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Multiparametric MRI (mpMRI) is validated for the diagnosis of clinically significant prostate cancer (csPCa). (68)Ga-PSMA-11 PET/CT ((68)Ga-PSMA PET/CT) combined with mpMRI has improved negative predictive value over mpMRI alone for csPCa. The aim of this post hoc analysis of the PRIMARY study was to evaluate the clinical significance of patterns of intraprostatic PSMA activity, proposing a 5-point PRIMARY score to optimize the accuracy of (68)Ga-PSMA PET/CT for csPCa in a low-prevalence population. Methods: The PRIMARY trial was a prospective multicenter phase II imaging trial that enrolled men with suspected PCa, no prior biopsy, and a recent mpMRI examination (6 mo) and for whom prostate biopsy was planned. In total, 291 men underwent mpMRI, (68)Ga-PSMA PET/CT, and systematic biopsy with or without targeted biopsy. The mpMRI was read separately using the Prostate Imaging Reporting and Data System (PI-RADS) (version 2). (68)Ga-PSMA PET/CT (pelvis only) was acquired a minimum of 60 min after injection. (68)Ga-PSMA PET/CT was centrally read for pattern (diffuse transition zone [TZ], symmetric central zone [CZ], focal TZ, or focal peripheral zone [PZ]) and intensity (SUV(max)). In this post hoc analysis, a 5-level PRIMARY score was assigned on the basis of analysis of the central read: no pattern (score of 1), diffuse TZ or CZ (not focal) (score of 2), focal TZ (score of 3), focal PZ (score of 4), or an SUV(max) of at least 12 (score of 5). Two further readers independently assigned a PRIMARY score to 118 scans to determine interrater agreement. Associations between PRIMARY score and csPCa (International Society of Urological Pathology grade group ≥ 2) were evaluated. Results: Of the 291 men enrolled, 162 (56%) had csPCa. A PRIMARY score of 1 was present in 16% (47); a score of 2, in 19% (55); a score of 3, in 10% (29); a score of 4 in 40% (117); and a score of 5, in 15% (43). The proportion of patients with csPCa and a PRIMARY score of 1, 2, 3, 4, and 5 was 8.5% (4/47), 27% (15/55), 38% (11/29), 76% (89/117), and 100% (43/43), respectively. Sensitivity, specificity, positive predictive value, and negative predictive value for a PRIMARY score of 1 or 2 (low-risk patterns) versus a PRIMARY score of 3–5 (high-risk patterns) were 88%, 64%, 76%, and 81%, respectively, compared with 83%, 53%, 69%, and 72%, respectively, for a PI-RADS score of 2 versus 3–5 on mpMRI. The Cohen κ for a PRIMARY score of 1 of 2 versus a PRIMARY score of 3–5 was 0.76 (95% CI, 0.64–0.88) for reader 1 and 0.64 (95% CI, 0.49–0.78) for reader 2. Conclusion: A PRIMARY score incorporating intraprostatic pattern and intensity on (68)Ga-PSMA PET/CT shows potential, with high diagnostic accuracy for csPCa. Further validation is warranted before implementation.

INTRODUCTION AND OBJECTIVE:The ability to accurately determine the location and extent of lymph node involvement has significant implications in the management of prostate cancer (PCa). Radioguided...

Our purpose was to determine and compare the interobserver variability of 3 clinically frequently used radiotracers targeting the prostate-specific membrane antigen (PSMA), namely 18F-DCFPyL, 18F-PSMA-1007, and 68Ga-PSMA-11, in primary prostate cancer (PCa) staging. Methods: Patients with newly diagnosed PCa in whom PSMA PET/CT was performed for primary staging purposes were retrospectively included. All PSMA PET/CT images were centrally overread within a high-volume PCa center, and original reports (from referring hospitals) were compared with overread reports (from the overreading hospital). To assess the interobserver variability, a Cohen κ analysis was used. To study possible differences in interobserver variability between the 3 applied PSMA radiotracers, multivariate logistic regression analyses were used. Results: In total, 584 patients with newly diagnosed PCa were included in the analysis. 18F-DCFPyL, 18F-PSMA-1007, and 68Ga-PSMA-11 were used in 205 (35.1%), 168 (28.8%), and 211 (36.1%) patients, respectively. The overall agreement (Cohen κ analysis) for locoregional lymph node metastases, distant lymph node metastases, bone metastases, and visceral metastases was 0.86, 0.86, 0.80, and 0.46, respectively. 18F-PSMA-1007 showed a significantly increased interobserver variability regarding bone metastases, compared with 18F-DCFPyL and 68Ga-PSMA-11 (P = 0.001 and 0.03, respectively). Additionally, 18F-PSMA-1007 showed a significantly increased interobserver variability regarding overall agreement and locoregional lymph node metastases, compared with 18F-DCFPyL (P < 0.001 and P = 0.01, respectively). Conclusion: Interobserver variability differs among the 3 clinically frequently used PSMA radiotracers (18F-DCFPyL, 18F-PSMA-1007, and 68Ga-PSMA-11) in patients with newly diagnosed PCa. The agreement in bone metastases is significantly worse for 18F-PSMA-1007, mainly due to nonspecific tracer uptake in osseous structures. On the basis of our findings, PSMA PET/CT scans undertaken with 18F-PSMA-1007 in primary staging should be interpreted carefully, and training on interpreting this specific PSMA radiotracer is strongly advised.

Objectives: To review the literature to determine the sensitivity and specificity of gallium-68 prostate-specific membrane antigen (68Ga-PSMA) positron-emission tomography (PET) for detecting pelvic lymph node metastases in patients with primary prostate cancer (PCa), and the positive predictive value in patients with biochemical recurrence (BCR) after initial curative treatment, and, in addition, to determine the detection rate and management impact of 68Ga-PSMA PET in patients with BCR after radical prostatectomy (RP). Materials and Methods: We performed a comprehensive literature search. Search terms used in MEDLINE, EMBASE and Science Direct were ‘(PSMA, 68Ga-PSMA, 68Gallium-PSMA, Ga-68-PSMA or prostate-specific membrane antigen)’ and ‘(histology, lymph node, staging, sensitivity, specificity, positive predictive value, recurrence, recurrent or detection)’. Relevant abstracts were reviewed and full-text articles obtained where possible. References to and from obtained articles were searched to identify further relevant articles. Results: Nine retrospective and two prospective studies described the sensitivity and specificity of 68Ga-PSMA PET for detecting pelvic lymph node metastases before initial treatment, which ranged from 33.3% to 100% and 80% to 100%, respectively. In eight retrospective studies, the positive predictive value of 68Ga-PSMA PET in patients with BCR before salvage lymph node dissection ranged from 70% to 100%. The detection rate of 68Ga-PSMA PET in patients with BCR after RP in the PSA subgroups

Objectives To examine the anatomical distribution of prostate cancer (PCa) recurrence on gallium-68 prostate-specific membrane antigen (68 Ga-PSMA) positron-emission tomography (PET)/computed tomography (CT) in patients with biochemical recurrence (BCR) after undergoing radical prostatectomy (RP) with pathological lymph node metastasis (pN1) in their extended pelvic lymph node dissection (ePLND), and to compare the location of PCa recurrence with the location of the initial lymph node metastasis at ePLND. Materials and methods We retrospectively reviewed 100 patients with BCR (PSA 0.05-5.00 ng/mL) after RP with pN1 ePLND who underwent 68 Ga-PSMA PET/CT to guide salvage therapy. Clinical and pathological features and anatomical locations of PCa recurrence on 68 Ga-PSMA PET/CT were obtained, and management impact was recorded. Results In all, 68 patients (68%) had a positive and 32 patients (32%) had a negative 68 Ga-PSMA PET/CT result. Of the 68 patients with a positive 68 Ga-PSMA PET/CT, 44 (65%) showed abnormal uptake only in the pelvic area, seven (10%) only outside the pelvic area, and 17 (25%) both within and outside the pelvic area. 68 Ga-PSMA PET/CT-positive pelvic lymph nodes were often (84%) detected on the same side as the lymph node metastasis diagnosed at ePLND. Based on the outcomes of the 68 Ga-PSMA PET/CT, change of management was noted in 68% of the patients. Conclusion Recurrence of PCa on 68 Ga-PSMA PET/CT was limited to the pelvis in the majority of patients with BCR after RP with pN1 ePLND. Moreover, recurrence was often detected on the same side as the lymph node metastasis at ePLND. The results confirm the diagnostic value of 68 Ga-PSMA PET/CT in patients with BCR after RP with pN1 ePLND. Prospective studies are needed to support the long-term benefit of 68 Ga-PSMA PET/CT-dictated management changes.

Background:68Ga PSMA PET CT (PSMA) is increasingly used in men with biochemical recurrence (BCR) post radical prostatectomy (RP), but its longer term prognostic / predictive potential in these men is unknown. The aim of this study was to evaluate the predictive value of PSMA PET for 3 year freedom from progression (FFP) in men with BCR post RP undergoing salvage radiotherapy (sRT). Methods: This prospective multi-center study enrolled 260 men between 2015 and 2017. Eligible patients were referred for PSMA with rising PSA following RP. Management following PSMA was recorded but not mandated. PSMA protocols were standardised across sites and reported prospectively. Clinical, pathological and surgical information, sRT, timing and duration of androgen deprivation (ADT), 3 year PSA results and clinical events were documented. FFP was defined as a PSA rise ≤ 0.2ng/mL above nadir post sRT, with no additional treatment. Results: The median PSA was 0.26ng/mL (IQR 0.15 - 0.59) and follow-up 38 months (IQR 31-43). PSMA was negative in 34.6% (90/260), confined to prostate fossa 21.5% (56/260), pelvic nodes 26.2% (68/260), and distant disease 17.7% (46/260). 71.5% (186/260) received sRT, 38.2% (71/186) to the fossa only, 49.4% (92/186) fossa + pelvic nodes and 12.4% (23/186) nodes alone/SBRT. PSMA was highly predictive of FFP at 3 years following sRT. Overall, FFP was achieved in 64.5% (120/186) of those who received sRT, 81% (81/100) with negative/fossa confined vs. 45% (39/86) for extra fossa disease (p

Objective To assess the activity and safety of cabazitaxel chemotherapy vs that of treatment with 177 Lu-PSMA-617, a novel radiolabelled small molecule that binds with high affinity to prostate-specific membrane antigen (PSMA), in men with metastatic castration-resistant prostate cancer (mCRPC) who have received prior docetaxel treatment. Patients and methods The TheraP trial (ANZUP 1603) is an open-label, randomized, stratified, two-arm multicentre phase 2 trial comparing the activity and safety of cabazitaxel chemotherapy vs 177 Lu-PSMA-617 therapy in the treatment of men with mCRPC. Key eligibility criteria include prior docetaxel chemotherapy, rising prostate-specific antigen (PSA) level, sufficient PSMA avidity, as defined by centrally reviewed 68 Ga-PSMA-11 and fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) with no discordant FDG-avid PSMA-negative sites of disease. Patients in the control group receive standard treatment with cabazitaxel (20 mg/m2 ) i.v. every 3 weeks with prednisolone 10 mg daily orally, for a maximum of 10 cycles. Patients in the experimental group receive 177 Lu-PSMA-617 (8.5 GBq decreasing by 0.5 GBq per cycle) i.v. every 6 weeks, for up to a maximum of six cycles. In the event of an exceptional response as defined on centrally reviewed post-therapy single-photon emission CT imaging, treatment will be suspended but can recommence on progression. The trial aims to include 200 patients who will be centrally randomized to one of the two treatment groups, in a 1:1 ratio. The primary endpoint is PSA response. Secondary endpoints are overall survival, progression-free survival (PFS), radiographic PFS, PSA PFS, objective tumour response, pain response, pain PFS, health-related quality of life, and frequency and severity of adverse events. The treatment and outcomes of patients excluded on the basis of low PSMA avidity or discordant FDG-avid disease on screening 68 Ga-PSMA-11 and Fluorine-18 (18 F)-FDG-PET/CT scan will also be assessed. Enrolment in the study commenced on 29 January 2018. Results and conclusions 177 Lu-PSMA-617 offers a potential additional life-prolonging treatment option for men with mCRPC. The results of this trial will determine, for the first time in a randomized design, the activity and safety of 177 Lu-PSMA-617, as compared with cabazitaxel chemotherapy in men with progressive mCRPC.

Summary Background Adjuvant dabrafenib plus trametinib therapy improves relapse-free survival in patients with resected stage III melanoma. We aimed to ascertain the proportion of patients who would have a pathological response and a response according to Response Evaluation Criteria in Solid Tumors (RECIST) after neoadjuvant dabrafenib plus trametinib therapy for resectable clinical stage III melanoma. Methods NeoCombi was a single-arm, open-label, single-centre, phase 2 study done at Melanoma Institute Australia (Sydney, NSW, Australia). Eligible patients were adults (aged ≥18 years) with histologically confirmed, resectable, RECIST-measurable, clinical stage IIIB–C (American Joint Committee on Cancer [AJCC] 7th edition), BRAFV600-mutant melanoma, and had an Eastern Cooperative Oncology Group performance status of 1 or lower. Patients received 150 mg dabrafenib orally, twice daily, plus 2 mg trametinib orally, once daily, for 52 weeks (12 weeks of neoadjuvant therapy before complete resection of the pre-therapy tumour bed, and 40 weeks of adjuvant therapy thereafter). CT and PET scans were done at baseline and before resection. The primary outcomes were the proportion of patients achieving a complete pathological response and the proportion of patients achieving a response according to RECIST at week 12, analysed as per protocol. This trial is registered with ClinicalTrials.gov , NCT01972347 , and follow-up of patients is ongoing. Findings Between Aug 20, 2014, and April 19, 2017, 40 patients were screened, of whom 35 eligible patients were enrolled, received neoadjuvant dabrafenib plus trametinib, and underwent resection. At the data cutoff (Sept 24, 2018), median follow-up was 27 months (IQR 21–36). At resection, 30 (86%) patients achieved a RECIST response; 16 (46%; 95% CI 29–63) had a complete response and 14 (40%; 24–58) had a partial response. Five patients (14%; 95% CI 5–30) had stable disease, and no patients progressed. After resection and pathological evaluation, all 35 patients achieved a pathological response, of whom 17 (49%; 95% CI 31–66) patients had a complete pathological response and 18 (51%; 95% CI 34–69) had a non-complete pathological response. Treatment-related serious adverse events occurred in six (17%) of 35 patients and grade 3–4 adverse events occurred in ten (29%) patients. No treatment-related deaths were reported. Interpretation Neoadjuvant dabrafenib plus trametinib therapy could be considered in the management of RECIST-measurable resectable stage III melanoma as it led to a high proportion of patients achieving a complete response according to RECIST and a high proportion of patients achieving a complete pathological response, with no progression during neoadjuvant therapy. Funding GlaxoSmithKline; Novartis; National Health and Medical Research Council, Australia; and Melanoma Institute Australia.

OBJECTIVE To determine the value of gallium-68-prostate-specific membrane antigen (68 Ga-PSMA)-11 positron emission tomography (PET) /computed tomography (CT) in men with newly diagnosed prostate cancer. PATIENTS AND METHODS We analysed results of 140 men with intermediate- and high-risk prostate cancer. All men underwent 68 Ga-PSMA-11 PET/CT and multiparametric magnetic resonance imaging (mpMRI) before radical prostatectomy (RP) with extended pelvic lymph node (LN) dissection. For each patient, the clinical and pathological features were recorded. Prostate-specific antigen (PSA) was documented at staging scan, and after RP, at a median (interquartile range) of 110 (49-132) days. A PSA level of ≥0.03 ng/mL was classified as biochemical persistence (BCP). Logistic regression was performed for association of clinical variables and BCP. RESULTS In these 140 patients with intermediate- and high-risk prostate cancer, 27.1% had PSMA PET/CT-positive findings in the pelvic LNs. Sensitivity and specificity for detection of LN metastases were 53% and 88% (PSMA PET/CT) and 14% and 99% (mpMRI), respectively. The overall BCP rate was 25.7%. The BCP rate was 16.7% in men who were PSMA PET/CT LN-negative compared to 50% in men who were PSMA PET/CT LN-positive (P

Background 177Lu–PSMA-617 (Lu-PSMA) is an emerging therapy in men with metastatic castration-resistant prostate cancer. Paired theranostic agents have the potential to visually identify phenotypes that will respond to targeted therapy. This study examined the value of 68Ga-HBEDD PSMA-11; prostate-specific membrane antigen (PSMA) positron emission tomography (PET) in predicting treatment response and disease progression in Lu-PSMA therapy within the context of a phase 2 prospective pilot trial. Patients and Methods Men with progressive, symptomatic metastatic castration-resistant prostate cancer previously treated with antiandrogens (abiraterone and/or enzalutamide) and taxane-based chemotherapy were prospectively enrolled. Eligibility criteria included uptake on PSMA PET above or equal to liver activity, with no 18F-Fluoro–deoxyglucose (FDG) PET-discordant disease. Men received up to 4 cycles of Lu-PSMA at 6 weekly intervals. Repeat FDG/PSMA PET imaging was performed after completion of therapy or at prostate-specific antigen (PSA) progression. The study assessed treatment response to Lu-PSMA using PSA response and correlated treatment response (PSA) to molecular imaging parameters at enrollment. Results Fourteen of 18 men screened underwent Lu-PSMA therapy. Ten (71%) of 14 had a PSA response (mean reduction, 59%). A ≥ 50% reduction in PSA occurred in 5 (36%), and ≥ 30% in 9 (64%). PSMA PET standardized uptake value (SUV) at screening was predictive of ≥ 30% PSA reduction: SUV max value 17 ± 9 versus 44 ± 15 (P Conclusion PSMA PET plays an important role in predicting treatment response to Lu-PSMA and in identifying subsequent patterns of failure, which may aid in determining the next best treatment options.

Background We have previously shown that 75% of patients treated with programmed cell death protein 1 (PD-1) with or without CTLA4 who have not progressed by 1 year have complete metabolic response (CMR), including two-thirds of patients with partial response (PR). We now report 5-year outcomes. Patients and methods Retrospective analysis of 104 patients with baseline and 1-year positron emission tomography (PET) and computed tomography (CT). The 1-year response was determined using RECIST for CT and European Organisation for Research and Treatment of Cancer (EORTC) criteria for PET. Progression-free survival (PFS) and overall survival (OS) were determined from the 1-year landmark. Results At the median follow-up of 61 months (range 58-64 months) from 1-year PET, 94% remained alive and all but one had discontinued treatment after a median treatment duration of 23 months (range 1-59 months). Disease progression occurred in 19 patients (18%): 10 (53%) while on treatment and 12 (63%) in solitary sites for which 8 (67%) received local treatment. RECIST PFS rate at 5 years after PET was higher in complete response (CR) compared with PR/stable disease (SD) (93% versus 76%, respectively) and CMR compared with non-CMR (90% versus 54%, respectively). In patients with PR, 5-year PFS rate was superior in CMR (88% and 59%). A total of 35 (34%) patients (14/29 in CR, 31/78 in CMR) discontinued treatment within 12 months, largely due to toxicity, with no impact on PFS rate compared with those that continued (84% versus 78%). Despite progression events, OS rate at 5 years was excellent and similar in patients with CR and PR/SD (100% versus 91%, respectively) as well as in those with CMR and non-CMR (96% versus 87%, respectively). Conclusions Five years after the 1-year PET, sustained responses are observed in the majority of patients, particularly in those with CMR. PET continues to predict progression better than CT, particularly in those with residual disease on CT. In the minority that progress, often in solitary sites and managed locally, OS rate remains excellent. PET is effective in evaluating residual lesions on CT and can predict long-term benefit.

Objectives To determine the activity and safety of lutetium-177 (177 Lu)-prostate-specific membrane antigen (PSMA)-617 in men with metastatic castration-resistant prostate cancer (mCRPC) commencing enzalutamide, who are at high risk of early progression, and to identify potential prognostic and predictive biomarkers from imaging, blood and tissue. Participants and methods ENZA-p (ANZUP 1901) is an open-label, randomized, two-arm, multicentre, phase 2 trial. Participants are randomly assigned (1:1) to treatment with enzalutamide 160 mg daily alone or enzalutamide plus 177 Lu-PSMA-617 7.5 GBq on Days 15 and 57. Two additional 177 Lu-PSMA-617 doses are allowed, informed by Day-92 Gallium-68 (68 Ga)-PSMA positron emission tomography (PET; up to four doses in total). The primary endpoint is prostate-specific antigen (PSA) progression-free survival (PFS). Other major endpoints include radiological PFS, PSA response rate, overall survival, health-related quality of life, adverse events and cost-effectiveness. Key eligibility criteria include: biochemical and/or clinical progression; 68 Ga-PSMA PET-avid disease; no prior androgen signalling inhibitor, excepting abiraterone; no prior chemotherapy for mCRPC; and ≥2 high-risk features for early enzalutamide failure. Assessments are 4 weekly during study treatment, then 6 weekly until radiographic progression. Response Evaluation Criteria in Solid Tumours (RECIST) are used to assess imaging conducted every 12 weeks, 68 Ga-PSMA PET at baseline, Days 15 and 92, and at progression, and 18 F-fluorine deoxyglucose (18 F-FDG) PET at baseline and progression. Translational samples include blood (and optional biopsies) at baseline, Day 92, and first progression. Correlative studies include identification of prognostic and predictive biomarkers from 68 Ga-PSMA and 18 F-FDG PET/CT, circulating tumour cells and circulating tumour DNA. The trial will enrol 160 participants, providing 80% power with a two-sided type-1 error rate of 5% to detect a hazard ratio of 0.625 assuming a median PSA-PFS of 5 months with enzalutamide alone. Results and conclusion The combination of 177 Lu-PSMA-617 and enzalutamide may be synergistic. ENZA-p will determine the safety and efficacy of the combination in addition to developing predictive and prognostic biomarkers to better guide treatment decisions.

Staging using positron emission tomography/computed tomography (PET/CT) is standard of care in many cancers that occur most frequently in pregnancy, particularly lymphoma. While expert guidelines generally recommend against PET/CT in pregnant women, there is emerging evidence that likely absorbed foetal doses in pregnancy are relatively low, and as such in certain circumstances PET/CT may be acceptable when balancing benefit and risk. We conducted a qualitative survey of nuclear medicine physicians in Australia and New Zealand to assess practice and attitudes with respect to PET/CT in pregnancy women, finding that most respondents considered PET/CT in pregnancy may be an appropriate modality in carefully selected clinical contexts with appropriate modifications. It is important to continue to define the role of PET/CT in pregnancy into the future, particularly as this imaging modality has emerged as the standard of care in staging and response assessment for many cancers.

Rationale The development of consensus guidelines for interpretation of Prostate-Specific Membrane Antigen (PSMA)-Positron Emission Tomography (PET) is needed to provide more consistent reports in clinical practice. The standardization of PSMA-PET interpretation may also contribute to increasing the data reproducibility within clinical trials. Finally, guidelines in PSMA-PET interpretation are needed to communicate the exact location of findings to referring physicians, to support clinician therapeutic management decisions. Methods A panel of worldwide experts in PSMA-PET was established. Panelists were selected based on their expertise and publication record in the diagnosis or treatment of PCa, in their involvement in clinical guidelines and according to their expertise in the clinical application of radiolabeled PSMA inhibitors. Panelists were actively involved in all stages of a modified, nonanonymous, Delphi consensus process. Results According to the findings obtained by modified Delphi consensus process, panelist recommendations were implemented in a structured report for PSMA-PET. Conclusions The E-PSMA standardized reporting guidelines, a document supported by the European Association of Nuclear Medicine (EANM), provide consensus statements among a panel of experts in PSMA-PET imaging, to develop a structured report for PSMA-PET in prostate cancer and to harmonize diagnostic interpretation criteria.

Prostate-specific membrane antigen (PSMA)-targeted radiopharmaceuticals are playing a large role at the time of initial staging and biochemical recurrence for localizing prostate cancer, as well as in other emerging clinical settings. PSMA PET has demonstrated increased detection rate compared with conventional imaging and has been shown to change management plans in a substantial percentage of cases. The aims of this narrative review are to highlight the development and clinical impact of PSMA PET radiopharmaceuticals, to compare PSMA to other agents such as fluorine 18 fluciclovine and carbon 11 choline, and to highlight some of the individual PSMA PET agents that have contributed to the advancement of prostate cancer imaging.

Prostate-specific membrane antigen (PSMA) PET/CT is a novel imaging technique for the detection and staging of either primary or recurrent prostate cancer. Early studies demonstrated its improved sensitivity and specificity over and in combination with other currently employed imaging techniques, such as multiparametric MRI, bone scan, PET and CT. However, the lack of strength and confidence in these studies has meant incorporation of PSMA PET/CT into clinical guidelines and practice has been limited to date. In response, a number of high-quality prospective studies have recently emerged and reflect exciting results seen in preceding publications. Here we recount some of the key earlier publications, report results from the latest studies and look to the future discussing some of the eagerly awaited ongoing clinical trials.

To assess the activity and safety of sequential lutetium-177 (UpFrontPSMA (NCT04343885) is an open-label, randomized, multicentre, phase 2 trial, recruiting 140 patients at 12 Australian centres. Key eligibility criteria include: prostate cancer with a histological diagnosis within 12 weeks of screening commencement; prostate-specific antigen (PSA)10 ng/mL at diagnosis; ≤4 weeks on ADT; evidence of metastatic disease on computed tomography (CT) and/or bone scan; high-volume prostate-specific membrane antigen (PSMA)-avid disease with a maximum standardized uptake value15; and absence of extensive discordant fluorodeoxyglcuose (FDG)-positive, PSMA-negative disease.The results of this trial will generate data on the activity and safety of

Background: Different nomograms exist for the preoperative prediction of pelvic lymph-node metastatic disease in individual patients with prostate cancer (PCa). These nomograms do not incorporate modern imaging techniques such as prostate-specific membrane antigen (PSMA) positron emission tomography (PET). Objective: To determine the predictive performance of the Briganti 2017, Memorial Sloan Kettering Cancer Center (MSKCC), and Briganti 2019 nomograms with the addition of PSMA-PET in an international, multicenter, present-day cohort of patients undergoing robot-assisted radical prostatectomy (RARP) and extended pelvic lymph-node dissection (ePLND) for localized PCa. Design, setting, and participants: All 757 eligible patients who underwent a PSMA-PET prior to RARP and ePLND in three reference centers for PCa surgery between January 2016 and November 2020 were included. Outcome measurements and statistical analysis: Performance of the three nomograms was assessed using the receiver operating characteristic curve–derived area under the curve (AUC), calibration plots, and decision curve analyses. Subsequently, recalibration and addition of PSMA-PET to the nomograms were performed. Results and limitations: Overall, 186/757 patients (25%) had pelvic lymph-node metastatic (pN1) disease on histopathological examination. AUCs of the Briganti 2017, MSKCC, and Briganti 2019 nomograms were 0.70 (95% confidence interval [95% CI]: 0.64–0.77), 0.71 (95% CI: 0.65–0.77), and 0.76 (95% CI: 0.71–0.82), respectively. PSMA-PET findings showed a significant association with pN1 disease when added to the nomograms (p < 0.001). Addition of PSMA-PET substantially improved the discriminative ability of the models yielding cross-validated AUCs of 0.76 (95% CI: 0.70–0.82), 0.77 (95% CI: 0.72–0.83), and 0.82 (95% CI: 0.76–0.87), respectively. In decision curve analyses, the addition of PSMA-PET to the three nomograms resulted in increased net benefits. Conclusions: The addition of PSMA-PET to the previously developed nomograms showed substantially improved predictive performance, which suggests that PSMA-PET is a likely future candidate for a modern predictive nomogram. Patient summary: Different tools have been developed to individualize the prediction of prostate cancer spread to lymph nodes before surgery. We found that the inclusion of modern imaging (prostate-specific membrane antigen positron emission tomography) improved substantially the overall performance of these prediction tools.

Background It is not known whether there is a survival benefit associated with more frequent surveillance imaging in patients with resected American Joint Committee on Cancer stage III melanoma. Objective The aim of this study was to investigate distant disease-free survival (DDFS), melanoma-specific survival (MSS), post distant recurrence MSS (dMSS), and overall survival for patients with resected stage III melanoma undergoing regular computed tomography (CT) or positron emission tomography (PET)/CT surveillance imaging at different intervals. Patients and Methods A closely followed longitudinal cohort of patients with resected stage IIIA–D disease treated at a tertiary referral center underwent 3- to 4-monthly, 6-monthly, or 12-monthly surveillance imaging between 2000 and 2017. Survival outcomes were estimated using the Kaplan–Meier method, and log-rank tests assessed the significance of survival differences between imaging frequency groups. Results Of 473 patients (IIIA, 19%; IIIB, 31%; IIIC, 49%; IIID, 1%) 30% underwent 3- to 4-monthly imaging, 10% underwent 6-monthly imaging, and 60% underwent 12-monthly imaging. After a median follow-up of 6.2 years, distant recurrence was recorded in 252 patients (53%), with 40% detected by surveillance CT or PET/CT, 43% detected clinically, and 17% with another imaging modality. Median DDFS was 5.1 years (95% confidence interval 3.9–6.6). Among 139 IIIC patients who developed distant disease, the median dMSS was 4.4 months shorter in those who underwent 3- to 4-monthly imaging than those who underwent 12-monthly imaging. Conclusion Selecting patients at higher risk of distant recurrence for more frequent surveillance imaging yields a higher proportion of imaging-detected distant recurrences but is not associated with improved survival. A randomized comparison of low versus high frequency imaging is needed.

5017 Background: The VISION and TheraP trials have established the safety and efficacy of 177Lu-PSMA-617 in mCRPC with a 50% PSA response rate (PSA50-RR) of 46% and 66% and median progression free survival (PFS) of 8.7 and 5.1 months, respectively. More effective treatments are required as disease progression remains universal. Immunotherapy has limited single-agent efficacy in mCRPC. We hypothesise that by potentially inducing immunogenic cell death, 177Lu-PSMA-617 may act synergistically with pembrolizumab, an anti-programmed death 1 inhibitor, to enhance the depth and durability of response. PRINCE is a Phase I trial evaluating the safety and efficacy of this combination. Methods: mCRPC patients with high PSMA expression (SUVmax ≥ 20 in an index lesion, SUVmax > 10 for all lesions ≥ 10mm), and no FDG+ve/PSMA-ve lesions on paired baseline PET/CT screening, received up to 6 cycles of 177Lu-PSMA-617 (starting at 8.5 GBq, reducing by 0.5 GBq with each cycle) every 6 weeks in conjunction with 200mg of pembrolizumab every 3 weeks for up to 2 years. Response evaluation was undertaken as per PCWG3 and RECIST criteria. Co-primary endpoints were safety and PSA50-RR. Secondary endpoints included PSA-PFS, radiographic PFS (rPFS), overall survival (OS), and patient reported outcomes (PROs). This analysis was undertaken after the last patient had 12 months follow-up. Results: 37 patients (median age 72 years; prior docetaxel 73%; prior androgen receptor targeted agent 100%) received a median of 5 cycles (range: 2 to 6) of 177Lu-PSMA-617 and 12 doses (range: 6 to 19) of pembrolizumab. The median follow up was 16 months. PSA50-RR was 76% (28/37 [95% CI 59-88]) and 7/10 (70%) patients with RECIST-measurable disease had a partial response. Median rPFS, PSA-PFS and OS was 11.2 months (95% CI: 5.1-14.1), 8.2 months (95% CI: 5.1-11.2) and 17.8 months (95% CI:13.4-not estimable). 12-month rPFS and OS was 38% (95% CI: 22-54) and 83% (95% CI: 67-92), respectively. Common (≥10%) treatment-related adverse events (TRAE) were mainly Grade (G) 1-2, including xerostomia (78%), fatigue (43%), pruritus (27%), nausea (27%), rash (24%), diarrhoea (14%), anorexia (16%), thrombocytopenia (16%), elevated ALT (11%), arthralgia (11%) and a flare in bone pain (11%). Haematologic TRAEs included G2-3 anaemia (8%), G1-2 thrombocytopenia (16%), and G1 neutropenia (3%). G3 immune-related AEs occurred in 10 (27%) patients with no dominant manifestation. 5 (14%) patients discontinued pembrolizumab due to toxicity. PROs including BPI-SF and FACT-P were stable throughout the study. Conclusions: The combination of 177Lu-PSMA-617 and pembrolizumab had promising activity. Toxicities were generally consistent with those of single-agent 177Lu-PSMA-617 and pembrolizumab and were not clearly augmented by combination use. No new safety concerns were observed. Clinical trial information: NCT03658447.

3092 Background: Breast cancers are most frequently oestrogen receptor (ER) and progesterone receptor (PR) positive and 18F-Fluorodeoxyglucose PET-CT (FDG) used in conventional staging of breast cancer has lower sensitivity for these subtypes. Gastrin releasing peptide receptors (GRPR) are a potential alternative diagnostic and theranostic target for ER+/PR+ breast cancers due to their overexpression of GRPR. This phase 1 study aims to assess the safety and potential of the novel radiotracer 64Cu-Sarcophagine(SAR)-Bombesin (BBN) in the re-staging of recurrent metastatic ER+/PR+/human epidermal growth factor 2 negative (HER2-) breast cancer. Methods: Patients with confirmed recurrent or primary metastatic ER+/PR+/HER2- breast cancer undergoing staging prior to a new treatment underwent 64Cu-SAR-BBN PET-CT with imaging at 1, 3 and 24 hours post-injection. Bloods and vital signs were acquired for patients at baseline, 1, 3 and 24 hours post-injection timepoints, and electrocardiogram (ECG) performed 1 hour pre and 1 hour post injection. Blood tracer-clearance and dosimetry was performed. GRPR receptor status was assessed in 4/7 patients from metastatic-site biopsy samples. Staging of the patients was assessed by conventional imaging (FDG, bone scan and diagnostic CT) within 3 weeks of 64Cu-SAR-BBN imaging. All PET scans were assessed visually, and quantitatively using MIM Software. Results: 9 patients were enrolled. 7/9 patients underwent all imaging modalities, while 2/9 did not undergo BBN imaging. 1/7 patient who underwent all imaging had de- novo metastatic ER+/PR+/Her 2- breast cancer and 6/7 recurrent metastatic disease. 2/7 had lobular subtype. There were no adverse events reported, and ECG, vitals and haematological, biochemical and coagulation markers remained unchanged. All 7 patients were positive on conventional imaging, while 6/7 were positive on FDG. BBN was positive in 5/7 patients. Both BBN negative patients had disease identified on FDG. Conversely, 1 patient was BBN positive but FDG negative. 4/7 patients were BBN positive and FDG positive. In these 4 patients, mean SUVmax was higher for BBN than FDG (15 vs. 12). In classical lobular subtype (2/7), BBN was highly avid compared to FDG (SUV max 20 vs 11, and 20 vs 64Cu-SAR-Bombesin is a novel tracer which appears safe and may have a diagnostic and theranostic role in patients with metastatic ER+/PR+/HER2- breast cancer, particularly lobular subtype. Further evaluation appears warranted.

9580 Background: Neoadjuvant D+T has a high pathologic response rate and impressive short-term survival. The NeoCombi trial (NCT01972347) enrolled 35 patients with resectable stage III melanoma, with last patient commencing treatment April 19th 2017. We report 5-year outcomes from this trial. Methods: Pts received 12 wks neoadjuvant standard dose D+T, then 40 wks adjuvant D+T. Eligible pts were ≥ 18 yrs, ECOG PS ≤ 1 with clinical stage III BRAF V600E/K melanoma. CT and PET scans were performed at baseline and prior to surgery. Pathologic response was determined as per International Neoadjuvant Melanoma Consortium (INMC) criteria and defined as complete (pCR), near complete, partial (pPR) or no response (pNR). CT monitoring was continued 12 wkly thereafter to 2 yrs, then 6 monthly to 3 yrs, then as standard care. The primary endpoints were the complete pathological response (pCR) and RECIST response rate (rRR) at wk 12. Secondary endpoints included relapse free survival (RFS), OS, and toxicity. Results: 35 pts were enrolled, 6 with IIIB, 29 IIIC (7 ITM only) disease (clinical AJCCv7). At data cut August 17th 2021, median F/U was 60 mo (95% CI 56-72). No patients progressed in the neoadjuvant phase, and (49%) had a pCR, 1 near pCR, 6 pPR, 11 pNR. 5-year RFS, DMFS and OS data are shown in the Table. The majority of recurrences occurred within the first 2 years, with no recurrences beyond 3y. 21 patients recurred; 12 (57%) had first recurrence locoregional (6/12 subsequent distant recurrence) and 9 (43%) had first recurrence in distant sites (3/9 in brain). Locoregional recurrence was managed with surgery alone in 4/12, systemic therapy alone in 2/12, or both surgery and systemic therapy in 5/12 (4/5 had adjuvant systemic therapy), 1 pt was observed until distant recurrence. Subsequent systemic therapy in the 15 patients with a distant recurrence included PD-1 based immunotherapy (N=14) and BRAF targeted therapy (N=10). Conclusions: Neoadjuvant D+T in clinical stage III melanoma has impressive early activity, however patients remain at high risk of recurrence. Pathologic response can identify patients at the highest risk of recurrence, offering a chance of alternative adjuvant therapy in non-responders. Clinical trial information: NCT01972347. [Table: see text]

5027 Background: The Phase I PRINCE trial (NCT03658447) is evaluating the efficacy of 177Lu-PSMA-617 plus pembrolizumab for mCRPC. The utility of serial monitoring of CTCs and PET as biomarkers of prognosis and clinical benefit of 177Lu-PSMA-617-based therapy remains unknown. Methods: 36 of 37 pts with high PSMA expression on PSMA PET underwent serial CTC collections in conjunction with PSMA PET at baseline, every 12 weeks for 48 weeks and every 24 weeks thereafter. CK+, CD45- CTCs were enumerated from 3ml of blood and stained for PSMA (Epic Sciences platform). Associations between PSMA+ CTC counts, PET molecular tumor volume (MTV), total lesional activity (TLA; MTVxSUVmean) were assessed by Spearman correlation. Cox models assessed the association of CTC and PSMA PET parameters with radiographic progression-free survival (rPFS) and PSA PFS. A subset of pre-treatment CTCs underwent single cell low-pass whole genome sequencing to characterize copy number aberrations. Results: 32/36 pt (89%) had detectable CTCs (median 7, range 0-514) with 23 (64%) being PSMA+ (median 1, range 0-224) at baseline. At w12, 23/33 (70%) had CTCs detected with 10 (30%) being PSMA+. Baseline PSMA+ CTC count and MTV were moderately correlated (rs= 0.57, p < 0.001). Of 22 evaluable pts with baseline PSMA+ CTC, 18 (82%) showed decrease by w12 with clearance in 13. This paralleled reductions in MTV (-18% med relative change, IQR: -57 to -1) and TLA (-48% med relative change, IQR: -77 to -28). Total CTC and PSMA+ CTC counts at baseline, and PET parameters were not associated with PSA PFS or rPFS. Clearance of PSMA+ CTC by w12 (13/22 pts) was associated with improved rPFS (med NR vs 3.0 mos, HR 0.23, 95%CI 0.07-0.74, p = 0.007) and PSA PFS (med 11.2 vs 3.5 mos, HR 0.28, 95%CI 0.11-0.73, p = 0.006). Persisting PSMA-neg CTCs at w12 trended to worse rPFS (med 4.1 vs 12.3 mos, p = 0.11) and PSA PFS (med 5.1 vs 12.3 mos, p = 0.07). Of pts not progressing by w12, decrease in PSA (HR 0.83 per 10% decrease, 95%CI 0.74-0.93, p < 0.001), MTV (HR 0.85 per 10% decrease, 95%CI 0.75-0.96, p = 0.008), MTV > 30% decrease (HR 0.30, 95% CI 0.08-1.08, p = 0.05) and TLA (HR 0.88 per 10% decrease, 95%CI 0.78-1.00, p = 0.04) associated with improved rPFS beyond w12. Pre-treatment CTCs (18 pts) exhibited genomic heterogeneity and frequent loss of PTEN, TP53 and RB1. Pts with compound TP53 and RB1 loss at baseline nonetheless had PSMA+ CTCs in high proportion (med 91.3% of total CTCs). Conclusions: PSMA PET-positive mCRPC is associated with high rates of PSMA+ CTCs which decline with 177Lu-PSMA-617 plus pembrolizumab in parallel with PSMA MTV/TLA. Despite imaging suitability for therapy, CTCs had heterogenous PSMA expression and genomic alterations associated with aggressive disease. Early changes in PSMA+ CTCs and MTV/TLA were associated with outcomes and may aid in determining clinical activity of LuPSMA-based therapy.

PSMA PET is more accurate than conventional imaging (CT/bone scan) for staging of intermediate- or high-risk prostate cancer (PCa), but 5–10% of primary tumours have low PSMA ligand uptake. FDG PET has been used to further define disease extent in end-stage castrate-resistant PCa and may be beneficial earlier in the disease course for more accurate staging. The objective of this study was to review the available evidence for patients undergoing both FDG and PSMA PET for PCa staging at initial diagnosis and in recurrent disease. A systematic literature review was performed for studies with direct, intraindividual comparison of PSMA and FDG PET for staging of PCa. Assessment for radioligand therapy eligibility was not considered. Risk of bias was assessed. 543 citations were screened and assessed. 13 case reports, three retrospective studies, and one prospective study were included. FDG after PSMA PET improved the detection of metastases from 65% to 73% in high-risk early castration-resistant PCa with negative conventional imaging (M0). Positive FDG PET was found in 17% of men with negative PSMA PET for postprostatectomy biochemical recurrence. Gleason score ≥8 and higher PSA levels predicted FDG-avid metastases in BCR and primary staging. Variant histology (ductal and neuroendocrine) was common in case reports, resulting in PSMA-negative FDG-positive imaging for 3 patients. Dual-tracer PET for PCa may assist in characterising high-risk disease during primary staging and restaging. Further studies are required to determine the additive benefit of FDG PET and if the FDG-positive phenotype may indicate a poorer prognosis.

Patients with clinically progressive metastatic ERTen women (mean age 57 years) underwent imaging. 8/10 demonstrated disease on both DOTA and FDG. 2/10 positive on conventional imaging, but DOTAWhilst we have not demonstrated DOTA to be superior to FDG in staging of ER

PURPOSE OF REVIEW Imaging of prostate cancer has been a rapidly evolving field in recent years with the introduction of multiple new PET tracer agents. Introduction of novel imaging techniques into clinical practice requires careful evaluation, with the ultimate aims of improved patient outcomes, better sequencing of treatments, and cost effectiveness. The increased sensitivity and specificity of these new PET agents present both challenges and opportunities. We know they frequently change management, but are these effective management changes, and is it always in the best interests of the patients? RECENT FINDINGS This review will focus on recent publications that provide high-level evidence for the use of PET in prostate cancer. It will discuss studies that have evaluated the clinical impact of PET imaging in prostate cancer and will review a number of trials that demonstrate the potential of PET to change current standard of care, from diagnosis, to prognostic capabilities in men with metastatic prostate cancer. SUMMARY Evidence for the use of PET in prostate cancer is building with studies evaluating diagnostic accuracy of PET at all stages of prostate cancer. We review the evidence available, focusing on prospective trials that are measuring the impact of new technology on patient outcomes.

Purpose Our purpose was to investigate the effect of the addition of prostate-specific membrane antigen (PSMA)-targeted positron emission tomography/computed tomography (PET/CT) in patients with recurrent prostate cancer post-primary radiation therapy. Methods and Materials A prospective, multi-institutional clinical trial evaluated 2-(3-{1-carboxy-5-[(6-[18F]fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid (18F-DCFPyL) PET/CT restaging in 79 men with recurrent prostate cancer post-primary radiation therapy. We report actual patient management and compare this with proposed management both before and after PSMA-targeted PET/CT. Results Most patients (59%) had a major change in actual management compared with pre-PET/CT proposed management. The rate of major change was underestimated by immediately post-PET/CT surveys (32%). Eighteen patients with PSMA avidity in the prostate gland suspicious for malignancy had a prostate biopsy. Sensitivity, specificity, and positive predictive values of PSMA uptake in the prostate were 86%, 67%, and 92%, respectively. Thirty percent of patients had directed salvage therapy and 41% underwent systemic therapy. Eleven out of 79 patients (14%) had high-dose-rate brachytherapy alone for local recurrence, and 91% were free of recurrence at a median follow-up of 20 months. Conclusions Most patients had a major change in actual management compared with pre–PSMA-targeted PET/CT planned management, and this was underestimated by post-PET/CT questionnaires.

Trials of lutetium prostate specific membrane antigen (PSMA) in men with metastatic castration-resistant prostate cancer (mCRPC) have demonstrated good safety and efficacy, but combination strategies may improve outcomes. Idronoxil is a synthetic flavonoid derivative with radiosensitising properties.To evaluate the safety and activity ofThirty-two men with progressive mCRPC previously treated with taxane-based chemotherapy (91% treated with both docetaxel and cabazitaxel) and abiraterone and/or enzalutamide were enrolled in this phase I dose escalation study with phase II dose expansion.Screening withAdverse events (AEs), pain inventory scores, prostate-specific antigen (PSA) response, progression-free survival, and overall survival were evaluated.Fifty-six men were screened and 32 (57%) were enrolled with a screen failure rate of 21% for PET imaging criteria. Dosing was as follows: 97% (31/32) received two or more doses and 47% (15/32) completed six doses. Common AEs included xerostomia, fatigue, and anaemia. Anal irritation attributable to NOX66 occurred in 28%. PSA responses were as follows: 91% (29/32) had any PSA response (median -74%; 95% confidence interval [CI] 76-97) and 62.5% (20/32) had a PSA fall of50% (95% CI 45-77). The median PSA progression-free survival was 6.1 mo (95% CI 2.8-9.2) and median overall survival was 17.1 mo (95% CI 6.5-27.1).NOX66 with LuPSMA-617 is a safe and feasible therapeutic strategy in men treated with third-line therapy and beyond for mCRPC.Addition of NOX66 to

Objective: To evaluate the ability of prostate-specific membrane antigen (PSMA)-positron-emission tomography (PET)/computed tomography (CT) to detect intermediate-grade intra-prostatic prostate cancer (PCa), and to determine if PSMA-PET improves the diagnostic accuracy of multiparametric magnetic resonance imaging (mpMRI). Patients and Methods: A total of 56 consecutive patients with International Society of Urological Pathology (ISUP) grade 2–3 PCa after radical prostatectomy, who underwent both mpMRI and PSMA-PET CT (hereafter PSMA-PET) preoperatively, were enrolled in this study. The accuracy of PSMA-PET, mpMRI alone, and the two procedures in combination was analysed for identifying ISUP grades 1–3 within a 12-segment model. The accuracy of a combined predictive model (PSMA-PET and mpMRI) was determined. Receiver-operating characteristic curve analysis to determine the optimal standardized uptake value (SUVmax) for PSMA-PET in discriminating between ISUP grades 1 and ≥2 was performed. Results: On a per-patient basis, the sensitivities for PSMA-PET and mpMRI in identifying ISUP grades 2–3 PCa were 100% and 97%, respectively. Assessing ISUP grade ≥2 PCa using a 12-segment analysis, PSMA-PET demonstrated greater diagnostic accuracy (area under the curve), sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV), with values of 0.91, 88%, 93%, 95% and 85%, respectively, than did mpMRI (Prostate Imaging Reporting and Data System [PI-RADS] 3–5), at 0.79, 68%, 91%, 87%, and 75%, respectively. When used in combination (PSMA-PET and mpMRI PIRADS 4–5), sensitivity, specificity, NPV and PPV were 92%, 90%, 96% and 81%, respectively. The sensitivity for both techniques reduced markedly when assessing ISUP grade 1 PCa (18% for PSMA-PET, 10% for mpMRI). An SUVmax value of 3.95 resulted in 94% sensitivity and 100% specificity. Conclusion: PSMA-PET is accurate in detecting segments containing intermediate-grade intra-prostatic PCa (ISUP grade ≥ 2), compared with and complementary to mpMRI. By contrast the detection rate for ISUP grade 1 disease for both PSMA-PET and mpMRI was low.

Objectives To examine the anatomical distribution of prostate cancer (PCa) recurrence on gallium‐68 prostate‐specific membrane antigen (68Ga‐PSMA) positron‐emission tomography (PET)/computed tomography (CT) in patients with biochemical recurrence (BCR) after undergoing radical prostatectomy (RP) with pathological lymph node metastasis (pN1) in their extended pelvic lymph node dissection (ePLND), and to compare the location of PCa recurrence with the location of the initial lymph node metastasis at ePLND. Materials and Methods We retrospectively reviewed 100 patients with BCR (PSA 0.05–5.00 ng/mL) after RP with pN1 ePLND who underwent 68Ga‐PSMA PET/CT to guide salvage therapy. Clinical and pathological features and anatomical locations of PCa recurrence on 68Ga‐PSMA PET/CT were obtained, and management impact was recorded. Results In all, 68 patients (68%) had a positive and 32 patients (32%) had a negative 68Ga‐PSMA PET/CT result. Of the 68 patients with a positive 68Ga‐PSMA PET/CT, 44 (65%) showed abnormal uptake only in the pelvic area, seven (10%) only outside the pelvic area, and 17 (25%) both within and outside the pelvic area. 68Ga‐PSMA PET/CT‐positive pelvic lymph nodes were often (84%) detected on the same side as the lymph node metastasis diagnosed at ePLND. Based on the outcomes of the 68Ga‐PSMA PET/CT, change of management was noted in 68% of the patients. Conclusion Recurrence of PCa on 68Ga‐PSMA PET/CT was limited to the pelvis in the majority of patients with BCR after RP with pN1 ePLND. Moreover, recurrence was often detected on the same side as the lymph node metastasis at ePLND. The results confirm the diagnostic value of 68Ga‐PSMA PET/CT in patients with BCR after RP with pN1 ePLND. Prospective studies are needed to support the long‐term benefit of 68Ga‐PSMA PET/CT‐dictated management changes.

166 Background: 177Lutetium PSMA-617 (LuPSMA) is an effective therapy for metastatic castrate-resistant prostate cancer (mCRPC). However, treatment resistance may occur. We developed a quantitative workflow for serial PSMA PET/CT to optimise predictive and prognostic imaging biomarker capability for progression free (PFS) and overall survival (OS). Methods: 56 men with mCRPC previously treated with taxane chemotherapy and androgen signaling inhibitor were enrolled, receiving up to 6 doses of LuPSMA and a radiation sensitizer idronoxil (NOX66). 68Ga-PSMA-11 PET/CT was performed at study entry and exit. Traffic Light (TL) quantification workflow was developed to track changes in both tumour volume and intensity at a total body and lesional level. Lesions were classified as responding in green (>30% decline in volume), stable in yellow (30% increase in volume/intensity, or new). Overall response pattern was categorised as responding ( green/yellow), low volume red (50% progressive disease). TL workflow results were correlated with PFS and OS. Results: 37/56 men underwent both entry and exit imaging. The median PSA decline was 77% (IQR 34-92%), and 70% (26/37) achieved PSA response >50%. PSA progression occurred in 54% (20/37) at exit imaging. Median PFS was 8.6 months (95%CI 5.6-11.6) and median OS 22 months (95% CI 18.6-25.6). 95% (35/37) had reduction in PSMA SUVmax (-26.1 (IQR +11.7 to -89.4)) and SUVmean (-3.3 (+2.9 to -14.2)). PSMA total tumor volume reduced in 68% (25/37) (median -0.64 liters (range +1.44 to -1.1)). On TL workflow, 24% (9/37) had responding/stable disease ( green/ yellow), 76% (28/37) had progressive disease ( red) of whom 41% (15/37) had low volume progression and 35% (13/37) high volume progression. Men with high volume progression had worse OS compared to responders (HR 0.18 (0.05-0.59), p 0.005), and low volume progression (HR 0.30 (0.11-0.80), p 0.02). 68% (19/28) had progression on both TL workflow and PSA, while 32% (9/28) had progression on TL workflow without PSA progression. In multivariable analysis, TL workflow and PSA progression at time of exit scans were independent predictors of OS (Table). Conclusions: This study demonstrates the feasibility of characterizing lesional response on molecular imaging with a quantification TL workflow. TL workflow response independently correlated with survival outcomes, indicating serial PSMA PET has prognostic biomarker potential. Clinical trial information: ACTRN12618001073291.[Table: see text]

Prostate-specific membrane antigen (PSMA) may be targeted for both diagnostic and therapeutic purposes in the management of prostate cancer (PCa). In preclinical models, androgen blockade (AB) increases expression of PSMA in both hormone-sensitive and castrate-resistant xenotypes. The aim of this study was to evaluate the effect of AB treatment on 68Ga-PSMA-11 PET imaging in hormone-naive (luteinizing hormone-releasing hormone [LHRH] ± bicalutamide) and in castrate-resistant men (enzalutamide or abiraterone) with metastatic PCa. Methods: Serial 68Ga-PSMA-11 PET was prospectively performed at baseline and on days 9, 18, and 28 in 8 men with measurable metastatic hormone-sensitive PCa commencing LHRH ± bicalutamide (cohort 1) and 7 men with castrate-resistant PCa commencing either enzalutamide or abiraterone (cohort 2). Gleason score, age, time since diagnosis, and prior treatments were documented. Testosterone and prostate-specific antigen (PSA) were measured at baseline and all imaging time points. PET/CT was quantitatively analyzed for SUVmax, SUVmean, and total tumor volume. Results: In cohort 1, a median 30% (interquartile range [IQR], 5-61) reduction in SUVmax was recorded by day 9 after AB. A reduction from baseline SUVmax occurred in 86.5% (6/7) men by day 9 (P < 0.04), with an associated PSA response in 100% men (P < 0.03). Total tumor volume reduced in all men by 74.5% (IQR, 27-97) (P < 0.02). After day 9, PSMA response heterogeneity was noted, with persistently high or increasing SUVmax in 37.5% (3/8) and marked reduction in 62.5% (5/8). In cohort 2, a median 45% (IQR, 12.7-66) increase in intensity of PSMA SUV was recorded by day 9 after AB. All men demonstrated an increase in SUVmax and SUVmean on PSMA PET compared with baseline (P < 0.04). This increase at day 9 plateaued by day 28. PSA responses were more delayed in cohort 2 (-15% [IQR, 70-138]), with 2 of 7 men demonstrating PSA progression. Conclusion: There is rapid dichotomous response on 68Ga-PSMA PET imaging to AB-dependent on the presence of a hormone-sensitive or castrate-resistant PCa phenotype. This has important implications for interpretation of PSMA PET, and in the timing and sequencing of PSMA-targeted therapy.

Background Immune checkpoint inhibitor therapy has resulted in impressive and durable clinical activity for many cancers including melanoma; however, there remain few reliable predictors for long-term response. This study investigated whether [18F]2-fluoro-2-deoxy-D-glucose (FDG-PET) imaging may better predict long-term outcomes compared with standard computed tomography (CT) response criteria. Patients and methods Retrospective analysis of metastatic melanoma patients treated with anti-PD-1-based immunotherapy with baseline and 1-year FDG-PET and CT imaging at Melanoma Institute Australia. One-year response was determined using RECIST for CT and EORTC criteria for PET, coded as complete response (CR or CMR), partial response (PR or PMR), stable disease (SD or SMD) or progressive disease (PD or PMD). Progression-free survival (PFS) was determined from the 1-year landmark. Results Patients (n = 104) were evaluated with median follow-up 30.1 months and 98% remain alive. Most received anti-PD-1 as monotherapy (67%) or combined with ipilimumab (31%). At 1 year, 28% had CR, 66% had PR and 6% had SD on CT, while 75% had CMR, 16% PMR and 9% SMD/PMD on PET. CMR was observed in 68% of patients with PR on CT. RECIST PFS post 1-year landmark was similar in patients with CR versus PR/SD, but improved in patients with CMR versus non-CMR {median not reached [NR] versus 12.8 month; hazard ratio [HR] 0.06 [95% confidence interval (CI) 0.02-0.23]; P

Aim To explore the utility of prostate specific membrane antigen (PSMA)-positron emission tomography (PET)/computed tomography (CT) in addition to conventional imaging prior to definitive external beam radiation treatment (EBRT) for prostate cancer. Methods All men undergoing PSMA-PET/CT prior to definitive EBRT for intermediate and high-risk prostate cancer were included in our ethics approved prospective database. For each patient, clinical and pathological results, in addition to scan results including site of PSMA positive disease and number of lesions, were recorded. Results of conventional imaging (bone scan, CT and multiparametric magnetic resonance imaging [MRI]) were reviewed and included. Results One hundred nine men underwent staging PSMA-PET/CT between May 2015 and June 2017; all patients had national comprehensive cancer network (NCCN) intermediate or high-risk prostate cancer and 87% had Gleason score (GS) 4 + 3 or higher. There was positive uptake corresponding to the primary in 108, equivocal in one. All patients with image detected nodal or bony lesions had GS 4 + 3 or more disease. Compared to conventional imaging with bone scan, CT and multiparametric MRI, PSMA-PET/CT upstaged an additional 7 patients (6.4%) from M0 to M1, 16 from N0M0 to N1M0 (14.7%) and downstaged 3 (2.8%) from M1 to M0 disease. Conclusion PSMA-PET/CT identified the primary in 99% of patients, and altered staging in 21% of men with intermediate or high-risk prostate cancer referred for definitive EBRT compared to CT, bone scan and multiparametric MRI. Following this audit, we recommend the routine use of PSMA-PET/CT prior to EBRT in this patient group.

Brain metastases from prostate cancer are rare and occur at a late stage in the natural history of the disease. Men usually present with neurological manifestations. We present a 66-year-old asymptomatic man who had incidental brain metastases detected on Ga-PSMA PET/CT, which was later confirmed on biopsy to be prostate adenocarcinoma. With newer androgen deprivation agents and improved imaging capabilities increasing the mean survival and thus the incidence of brain metastases from prostate cancer, it is important to consider this important differential not only in men who display neurological symptoms but also in men who are asymptomatic.

Imaging plays a critical role in the current multi-disciplinary management of patients with melanoma. It is used for primary disease staging, surgical planning, and surveillance in high-risk patients, and for monitoring the effects of systemic or loco-regional therapies. Several different imaging modalities have been utilised in the past. Contemporary imaging practises vary geographically depending on clinical guidelines, physician preferences, availability and cost. Targeted therapies and immunotherapies have revolutionised the treatment of patients with metastatic melanoma over the last few years. With this have come new patterns of disease that were not observed after conventional therapies, and new criteria to assess therapeutic responses. In this article we review the role of imaging for patients with melanoma in the era of effective systemic therapies and discuss likely future developments.

68Ga-PSMA (prostate-specific membrane antigen) PET/CT is increasingly used in men with prostate-specific antigen (PSA) failure after radical prostatectomy (RP) to triage those who will benefit from salvage radiation treatment (SRT). This study examines the value of PSMA-informed SRT in improving treatment outcomes in the context of biochemical failure after RP. Methods: We analyzed men with rising PSA after RP with PSA readings between 0.05 and 1.0 ng/mL, considered eligible for SRT at the time of PSMA. For each patient, clinical and pathologic features as well as scan results, including site of PSMA-positive disease, number of lesions, and a certainty score, were documented. Subsequent management, including SRT, and most recent PSA were recorded using medical records. Treatment response was defined as both PSA ≤ 0.1 ng/mL and >50% reduction in PSA. Multivariate logistic regression analysis was performed for association of clinical variables and treatment response to SRT. Results: One hundred sixty-four men were included. PSMA was positive in 62% (n = 102/164): 38 of 102 in the prostatic fossa, 41 of 102 in pelvic nodes, and 23 of 102 distantly. Twenty-four patients received androgen-deprivation therapy (ADT) and were excluded for outcomes analysis. In total, 99 of 146 received SRT with a median follow-up after radiation treatment of 10.5 mo (interquartile range, 6-14 mo). Overall treatment response after SRT was 72% (n = 71/99). Forty-five percent (n = 27/60) of patients with a negative PSMA underwent SRT whereas 55% (33/60) did not. In men with a negative PSMA who received SRT, 85% (n = 23/27) demonstrated a treatment response, compared with a further PSA increase in 65% (22/34) in those not treated. In 36 of 99 patients with disease confined to the prostate fossa on PSMA, 81% (n = 29/36) responded to SRT. In total, 26 of 99 men had nodal disease on PSMA, of whom 61% (n = 16/26) had treatment response after SRT. On multivariate logistic regression analysis, PSMA and serum PSA significantly correlated with treatment response, whereas pT stage, Gleason score, and surgical margin status did not. Conclusion: PSMA PET is independently predictive of treatment response to SRT and stratifies men into a high treatment response to SRT (negative or fossa-confined PSMA) versus men with poor response to SRT (nodes or distant-disease PSMA). In particular, a negative PSMA PET result predicts a high response to salvage fossa radiotherapy.

68Ga-PSMA PET/CT scanning has been shown to be more sensitive than conventional imaging techniques in patients with prostate cancer. This prospective Australian multicenter study assessed whether 68Ga-PSMA PET/CT imaging affects management intent in patients with primary or recurrent prostate cancer. Methods: Before undertaking 68Ga-PSMA PET imaging, referring medical specialists completed a questionnaire detailing relevant demographic and clinical data as well as their proposed management plan. A separate follow-up questionnaire was completed after the 68Ga-PSMA PET/CT scan results were available to determine whether the management plan would change. Results: A total of 431 patients with prostate cancer from 4 Australian centers had pre- and post-68Ga-PSMA management plans completed. Scans were obtained for primary staging of intermediate- and high-risk disease in 25% of patients and for restaging/biochemical recurrence in 75% of patients. Overall, 68Ga-PSMA PET/CT scanning led to a change in planned management in 51% of patients. The impact was greater in the group of patients with biochemical failure after definitive surgery or radiation treatment (62% change in management intent) than in patients undergoing primary staging (21% change). Imaging with 68Ga-PSMA PET/CT revealed unsuspected disease in the prostate bed in 27% of patients, locoregional lymph nodes in 39%, and distant metastatic disease in 16%. Conclusion:68Ga-PSMA PET/CT scans detect previously unsuspected disease and may influence planned clinical management in a high proportion of patients with prostate cancer. The impact was greater in patients with biochemical recurrence. These results demonstrate the potential clinical value of 68Ga-PSMA PET/CT in management of prostate cancer.

ObjectivesTo evaluate the safety and short-term oncological outcomes of (68)gallium-labelled prostate-specific membrane antigen (Ga-68-PSMA) positron-emission tomography (PET)/computed tomography (CT)-directed robot-assisted salvage node dissection (RASND) for prostate cancer oligometastatic nodal recurrence.

Introduction 68Ga-PSMA positron emission tomography–computed tomography (PET/CT) is useful for both staging and assessment of biochemical relapse in men with prostate cancer. Renal excretion of 68Ga-PSMA can lead to difficulties in scan interpretation, particularly in the pelvis. We evaluated if intravenous Frusemide at the time of 68Ga-PSMA injection reduces excreted activity artefact and improves diagnostic certainty. Methods Sixty-two men with prostate cancer undergoing clinically indicated 68Ga-PSMA PET/CT were prospectively included, 30 men receiving Frusemide at the time of radiotracer injection. Clinical information and reasons for the scan were documented. Intensity of excreted activity was assessed semi quantitatively for each patient (SUV max). PET/CT images were interpreted by two experienced readers for image quality, and presence/absence of PSMA-positive disease. Results Twenty-nine percent (18/62) were staging scans, and 71% (44/62) re-staging. PSMA-positive findings were identified in 95% (59/62). Staging scans had PSMA-positive findings within the prostate in 100% (18/18) and re-staging scans, 50% (22/44) in the prostate fossa, 64% (28/44) in lymph nodes and 21% (9/44) in viscera and bone. Administration of Frusemide had a significant impact on intensity of excreted activity in the ureters and bladder. Impaired image quality was noted in 33% (10/30) of men not given Frusemide, compared to only 3% (1/32) in men given Frusemide (P = 0.002). Reporter confidence on the presence/absence of PSMA avid disease in the prostate fossa improved from 63% (19/30) without Frusemide, to 91% (29/32) with Frusemide (P

METHODS: After primary treatment, biochemical relapse (BCR) occurs in a substantial number of patients with prostate cancer (PCa). PET/CT imaging with prostate-specific membrane antigen based tracers (68Ga-PSMA) has shown promising results for BCR patients. However, a standardized image interpretation methodology has yet to be properly agreed. The aim of this study, which was promoted and funded by European Association of Nuclear Medicine (EANM), is to define standardized image interpretation criteria for 68Ga-PSMA PET/CT to detect recurrent PCa lesions in patients treated with primary curative intent therapy (radical prostatectomy or radiotherapy) who presented a biochemical recurrence. In the first phase inter-rater agreement between seven readers from seven international centers was calculated on the reading of 68Ga-PSMA PET/CT images of 49 patients with BCR. Each reader evaluated findings in five different sites of recurrence (local, loco-regional lymph nodes, distant lymph nodes, bone, and other). In the second phase the re-analysis was limited to cases with poor, slight, fair, or moderate agreement [Krippendorff's (K) alpha

OBJECTIVES: Primary objectives: To determine the additive value of gallium-68 prostate-specific membrane antigen (PSMA) positron emission topography (PET)/computed tomography (CT) when combined with multiparametric magnetic resonance imaging (mpMRI) detecting clinically significant prostate cancer (csPCa) in men undergoing initial biopsy for suspicion of PCa, and to determine the proportion of men who could have avoided prostate biopsy with positive mpMRI (PI-RADS ≥3) but negative PSMA-PET/CT. Secondary objectives: To determine the proportion of men who had csPCa detected only by PSMA-PET/CT or only by systematic prostate biopsy; to compare index lesions by template biopsies vs targeted lesions identified on mpMRI or PSMA-PET/CT; to assess whether there may be health economic benefit or harm if PSMA-PET/CT is incorporated into the diagnostic algorithm; and to develop a nomogram which combines clinical, imaging and biomarker data to predict the likelihood of csPCa. PATIENTS AND METHODS: The PRIMARY trial is a multicentre, prospective, cross-sectional study that meets the criteria for level 1 evidence in diagnostic test evaluation. PRIMARY will investigate if a limited (pelvic-only) PSMA-PET/CT in combination with routine mpMRI can reliably discriminate men with csPCa from those without csPCa. We conducted a power calculation based on pilot data and will recruit up to 600 men who will undergo PSMA-PET/CT (the index test), mpMRI (standard test) and transperineal template + targeted (PSMA-PET/CT and/or mpMRI) biopsies (reference test). The conduct and reporting of the mpMRI and PSMA-PET/CT will be blinded to each other. RESULTS: The PRIMARY trial will measure and compare sensitivity, specificity, positive predictive value and negative predictive value of both mpMRI and PSMA-PET/CT vs targeted prostrate biopsy. The results will be used to determine the proportion of men who could safely avoid biopsy without compromising detection of csPCa. Furthermore, we will assess whether there is a health economic benefit in incorporating PSMA-PET/CT into the diagnostic algorithm. CONCLUSIONS: This trial will provide robust prospective data to determine the diagnostic ability of PSMA-PET/CT used in addition to mpMRI. It will establish if certain patients can avoid biopsy in the investigation of PCa.

© 2020, Springer-Verlag GmbH Germany, part of Springer Nature. Purpose: Prostate-specific membrane antigen (PSMA) positron emission tomography (PSMA-PET) improves prostate cancer staging. Intraprostatic PSMA intensity may predict clinically relevant oncological outcomes. The aim of this study was to investigate the relationship between intraprostatic PSMA intensity and adverse pathology outcomes, including biochemical progression-free survival (PFS) after radical prostatectomy. Methods: This is a cohort study of 71 patients with MRI-guided, biopsy-proven prostate cancer and pre-operative 68Ga-PSMA-11 PET/CT prior to radical prostatectomy (RP). Intraprostatic PSMA intensity was correlated to adverse pathology outcomes (Gleason score and upgrading from biopsy, pathological stage) and PFS using multivariate statistical analysis. Results: 68Ga-PSMA-11 PET/CT intensity in vivo predicted all of Gleason score on RP, upgrading from biopsy to RP histopathology, pathological stage, positive surgical margins and PFS. 74.6% (53/71) of patients were free from progression at a median follow-up of 19.5 months (0.4–48 months). Predictive accuracy was particularly enhanced by PSMA among patients with biopsy Gleason score ≤ 3 + 4 (n = 39) as the most significant predictor of PFS according to Cox-proportional hazards regression. Cox-regression adjusted survival analysis predicted a 5.48-fold increase in hazard for Gleason score ≤ 3 + 4 patients with high (SUVmax > 8) compared with low (SUVmax < 8) PSMA intensity. Conclusion: Intraprostatic 68Ga-PSMA-11 intensity is prognostic and may be a valuable new biomarker in localised prostate cancer, especially in men with biopsy-proven Gleason 3 + 4 disease considering an initial approach of active surveillance or focal therapy.

To assess the activity and safety of cabazitaxel chemotherapy vs that of treatment withThe TheraP trial (ANZUP 1603) is an open-label, randomized, stratified, two-arm multicentre phase 2 trial comparing the activity and safety of cabazitaxel chemotherapy vs