergone 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography (PET) before CAR T-cell therapy with tisagenlecleucel or axicabtagene ciloleucel. We first determined the predictive value of conventional risk factors, treatment lines, and response to bridging therapy for progression-free survival (PFS) through forward selection based on Cox regression. In a second step, the additive potential of two common PET parameters was assessed. Their optimal dichotomizing thresholds were calculated individually for each CAR T-cell product. RESULTS: Extra-nodal involvement emerged as the most relevant of the conventional tumor and patient characteristics. Moreover, we found that inclusion of metabolic tumor volume (MTV) further improves outcome prediction. The hazard ratio for a PFS event was 1.68 per unit increase of our proposed risk score (95% confidence interval [1.20, 2.35], P = 0.003), which comprised both extra-nodal disease and lymphoma burden. While the most suitable MTV cut-off among patients receiving tisagenlecleucel was 11 mL, a markedly higher threshold of 259 mL showed optimal predictive performance in those undergoing axicabtagene ciloleucel treatment. CONCLUSION: Our analysis demonstrates that the presence of more than one extra-nodal lesion and higher MTV in LBCL are associated with inferior outcome after CAR T-cell treatment. Based on an assessment tool including these two factors, patients can be assigned to one of three risk groups. Importantly, as shown by our study, metabolic tumor burden might facilitate CAR T-cell product selection and reflect the individual need for bridging therapy.
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Inmunoterapia Adoptiva , Linfoma de Células B Grandes Difuso , Humanos , Inmunoterapia Adoptiva/efectos adversos , Inmunoterapia Adoptiva/métodos , Linfoma de Células B Grandes Difuso/diagnóstico por imagen , Linfoma de Células B Grandes Difuso/terapia , Pronóstico , Tomografía de Emisión de Positrones , Medición de RiesgoRESUMEN
To sensitively determine 99Tc, a new method for internal quantification of its most common and stable species, [99Tc]Tc O 4 - , was developed. Anion-exchange chromatography (IC) was coupled to inductively coupled plasma-mass spectrometry (ICP-MS) and equipped with an aerosol desolvation system to provide enhanced detection power. Due to a lack of commercial Tc standards, an isotope dilution-like approach using a Ru spike and called isobaric dilution analysis (IBDA) was used for internal quantification of 99Tc. This approach required knowledge of the sensitivities of 99Ru and 99Tc in ICP-MS. The latter was determined using an in-house prepared standard manufactured from decayed medical 99mTc-generator eluates. This standard was cleaned and preconcentrated using extraction chromatography with TEVA resin and quantified via total reflection X-ray fluorescence (TXRF) analysis. IC coupled to ICP-MS enabled to separate, detect and quantify [99Tc]Tc O 4 - as most stable Tc species in complex environments, which was demonstrated in a proof of concept. We quantified this species in untreated and undiluted raw urine collected from a patient, who previously underwent scintigraphy with a 99mTc-tracer, and determined a concentration of 19.6 ± 0.5 ng L-1. The developed method has a high utility to characterize a range of Tc-based radiopharmaceuticals, to determine concentrations, purity, and degradation products in complex samples without the need to assess activity parameters of 99(m)Tc.
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Cromatografía , Humanos , Espectrometría de Masas/métodos , Análisis Espectral , Aniones , Indicadores y ReactivosRESUMEN
BACKGROUND: In VISION, the prostate-specific membrane antigen (PSMA)-targeted radioligand therapy lutetium-177 [177Lu]Lu-PSMA-617 (vipivotide tetraxetan) improved radiographic progression-free survival and overall survival when added to protocol-permitted standard of care in patients with metastatic castration-resistant prostate cancer. Here, we report additional health-related quality of life (HRQOL), pain, and symptomatic skeletal event results. METHODS: This multicentre, open-label, randomised, phase 3 trial was conducted at 84 cancer centres in nine countries in North America and Europe. Eligible patients were aged 18 years or older; had progressive PSMA-positive metastatic castration-resistant prostate cancer; an Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2; and had previously received of at least one androgen receptor pathway inhibitor and one or two taxane-containing regimens. Patients were randomly assigned (2:1) to receive either [177Lu]Lu-PSMA-617 plus protocol-permitted standard of care ([177Lu]Lu-PSMA-617 group) or standard of care alone (control group) using permuted blocks. Randomisation was stratified by baseline lactate dehydrogenase concentration, liver metastases, ECOG performance status, and androgen receptor pathway inhibitor inclusion in standard of care. Patients in the [177Lu]Lu-PSMA-617 group received intravenous infusions of 7·4 gigabecquerel (GBq; 200 millicurie [mCi]) [177Lu]Lu-PSMA-617 every 6 weeks for four cycles plus two optional additional cycles. Standard of care included approved hormonal treatments, bisphosphonates, and radiotherapy. The alternate primary endpoints were radiographic progression-free survival and overall survival, which have been reported. Here we report the key secondary endpoint of time to first symptomatic skeletal event, and other secondary endpoints of HRQOL assessed with the Functional Assessment of Cancer Therapy-Prostate (FACT-P) and EQ-5D-5L, and pain assessed with the Brief Pain Inventory-Short Form (BPI-SF). Patient-reported outcomes and symptomatic skeletal events were analysed in all patients who were randomly assigned after implementation of measures designed to reduce the dropout rate in the control group (on or after March 5, 2019), and safety was analysed according to treatment received in all patients who received at least one dose of treatment. This trial is registered with ClinicalTrials.gov, NCT03511664, and is active but not recruiting. FINDINGS: Between June 4, 2018, and Oct 23, 2019, 831 patients were enrolled, of whom 581 were randomly assigned to the [177Lu]Lu-PSMA-617 group (n=385) or control group (n=196) on or after March 5, 2019, and were included in analyses of HRQOL, pain, and time to first symptomatic skeletal event. The median age of patients was 71 years (IQR 65-75) in the [177Lu]Lu-PSMA-617 group and 72·0 years (66-76) in the control group. Median time to first symptomatic skeletal event or death was 11·5 months (95% CI 10·3-13·2) in the [177Lu]Lu-PSMA-617 group and 6·8 months (5·2-8·5) in the control group (hazard ratio [HR] 0·50, 95% CI 0·40-0·62). Time to worsening was delayed in the [177Lu]Lu-PSMA-617 group versus the control group for FACT-P score (HR 0·54, 0·45-0·66) and subdomains, BPI-SF pain intensity score (0·52, 0·42-0·63), and EQ-5D-5L utility score (0·65, 0·54-0·78). Grade 3 or 4 haematological adverse events included decreased haemoglobin (80 [15%] of 529 assessable patients who received [177Lu]Lu-PSMA-617 plus standard of care vs 13 [6%] of 205 who received standard of care only), lymphocyte concentrations (269 [51%] vs 39 [19%]), and platelet counts (49 [9%] vs five [2%]). Treatment-related adverse events leading to death occurred in five (1%) patients who received [177Lu]Lu-PSMA-617 plus standard of care (pancytopenia [n=2], bone marrow failure [n=1], subdural haematoma [n=1], and intracranial haemorrhage [n=1]) and no patients who received standard of care only. INTERPRETATION: [177Lu]Lu-PSMA-617 plus standard of care delayed time to worsening in HRQOL and time to skeletal events compared with standard of care alone. These findings support the use of [177Lu]Lu-PSMA-617 in patients with metastatic castration-resistant prostate cancer who received previous androgen receptor pathway inhibitor and taxane treatment. FUNDING: Advanced Accelerator Applications (Novartis).
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Neoplasias de la Próstata Resistentes a la Castración , Calidad de Vida , Masculino , Humanos , Anciano , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Receptores Androgénicos , Nivel de Atención , Antagonistas de Receptores Androgénicos/efectos adversos , Dolor/inducido químicamente , Taxoides , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversosRESUMEN
Background Prostate-specific membrane antigen (PSMA) PET has high specificity in localizing primary tumors and metastases in patients with prostate cancer, but the individual overall survival probability is still difficult to estimate. Purpose To develop a prognostic risk score using PSMA PET-derived organ-specific total tumor volumes for predicting overall survival in patients with prostate cancer. Materials and Methods Men with prostate cancer who underwent PSMA PET/CT from January 2014 to December 2018 were evaluated retrospectively. All patients from center A were split into training (80%) and internal validation (20%) cohorts. Randomly selected patients from center B were used for external validation. Organ-specific tumor volumes were automatically quantified from PSMA PET scans by a neural network. A prognostic score was selected using multivariable Cox regression guided by the Akaike information criterion (AIC). The final prognostic risk score fitted on the training set was applied to both validation cohorts. Results A total of 1348 men (mean age, 70 years ± 8 [SD]) were included, with 918 patients in the training cohort, 230 in the internal validation cohort, and 200 in the external validation cohort. The median follow-up time was 55.7 months (IQR, 46.7-65.1 months; >4 years; 429 deaths occurred). A body weight-adjusted prognostic risk score integrating total, bone, and visceral tumor volumes obtained high C index values in the internal (0.82) and external (0.74) validation cohorts, as well as in patients with castration-resistant (0.75) and hormone-sensitive (0.68) disease. The fit of the statistical model for the prognostic score was improved compared with a model containing total tumor volume only (AIC, 3324 vs 3351; likelihood ratio test, P < .001). Calibration plots ascertained good model fit. Conclusion The newly developed risk score that included prostate-specific membrane antigen PET-derived organ-specific tumor volumes had good model fit for predicting overall survival in both internal and external validation cohorts. Published under a CC BY 4.0 license. Supplemental material is available for this article. See also the editorial by Civelek in this issue.
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Tomografía Computarizada por Tomografía de Emisión de Positrones , Neoplasias de la Próstata , Masculino , Humanos , Anciano , Pronóstico , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Estudios Retrospectivos , Carga Tumoral , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/patología , Factores de Riesgo , Radioisótopos de GalioRESUMEN
Prostate-specific membrane antigen (PSMA) is expressed by the majority of clinically significant prostate adenocarcinomas, and patients with target-positive disease can easily be identified by PSMA PET imaging. Promising results with PSMA-targeted radiopharmaceutical therapy have already been obtained in early-phase studies using various combinations of targeting molecules and radiolabels. Definitive evidence of the safety and efficacy of [177Lu]Lu-PSMA-617 in combination with standard-of-care has been demonstrated in patients with metastatic castration-resistant prostate cancer, whose disease had progressed after or during at least one taxane regimen and at least one novel androgen-axis drug. Preliminary data suggest that 177Lu-PSMA-radioligand therapy (RLT) also has high potential in additional clinical situations. Hence, the radiopharmaceuticals [177Lu]Lu-PSMA-617 and [177Lu]Lu-PSMA-I&T are currently being evaluated in ongoing phase 3 trials. The purpose of this guideline is to assist nuclear medicine personnel, to select patients with highest potential to benefit from 177Lu-PSMA-RLT, to perform the procedure in accordance with current best practice, and to prepare for possible side effects and their clinical management. We also provide expert advice, to identify those clinical situations which may justify the off-label use of [177Lu]Lu-PSMA-617 or other emerging ligands on an individual patient basis.
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Medicina Nuclear , Neoplasias de la Próstata Resistentes a la Castración , Masculino , Humanos , Antígeno Prostático Específico , Neoplasias de la Próstata Resistentes a la Castración/diagnóstico por imagen , Neoplasias de la Próstata Resistentes a la Castración/radioterapia , Radiofármacos/efectos adversos , Compuestos Heterocíclicos con 1 Anillo/uso terapéutico , Dipéptidos/uso terapéutico , Lutecio/uso terapéutico , Resultado del TratamientoRESUMEN
PURPOSE: We assessed the diagnostic yield of consecutive transperineal targeted biopsy of multiparametric magnetic resonance imaging index lesion and secondary lesion and additive systematic biopsy in patients who received combined targeted biopsy+systematic biopsy of prostate. MATERIALS AND METHODS: Of 1,467 patients with targeted biopsy+systematic biopsy, analyses were restricted to 571 patients with index lesion+secondary lesion, Prostate Imaging-Reporting and Data System score ≥3. Index lesion was defined as having the greatest Prostate Imaging-Reporting and Data System score and/or lesion volume as opposed to secondary lesion. We retrospectively compared clinically significant prostate cancer rates (ie, Gleason Grade Group ≥2) between index lesion+secondary lesion and index lesion+secondary lesion+systematic biopsy. Subgroup analyses in men with ipsilateral index lesion+secondary lesion focused on contralateral systematic biopsy. Multivariable logistic regression analyses to predict any clinically significant prostate cancer included age, previous biopsies, prostate specific antigen density, respective index lesion/secondary lesion volumes, side relation, Prostate Imaging-Reporting and Data System strata, and number of targeted biopsy and systematic biopsy cores. RESULTS: Clinically significant prostate cancer rates for index lesion+secondary lesion vs index lesion+secondary lesion+systematic biopsy were 38% vs 42% (P = .2) at expense of significantly higher median number of biopsy cores (9 vs 25, P < .001). In the subgroup with ipsilateral index lesion+secondary lesion (n = 236), contralateral systematic biopsy detected clinically significant prostate cancer in 17%. In the narrower subgroup with ipsilateral index lesion+secondary lesion (n = 131) without any clinically significant prostate cancer, contralateral systematic biopsy detected clinically significant prostate cancer in 3.8%. Multivariable logistic regression analyses confirmed contralateral systematic biopsy as independent predictor, but performed similarly without systematic biopsy information (area under the curve 87.1% vs 86.6%). CONCLUSIONS: Targeted biopsy of secondary lesion should be included in targeted biopsy protocols due to added diagnostic information. However, for targeted biopsy of index lesion+secondary lesion additional systematic biopsy is of limited informative value in terms of overall clinically significant prostate cancer detection. However, when index lesion+secondary lesion are ipsilateral, contralateral systematic biopsy should be recommended for purpose of prostate lobe information. Our results indicate great potential to reduce systematic biopsy cores and associated potential morbidity, and warrant prospective evaluation.
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Neoplasias de los Genitales Femeninos , Imágenes de Resonancia Magnética Multiparamétrica , Neoplasias de la Próstata , Masculino , Femenino , Humanos , Biopsia Guiada por Imagen/métodos , Estudios Retrospectivos , Ultrasonografía Intervencional/métodos , Estudios Prospectivos , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/patología , Imagen por Resonancia Magnética/métodos , Clasificación del TumorRESUMEN
BACKGROUND: In patients with bone metastatic castration-resistant prostate cancer (bmCRPC) on systemic treatment, it is difficult to differentiate between continuous rise of prostate specific antigen (PSA) representing progression, and PSA-surge, which is followed by clinical response or stable disease. The purpose of this study was to evaluate the prognostic value of dynamic changes of alkaline phosphatase (ALP) and lactic acid dehydrogenase (LDH) levels as a predictor of clinical efficacy or therapeutic resistance of patients who do not show a sufficient initial PSA decline of ≥50% from baseline during early therapy with Enzalutamide. METHODS: Forty-eight men with bmCRPC on Enzalutamide 07/2010-09/2019 with initially rising PSA were analyzed. We monitored PSA, LDH and ALP at week 0, 2, 4, and every 4 weeks thereafter and analyzed the correlation between ALP rising at 12 weeks with or without LDH-normalization and the association with survival. For this we used Kaplan Meier analysis and uni- and multivariate cox-regression models. RESULTS: In Kaplan-Meier analysis, ALP rising at 12 weeks with or without LDH-normalization was associated with significantly worse median progression-free survival (PFS) of 3 months vs. 5 months (Log rank P = 0.02) and 3 months vs. 5 months (P = 0.01), respectively and overall survival (OS) with 8 months vs. 15 months (P = 0.02) and 8 months vs. 17 months (P < 0.01). In univariate analysis of PFS, ALP rising at 12 weeks alone, ALP rising at 12 weeks without LDH-normalization and application of Enzalutamide after chemotherapy showed a statistically significant association towards shorter PFS (hazard ratio (HR): 0.51, P = 0.04; HR: 0.48, P = 0.03; HR: 0.48, P = 0.03). Worse OS was significantly associated with ALP rising at 12 weeks alone, ALP rising at 12 weeks without LDH-normalization, and application of Enzalutamide after chemotherapy (HR: 0.47, P = 0.02; HR: 0.36, P < 0.01; HR: 0.31, P < 0.01). In multivariate analysis only the application of Enzalutamide after chemotherapy remained an independent prognostic factor for worse OS (HR: 0.36, P = 0.01). CONCLUSIONS: Dynamic changes of ALP (non-rise) and LDH (normalization) under therapy with Enzalutamide may be associated with clinical benefit, better PFS, and OS in patients with bmCRPC who do not show a PSA decline.
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Antígeno Prostático Específico , Neoplasias de la Próstata Resistentes a la Castración , Fosfatasa Alcalina , Benzamidas , Humanos , L-Lactato Deshidrogenasa , Ácido Láctico , Masculino , Nitrilos/uso terapéutico , Feniltiohidantoína , Pronóstico , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/patología , Resultado del TratamientoRESUMEN
BACKGROUND: We aimed to compare the prognostic value of myocardial perfusion scintigraphy (MPS) and dobutamine stress echocardiography (DSE) in patients with end-stage renal disease (ESRD) without known coronary artery disease. METHODS: Two-hundred twenty-nine ESRD patients who applied for kidney transplantation at our centre were prospectively evaluated by MPS and DSE. The primary endpoint was a composite of myocardial infarction (MI) or all-cause mortality. The secondary endpoint included MI or coronary revascularization (CR) not triggered by MPS or DSE at baseline. RESULTS: MPS detected reversible ischemia in 31 patients (13.5%) and fixed perfusion defects in 13 (5.7%) patients. DSE discovered stress-induced wall motion abnormalities (WMAs) in 28 (12.2%) and at rest in 18 (7.9%) patients. MPS and DSE results agreed in 85.6% regarding reversible defects (κ = 0.358; P < .001) and in 90.8% regarding fixed defects (κ = 0.275; P < .001). Coronary angiography detected relevant stenosis > 50% in only 15 of 38 patients (39.5%) with pathological findings in MPS and/or DSE. At a median follow-up of 8 years and 10 months, the primary endpoint occurred in 70 patients (30.6%) and the secondary endpoint in 24 patients (10.5%). The adjusted Cox hazard ratios (HRs) for the primary endpoint were 1.77 (95% CI 1.02-3.08; P = .043) for perfusion defects in MPS and 1.36 (95% CI 0.78-2.37; P = ns) for WMA in DSE. The secondary endpoint was significantly correlated with the findings of both modalities, MPS (HR 3.21; 95% CI 1.35-7.61; P = .008) and DSE (HR 2.67; 95% CI 1.15-6.20; P = .022). CONCLUSION: Perfusion defects in MPS are a stronger determinant of all-cause mortality, MI and the need for future CR compared with WMAs in DSE. Given the complementary functional information provided by MPS vs DSE, results are sometimes contradictory, which may indicate differences in the underlying pathophysiology.
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Fallo Renal Crónico , Infarto del Miocardio , Humanos , Ecocardiografía de Estrés , Dobutamina , Pronóstico , Tomografía Computarizada por Rayos X , Infarto del Miocardio/complicaciones , Perfusión , Fallo Renal Crónico/diagnóstico por imagen , Fallo Renal Crónico/complicaciones , Imagen de PerfusiónRESUMEN
PURPOSE: The aim of this narrative review is to give an overview on current and emerging imaging methods and liquid biopsy for prediction and evaluation of response to PRRT. Current limitations and new perspectives, including artificial intelligence, are discussed. METHODS: A literature review of PubMed/Medline was performed with representative keywords. The search included articles published online through August 31, 2020. All searches were restricted to English language manuscripts. RESULTS: Peptide radio receptor therapy (PRRT) is a prospectively evaluated and approved therapy option in neuroendocrine tumors (NETs). Different ligands targeting the somatostatin receptor (SSTR) are used as theranostic pairs for imaging NET and for PRRT. Response assessment in prospective trials often relies on the morphological RECIST 1.1 criteria, based on lesion size in CT or MRI. The role of SSTR-PET and quantitative uptake parameters and volumetric data is still not defined. Monoanalyte tumor marker chromogranin A has a limited value for response assessment after PRRT. New emerging liquid biopsy techniques are offering prediction of response to PRRT and prognostic value. CONCLUSIONS: New response criteria for NET patients undergoing PRRT will comprise multiparametric hybrid imaging and blood-based multianalyte markers. This represents tumor biology and heterogeneity.
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Inteligencia Artificial , Tumores Neuroendocrinos , Humanos , Biopsia Líquida , Tumores Neuroendocrinos/diagnóstico por imagen , Octreótido , Tomografía Computarizada por Tomografía de Emisión de Positrones , Estudios Prospectivos , Receptores de SomatostatinaRESUMEN
INTRODUCTION: [177Lu]Lu-PSMA-617 (Lu-PSMA) radioligand therapy is an emerging treatment option for patients with end-stage prostate cancer. However, response to Lu-PSMA therapy is only achieved in approximately half of patients. It is clinically important to identify patients at risk of poor outcome. Therefore, the aim of this study was to evaluate pretherapeutic PSMA PET derived total tumor volume and related metrics as prognosticators of overall survival in patients receiving Lu-PSMA therapy. METHODS: A total number of 110 patients form the Departments of Nuclear Medicine Münster and Essen were included in this retrospective analysis. Baseline PSMA PET-CT was available for all patients. Employing a previously published approach, all tumor lesions were semi-automatically delineated in PSMA PET-CT acquisitions. Total lesion number, total tumor volume (PSMA-TV), total lesion uptake (PSMA-TLU = PSMA-TV * SUVmean), and total lesion quotient (PSMA-TLQ = PSMA-TV / SUVmean) were quantified for each patient. Log2 transformation was used for regressions. RESULTS: Lesion number, PSMA-TV, and PSMA-TLQ were prognosticators of overall survival (HR = 1.255, p = 0.009; HR = 1.299, p = 0.005; HR = 1.326, p = 0.002). In a stepwise backward Cox regression including lesion number, PSMA-TV, PSA, LDH, and PSMA-TLQ, only the latter two remained independent and statistically significant negative prognosticators of overall survival (HR = 1.632, p = 0.011; HR = 1.239, p = 0.024). PSMA-TLQ and LDH were significant negative prognosticators in multivariate Cox regression in contrast to PSA value. CONCLUSION: PSMA-TV was a statistically significant negative prognosticator of overall survival in patients receiving Lu-PSMA therapy. PSMA-TLQ was an independent and superior prognosticator of overall survival compared with PSMA-TV.
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Tomografía Computarizada por Tomografía de Emisión de Positrones , Neoplasias de la Próstata Resistentes a la Castración , Dipéptidos/uso terapéutico , Compuestos Heterocíclicos con 1 Anillo , Humanos , Masculino , Antígeno Prostático Específico , Estudios Retrospectivos , Resultado del Tratamiento , Carga TumoralRESUMEN
INTRODUCTION: Prostate-specific membrane antigen (PSMA)-based radioligand therapy (RLT) showed in a multicentre WARMTH (World Association of Radiopharmaceutical and Molecular Therapy) study that the presence of bone metastases is a negative prognosticator for the survival. The current multicentre retrospective analysis aims to evaluate the response rate to RLT, the overall survival (OS) of patients and the safety of the treatment according to the extent of bone involvement. METHODS: The study included patients with progressive metastatic castration-resistant prostate cancer (mCRPC), who underwent RLT with [177Lu]Lu-PSMA-617 and a follow-up of at least 6 months. Tumour burden in the bone was classified prior to RLT as follows: less than 6 lesions, 6-20 lesions, more than 20 lesions and diffuse involvement. The response rate was evaluated using changes of the prostate-specific antigen (PSA) after the first treatment cycle. Overall survival was calculated from the date of the first treatment. Haematological adverse events were classified according to Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. RESULTS: A total of 319 males were included in the analysis. The extent of bone metastases and PSA response did not correlate significantly. Any PSA decline was observed in 73% patients; 44% showed a decline of ≥50%. The median OS of patient in the different subgroups was 18 months (less than 6 lesions), 13 months (6-20 lesions), 11 months (more than 20 lesions) and 8 months (diffuse involvement), respectively (p < 0.0001). Patients with prior Ra-223-therapy showed longer OS in all subgroups, especially in the subgroups with 6-20 lesions (OS: 16 vs. 12 months; p = 0.038) as well as diffuse involvement (OS: 11 vs. 7 months; p = 0.034). Significant negative prognosticators of OS were the existence of liver metastases in all subgroups and prior chemotherapy in patients with <6 bone lesions. Anaemia and thrombocytopenia correlated positively with the extent of bone metastases: p < 0.0001 and 0.005, respectively. No patient showed a high grade leukopenia. CONCLUSION: The extent of bone involvement correlated negatively with the OS after RLT; however, it showed no relevant correlation with the PSA response rate. Prior therapy with Ra-223 may have a positive impact on OS. Haematotoxicity was higher in patients with more than 20 bone lesions; nevertheless, the majority of these patients did not show a relevant haematotoxicity.
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Neoplasias de la Próstata Resistentes a la Castración , Radio (Elemento) , Dipéptidos/efectos adversos , Compuestos Heterocíclicos con 1 Anillo/efectos adversos , Humanos , Masculino , Antígeno Prostático Específico , Neoplasias de la Próstata Resistentes a la Castración/radioterapia , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
INTRODUCTION: The impact of prior therapies, especially chemotherapy, on overall survival (OS) in patients with castration-resistant prostate cancer (CRPC) receiving [177Lu]Lu-PSMA-617 therapy has been the subject of controversy. Therefore, WARMTH decided to plan a multicenter retrospective analysis (the "617 trial") to evaluate response rate and OS as well as the impact of prior therapies on OS in more than 300 patients treated with 177Lu-PSMA-617. MATERIALS AND METHODS: The data of 631 metastatic CRPC (mCRPC) patients from 11 different clinics were evaluated. According to the inclusion and exclusion criteria, all patients had to have received at least abiraterone or enzalutamide prior to [177Lu]Lu-PSMA-617 therapy. The patients were divided into three groups: patients who had received prior chemotherapy, patients who avoided chemotherapy, and patients for whom a chemotherapy was contraindicated. RESULTS: The analysis included the data of 416 patients, with a median age of 71.9 years. At the time of analysis, 87 patients (20,9%) were still alive. A total of 53.6% of patients had received both abiraterone and enzalutamide; 75.5% and 26.4% had a history of chemotherapy with docetaxel and cabazitaxel, respectively. A total of 20.4% had had Ra-223. The median OS was 11.1 months. Prior chemotherapy, the existence of bone and liver metastases, as well as Eastern Cooperative Oncology Group (ECOG) status, were significant prognosticators of worse overall survival in both univariate and multivariate analyses. Patients without any prior chemotherapy showed a significantly longer OS (14.6 months). The median OS in patients who received one or two lines of chemotherapy with docetaxel or docetaxel followed by cabazitaxel, respectively, was 10.9 months and 8.9 months. There was no difference in OS between patients who had not received chemotherapy and patients for whom chemotherapy was contraindicated. The other prior therapies did not have any significant impact on OS. CONCLUSION: In the present multicenter analysis, chemotherapy-naïve mCRPC patients receiving [177Lu]Lu-PSMA-617 therapy had a significantly longer OS than patients with a history of chemotherapy. This remained independent in the multivariate analysis besides presence of bone and liver metastases as negative prognosticators for survival, whereas an ECOG of 0-1 is associated with a longer OS.
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Neoplasias de la Próstata Resistentes a la Castración , Radio (Elemento) , Anciano , Dipéptidos , Compuestos Heterocíclicos con 1 Anillo , Humanos , Masculino , Pronóstico , Antígeno Prostático Específico , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Radiofármacos , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Metastatic colorectal cancer (mCRC) is associated with different molecular biology, clinical characteristics, and outcome depending on the primary tumor localization. We aimed to evaluate the effectiveness of 90Y-radioembolization (RE) for therapy of colorectal liver metastases depending on the primary tumor side. METHODS: We performed a retrospective analysis of n = 73 patients with mCRC and RE in our university liver center between 2009 and 2018. Patients were stratified according to the primary tumor side (left vs. right hemicolon), treatment response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) at follow-up after 3 months. Kaplan-Meier analysis was performed to analyze survival followed by Cox regression to determine independent prognostic factors for survival. RESULTS: Prior to RE, all patients had received systemic therapy, with either stable or progressive disease, but no partial or complete response. In n = 22/73 (30.1%) patients, the primary tumor side was in the right colon; in n = 51/73 (69.9%) patients, in the left colon. Hepatic tumor burden was ≤25% in n = 36/73 (49.3%) patients and >25% in n = 37/73 (50.7%) patients. At 3 months, n = 21 (33.8%) patients showed treatment response (n = 2 [3.2%]; complete response, n = 19 [30.6%]; partial response), n = 13 (21.0%) stable disease, and n = 28 (45.2%) progressive disease after RE. The median survival in case of primary tumor side in the left colon was significantly higher than for primary tumors in the right colon (8.7 vs. 6.0 months, p = 0.033). The median survival for a hepatic tumor burden ≤25% was significantly higher than that of >25% (13.9 vs. 4.3 months, p < 0.001). The median overall survival was 6.1 months. CONCLUSION: The median survival after RE in hepatic-mCRC depends on the primary tumor side and the preprocedural hepatic tumor burden.
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Neoplasias Colorrectales/terapia , Embolización Terapéutica/métodos , Neoplasias Hepáticas/terapia , Radioisótopos de Itrio/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Embolización Terapéutica/mortalidad , Femenino , Humanos , Estimación de Kaplan-Meier , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/secundario , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del Tratamiento , Carga TumoralRESUMEN
BACKGROUND: Radioligand therapy with [177Lu]Lu-PSMA-617 is efficacious for the treatment of patients with metastasized castration-resistant prostate cancer (mCRPC). Various studies have evaluated the efficacy and safety of [177Lu]Lu-PSMA-617 using a dose of 6.0 GBq and an 8-week therapy interval. However, the first prospective phase III trial (VISION) plans to use an elevated cumulative dose by applying 7.5 GBq in a 6-week interval. The aim of the present study was to compare safety and efficacy of the two aforementioned [177Lu]Lu-PSMA-617 therapy regimes (7.5 GBq every 6 weeks vs. 6.0 GBq every 8 weeks). METHODS: A total number of 78 consecutive patients with mCRPC and a history of first-line chemotherapy were included in this retrospective analysis. The outcome of patients treated with 6.0 GBq [177Lu]Lu-PSMA-617 per cycle (n = 37) were compared with those treated with 7.5 GBq (n = 41) per cycle. The median therapy intervals were 8.4 weeks (6.0 GBq group) vs. 6.5 (7.5 GBq group). PSA response, PSA progression-free survival (PSA-PFS), overall survival, and adverse events were evaluated and compared between both groups. Chi-squared test, Kaplan Meier estimates, Cox regression, and log-rank test were used. The highest decline from pretherapeutic PSA levels was measured as percentage (best PSA response) and compared between groups by Wilcoxon test. RESULTS: There was no significant difference comparing the rate of > 50% PSA decline or best PSA response between the 6.0 GBq and 7.5 GBq group (35% vs. 54%, p = 0.065; and - 40.2% vs. - 57.8%, p = 0.329). The median estimated survival and PSA-PFS did not significantly differ between the 6.0 GBq and 7.5 GBq groups as well (11.3 vs. 12.7 months, p = 0.384; and 9.5 vs. 12.3 months, p = 0.258). There was no significant difference regarding the change of kidney, liver, and blood cell parameters under therapy between the treatment groups. CONCLUSION: Higher cumulated doses of [177Lu]Lu-PSMA-617 were well tolerated and caused no significantly increased rate of adverse reactions. Moreover, 7.5 GBq of [177Lu]Lu-PSMA-617 every 6 weeks causes slightly higher, though not statistically significant, response rates and seems therefore to be the preferable treatment regime. However, future studies are needed to elucidate the dose-related efficacy of [177Lu]Lu-PSMA-617 as a way to personalized medicine.
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Neoplasias de la Próstata Resistentes a la Castración , Dipéptidos/efectos adversos , Compuestos Heterocíclicos con 1 Anillo/efectos adversos , Humanos , Masculino , Estudios Prospectivos , Antígeno Prostático Específico , Neoplasias de la Próstata Resistentes a la Castración/radioterapia , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
INTRODUCTION: Efficient therapy of recurrent differentiated thyroid cancer (DTC) is dependent on precise molecular imaging techniques targeting the human sodium iodide symporter (hNIS), which is a marker both of thyroid and DTC cells. Various iodine isotopes have been utilized for detecting DTC; however, these come with unfavorable radiation exposure and image quality ([131I]iodine) or limited availability ([124I]iodine). In contrast, [18F]tetrafluoroborate (TFB) is a novel radiolabeled PET substrate of hNIS, results in PET images with high-quality and low radiation doses, and should therefore be suited for imaging of DTC. The aim of the present study was to compare the diagnostic performance of [18F]TFB-PET to the clinical reference standard [131I]iodine scintigraphy in patients with recurrent DTC. METHODS: Twenty-five patients with recurrent DTC were included in this retrospective analysis. All patients underwent [18F]TFB-PET combined with either CT or MRI due to newly discovered elevated TG levels, antiTG levels, sonographically suspicious cervical lymph nodes, or combinations of these findings. Correlative [131I]iodine whole-body scintigraphy (dxWBS) including SPECT-CT was present for all patients; correlative [18F]FDG-PET-CT was present for 21 patients. Histological verification of [18F]TFB positive findings was available in 4 patients. RESULTS: [18F]TFB-PET detected local recurrence or metastases of DTC in significantly more patients than conventional [131I]iodine dxWBS and SPECT-CT (13/25 = 52% vs. 3/25 = 12%, p = 0.002). The diagnosis of 6 patients with cervical lymph node metastases that showed mildly increased FDG metabolism but negative [131I]iodine scintigraphy was changed: [18F]TFB-PET revealed hNIS expression in the metastases, which were therefore reclassified as only partly de-differentiated (histological confirmation present in two patients). Highest sensitivity for detecting recurrent DTC had the combination of [18F]TFB-PET-CT/MRI with [18F]FDG-PET-CT (64%). CONCLUSION: In the present cohort, [18F]TFB-PET shows higher sensitivity and accuracy than [131I]iodine WBS and SPECT-CT in detecting recurrent DTC. The combination of [18F]TFB-PET with [18F]FDG-PET-CT seems a reasonable strategy to characterize DTC tumor manifestations with respect to their differentiation and thereby also individually plan and monitor treatment. Future prospective studies evaluating the potential of [18F]TFB-PET in recurrent DTC are warranted.
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Yodo , Neoplasias de la Tiroides , Diferenciación Celular , Fluorodesoxiglucosa F18 , Humanos , Radioisótopos de Yodo , Recurrencia Local de Neoplasia/diagnóstico por imagen , Tomografía Computarizada por Tomografía de Emisión de Positrones , Estudios Prospectivos , Estudios Retrospectivos , Tiroglobulina , Neoplasias de la Tiroides/diagnóstico por imagenRESUMEN
PURPOSE: Dual-time point PET/CT scanning with [68Ga]Ga-PSMA-11 in the diagnosis of prostate cancer (PC) has been advanced as a method to increase detection of PC lesions, particularly at early stages of biochemical recurrence and as a potential means to aid the discrimination between benign and pathological prostate-specific membrane antigen (PSMA) uptake. However, the assumption that all PC lesions uniformly exhibit increasing tracer uptake at delayed imaging has not yet been investigated, which this present study aims to address. METHODS: One hundred consecutive patients with biochemically recurrent PC who received standard and late [68Ga]Ga-PSMA-11 PET/CT (by local protocol at 1.5 h "standard" and 2.5 h p.i. "late") underwent retrospective evaluation. All lesions with a tracer uptake above local background were analysed with regard to their maximum standardised uptake values at standard and late images (SUVmax) and characterised according to their morphological characteristics. RESULTS: Seventy-nine of 100 patients had PSMA-positive scans, in whom a total of 185 individual PSMA-positive lesions were identified. These were morphologically characterised as bone lesions (n = 48), solid organ lesions (n = 3), lymph node (LN) lesions (n = 78) and locally recurrent lesions in the prostatic fossa or seminal vesicles (n = 56). The relative uptake between standard and late imaging was considered; all lesions classified as local recurrence presented with increasing (86%) or stable patterns of tracer uptake (14%). In contrast, only 58% of bone lesions exhibited increasing tracer uptake, with 21% exhibiting a stable pattern and 21% exhibiting a decreasing tracer uptake at late imaging. CONCLUSION: A heterogeneous pattern of dynamic tracer uptake was observed, with a largely increasing pattern observed for locally recurrent lesions and lymph nodes and a significant proportion of bone lesions exhibiting decreasing tracer uptake. The results are of significance not only in the imaging and identification of PC lesions, but they also have implications for PSMA-directed ligand therapy.