Sir Peter MacCallum Department of Oncology - Research Publications
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ItemNo Preview AvailableIs Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography Imaging Cost-effective in Prostate Cancer: An Analysis Informed by the proPSMA Trial(ELSEVIER, 2021-03)BACKGROUND: Before integrating prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) into routine care, it is important to assess if the benefits justify the differences in resource use. OBJECTIVE: To determine the cost-effectiveness of PSMA-PET/CT when compared with conventional imaging. DESIGN, SETTING, AND PARTICIPANTS: A cost-effectiveness analysis was developed using data from the proPSMA study. proPSMA included patients with high-risk prostate cancer assigned to conventional imaging or 68Ga-PSMA-11 PET/CT with planned health economics data collected. The cost-effectiveness analysis was conducted from an Australian societal perspective. INTERVENTION: 68Ga-PSMA-11 PET/CT compared with conventional imaging (CT and bone scan). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome from proPSMA was diagnostic accuracy (nodal and distant metastases). This informed a decision tree analysis of the cost per accurate diagnosis. RESULTS AND LIMITATIONS: The estimated cost per scan for PSMA PET/CT was AUD$1203, which was less than the conventional imaging cost at AUD$1412. PSMA PET/CT was thus dominant, having both better accuracy and a lower cost. This resulted in a cost of AUD$959 saved per additional accurate detection of nodal disease, and AUD$1412 saved for additional accurate detection of distant metastases. The results were most sensitive to variations in the number of men scanned for each 68Ga-PSMA-11 production run. Subsequent research is required to assess the long-term costs and benefits of PSMA PET/CT-directed care. CONCLUSIONS: PSMA PET/CT has lower direct comparative costs and greater accuracy compared to conventional imaging for initial staging of men with high-risk prostate cancer. This provides a compelling case for adopting PSMA PET/CT into clinical practice. PATIENT SUMMARY: The proPSMA study demonstrated that prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) better detects disease that has spread beyond the prostate compared with conventional imaging. Our analysis shows that PSMA PET/CT is also less costly than conventional imaging for the detection of disease spread. This research was presented at the European Association of Nuclear Medicine Scientific Meeting in October 2020.
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ItemVoxel-wise correlation of positron emission tomography/computed tomography with multiparametric magnetic resonance imaging and histology of the prostate using a sophisticated registration framework(WILEY, 2019-06)OBJECTIVES: To develop a registration framework for correlating positron emission tomography/computed tomography (PET/CT) images with multiparametric magnetic resonance imaging (mpMRI) and histology of the prostate, thereby enabling voxel-wise analysis of imaging parameters. PATIENTS AND METHODS: In this prospective proof-of-concept study, nine patients scheduled for radical prostatectomy underwent mpMRI and PET/CT imaging before surgery. One had PET imaging using 18 F-fluoromethylcholine, five using 68 Ga-labelled prostate-specific membrane antigen (PSMA)-HBED-CC (PMSA-11), and three using a trial 68 Ga-labelled THP-PSMA tracer. PET/CT data were co-registered with mpMRI via the CT scan and an in vivo three-dimensional T2-weighted (T2w) MRI, and then co-registered with ground truth histology data using ex vivo MRI of the prostate specimen. Maximum and mean standardised uptake values (SUVmax and SUVmean ) were extracted from PET data using tumour annotations from histology, and Kolmogorov-Smirnov tests were used to compare between tumour- and benign-voxel values. Correlation analysis was performed between mpMRI and PET SUV tumour voxel values using Pearson's correlation coefficient and R2 statistics. RESULTS: PET/CT data from all nine patients were successfully registered with mpMRI and histology data. SUVmax and SUVmean ranged from 2.21 to 12.11 and 1.08 to 4.21, respectively. All patients showed the PET SUV values in benign and tumour voxels were from statistically different distributions. Correlation analysis showed no consistent trend between the T2w or apparent diffusion coefficient values and PET SUV. However, parameters from dynamic contrast-enhanced (DCE) MRI including the maximum enhancement, volume transfer constant (Ktrans ), and the initial area under the contrast agent concentration curve for the first 60 s after injection (iAUGC60), showed consistent positive correlations with PET SUV. Furthermore, R2* values from blood oxygen level-dependent (BOLD) MRI showed consistent negative correlations with PET SUV-voxel values. CONCLUSION: We have developed a novel framework for registering and correlating PET/CT data at a voxel-level with mpMRI and histology. Despite registration uncertainties, perfusion and oxygenation parameters from DCE MRI and BOLD imaging showed correlations with PET SUV. Further analysis will be performed on a larger patient cohort to quantify these proof-of-concept findings. Improved understanding of the correlation between mpMRI and PET will provide supportive information for focal therapy planning of the prostate.
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ItemA prospective randomized multicentre study of the impact of gallium-68 prostate-specific membrane antigen (PSMA) PET/CT imaging for staging high-risk prostate cancer prior to curative-intent surgery or radiotherapy (proPSMA study): clinical trial protocol(WILEY, 2018-11)BACKGROUND: Accurate staging of patients with prostate cancer (PCa) is important for therapeutic decision-making. Relapse after surgery or radiotherapy of curative intent is not uncommon and, in part, represents a failure of staging with current diagnostic imaging techniques to detect disease spread. Prostate-specific membrane antigen (PSMA) positron-emission tomography (PET)/computed tomography (CT) is a new whole-body scanning technique that enables visualization of PCa with high contrast. The hypotheses of this study are that: (i) PSMA-PET/CT has improved diagnostic performance compared with conventional imaging; (ii) PSMA-PET/CT should be used as a first-line diagnostic test for staging; (iii) the improved diagnostic performance of PSMA-PET/CT will result in significant management impact; and (iv) there are economic benefits if PSMA-PET/CT is incorporated into the management algorithm. OBJECTIVES AND METHODS: The proPSMA trial is a prospective, multicentre study in which patients with untreated high-risk PCa will be randomized to gallium-68-PSMA-11 PET/CT or conventional imaging, consisting of CT of the abdomen/pelvis and bone scintigraphy with single-photon emission CT/CT. Patients eligible for inclusion are those with newly diagnosed PCa with select high-risk features, defined as International Society of Urological Pathology grade group ≥3 (primary Gleason grade 4, or any Gleason grade 5), prostate-specific antigen level ≥20 ng/mL or clinical stage ≥T3. Patients with negative, equivocal or oligometastatic disease on first line-imaging will cross over to receive the other imaging arm. The primary objective is to compare the accuracy of PSMA-PET/CT with that of conventional imaging for detecting nodal or distant metastatic disease. Histopathological, imaging and clinical follow-up at 6 months will define the primary endpoint according to a predefined scoring system. Secondary objectives include comparing management impact, the number of equivocal studies, the incremental value of second-line imaging in patients who cross over, the cost of each imaging strategy, radiation exposure, inter-observer agreement and safety of PSMA-PET/CT. Longer-term follow-up will also assess the prognostic value of a negative PSMA-PET/CT. OUTCOME AND SIGNIFICANCE: This trial will provide data to establish whether PSMA-PET/CT should replace conventional imaging in the primary staging of select high-risk localized PCa, or whether it should be used to provide incremental diagnostic information in selected cases.
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ItemProstate-specific membrane antigen theranostics in advanced prostate cancer: an evolving option(WILEY, 2020-11)OBJECTIVES: To review current data for the role of prostate specific membrane antigen (PSMA) radioligand therapy (RLT) for patients with advanced prostate cancer. This review provides an update for multidisciplinary teams on the current and potential future applications of theranostics in prostate cancer. METHODS: Narrative review focussing on PSMA as a target for RLT, and data using RESULTS: RLT with PSMA is an exciting therapeutic alternative to the existing management options already in use for patients with metastatic castrate-resistant prostate cancer (mCRPC). To date, most evidence exists regarding small-molecule PSMA inhibitors bound to beta-emitting radioisotopes such as 177Lu (Lu-PSMA). Prospective phase II data supports the safety and efficacy of Lu-PSMA in men with heavily pre-treated progressive mCRPC, and several late-phase randomised trials of Lu-PSMA are underway, with many more in the pipeline. Early results are encouraging, indicating that the theranostic approach may play a vital role in management of advanced prostate cancer and perhaps even in much earlier disease states. CONCLUSIONS: PSMA RLT is a promising new treatment option for men with mCPRC, and may also have utility in less advanced prostate cancer.
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ItemDetection and localisation of primary prostate cancer using 68gallium prostate-specific membrane antigen positron emission tomography/computed tomography compared with multiparametric magnetic resonance imaging and radical prostatectomy specimen pathology(WILEY, 2020-07)OBJECTIVE: To compare the accuracy of 68 gallium prostate-specific membrane antigen positron emission tomography/computed tomography (68 Ga-PSMA PET/CT) with multiparametric MRI (mpMRI) in detecting and localising primary prostate cancer when compared with radical prostatectomy (RP) specimen pathology. PATIENTS AND METHODS: Retrospective review of men who underwent 68 Ga-PSMA PET/CT and mpMRI for primary prostate cancer before RP across four centres between 2015 and 2018. Patients undergoing imaging for recurrent disease or before non-surgical treatment were excluded. We defined pathological index tumour as the lesion with highest International Society of Urological Pathology Grade Group (GG) on RP specimen pathology. Our primary outcomes were rates of accurate detection and localisation of RP specimen pathology index tumour using 68 Ga-PSMA PET/CT or mpMRI. We defined tumour detection as imaging lesion corresponding with RP specimen tumour on any imaging plane, and localisation as imaging lesion matching RP specimen index tumour in all sagittal, axial, and coronal planes. Secondary outcomes included localisation of clinically significant and transition zone (TZ) index tumours. We defined clinically significant disease as GG 3-5. We used descriptive statistics and the Mann-Whitney U-test to define and compare demographic and pathological characteristics between detected, missed and localised tumours using either imaging modality. We used the McNemar test to compare detection and localisation rates using 68 Ga-PSMA PET/CT and mpMRI. RESULTS: In all, 205 men were included in our analysis, including 133 with clinically significant disease. There was no significant difference between 68 Ga-PSMA PET/CT and mpMRI in the detection of any tumour (94% vs 95%, P > 0.9). There was also no significant difference between localisation of all index tumours (91% vs 89%, P = 0.47), clinically significant index tumours (96% vs 91%, P = 0.15) or TZ tumours (85% vs 80%, P > 0.9) using 68 Ga-PSMA PET/CT and mpMRI. Limitations include retrospective study design and non-central review of imaging and pathology. CONCLUSION: We found no significant difference in the detection or localisation of primary prostate cancer between 68 Ga-PSMA PET/CT and mpMRI. Further prospective studies are required to evaluate a combined PET/MRI model in minimising tumours missed by either modality.
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ItemProtocol for the PRIMARY clinical trial, a prospective, multicentre, cross-sectional study of the additive diagnostic value of gallium-68 prostate-specific membrane antigen positron-emission tomography/computed tomography to multiparametric magnetic resonance imaging in the diagnostic setting for men being investigated for prostate cancer(WILEY, 2020-04)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.
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Item68Ga PSMA-11 PET with CT urography protocol in the initial staging and biochemical relapse of prostate cancer(BMC, 2017-12-21)BACKGROUND: 68Ga-labelled prostate specific membrane antigen (PSMA) ligand PET/CT is a promising modality in primary staging (PS) and biochemical relapse (BCR) of prostate cancer (PC). However, pelvic nodes or local recurrences can be difficult to differentiate from radioactive urine. CT urography (CT-U) is an established method, which allows assessment of urological malignancies. The study presents a novel protocol of 68Ga-PSMA-11 PET/CT-U in PS and BCR of PC. METHODS: A retrospective review of PSMA PET/CT-U preformed on 57 consecutive patients with prostate cancer. Fifty mL of IV contrast was administered 10 min (range 8-15) before the CT component of a combined PET/CT study, acquired approximately 60 min (range 40-85) after administration of 166 MBq (range 91-246) of 68Ga-PSMA-11. PET and PET/CT-U were reviewed by two nuclear medicine physicians and CT-U by a radiologist. First, PET images were reviewed independently followed by PET/CT-U images. Foci of activity which could not unequivocally be assessed as disease or urinary activity were recorded. PET/CT-U was considered of potential benefit in final interpretation when the equivocal focal activity in PET images corresponded to opacified ureter, bladder, prostate bed, seminal vesicles, or urethra. Student's T test and Pearson's correlation coefficient was used for assessment of variables including lymph node size and standardized uptake value. RESULTS: Overall 50 PSMA PET/CT-U studies were performed for BCR and 7 for PS. Median PSA with BCR and PS were 2.0 ± 11.4 ng/ml (0.06-57.3 ng/ml) and 18 ± 35.3 ng/ml (6.8-100 ng/ml), respectively. The median Gleason-score for both groups was 7 (range 6-10). In BCR group, PSMA PET was reported positive in 36 (72%) patients, CT-U in 11(22%) patients and PET/CT-U in 33 (66%) patients. In PS group, PSMA PET detected the primary site in all seven patients, of which one patient with metastatic nodal disease had negative CT finding. Of 40 equivocal foci (27/57 patients) on PET, 11 foci (10/57 patients, 17.5%) were localized to enhanced urine on PET/CT-U, hence considered of potential benefit in interpretation. Of those, 3 foci (3 patients) were solitary sites of activity on PSMA imaging including two local and one nodal site and 4 foci (3 patients) were in different nodal fields. CONCLUSIONS: PET/CT-U protocol is a practical approach and may assist in interpretation of 68Ga-PSMA-11 imaging by delineation of the contrast opacified genitourinary system and matching focal PSMA activity with urinary contrast.