Whole-body tumour burden on [18F]DCFPyL PET/CT in biochemical recurrence of prostate cancer: association with tumour biology and PSA kinetics.

PURPOSE: The objective was to assess the association between molecular imaging (mi) variables on [18F]DCFPyL-PET/CT with clinical and disease characteristics and prostate specific antigen (PSA) related variables in patients with biochemical recurrence of prostate cancer (BRPC). MATERIAL AND METHODS: We analysed patients with BRPC after radical treatment. We obtained clinical and PSA variables: International Society of Urology Pathology (ISUP) grade group, European Association of Urology (EAU) risk classification, PSA (PSA≤1ng/ml, 12), PSA doubling time (PSAdt) and PSA velocity (PSAvel). All PET/CT scans were reviewed with the assistance of automated Prostate Molecular Imaging Standardized Evaluation (aPROMISE) software and lesions' segmentation in positive scans was performed using this platform. Standardized uptake value (SUV) derived variables; tumour burden variables [whole-body tumour volume (wbTV), whole-body tumour lesion activity (wbTLA) and whole-body mi PSMA (wbPSMA)] and miTNM staging were obtained. Cut-off of PSA and kinetics able to predict PET/CT results were obtained. Associations between disease and mi variables were analysed using ANOVA, Kruskal-Wallis and Spearman's correlation tests. Multivariate analysis was also performed. RESULTS: Two hundred and seventy-five patients were studied. [18F]DCFPyL-PET/CT were positive in 165/275 patients. In multivariate analysis, moment of biochemical recurrence, ISUP group, PSA level and PSAvel showed significant association with the detection rate. miTNM showed significant association with PSA level (p<0.001) and kinetics (p<0.001), being higher in patients with metastatic disease. Both PSA and PSAvel showed moderate correlation with wbTV, wbTLA and wbPSMA (p<0.001). A weak correlation with SUVs was found. Mean wbTV, wbTLA and wbPSMA values were significantly higher in PSA > 2ng/ml, PSAdt ≤ 6 months and PSAvel ≥ 0.2ng/ml/month groups. Also, wbTV (p=0.039) and wbPSMA (p=0.020) were significantly higher in patients with ISUP grade group 5. PSA and PSAvel cut-offs (1.15 ng/ml and 0.065 ng/ml/month) were significantly associated with a positive PET/CT. CONCLUSION: Higher PSA values, unfavourable PSA kinetics and ISUP grade group 5 were robust predictive variables of larger tumour burden variables on [18F]DCFPyL PET/CT assessed by aPROMISE platform.

The CONFIRM trial protocol: the utility of prostate-specific membrane antigen positron emission tomography/computed tomography in active surveillance for prostate cancer.

OBJECTIVES: Primary objectives: To determine the additive value of prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) in the risk stratification of men with newly diagnosed prostate cancer (PCa) who would have otherwise been deemed suitable for active surveillance (AS). Specifically, we aim to determine if PSMA PET/CT can detect a cohort of men on AS that are in fact high risk and likely to experience unfavourable outcomes should they remain on their current treatment pathway. SECONDARY OBJECTIVES: to determine the additive value of PSMA PET/CT to repeat multiparametric magnetic resonance imaging (mpMRI) of the prostate and explore whether a confirmatory biopsy may be avoided in men with a negative PSMA PET/CT and a negative repeat mpMRI of the prostate (Prostate Imaging-Reporting and Data System score of <3). Furthermore, to develop a nomogram combining clinical, imaging and biomarker data to predict the likelihood of failure on AS in men with high-risk features. Also, a blood sample will be taken to perform a Prostate Health Index test at the time of confirmatory biopsy. Furthermore, a portion of this blood will be stored at a biobank for up to 5 years if a follow-up study on molecular biomarkers and genetic assays in this cohort of men is indicated, based on the results from the CONFIRM trial. PATIENTS AND METHODS: The CONFIRM trial is a prospective, multicentre, pre-test/post-test, cohort study across Victoria, Australia, involving men with newly diagnosed low-risk PCa with high-risk features, considered suitable for AS and undergoing confirmatory biopsy. The trial's goal is to provide high-quality evidence to establish whether PSMA PET/CT has a role in risk-stratifying men deemed suitable for AS despite having high-risk feature(s). RESULTS: The CONFIRM trial will measure the proportion of men deemed unsuitable for ongoing AS based on pathological upgrading and multidisciplinary team recommendation due to PSMA PET/CT scan and PSMA-targeted confirmatory biopsy. Additionally, the positive and negative predictive values, sensitivity, and specificity of PSMA PET/CT will be calculated in isolation and combined with repeat mpMRI of the prostate. CONCLUSIONS: This trial will provide robust prospective data to determine if PSMA-PET/CT and standard of care (prostate biopsy ± repeat mpMRI) can improve diagnostic certainty in men undergoing confirmatory biopsy for low-grade PCa with high-risk features.

Lack of repeatability of radiomic features derived from PET scans: Results from a 18 F-DCFPyL test-retest cohort.

OBJECTIVES: PET-based radiomic metrics are increasingly utilized as predictive image biomarkers. However, the repeatability of radiomic features on PET has not been assessed in a test-retest setting. The prostate-specific membrane antigen-targeted compound 18 F-DCFPyL is a high-affinity, high-contrast PET agent that we utilized in a test-retest cohort of men with metastatic prostate cancer (PC). METHODS: Data of 21 patients enrolled in a prospective clinical trial with histologically proven PC underwent two 18 F-DCFPyL PET scans within 7 days, using identical acquisition and reconstruction parameters. Sites of disease were segmented and a set of 29 different radiomic parameters were assessed on both scans. We determined repeatability of quantification by using Pearson's correlations, within-subject coefficient of variation (wCOV), and Bland-Altman analysis. RESULTS: In total, 230 lesions (177 bone, 38 lymph nodes, 15 others) were assessed on both scans. For all investigated radiomic features, a broad range of inter-scan correlation was found (r, 0.07-0.95), with acceptable reproducibility for entropy and homogeneity (wCOV, 16.0% and 12.7%, respectively). On Bland-Altman analysis, no systematic increase or decrease between the scans was observed for either parameter (±1.96 SD: 1.07/-1.30, 0.23/-0.18, respectively). The remaining 27 tested radiomic metrics, however, achieved unacceptable high wCOV (≥21.7%). CONCLUSION: Many common radiomic features derived from a test-retest PET study had poor repeatability. Only Entropy and homogeneity achieved good repeatability, supporting the notion that those image biomarkers may be incorporated in future clinical trials. Those radiomic features based on high frequency aspects of images appear to lack the repeatability on PET to justify further study.

Test-retest repeatability of organ uptake on PSMA-targeted 18 F-DCFPyL PET/CT in patients with prostate cancer.

OBJECTIVES: We evaluated 18 F-DCFPyL test-retest repeatability of uptake in normal organs. METHODS: Twenty-two prostate cancer (PC) patients underwent two 18 F-DCFPyL PET scans within 7 days within a prospective clinical trial (NCT03793543). In both PET scans, uptake in normal organs (kidneys, spleen, liver, and salivary and lacrimal glands) was quantified. Repeatability was determined by using within-subject coefficient of variation (wCOV), with lower values indicating improved repeatability. RESULTS: For SUVmean , repeatability was high for kidneys, spleen, liver, and parotid glands (wCOV, range: 9.0%-14.3%) and lower for lacrimal (23.9%) and submandibular glands (12.4%). For SUVmax , however, the lacrimal (14.4%) and submandibular glands (6.9%) achieved higher repeatability, while for large organs (kidneys, liver, spleen, and parotid glands), repeatability was low (range: 14.1%-45.2%). CONCLUSION: We found acceptable repeatability of uptake on 18 F-DCFPyL PET for normal organs, in particular for SUVmean in the liver or parotid glands. This may have implications for both PSMA-targeted imaging and treatment, as patient selection for radioligand therapy and standardized frameworks for scan interpretation (PROMISE, E-PSMA) rely on uptake in those reference organs.

Evaluation of PSMA target diagnostic PET tracers for therapeutic monitoring of [177Lu]ludotadipep of prostate cancer: Screening of PSMA target efficiency and biodistribution using [18F]DCFPyL and [68Ga]PSMA-11.

We have compared the similarity of the in vivo distribution of the prostate-specific membrane antigen (PSMA)-targeted positron emission tomography (PET) imaging agents [18F]DCFPyL, [68Ga]galdotadipep, and [68Ga]PSMA-11. This study is designed for a further selection of a PSMA-targeted PET imaging agent for the therapeutic evaluation of [177Lu]ludotadipep, our previously developed prostate-specific membrane antigen (PSMA)-targeted prostate cancer therapeutic radiopharmaceutical. In vitro cell uptake was performed to evaluate the affinity to PSMA using PSMA + PC3-PIP, and PSMA- PC3-flu was used for the study. MicroPET/CT 60 min dynamic imaging and biodistribution were performed at 1, 2, and 4 h after injection. Autoradiography and immunohistochemistry were performed to evaluate the PSMA + tumor target efficiency. In the microPET/CT image, [68Ga]PSMA-11 showed the highest uptake in the kidney among all three compounds. [18F]DCFPyL and [68Ga]PSMA-11 showed similar patterns of in vivo biodistribution and high tumor targeting efficiency, similar to those of[68Ga]galdotadipep. All three agents showed high uptake in tumor tissue on autoradiography, and PSMA expression was confirmed by immunohistochemistry. Thus, [18F]DCFPyL or [68Ga]PSMA-11 can be used as a PET imaging agent to monitor [177Lu]ludotadipep therapy in prostate cancer patients.

[18F]DCFPyL PET/CT versus [18F]fluoromethylcholine PET/CT in Biochemical Recurrence of Prostate Cancer (PYTHON): a prospective, open label, cross-over, comparative study.

PURPOSE: Primary objective was to compare the per-patient detection rates (DR) of [18F]DCFPyL versus [18F]fluoromethylcholine positron emission tomography/computed tomography (PET/CT), in patients with first prostate cancer (PCa) biochemical recurrence (BCR). Secondary endpoints included safety and impact on patient management (PM). METHODS: This was a prospective, open label, cross-over, comparative study with randomized treatment administration of [18F]DCFPyL (investigational medicinal product) or [18F]fluoromethylcholine (comparator). Men with rising prostate-specific antigen (PSA) after initial curative therapy were enrolled. [18F]DCFPyL and [18F]fluoromethylcholine PET/CTs were performed within a maximum time interval of 12 days. DR was defined as the percentage of positive PET/CT scans identified by 3 central imaging readers. PM was assessed by comparing the proposed pre-PET/CT treatment with the local treatment", defined after considering both PET/CTs. RESULTS: A total of 205 patients with first BCR after radical prostatectomy (73%; median PSA = 0.46 ng/ml [CI 0.16;27.0]) or radiation therapy (27%; median PSA = 4.23 ng/ml [CI 1.4;98.6]) underwent [18F]DCFPyL- and/or [18F]fluoromethylcholine -PET/CTs, between July and December 2020, at 22 European sites. 201 patients completed the study. The per-patient DR was significantly higher for [18F]DCFPyL- compared to [18F]fluoromethylcholine -PET/CTs (58% (117/201 patients) vs. 40% (81/201 patients), p < 0.0001). DR increased with higher PSA values for both tracers (PSA ≤ 0.5 ng/ml: 26/74 (35%) vs. 22/74 (30%); PSA 0.5 to ≤ 1.0 ng/ml: 17/31 (55%) vs. 10/31 (32%); PSA 1.01 to < 2.0 ng/ml: 13/19 (68%) vs. 6/19 (32%);PSA > 2.0: 50/57 (88%) vs. 39/57 (68%) for [18F]DCFPyL- and [18F]fluoromethylcholine -PET/CT, respectively). [18F]DCFPyL PET/CT had an impact on PM in 44% (90/204) of patients versus 29% (58/202) for [18F]fluoromethylcholine. Overall, no drug-related nor serious adverse events were observed. CONCLUSIONS: The primary endpoint of this study was achieved, confirming a significantly higher detection rate for [18F]DCFPyL compared to [18F]fluoromethylcholine, in men with first BCR of PCa, across a wide PSA range. [18F]DCFPyL was safe and well tolerated.

Prospective analysis of clinically significant prostate cancer detection with [18F]DCFPyL PET/MRI compared to multiparametric MRI: a comparison with the histopathology in the radical prostatectomy specimen, the ProStaPET study.

PURPOSE: Multiparametric magnetic resonance imaging (mpMRI) is a well-established imaging method for localizing primary prostate cancer (PCa) and for guiding targeted prostate biopsies. [18F]DCFPyL positron emission tomography combined with MRI (PSMA-PET/MRI) might be of additional value to localize primary PCa. The aim of this study was to assess the diagnostic performance of [18F]DCFPyL-PET/MRI vs. mpMRI in tumour localization based on histopathology after robot-assisted radical-prostatectomy (RARP), also assessing biopsy advice for potential image-guided prostate biopsies. METHODS: Thirty prospectively included patients with intermediate to high-risk PCa underwent [18F]DCFPyL-PET/MRI and mpMRI prior to RARP. Two nuclear medicine physicians and two radiologists assessed tumour localization on [18F]DCFPyL-PET/MRI and on mpMRI respectively, and gave a prostate biopsy advice (2 segments) using a 14-segment model of the prostate. The uro-pathologist evaluated the RARP specimen for clinically significant PCa (csPCa) using the same model. csPCa was defined as any PCa with Grade Group (GG) ≥ 2. The biopsy advice based on imaging was correlated with the final histology in the RARP specimen for a total-agreement analysis. An additional near-agreement correlation was performed to approximate clinical reality. RESULTS: Overall, 142 of 420 (33.8%) segments contained csPCa after pathologic examination. The segments recommended for targeted biopsy contained the highest GG PCa segment in 27/30 patients (90.0%) both for [18F]DCFPyL-PET/MRI and mpMRI. Areas under the receiver operating characteristics curves (AUC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for the total-agreement detection of csPCa per segment using [18F]DCFPyL-PET/MRI were 0.70, 50.0%, 89.9%, 71.7%, and 77.9%, respectively. These results were 0.75, 54.2%, 94.2%, 82.8%, and 80.1%, respectively, for mpMRI only. CONCLUSION: Both [18F]DCFPyL-PET/MRI and mpMRI were only partly able to detect csPCa on a per-segment basis. An accurate detection (90.0%) of the highest GG lesion at patient-level was observed when comparing both [18F]DCFPyL-PET/MRI and mpMRI biopsy advice with the histopathology in the RARP specimen. So, despite the finding that [18F]DCFPyL-PET/MRI adequately detects csPCa, it does not outperform mpMRI.

Non-prostate cancer tumours: incidence on 18F-DCFPyL PSMA PET/CT and uptake characteristics in 1445 patients.

PURPOSE: With increasing use of PSMA PET/CT in the staging and restaging of prostate cancer (PCa), the identification of non-prostate cancer tumours (NPCaT) has become an increasing clinical dilemma. Atypical presentations of PSMA expression in prostate cancer and expression in NPCaT are not well established. Understanding the normal and abnormal distribution of PSMA expression is essential in preparing clinically relevant reports and in guiding multidisciplinary discussion and decisions. METHODS: Retrospective review of 1445 consecutive 18F-DCFPyL PSMA PET/CT studies by experienced radiologists and nuclear medicine physicians. Lesions indeterminate for PCa were identified. Correlation was made with patient records, biopsy results, and dedicated imaging. Lesions were then categorized into four groups: 1. Confirmed prostate cancer, metastases, 2. NPCaT 3. Benign, and 4. Indeterminate lesions. RESULTS: 68/1445 patients had lesions atypical for prostate cancer metastases. These comprised 8/68 (11.8%) atypical prostate cancer metastases, 17/68 (25.0%) NPCaT, 29/68 (42.6%) indeterminate, and 14/68 (20.6%) benign. In the context of the entire cohort, these are adjusted to 8/1445 (0.6%), 17/1445 (1.2%), 29/1445 (2.0%), and 14/1445 (1.0%) respectively. With the exception of Renal Cell Carcinoma (RCC), NPCaT demonstrated no or low PSMA expression. A similar trend was also observed for indeterminate and benign lesions. Conversely, most atypical PCa metastases demonstrated intermediate or high PSMA expression. CONCLUSION: 18F-DCFPyL PSMA PET/CT detection of NPCaT is low. Lesions demonstrating intermediate to high PSMA expression were exclusively prostate cancer metastases, aside from RCC, and lesions detected in organs with high background expression.

Pathological predictors of 18 F-DCFPyL prostate-specific membrane antigen-positive recurrence after radical prostatectomy.

OBJECTIVES: To assess the correlation of pathological radical prostatectomy (RP) specimen features and prostate-specific antigen (PSA) characteristics to imaging findings on subsequent 18 F-DCFPyL positron emission tomography/computed tomography (PET/CT) in patients with biochemical failure (BF). PATIENTS AND METHODS: Retrospective analysis of combined 18 F-DCFPyL PET/CT database of patients from centres in Australia and New Zealand was performed. A total of 205 patients presenting with BF after RP were included in this study. Imaging findings on 18 F-DCFPyL PET/CT were recorded and correlated with the PSA characteristics at BF and pathological features of the original tumour. RESULTS: Of the 205 patients, 120 (58.5%) had evidence of abnormal prostate-specific membrane antigen (PSMA) expression compatible with recurrent prostate cancer. Increasing PSA velocity (P = 0.01), International Society of Urological Pathology (ISUP) Grade Group (P = 0.02), lymphovascular invasion (P = 0.05) and nodal positivity (P = 0.02) at the time of RP were more likely to demonstrate PSMA positivity. Multivariable logistic regression revealed a higher PSA level prior to PSMA PET/CT (P < 0.01), adjuvant radiotherapy (P = 0.09), Gleason score ≥8 (P < 0.01) and nodal positivity (P = 0.05) were all predictive of PSMA positivity. CONCLUSION: 18 F-DCFPyL PET/CT positivity, both generally and site specific, correlates with PSA and RP pathological factors. Our results echo cohorts focussing on post-RP patients, those imaged with 68 Ga-PSMA and those concerning biochemical persistence. Nomograms that include risk factors for 'PSMA-positive recurrence' in the BF population may increase the catchment of patients with disease confined to the prostate bed or pelvis who have a greater probability of prolonged disease-free survival.

Standardised uptake values as determined on prostate-specific membrane antigen positron emission tomography/computed tomography is associated with oncological outcomes in patients with prostate cancer.

OBJECTIVES: To investigate the association between intraprostatic, intratumoral maximum standardised uptake values (SUVmax ) on prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) in patients with prostate cancer (PCa) prior to robot-assisted radical prostatectomy (RARP) and pathology outcomes, including pathological International Society of Urological Pathology score (pISUP) and lymph node (LN) status (pN0/pN1). PATIENTS AND METHODS: A bi-centric, secondary analysis of two previous, prospective cohort studies was performed in 318 patients with biopsy confirmed PCa and who were scheduled for RARP. Before surgery, patients received a PSMA PET/CT with either 68 Ga-PSMA-11 (59% of the patients) or 18 F-PSMA (DCFPyL; 41%) as radiotracer. PET/CT images were analysed both visually and semi-quantitatively by measuring the SUVmax of the most intense suspect lesion in the prostate. The association between the SUVmax of the primary tumour and pre- and postoperative variables was analysed. RESULTS: The SUVmax was associated with clinical and biopsy preoperative variables, as well as with pISUP score and pathological tumour stage. Patients with a pISUP of ≤2 showed significantly lower SUVmax compared to patients with a pISUP of >2 for both tracers (SUVmax18 F-PSMA: median 5.1 vs 9.6, P = 0.002; SUVmax68 Ga-PSMA-11: 6.6 vs 8.6, P = 0.003). Moreover, patients with pN1 had significantly higher median SUVmax than those with pN0/pNx for both tracers (SUVmax18 F-PSMA: 7.9 vs 12.3, P = 0.04; SUVmax68 Ga-PSMA-11: 7.6 vs 12.0, P < 0.001). On multivariable logistic regression analysis, the intraprostatic SUVmax was an independent predictor of pN1 for both 68 Ga-PSMA-11 (per doubling: odds ratio [OR] 1.96, 95% confidence interval [CI] 1.27-3.01)) and 18 F-PSMA (per doubling: OR 1.79, 95% CI 1.06-3.03). CONCLUSION: Intraprostatic, intratumoral PSMA intensity on PET/CT, as semi-quantitatively expressed by SUVmax , may be a valuable innovative biomarker in patients with localised PCa, as it is highly associated with known conventional prognostic factors, such as pISUP and LN status.

Detection of clinically significant prostate cancer with 18F-DCFPyL PET/multiparametric MR.

PURPOSE: To assess whether 18F-DCFPyL PET/multiparametric (mp)MR contributes to the diagnosis of clinically significant (cs) prostate cancer (PCa) compared to mpMR in patients with suspicion of PCa, or patients being considered for focal ablative therapies (FT). PATIENTS AND METHODS: This ethics review board-approved, prospective study included 55 men with suspicion of PCa and negative systematic biopsies or clinically discordant low-risk PCa (n = 21) or those being considered for FT (n = 34) who received 18F-DCFPyL PET/mpMR. Each modality, PET, mpMR, and PET/MR (using the PROMISE classification), was assessed independently. All suspicious lesions underwent PET/MR-ultrasound fusion biopsies. RESULTS: There were 45/55 patients (81.8%) that had histologically proven PCa and 41/55 (74.5%) were diagnosed with csPCa. Overall, 61/114 lesions (53.5%) identified on any modality were malignant; 49/61 lesions (80.3%) were csPCa. On lesion-level analysis, for detection of csPCa, the sensitivity of PET was higher than that of mpMR and PET/MR (86% vs 67% and 69% [p = 0.027 and 0.041, respectively]), but at a lower specificity (32% vs 85% and 86%, respectively [p < 0.001]). The performance of MR and PET/MR was comparable. For identification of csPCa in PI-RADS ≥ 3 lesions, the AUC (95% CI) for PET, mpMR, and PET/MR was 0.75 (0.65-0.86), 0.69 (0.56-0.82), and 0.78 (0.67-0.89), respectively. The AUC for PET/MR was significantly larger than that of mpMR (p = 0.04). CONCLUSION: PSMA PET detects more csPCa than mpMR, but at low specificity. The performance PET/MR is better than mpMR for detection of csPCa in PI-RADS ≥ 3 lesions. CLINICAL REGISTRATION: NCT03149861.

18F-DCFPyL PET/CT for primary staging in 160 high-risk prostate cancer patients; metastasis detection rate, influence on clinical management and preliminary results of treatment efficacy.

PURPOSE: Prostate-specific membrane antigen (PSMA) PET/CT shows better diagnostic performance for detection of lymph node and bone metastases as compared to conventional imaging. Studies of PSMA PET/CT in primary staging comprise highly selected patient cohorts. This study evaluates 18F-DCFPyL PET/CT as first-line imaging modality for primary staging of high-risk prostate cancer. MATERIAL: From February 2018 until April 2019, all patients with high-risk prostate cancer received 18F-DCFPyL PET/CT for staging of prostate cancer. Baseline characteristics, findings at 18F-DCFPyL PET/CT, number and type of required additional diagnostic procedures, findings at additional diagnostic procedures, and effects of therapy on PSA levels for all patients treated with curative intent were collected and evaluated. RESULTS: One hundred-sixty patients were included in the study of which 90 (56%) had evidence of metastasized disease (N1, M1a, M1b and, M1c in 49%, 28%, 31%, and 3% respectively). Additional diagnostic imaging was needed in 2/160 patients (1%) because of equivocal findings on 18F-DCFPyL PET/CT. Eighty-one patients had evidence of PSMA-positive lymph node metastases, of whom 39 (48%) had no enlarged lymph nodes on CT; 18F-DCFPyL PET detected additional metastatic lymph nodes in 41/42 patients that had evidence of lymph node metastases on CT. 18F-DCFPyL PET altered patients' management in 17% of patients. CONCLUSION: 18F-DCFPyL PET/CT can be used as first-line imaging modality for therapy selection in patients with primary high-risk prostate cancer, without need for further diagnostic imaging procedures in the majority of patients.

Management impact of 18F-DCFPyL PET/CT in hormone-sensitive prostate cancer patients with biochemical recurrence after definitive treatment: a multicenter retrospective study.

PURPOSE: The aim of this study was to investigate whether an early, accurate identification of disease using 18F-DCFPyL PET/CT imaging resulted in a change of decision on treatment management, for individual patients with biochemically recurrent (BCR), hormone-sensitive prostate cancer. METHODS: In this retrospective study, a total of 253 patients with BCR who underwent restaging 18F-DCFPyL PET/CT were assessed. Two urologists specialized in uro-oncology were asked to formulate a preferred treatment for each patient before and after knowing the results of the 18F-DCFPyL PET/CT. RESULTS: Out of 253 patients, 191 (75%) underwent robot-assisted radical prostatectomy (RARP) as primary therapy, and 62 (25%) external beam radiation therapy (EBRT). In 103/253 cases (40.7%), a preferred treatment change based on the 18F-DCFPyL PET/CT findings was reported. In patients post-RARP, a positive 18F-DCFPyL PET/CT (OR 6.21; 95%CI 2.78-13.8; p < 0.001) and positive pathological lymph node status (pN1) (OR 2.96; 95%CI 1.15-7.60; p = 0.024) were significant predictors for an intended change of management, whereas a positive surgical margin (OR 0.42; 95%CI 0.20-0.88; p = 0.022) was inversely associated with an intended change of management. CONCLUSION: In this study, we found a significant impact of 18F-DCFPyL PET/CT on the intended management of patients with biochemically recurrent hormone-sensitive prostate cancer. A positive 18F-DCFPyL PET/CT scan, positive pathological lymph node status, and a negative surgical margin status were significantly associated with increased odds of having a change of management based on 18F-DCFPyL PET/CT findings.

Pelvic lymph-node staging with 18F-DCFPyL PET/CT prior to extended pelvic lymph-node dissection in primary prostate cancer - the SALT trial.

PURPOSE: The detection of lymph-node metastases (N1) with conventional imaging such as magnetic resonance imaging (MRI) and computed tomography (CT) is inadequate for primarily diagnosed prostate cancer (PCa). Prostate-specific membrane antigen (PSMA) PET/CT is successfully introduced for the staging of (biochemically) recurrent PCa. Besides the frequently used 68gallium-labelled PSMA tracers, 18fluorine-labelled PSMA tracers are available. This study examined the diagnostic accuracy of 18F-DCFPyL (PSMA) PET/CT for lymph-node staging in primary PCa. METHODS: This was a prospective, multicentre cohort study. Patients with primary PCa underwent 18F-DCFPyL PET/CT prior to robot-assisted radical prostatectomy (RARP) with extended pelvic lymph-node dissection (ePLND). Patients were included between October 2017 and January 2020. A Memorial Sloan Kettering Cancer Centre (MSKCC) nomogram risk probability of ≥ 8% of lymph-node metastases was set to perform ePLND. All images were reviewed by two experienced nuclear physicians, and were compared with post-operative histopathologic results. RESULTS: A total of 117 patients was analysed. Lymph-node metastases (N1) were histologically diagnosed in 17/117 patients (14.5%). The sensitivity, specificity, positive predictive value and negative predictive value for the 18F-DCFPyL PET/CT detection of pelvic lymph-node metastases on a patient level were 41.2% (confidence interval (CI): 19.4-66.5%), 94.0% (CI 86.9-97.5%), 53.8% (CI 26.1-79.6%) and 90.4% (CI 82.6-95.0%), respectively. CONCLUSION: 18F-DCFPyL PET/CT showed a high specificity (94.4%), yet a limited sensitivity (41.2%) for the detection of pelvic lymph-node metastases in primary PCa. This implies that current PSMA PET/CT imaging cannot replace diagnostic ePLND. Further research is necessary to define the exact place of PSMA PET/CT imaging in the primary staging of PCa.

Patterns of disease detection using [18F]DCFPyL PET/CT imaging in patients with detectable PSA post prostatectomy being considered for salvage radiotherapy: a prospective trial.

PURPOSE: Prostate-specific membrane antigen (PSMA) PET/CT is increasingly used in patients with biochemical recurrence post prostatectomy to detect local recurrence and metastatic disease at low PSA levels. The aim of this study was to assess patterns of disease detection, predictive factors and safety using [18F]DCFPyL PET/CT versus diagnostic CT in patients being considered for salvage radiotherapy with biochemical recurrence post prostatectomy. METHODS: We conducted a prospective trial recruiting 100 patients with detectable PSA post prostatectomy (PSA 0.2-2.0 ng/mL) and referred for salvage radiotherapy from August 2018 to July 2020. All patients underwent a PSMA PET/CT using the [18F]DCFPyL tracer and a diagnostic CT. The detection rates of [18F]DCFPyL PET/CT vs diagnostic CT were compared and patterns of disease are reported. Clinical patient and tumour characteristics were analysed for predictive utility. Thirty-day post-scan safety is reported. RESULTS: Of 100 patients recruited, 98 were suitable for analysis with a median PSA of 0.32 ng/mL. [18F]DCFPyL PET/CT was positive 46.4% and equivocal 5.2%, compared to 15.5% positivity for diagnostic CT. Local recurrence was detected on [18F]DCFPyL PET/CT in 28.5%, nodal disease in 27.5% and bony metastases in 6.1% of patients. Both ISUP grade group (p < 0.001) and pre-scan PSA (p = 0.029) were significant predictors of [18F]DCFPyL PET/CT positivity, and logistic regression generated probabilities combining the two showed improved prediction rates. No significant safety events were reported post [18F]DCFPyL administration. CONCLUSIONS: [18F]DCFPyL PET/CT increases detection of disease in patients with biochemical recurrence post prostatectomy compared to diagnostic CT. Patients being considered for salvage radiotherapy with a PSA >0.2 ng/mL should be considered for [18F]DCFPyL PET/CT scan. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry Number: ACTRN12618001530213 ( http://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=375932&isReview=true ).

[18F]DCFPyL PET/CT in detection and localization of recurrent prostate cancer following prostatectomy including low PSA < 0.5 ng/mL.

PURPOSE: The primary aim of this retrospective multicenter analysis was to assess the performance of PSMA PET/CT using [18F]DCFPyL in the detection and localization of recurrent prostate cancer post radical prostatectomy (RP). Particular reference is given to low PSA groups < 0.5 ng/mL to aid discussion around the inclusion of this group in PSMA guidelines and funding pathways. METHODS: Retrospective analysis of combined PSMA database patients from centers in Australia and New Zealand. Two hundred twenty-two patients presenting with recurrence post RP were stratified into five PSA groups (ng/mL): 0-0.19, 0.2-0.49, 0.5-0.99, 1-1.99, and ≥ 2. Lesions detected by [18F]DCFPyL PET/CT were recorded as local recurrence, locoregional nodes, and metastases. RESULTS: Of 222 patients, 155 (69.8%) had evidence of abnormal uptake suggestive of recurrent prostate cancer. The detection efficacies for [18F]DCFPyL PET/CT were 91.7% (44/48) for PSA levels ≥ 2 ng/mL, 82.1% (23/28) for PSA levels 1-1.99 ng/mL, 62.8% (27/43) for PSA levels 0.5-0.99 ng/mL, 58.7% (54/92) for PSA levels 0.2-0.49 ng/mL, and 63.6% (7/11) for PSA levels ≤ 0.2 ng/mL. In those with PSA < 0.5 ng/mL, 47.6% (49/103) had detectable lesions, 71.4% (35/49) had disease confined to the pelvis, 22.4% (11/49) had prostate bed recurrence, 49.0% (24/49) had pelvic lymph nodes, and 28.6% (14/49) had extra pelvic disease. CONCLUSION: [18F]DCFPyL PET/CT has a high detection rate in recurrence following RP even at low PSA levels with similar detection levels in the PSA subgroups < 0.5 ng/mL. Employing rigid PSA thresholds when constructing guidelines for PSMA PET/CT funding eligibility may result in a significant number of patients below such thresholds having delayed or inappropriate treatment.

Detection of prostate cancer with 18F-DCFPyL PET/CT compared to final histopathology of radical prostatectomy specimens: is PSMA-targeted biopsy feasible? The DeTeCT trial.

PURPOSE: In primary prostate cancer (PCa) patients, accurate staging and histologic grading are crucial to guide treatment decisions. 18F-DCFPyL (PSMA)-PET/CT has been successfully introduced for (re)staging PCa, showing high accuracy to localise PCa in lymph nodes and/or osseous structures. The diagnostic performance of 18F-DCFPyL-PET/CT in localizing primary PCa within the prostate gland was assessed, allowing for PSMA-guided targeted-prostate biopsy. METHODS: Thirty patients with intermediate-/high-risk primary PCa were prospectively enrolled between May 2018 and May 2019 and underwent 18F-DCFPyL-PET/CT prior to robot-assisted radical prostatectomy (RARP). Two experienced and blinded nuclear medicine physicians assessed tumour localisation within the prostate gland on PET/CT, using a 12-segment mapping model of the prostate. The same model was used by a uro-pathologist for the RARP specimens. Based on PET/CT imaging, a potential biopsy recommendation was given per patient, based on the size and PET-intensity of the suspected PCa localisations. The biopsy recommendation was correlated to final histopathology in the RARP specimen. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for clinically significant PCa (csPCa, Gleason score ≥ 3 + 4 = 7) were assessed. RESULTS: The segments recommended for potential targeted biopsy harboured csPCA in 28/30 patients (93%), and covered the highest Gleason score PCa segment in 26/30 patient (87%). Overall, 122 of 420 segments (29.0%) contained csPCa at final histopathological examination. Sensitivity, specificity, PPV and NPV for csPCa per segment using 18F-DCFPyL-PET/CT were 61.4%, 88.3%, 68.1% and 84.8%, respectively. CONCLUSIONS: When comparing the PCa-localisation on 18F-DCFPyL-PET/CT with the RARP specimens, an accurate per-patient detection (93%) and localisation of csPCa was found. Thus, 18F-DCFPyL-PET/CT potentially allows for accurate PSMA-targeted biopsy.

Early lesion detection with 18F-DCFPyL PET/CT in 248 patients with biochemically recurrent prostate cancer.

PURPOSE: Prostate-specific membrane antigen (PSMA) PET/CT is increasingly used in patients with biochemically recurrent prostate cancer (BCR), mostly using gallium-68 (168Ga)-labelled radiotracers. Alternatively, fluorine-18 (18F)-labelled PSMA tracers are available, such as 18F-DCFPyL, which offer enhanced image quality and therefore potentially increased detection of small metastases. In this study we evaluate the lesion detection efficacy of 18F-DCFPyL PET/CT in patients with BCR and determine the detection efficacy as a function of their PSA value. METHODS: A total of 248 consecutive patients were evaluated and underwent scanning with 18F-DCFPyL PET/CT for BCR between November 2016 and 2018 in two hospitals in the Netherlands. Patients were examined after radical prostatectomy (52%), external-beam radiation therapy (42%) or brachytherapy (6%). Imaging was performed 120 min after injection of a median dose of 311 MBq 18F-DCFPyL. RESULTS: In 214 out of 248 PET/CT scans (86.3%), at least one lesion suggestive of cancer recurrence was detected ('positive scan'). Scan positivity increased with higher PSA values: 17/29 scans (59%) with PSA values <0.5 ng/ml; 20/29 (69%) with PSA 0.5 to <1.0 ng/ml; 35/41 (85%) with PSA 1.0 to <2.0 ng/ml; 69/73 (95%) with PSA 2.0 to <5.0 ng/ml; and 73/76 (96%) with PSA ≥5.0 ng/ml. Interestingly, suspicious lesions outside the prostatic fossa were detected in 39-50% of patients with PSA <1.0 ng/ml after radical prostatectomy (i.e. candidates for salvage radiotherapy). CONCLUSION: 18F-DCFPyL PET/CT offers early detection of lesions in patients with BCR, even at PSA levels <0.5 ng/ml. These results appear to be comparable to those reported for 68Ga-PSMA and 18F-PSMA-1007, with potentially increased detection efficacy compared to 68Ga-PSMA for patients with PSA <2.0.

Effect of 18F-DCFPyL PET on changes in management of patients with prostate cancer: a systematic review and meta-analysis.

Purpose: Prostate-specific membrane antigen (PSMA)-targeted imaging has gained increasing interest in its application in prostate cancer lesion detection. Compared with 68Galium (68Ga), 18Fluoride (18F)-labeled imaging agent has easier syntheses, lower price, and a longer half-time. 2-(3-{1-Carboxy-5-[(6-[18F]fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid positron emission tomography (18F-DCFPyL PET) has been recently approved by the U.S. Food and Drug Administration. Several studies have proven its superiority to conventional imaging techniques in detecting prostate cancer lesions. However, the impact of 18F-DCFPyL PET on the management of patients with prostate cancer is not well established. Thus, we performed a systematic review and meta-analysis of available data to evaluate the impact of 18F-DCFPyL PET on the management of patients with prostate cancer. Methods: The PubMed, Embase, Scopus, and Cochrane databases were searched up to April 2024. Studies that reported the proportion of changes in management after 18F-DCFPyL PET was performed in patients with prostate cancer were included. The Grading of Recommendations Assessment, Development, and Evaluation system was used for the quality evaluation of the included studies. The proportion of changes in management was pooled using a random effects model. Meta-regression analyses were performed to assess the potential correlation between the PET positivity and management changes. Results: Fourteen studies (3,078 patients with prostate cancer) were included in our review and analysis. The pooled percentage of management changes was 43.5% (95% confidence interval [CI]: 33-54%). In patients with biochemical recurrent and for primary staging, the pooled percentage was 50% (95% CI: 39-60%) and 22% (95% CI: 15-29%), respectively. In the meta-regression analyses, PET positivity was detected as a significant predictor of management change (p = 0.0023). Conclusion: 18F-DCFPyL PET significantly affects the management of patients with prostate cancer. Higher PET positivity rate significantly correlated with a higher proportion of management changes in patients with prostate cancer. However, more studies are still needed to confirm the important role of 18F-DCFPyL PET in the management of prostate cancer. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/#myprospero, CRD42022339178.

18F-DCFPyL PSMA PET/CT Tracheobronchial Uptake in Patients with Prostate Cancer: Incidence and Etiology.

We evaluated the incidence and potential etiology of tracheobronchial uptake in patients being evaluated by 18F-DCFPyL PET/CT for prostate cancer (PCa). Methods: The study included a consecutive 100 PCa patients referred for 18F-DCFPyL PET/CT. The PET/CT scans were retrospectively reviewed. The presence or absence of physiologic tracheobronchial uptake on PET/CT was recorded. To further evaluate tracheal prostate-specific membrane antigen (PSMA) expression, immunohistochemistry was performed on tracheal samples taken from 2 men who had surgical resection of lung cancer. Results: Tracheal uptake was present in 31 of 100 patients (31%). When tracheal uptake was present, the SUVmax was significantly higher in the left main bronchus (mean, 2.7) than in the right (mean, 2.3) (P < 0.001). Histopathologic testing of tracheobronchial samples showed PSMA expression in bronchial submucosal glands. Conclusion: In PCa patients undergoing 18F-DCFPyL PET/CT, tracheobronchial uptake occurred in 31% of patients. This is attributed to normal physiologic PSMA expression in bronchial submucosal glands.