Prognostic biomarkers in men with metastatic castration-resistant prostate cancer receiving [177Lu]-PSMA-617.

PURPOSE: We analysed quantitative biomarkers derived from both baseline whole-body imaging and blood serum to identify prognostic markers in patients treated within the lutetium-177 prostate-specific membrane antigen (LuPSMA) phase 2 trial. METHODS: PET image analysis was carried out using whole-body segmentation quantifying molecular tumour volume (SUV > 3 threshold for PSMA, SUV > liver+2sd for fluorodeoxyglucose (FDG) including SUVmax and SUVmean. For baseline bone scans, EXINI bone scan index (BSI) was used to calculate the percentage of involved bone. Baseline alkaline phosphatase (ALP), lactate dehydrogenase (LDH), prostate specific antigen (PSA) and PSA doubling time were also used in this analysis. We used univariate cox regression analysis and log-rank comparison with optimised cut-offs to find suitable biomarkers prognostic of overall survival from time of enrolment. RESULTS: This analysis identified FDG-positive tumour volume (FDGvol; HR 2.6; 95% CI, 1.4-4.8), mean intensity of PSMA-avid tumour uptake (PSMAmean; HR 0.89; 95% CI, 0.8-0.98), bone scan index (BSI; HR 2.3; 95% CI, 1.2-4.4), ALP (HR 1.1; 95% CI, 1-1.2) and LDH (HR 1.2; 95% CI, 1-1.5) as biomarkers prognostic of overall survival. CONCLUSIONS: In addition to established biomarkers, both FDG and PSMA PET/CT parameters have prognostic significance for survival in men undergoing LuPSMA therapy.

Prostate-specific membrane antigen PET/computed tomography for staging prostate cancer.

PURPOSE OF REVIEW: Molecular imaging with PET/CT targeting the prostate-specific membrane antigen (PSMA) receptor is increasingly utilized in men with prostate cancer (PCa), with clinical indications now expanding beyond biochemical recurrence. PSMA PET/CT often detects sub-centimetre size pathologic nodes and low-volume bone marrow disease that are occult on conventional imaging when the lesion does not cause sclerosis or osteoblastic reaction in surrounding bone. This review focuses on recent evidence for PSMA PET/CT in initial disease staging. RECENT FINDINGS: Several recent studies including a large randomized trial have evaluated the clinical impact of PSMA PET/CT in initial staging of PCa. PSMA PET/CT is more sensitive and accurate than the conventional imaging standard of CT and bone scan. Change in treatment plan or modality of therapy occurs frequently when PSMA PET/CT forms part of the diagnostic algorithm. Hybrid PET/MRI also has potential utility, particularly in evaluating pelvic disease, but evidence base remains very limited. SUMMARY: PSMA PET/CT has emerged as a new standard in primary staging of PCa. Reimbursement by national funding bodies and incorporation into international clinical guidelines is anticipated within the next few years.

Characteristics and outcomes of therapy-related myeloid neoplasms after peptide receptor radionuclide/chemoradionuclide therapy (PRRT/PRCRT) for metastatic neuroendocrine neoplasia: a single-institution series.

PURPOSE: Peptide receptor radionuclide/chemoradionuclide therapy (PRRT/PRCRT) is an effective therapy for metastatic neuroendocrine neoplasia (NEN), but therapy-related myeloid neoplasms (t-MN) remain of concern. The study reviewed the clinicopathological features and outcomes of patients who developed t-MN. METHODS: Retrospective analysis of all patients diagnosed with t-MN by 2016 WHO classification, from a cohort of 521 patients who received PRRT/PRCRT over a 12-year period. Molecular next-generation sequencing using an in-house 26-gene panel was performed. RESULTS: Twenty-five of 521 (4.8%) patients were diagnosed with t-MN, including six acute myeloid leukaemia (AML) and 19 myelodysplastic syndrome (MDS). The median time from first cycle PRRT/PRCRT to diagnosis of t-MN was 26 months (range 4-91). Twenty-two of 25 (88%) patients had grade 1-2 pancreatic or small bowel NEN with moderate metastatic liver burden. Six patients (24%) had prior chemotherapy. Median number of PRRT cycles = 5 (22/25 (88%) with concomitant radiosensitising chemotherapy). All 25 patients achieved disease stabilisation (68%) or partial response (32%) on RECIST 1.1 at 3 months post-PRRT. At t-MN diagnosis, all patients presented with thrombocytopenia (median nadir 33 × 109/L, range 3-75) and 17 (68%) remained NEN progression-free. Marrow genetic analysis revealed unfavourable karyotype in 16/25 (66%) patients with tumour protein 53 (TP53) mutation in nine (36%). Azacitidine therapy was utilised in ten eligible patients, while four received induction chemotherapy for AML. The median overall survival from first PRRT was 62 months (19-94), but from t-MN diagnosis was only 13 months (1-56), with death due primarily to haematological disease progression. CONCLUSIONS: The diagnosis of t-MN after PRRT/PRCRT is an infrequent but serious complication with poor overall survival. Most patients present with thrombocytopenia; unfavourable genetic mutations have a poor response to t-MN treatment. Prospective data are needed to explore potential pre-existing genetic factors and predictive biomarkers to minimise the risk of t-MN.

[177Lu]-PSMA-617 radionuclide treatment in patients with metastatic castration-resistant prostate cancer (LuPSMA trial): a single-centre, single-arm, phase 2 study.

BACKGROUND: Progressive metastatic castration-resistant prostate cancer is a highly lethal disorder and new effective therapeutic agents that improve patient outcomes are urgently needed. Lutetium-177 [177Lu]-PSMA-617, a radiolabelled small molecule, binds with high affinity to prostate-specific membrane antigen (PSMA) enabling beta particle therapy targeted to metastatic castration-resistant prostate cancer. We aimed to investigate the safety, efficacy, and effect on quality of life of [177Lu]-PSMA-617 in men with metastatic castration-resistant prostate cancer who progressed after standard treatments. METHODS: In this single-arm, single-centre, phase 2 trial, we recruited men (aged 18 years and older) with metastatic castration-resistant prostate cancer and progressive disease after standard treatments, including taxane-based chemotherapy and second-generation anti-androgens, from the Peter MacCallum Cancer Centre, Melbourne, VIC, Australia. Patients underwent a screening PSMA and FDG-PET/CT to confirm high PSMA-expression. Eligible patients had progressive disease defined by imaging (according to Response Evaluation Criteria In Solid Tumours [RECIST] or bone scan) or new pain in an area of radiographically evident disease, and were required to have an Eastern Cooperative Oncology Group (ECOG) performance status score of 2 or lower. Eligible patients received up to four cycles of intravenous [177Lu]-PSMA-617, at six weekly intervals. The primary endpoint was PSA response according to Prostate Cancer Clinical Trial Working Group criteria defined as a greater than 50% PSA decline from baseline and toxicity according to CTCAE. Additional primary endpoints were imaging responses (as measured by bone scan, CT, PSMA, and FDG PET/CT) and quality of life (assessed with the EORTC-Q30 and Brief Pain Inventory-Short Form questionnaires), all measured up to 3 months post completion of treatment. This trial is registered with the Australian New Zealand Clinical Trials Registry, number 12615000912583. FINDINGS: Between Aug 26, 2015, and Dec 8, 2016, 43 men were screened to identify 30 patients eligible for treatment. 26 (87%) had received at least one line of previous chemotherapy (80% docetaxel and 47% cabazitaxel) and 25 (83%) received prior abiraterone acetate, enzalutamide, or both. The mean administered radioactivity was 7·5 GBq per cycle. 17 (57%) of 30 patients (95% CI 37-75) achieved a PSA decline of 50% or more. There were no treatment-related deaths. The most common toxic effects related to [177Lu]-PSMA-617 were grade 1 dry mouth recorded in 26 (87%) patients, grade 1 and 2 transient nausea in 15 (50%), and G1-2 fatigue in 15 (50%). Grade 3 or 4 thrombocytopenia possibly attributed to [177Lu]-PSMA-617 occurred in four (13%) patients. Objective response in nodal or visceral disease was reported in 14 (82%) of 17 patients with measurable disease. Clinically meaningful improvements in pain severity and interference scores were recorded at all timepoints. 11 (37%) patients experienced a ten point or more improvement in global health score by the second cycle of treatment. INTERPRETATION: Our findings show that radionuclide treatment with [177Lu]-PSMA-617 has high response rates, low toxic effects, and reduction of pain in men with metastatic castration-resistant prostate cancer who have progressed after conventional treatments. This evidence supports the need for randomised controlled trials to further assess efficacy compared with current standards of care. FUNDING: None.

Comparison of objective criteria and expert visual interpretation to classify benign and malignant hilar and mediastinal nodes on 18-F FDG PET/CT.

BACKGROUND AND OBJECTIVE: There is widespread adoption of FDG-PET/CT in staging of lung cancer, but no universally accepted criteria for classifying thoracic nodes as malignant. Previous studies show high negative predictive values, but reporting criteria and positive predictive values varies. Using Endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) results as gold standard, we evaluated objective FDG-PET/CT criteria for interpreting mediastinal and hilar nodes and compared this to expert visual interpretation (EVI). METHODS: A retrospective review of all patients with lung cancer who had both FDG-PET/CT and EBUS-TBNA from 2008 to 2010 was performed. Scan interpretation was blinded to histology. Patients from 2008/2009 were used for the prediction set. The validation set analysed patients from 2010. Objective FDG-PET/CT criteria were SUVmax lymph node (SUVmaxLN), ratio SUVmaxLN/SUVmax primary lung malignancy, ratio SUVmaxLN/SUVaverage liver, ratio SUVmaxLN/SUVmax liver and ratio SUVmaxLN/SUVmax blood pool. A nuclear medicine physician reviewed all scans and classified nodal stations as benign or malignant. RESULTS: Eighty-seven malignant lymph nodes and 41 benign nodes were in the prediction set. All objective FDG-PET/CT criteria analysed were significantly higher in the malignant group (P < 0.0001). EVI correctly classified 122/128 nodes (95.3%). Thirty-four malignant nodes and 19 benign nodes were in the validation set. The new proposed cut-off values of the objective criteria from the prediction set correctly classified 44/53 (83.0%) nodes: 28/34 (82.4%) malignant nodes and 16/19 (84.2%) benign nodes. EVI had 91% accuracy: 33/34 (97.1%) malignant nodes and 15/19 (79.0%) benign nodes. CONCLUSIONS: Objective analysis of 18-F FDG PET/CT can differentiate between malignant and benign nodes but is not superior to EVI.

Grey scale texture analysis of endobronchial ultrasound mini probe images for prediction of benign or malignant aetiology.

BACKGROUND AND OBJECTIVE: Expert analysis of endobronchial ultrasound mini probe (EBUS-MP) images has established subjective criteria for discriminating benign and malignant disease. Minimal data are available for objective analysis of these images. The aim of this study was to determine if greyscale texture analysis could differentiate between benign and malignant lung lesions. METHODS: Digital EBUS-MP images with a gain setting of 10/19 and contrast setting of 4/8 from 2007 until 2012 inclusive were included. These images had an expert-defined region of interest (ROI) mapped. ROI were analysed for the following greyscale texture features: mean pixel value, difference between maximum and minimum pixel value, standard deviation of the mean pixel value, entropy, correlation, energy and homogeneity. Significant greyscale texture features differentiating benign from malignant disease were used by two physicians to assess a validation set. RESULTS: A total of 167 images were available. The first 85 lesions were used in the prediction set. Benign lesions had larger differences between maximum and minimum pixel values, larger standard deviations of the mean pixel values and higher entropy than malignant lesions (P < 0.0001 for all values). A total of 82 peripheral lesions were in the validation set. Physician 1 correctly classified 63/82 (76.8%) with a negative predictive value (NPV) for malignancy of 82% and positive predictive value (PPV) of 75%. Physician 2 correctly classified 62/82 (75.6%) with a NPV of 100% and PPV of 71.0%. CONCLUSIONS: Greyscale texture analysis of EBUS-MP images can help establish aetiology with a high NPV for malignancy.

Prostate-specific Membrane Antigen Positron Emission Tomography-detected Disease Extent and Overall Survival of Patients with High-risk Nonmetastatic Castration-resistant Prostate Cancer: An International Multicenter Retrospective Study.

Previously, we demonstrated that prostate-specific membrane antigen positron emission tomography (PSMA-PET) revealed distant metastases in 109/200 patients (39% distant nodes, 24% bone, and 6% visceral organ) with nonmetastatic castration-resistant prostate cancer (nmCRPC) and high-risk features (International Society of Urological Pathology score ≥4 and/or prostate-specific antigen doubling time ≤10 mo) without metastases by conventional imaging. However, the impact of disease extent determined by PSMA-PET on patient outcomes is unknown. We followed these 200 patients for a median of 43 mo after PSMA-PET and retrospectively assessed the association between patient characteristics, PSMA-PET findings, treatment management, and outcomes using a Kaplan-Meier model and Cox multivariable regressions. Among assessed disease characteristics, polymetastatic disease (five or more distant lesions on PET) was independently associated with shorter overall survival (OS; median 61 mo vs not reached; hazard ratio [95% confidence interval], 1.81 [1.00-3.27]; p = 0.050) and time to new metastases (median 38 vs 60 mo; 1.80 [1.10-2.96]; p = 0.019), and initial pN1 status with shorter OS (55 mo vs not reached; 1.94 [1.12-3.37]; p = 0.019). Following PSMA-PET, locoregional salvage therapies were used most commonly in no/local disease (58%), and androgen receptor signaling inhibitors were used in distant metastatic disease (51%). PSMA-PET provides additional risk stratification for patients with nmCRPC. Polymetastatic disease (five or more distant lesions) is associated with worse outcomes. PATIENT SUMMARY: A novel sensitive imaging technology, called prostate-specific membrane antigen positron emission tomography (PSMA-PET), allows doctors to detect the spread of prostate cancer, known as distant metastases, earlier and more accurately than in the past. In our study, PSMA-PET detected none to many metastases in patients who were considered free of distant metastasis by conventional imaging. These findings predicted outcomes and were used to select appropriate treatment.

Radiation Dosimetry in 177Lu-PSMA-617 Therapy.

Radionuclide therapy using the small molecule PSMA bound to the beta-emitting radionuclide, Lutetium-177 (177Lu-PSMA) has demonstrated efficacy and survival benefit castrate resistant metastatic disease and represents a novel new line of therapy. Whilst dosimetry was critical for early development, it was not incorporated into either the TheraP or VISION randomized studies, highlighting the difficulty of adopting dosimetry in routine clinical practice. Accumulated clinical experience has also shown that the common (and generally low grade) toxicities such as nausea, xerostomia, and cytopenias are not readily predicted on the basis of dosimetry estimates. The majority of dosimetry and clinical literature deals with the radiopharmaceutical 177Lu-PSMA-617 which displays relatively consistent patterns of retention among normal tissues and high specificity for metastatic prostate cancer phenotypes. Population dosimetry incorporating estimates to the kidneys, salivary glands, and bone marrow have been widely reported the typical range of doses is becoming well established. There is growing interest on tumor dosimetry in 177Lu-PSMA-617 therapy as an overall modest side-effect profile from primary organ retention has been observed. A focus away from normal organ dosimetry to whole body tumor dosimetry may enable early prediction of treatment failure. Given the safety of 177Lu-PSMA there is also potential to escalate administered radioactivity to further improve outcomes. Importantly, the variability of uptake between individuals, both to tumor and normal organs, has also been highlighted which provides some rationale for the utility of personalized radiation analysis to optimize treatment based on potential toxicity thresholds or tumor control. Methods to perform dosimetry using serial post treatment imaging may incorporate planar, 3D SPECT, or hybrid datasets. Reliable measurements may be obtained through either method, however, continued developments in computational analysis are better suited to fully 3D imaging; particularly in conjunction with volumetric CT to assist with alignment and contouring. Dose analysis over sequential treatment cycles is vital to understand the radiobiology of these treatments which is unique compared to external beam therapy due to dose rate, fractionation scheme, and potential for intratumoral nonuniformity.

Actinium-225 Prostate-specific Membrane Antigen Theranostics: Will α Beat ß?

Optimisation of prostate-specific membrane antigen (PSMA) based radioligand therapy (RLT) requires a focus on prospective trials.

A role of PSMA PET/CT in multimodality imaging approach in adenoid cystic carcinoma.

Adenoid cystic carcinoma is a rare disease and characterised by slow but unrelenting local progression and risk of haematogenous metastases. We present a case of locally unresectable disease where PSMA PET/CT provided complementary staging and early treatment response assessment.

Mechanistic Insights for Optimizing PSMA Radioligand Therapy.

PSMA radioligand therapy is a promising new class of therapy for prostate cancer. Heterogeneity of PSMA expression is an important factor explaining variability in clinical results. The ability to visualize the target with theranostics provides unique mechanistic insights. Potential clinically applicable strategies to improve patient selection and optimize therapeutic efficacy are discussed.See related article by Current et al., p. 2946.

Efficacy of Peptide Receptor Radionuclide Therapy for Esthesioneuroblastoma.

Esthesioneuroblastoma is rare, with limited therapeutic options when unresectable or metastatic; however, expression of somatostatin receptors qualifies it for peptide receptor radionuclide therapy (PRRT). We report outcomes of PRRT in esthesioneuroblastoma from 2 referral centers. Methods: Using PRRT databases at 2 European Neuroendocrine Tumor Society Centers of Excellence, cases were sought between 2004 and 2018 of patients who had PRRT with recurrent or metastatic esthesioneuroblastoma deemed unsuitable for further conventional therapies. Evaluations of survival and of response using a composite reference standard were performed. Results: Of 7 patients, 4 had partial response, 2 had disease stabilization, and one had early progression. Possible side effects include worsening cerebrospinal fluid leaks. Median progression-free survival was 17 mo (range, 0-30 mo), and median overall survival was 32 mo (range, 4-53 mo). Conclusion: PRRT shows promising efficacy and moderate survival duration in unresectable locally advanced or metastatic esthesioneuroblastoma warranting larger cohort studies incorporating measures of quality of life.

The segmental distribution and clinical significance of colorectal fluorodeoxyglucose uptake incidentally detected on PET-CT.

BACKGROUND: Unexpected focal colorectal fluorodeoxyglucose (FDG) uptake is becoming a common clinical dilemma with the increasing utilization of positron emission tomography (PET). These findings may subsequently reveal malignant or premalignant pathology. AIM: In addition to reporting the prevalence of clinically significant colonic pathology associated with unexpected focal FDG uptake, this study analysed the correlation between pathological colonic segments with those reported on the FDG-PET scan. METHODS: The reports of 2071 consecutive PET-computed tomography (PET-CT) scans performed in a calendar year were reviewed. Information regarding subsequent patient investigation and management was collected from medical records. The segments harbouring foci of unexpected bowel FDG uptake were compared against the eventual outcome(s) of the endoscopic and pathological investigations. RESULTS: Among the 62 individual patients represented, 37 (60%) were investigated further. Clinically unsuspected neoplasms were found in 68% of those investigated, including 10 diagnosed with carcinoma. In addition, an unknown bowel lymphoma and 19 colonic adenomas were discovered. The positive predictive value for pathology was higher in the proximal colon than the distal colon. The segments in which the pathological findings were identified correlated well with those reported as abnormal on PET-CT. CONCLUSION: Unexpected bowel FDG uptake on PET-CT is associated with a high incidence of neoplastic pathology. In particular, focal FDG uptake in the proximal colon is associated with a high positive predictive value for neoplasm. The location of pathology is strongly concordant with endoscopic findings.

Setting the stage: Contemporary staging of non-melanomatous skin cancer and implementation of the new American Joint Committee on cancer eighth edition staging manual.

Non-melanomatous skin cancer (NMSC) generally refers to basal cell and squamous cell carcinoma of the skin. The majority of patients are curatively treated with simple excision. Only few present with locally advanced disease or have evidence of high-risk features, placing them at an elevated risk of relapse. In such cases, further investigations may guide the multidisciplinary management plan. There are no universally agreed on indications for recommending additional staging investigations, due to a lack of prospective data reporting their impact on patient outcomes. Some generally agreed upon indications are discussed in this review article. Most commonly, computed tomography (CT) and magnetic resonance imaging (MR) are used in cases of locally advanced NMSC for staging purposes and surgical planning. While Positron Emission Tomography (PET)/CT and sentinel lymph node biopsy have shown utility, data is lacking to establish their roles in the staging algorithm. An updated NMSC system was included in The American Joint Committee for Cancer eighth edition staging manual (AJCC8). Under AJCC8 the majority of patients with regional disease are upstaged by the presence of extranodal extension, however, this updated system appears to provide limited prognostic discrimination between the nodal categories and the overall TNM stages. This review article will explore the contemporary role of staging investigations, including evolving technologies, and review the changes implemented in AJCC8. It will also discuss the implications of the AJCC8 decision to assign patients with p16-positive cervical nodal SCC with an unknown primary to the oropharyngeal staging system, with particular relevance to clinicians working in areas of high NMSC incidence.

Mitogen-Activated Protein Kinase Pathway Inhibition for Redifferentiation of Radioiodine Refractory Differentiated Thyroid Cancer: An Evolving Protocol.

Background: Some patients with metastatic differentiated thyroid cancer (DTC) lack iodine avidity and are therefore unsuitable for radioactive iodine (RAI) therapy. Limited experience suggests that single-agent selective mitogen-activated protein kinase (MAPK) pathway inhibitors can restore expression of the sodium-iodide symporter rendering RAI refractory (RAIR) DTC patients amenable to RAI therapy. The aim of this study was to assess the feasibility of mutation-guided MAPK-pathway blockade combined with thyroid hormone withdrawal (THW) for redifferentiation. Methods: This is a retrospective review of metastatic RAIR DTC and driver mutation in MAPK pathway, treated on a redifferentiation protocol. All patients had metastatic disease that had never been RAI-avid and/or imaging and biochemical progression despite treatment with RAI within the past 12 months. Patients with tumors harboring an NRAS mutation were treated with an MEK inhibitor (trametinib), and tumors with a BRAFV600E mutation with combined BRAF and MEK inhibition (dabrafenib and trametinib; or vemurafenib and cobimetinib) for four weeks. Thyrotropin stimulation was performed by THW for four weeks. Restoration of RAI uptake was determined by 124I positron emission tomography/computed tomography imaging. The response was assessed at least three months post-RAI. Results: From 2015 to 2017, six patients (age 45-70, four females) received redifferentiation therapy. Three patients had an NRAS mutation; two with follicular thyroid carcinoma (FTC) and one with a poorly differentiated thyroid carcinoma (PDTC); and three patients had a BRAFV600E mutation and papillary thyroid carcinoma (PTC). One NRAS and all BRAFV600E mutation cases demonstrated restoration of RAI uptake and proceeded to RAI therapy with a median follow-up of 16.6 months (range 13.5-42.3 months). The patient with an NRAS mutation and two of three patients with a BRAFV600E demonstrated partial imaging response beyond a three-month follow-up. Grade 3 adverse events (acneiform rash) were observed in two patients with NRAS mutations. Conclusions: Mutation-guided MAPK pathway inhibition with MEK inhibitor or a combination of BRAF inhibitor and MEK inhibitor under concurrent THW is a feasible and a promising strategy to redifferentiate RAIR DTC, thereby rendering them suitable for RAI therapy with satisfactory retention following treatment.

Poor Outcomes for Patients with Metastatic Castration-resistant Prostate Cancer with Low Prostate-specific Membrane Antigen (PSMA) Expression Deemed Ineligible for 177Lu-labelled PSMA Radioligand Therapy.

BACKGROUND: Prostate-specific membrane antigen (PSMA) is overexpressed in metastatic castration-resistant prostate cancer (mCRPC) and represents a target for imaging and therapy. We undertook a prospective trial of 177Lu-PSMA-617 radioligand therapy in men with high PSMA expression who progressed after standard therapies. OBJECTIVE: To determine outcomes for men screened for the trial but not treated because of low PSMA expression. DESIGN, SETTING, AND PARTICIPANTS: Patients screened with 68Ga-PSMA-11 and 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography in a prospective trial. Patients ineligible for enrolment with low PSMA expression or FDG-positive PSMA-negative (discordant FDG-avid) disease were assessed. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Subsequent treatments received were recorded. Kaplan-Meier analysis was used to determine overall survival from date of screening. RESULTS AND LIMITATIONS: Sixteen patients (24%) had low PSMA expression (n=8) or discordant FDG-avid disease (n=8). The median prostate-specific antigen doubling-time was 2.1mo. Eleven patients had Gleason ≥8 disease. All patients had previously progressed after docetaxel, 44% after cabazitaxel, and 94% after abiraterone and/or enzalutamide. Nine patients had subsequent systemic antitumour treatment. Fifteen patients died, with median OS of 2.5mo (95% confidence interval 1.7-5.0). Study limitations include uncertainty for imaging thresholds that define low PSMA expression. It is also possible that theranostic therapy could have improved survival in this cohort. CONCLUSIONS: Low PSMA expression or discordant FDG-avid disease in patients with mCRPC who progress after conventional therapies identifies a group with poor prognosis and short survival. PATIENT SUMMARY: The 177Lu-PSMA-617 radioligand may be an effective therapy for patients with advanced prostate cancer who progress after standard therapies. In this report we looked at outcomes for patients who were not eligible for this novel therapy on the basis of low prostate-specific membrane antigen uptake on screening positron emission tomography scans. We found that their outcomes were poor, with short survival.

The Role of 68Ga-DOTA-Octreotate PET/CT in Follow-Up of SDH-Associated Pheochromocytoma and Paraganglioma.

PURPOSE: Germline succinate dehydrogenase (SDHx) mutation carriers, especially SDHB, are at increased risk for malignancy and require life-long surveillance. Current guidelines recommend periodic whole-body MRI imaging. We assessed the incremental value of 68Ga-DOTA-octreotate (GaTate) positron emission tomography (PET)/CT compared with conventional imaging in such patients. METHODS: SDHx mutation carriers who had GaTate PET/CT were retrospectively reviewed. Detection of lesions were compared with MRI or CT on a per-patient and per-lesion basis. Proof of lesions were based on histopathology or clinical/imaging follow-up. RESULTS: Twenty consecutive patients (median age, 46 years; 10 males) were reviewed. Fourteen patients had SDHB, four, SDHD, one SDHC, and one SDHA mutation. Fifteen had prior surgery and/or radiotherapy. Indications for PET/CT were as follows: 7 patients for surveillance for previously treated disease, 9 residual disease, 2 asymptomatic mutation carriers, and 2 for elevated catecholamines. Median time between modalities was 1.5 months.GaTate PET/CT had higher sensitivity and specificity than conventional imaging. On a per-patient basis: PET/CT sensitivity 100%, specificity 100%; MRI/CT 85% and 50%. Per-lesion basis: PET/CT sensitivity 100%, specificity 75%; MRI/CT 80% and 25%. PET/CT correctly identified additional small nodal and osseous lesions. MRI/CT had more false-positive findings. Change of management resulted in 40% (8/20 patients): 3 received localized treatment instead of observation, 1 changed to observation given extra disease detected, 4 with metastases had radionuclide therapy. CONCLUSIONS: GaTate PET/CT provided incremental diagnostic information with consequent management impact in SDHx-pheochromocytoma and paraganglioma. Incorporating this modality as part of a surveillance program seems prudent. Further research is needed to define the optimal surveillance strategy including use of MRI.