PurposeThe introduction of ligands targeting prostate-specific membrane antigen (PSMA), especially 68Ga-PSMA-11, has changed the management of patients with prostate cancer (PCa). 18F-Labelled ligands can be produced in larger amounts and therefore can improve availability for a larger group of patients. The aim of this study was to evaluate the diagnostic performance of the recently introduced 18F-PSMA-1007 in patients with recurrent PCa.MethodsThis retrospective analysis included 100 consecutive patients with biochemical relapse (mean age 68.75 ± 7.6 years) referred for PSMA PET/CT. Whole-body PET/CT imaging (from the lower limbs to the skull) was performed in all patients 120 min after injection of 338 ± 44.31 MBq 18F-PSMA-1007. Prostatectomy, radiation beam therapy of the prostate bed and androgen-deprivation therapy had been performed in 92%, 45% and 27% of the patients, respectively. Radiation beam therapy of the prostate bed had been performed in addition to surgery in 38 patients (38%) and 10 patients (10%) had received all three therapy modalities. The probability of a 18F-PSMA-1007 PET/CT scan suggestive of pathology was compared with the Gleason score (GS) and PSA level.ResultsOf the 100 patients, 95 (95%) showed at least one pathological finding on 18F-PSMA-1007 PET/CT. The overall median PSA level was 1.34 ng/ml (range 0,04–41.3 ng/ml). The rates of pathological scans were 86%, 89%, 100% and 100% among patients with PSA levels ≤0.5, 0.51–1.0, 1.1–2.0 and > 2.0 ng/ml, respectively. The median GS was 7 (range 5–10). The majority of patients (70) with a GS available had a score in the range 7–9. The rate of pathological scans in these patients was 93% (65/70). The median SUVmax values of the pathological findings were 10.25, 14.32, 13.16 and 28.87 in patients with PSA levels ≤0.5, 0.51–1.0, 1.1–2.0 and >2.0 ng/ml, respectively. The median SUVmax in patients with a PSA level of >2.0 ng/ml was significantly higher than in all other PSA groups.Conclusion18F-PSMA-1007 PET/CT can detect recurrent PCa in a high percentage of patients with biochemical relapse. The probability of a pathological 18F-PSMA-1007 PET/CT scan seems to be high even in patients with a low PSA level ≤0.5 ng/ml, and this may have a significant impact on the management of this relevant group of patients.

Introduction The impact of prior therapies, especially chemotherapy, on overall survival (OS) in patients with castration-resistant prostate cancer (CRPC) receiving [ 177 Lu]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 177 Lu-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 [ 177 Lu]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 [ 177 Lu]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. Electronic supplementary material The online version of this article (10.1007/s00259-020-04797-9) contains supplementary material, which is available to authorized users.

ET with fluorine 18 (18 F) fluorodeoxyglucose (FDG) has a substantial impact on the diagnosis and clinical decisions of oncological diseases. 18 F-FDG uptake highlights regions of high glucose metabolism that include both pathologic and physiologic processes (1,2). 18 F-FDG PET/CT adds value to the initial diagnosis, detection of recurrent tumor, and evaluation of response to therapy in lung cancer and lymphoma (3-6). In lung cancer or lymphoma staging, 18 F-FDG PET images are interpreted by trained nuclear medicine readers to help identify foci positive for 18 F-FDG uptake (hereafter, referred to as 18 F-FDG2positive foci) that are suspicious for tumor. This classification of 18 F-FDG2positive foci is particularly challenging for malignant tumors with a low avidity, unusual tumor sites, and motion and attenuation artifacts, and the wide range of 18 F-FDG uptake related to inflammation, infection, or physiologic glucose consumption (7-9). Whereas the intra-and interobserver interpretation of 18 F-FDG PET/CT findings has a high level of agreement in studies involving single site and experienced readers for lymphoma, lung, and head and neck cancer (10-12), there remains an unmet need to assist the reader in analyzing these examinations more efficiently. Convolutional neural networks (CNNs) are a branch of machine learning that is finding applications 18

Rationale: PSMA-PET-CT enables measuring molecular expression of prostate-specific membrane antigen (PSMA) in vivo , which is the target molecule of 177 Lu-PSMA-617 (Lu-PSMA) therapy. However, the correlation of PSMA expression and overall survival (OS) in patients treated with Lu-PSMA therapy is currently unclear; especially with regard to coexistence of high and low PSMA expressing metastases. To this end, this retrospective single arm study elucidates the correlation of PSMA expression and overall survival in patients treated with Lu-PSMA therapy. Additionally, PET based criteria to define low PSMA expression were explored. Methods: Eighty-five patients referred to Lu-PSMA therapy were included in the analysis. Pretherapeutic 68 Ga-PSMA-PET-CT scans were available for all patients. SUV max of the highest PSMA expressing metastasis (PSMA max ), SUV max of the lowest PSMA expressing metastasis (PSMA min ), and average SUV max of all metastases (PSMA average ) amongst other PET parameters were measured for each patient. A log-rank cutoff-finder was used to determine low (lowPSMA average ) and high (highPSMA average ) average PSMA expression as well as low (lowPSMA min ) and high (highPSMA min ) minimal PSMA expression. Results: PSMA average was a significant prognosticator of overall survival in contrast to PSMA max (HR: 0.959; p = 0.047 vs. HR: 0.992; p = 0.231). Optimal log rank cut-offs were: PSMA average = 14.3; PSMA min = 10.2. Patients with low average PSMA expression (lowPSMA average ) had significantly shorter survival compared to those with high average expression (highPSMA average ) (5.3 vs. 15.1 months; p < 0.001; HR: 3.738, 95%CI = 1.953-7.154; p < 0.001). Patients with low PSMA expressing metastases (lowPSMA min ) had shorter survival compared to those without a low PSMA expressing metastasis (highPSMA min ) (p = 0.003; 7.9 months vs. 21.3; HR: 4.303, 95%CI = 1.521-12.178; p = 0.006). Patients that were classified as highPSMA average but with lowPSMA min had an intermediate overall survival (11.4 months; longer compared to lowPSMA average , 5.3 months, p = 0.002; but shorter compared to highPSMA min , 21.3 months, p = 0.02). Conclusion: Low average PSMA expression is a negative prognosticator of overall survival. Absence of low PSMA expressing metastases is associated with best overall survival and the maximum PSMA expression seems not suited to p...

Prostate-specific membrane antigen (PSMA)-targeting PET imaging is becoming the reference standard for prostate cancer staging, especially in advanced disease. Yet, the implications of PSMA PET-derived whole-body tumor volume for overall survival are poorly elucidated to date. This might be because semiautomated quantification of whole-body tumor volume as a PSMA PET biomarker is an unmet clinical challenge. Therefore, in the present study we propose and evaluate a software that enables the semiautomated quantification of PSMA PET biomarkers such as whole-body tumor volume. Methods: The proposed quantification is implemented as a research prototype. PSMA-accumulating foci were automatically segmented by a percental threshold (50% of local SUV max ). Neural networks were trained to segment organs in PET/CT acquisitions (training CTs: 8,632, validation CTs: 53). Thereby, PSMA foci within organs of physiologic PSMA uptake were semiautomatically excluded from the analysis. Pretherapeutic PSMA PET/CTs of 40 consecutive patients treated with 177 Lu-PSMA-617 were evaluated in this analysis. The whole-body tumor volume (PSMA TV50 ), SUV max , SUV mean , and other whole-body imaging biomarkers were calculated for each patient. Semiautomatically derived results were compared with manual readings in a subcohort (by 1 nuclear medicine physician). Additionally, an interobserver evaluation of the semiautomated approach was performed in a subcohort (by 2 nuclear medicine physicians). Results: Manually and semiautomatically derived PSMA metrics were highly correlated (PSMA TV50 : R 2 5 1.000, P , 0.001; SUV max : R 2 5 0.988, P , 0.001). The interobserver agreement of the semiautomated workflow was also high (PSMA TV50 : R 2 5 1.000, P , 0.001, interclass correlation coefficient 5 1.000; SUV max : R 2 5 0.988, P , 0.001, interclass correlation coefficient 5 0.997). PSMA TV50 (ml) was a significant predictor of overall survival (hazard ratio: 1.004; 95% confidence interval: 1.001-1.006, P 5 0.002) and remained so in a multivariate regression including other biomarkers (hazard ratio: 1.004; 95% confidence interval: 1.001-1.006 P 5 0.004). Conclusion: PSMA TV50 is a promising PSMA PET biomarker that is reproducible and easily quantified by the proposed semiautomated software. Moreover, PSMA TV50 is a significant predictor of overall survival in patients with advanced prostate cancer who receive 177 Lu-PSMA-617 therapy.