Sir Peter MacCallum Department of Oncology - Research Publications

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    Management of Patients with Advanced Prostate Cancer: Report from the Advanced Prostate Cancer Consensus Conference 2021.
    Gillessen, S ; Armstrong, A ; Attard, G ; Beer, TM ; Beltran, H ; Bjartell, A ; Bossi, A ; Briganti, A ; Bristow, RG ; Bulbul, M ; Caffo, O ; Chi, KN ; Clarke, CS ; Clarke, N ; Davis, ID ; de Bono, JS ; Duran, I ; Eeles, R ; Efstathiou, E ; Efstathiou, J ; Ekeke, ON ; Evans, CP ; Fanti, S ; Feng, FY ; Fizazi, K ; Frydenberg, M ; George, D ; Gleave, M ; Halabi, S ; Heinrich, D ; Higano, C ; Hofman, MS ; Hussain, M ; James, N ; Jones, R ; Kanesvaran, R ; Khauli, RB ; Klotz, L ; Leibowitz, R ; Logothetis, C ; Maluf, F ; Millman, R ; Morgans, AK ; Morris, MJ ; Mottet, N ; Mrabti, H ; Murphy, DG ; Murthy, V ; Oh, WK ; Ost, P ; O'Sullivan, JM ; Padhani, AR ; Parker, C ; Poon, DMC ; Pritchard, CC ; Rabah, DM ; Rathkopf, D ; Reiter, RE ; Rubin, M ; Ryan, CJ ; Saad, F ; Sade, JP ; Sartor, O ; Scher, HI ; Shore, N ; Skoneczna, I ; Small, E ; Smith, M ; Soule, H ; Spratt, DE ; Sternberg, CN ; Suzuki, H ; Sweeney, C ; Sydes, MR ; Taplin, M-E ; Tilki, D ; Tombal, B ; Türkeri, L ; Uemura, H ; Uemura, H ; van Oort, I ; Yamoah, K ; Ye, D ; Zapatero, A ; Omlin, A (Elsevier BV, 2022-07)
    BACKGROUND: Innovations in treatments, imaging, and molecular characterisation in advanced prostate cancer have improved outcomes, but various areas of management still lack high-level evidence to inform clinical practice. The 2021 Advanced Prostate Cancer Consensus Conference (APCCC) addressed some of these questions to supplement guidelines that are based on level 1 evidence. OBJECTIVE: To present the voting results from APCCC 2021. DESIGN, SETTING, AND PARTICIPANTS: The experts identified three major areas of controversy related to management of advanced prostate cancer: newly diagnosed metastatic hormone-sensitive prostate cancer (mHSPC), the use of prostate-specific membrane antigen ligands in diagnostics and therapy, and molecular characterisation of tissue and blood. A panel of 86 international prostate cancer experts developed the programme and the consensus questions. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The panel voted publicly but anonymously on 107 pre-defined questions, which were developed by both voting and non-voting panel members prior to the conference following a modified Delphi process. RESULTS AND LIMITATIONS: The voting reflected the opinions of panellists and did not incorporate a standard literature review or formal meta-analysis. The answer options for the consensus questions received varying degrees of support from panellists, as reflected in this article and the detailed voting results reported in the Supplementary material. CONCLUSIONS: These voting results from a panel of experts in advanced prostate cancer can help clinicians and patients to navigate controversial areas of management for which high-level evidence is scant. However, diagnostic and treatment decisions should always be individualised according to patient characteristics, such as the extent and location of disease, prior treatment(s), comorbidities, patient preferences, and treatment recommendations, and should also incorporate current and emerging clinical evidence and logistic and economic constraints. Enrolment in clinical trials should be strongly encouraged. Importantly, APCCC 2021 once again identified salient questions that merit evaluation in specifically designed trials. PATIENT SUMMARY: The Advanced Prostate Cancer Consensus Conference is a forum for discussing current diagnosis and treatment options for patients with advanced prostate cancer. An expert panel votes on predefined questions focused on the most clinically relevant areas for treatment of advanced prostate cancer for which there are gaps in knowledge. The voting results provide a practical guide to help clinicians in discussing treatment options with patients as part of shared decision-making.
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    What Experts Think About Prostate Cancer Management During the COVID-19 Pandemic: Report from the Advanced Prostate Cancer Consensus Conference 2021.
    Turco, F ; Armstrong, A ; Attard, G ; Beer, TM ; Beltran, H ; Bjartell, A ; Bossi, A ; Briganti, A ; Bristow, RG ; Bulbul, M ; Caffo, O ; Chi, KN ; Clarke, C ; Clarke, N ; Davis, ID ; de Bono, J ; Duran, I ; Eeles, R ; Efstathiou, E ; Efstathiou, J ; Evans, CP ; Fanti, S ; Feng, FY ; Fizazi, K ; Frydenberg, M ; George, D ; Gleave, M ; Halabi, S ; Heinrich, D ; Higano, C ; Hofman, MS ; Hussain, M ; James, N ; Jones, R ; Kanesvaran, R ; Khauli, RB ; Klotz, L ; Leibowitz, R ; Logothetis, C ; Maluf, F ; Millman, R ; Morgans, AK ; Morris, MJ ; Mottet, N ; Mrabti, H ; Murphy, DG ; Murthy, V ; Oh, WK ; Ekeke Onyeanunam, N ; Ost, P ; O'Sullivan, JM ; Padhani, AR ; Parker, C ; Poon, DMC ; Pritchard, CC ; Rabah, DM ; Rathkopf, D ; Reiter, RE ; Rubin, M ; Ryan, CJ ; Saad, F ; Pablo Sade, J ; Sartor, O ; Scher, HI ; Shore, N ; Skoneczna, I ; Small, E ; Smith, M ; Soule, H ; Spratt, D ; Sternberg, CN ; Suzuki, H ; Sweeney, C ; Sydes, M ; Taplin, M-E ; Tilki, D ; Tombal, B ; Türkeri, L ; Uemura, H ; Uemura, H ; van Oort, I ; Yamoah, K ; Ye, D ; Zapatero, A ; Gillessen, S ; Omlin, A (Elsevier BV, 2022-07)
    Patients with advanced prostate cancer (APC) may be at greater risk for severe illness, hospitalisation, or death from coronavirus disease 2019 (COVID-19) due to male gender, older age, potential immunosuppressive treatments, or comorbidities. Thus, the optimal management of APC patients during the COVID-19 pandemic is complex. In October 2021, during the Advanced Prostate Cancer Consensus Conference (APCCC) 2021, the 73 voting members of the panel members discussed and voted on 13 questions on this topic that could help clinicians make treatment choices during the pandemic. There was a consensus for full COVID-19 vaccination and booster injection in APC patients. Furthermore, the voting results indicate that the expert's treatment recommendations are influenced by the vaccination status: the COVID-19 pandemic altered management of APC patients for 70% of the panellists before the vaccination was available but only for 25% of panellists for fully vaccinated patients. Most experts (71%) were less likely to use docetaxel and abiraterone in unvaccinated patients with metastatic hormone-sensitive prostate cancer. For fully vaccinated patients with high-risk localised prostate cancer, there was a consensus (77%) to follow the usual treatment schedule, whereas in unvaccinated patients, 55% of the panel members voted for deferring radiation therapy. Finally, there was a strong consensus for the use of telemedicine for monitoring APC patients. PATIENT SUMMARY: In the Advanced Prostate Cancer Consensus Conference 2021, the panellists reached a consensus regarding the recommendation of the COVID-19 vaccine in prostate cancer patients and use of telemedicine for monitoring these patients.
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    Is Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography Imaging Cost-effective in Prostate Cancer: An Analysis Informed by the proPSMA Trial
    Cardet, REDF ; Hofman, MS ; Segard, T ; Yim, J ; Williams, S ; Francis, RJ ; Frydenberg, M ; Lawrentschuk, N ; Murphy, DG ; Lourenco, RDA (ELSEVIER, 2021-02-11)
    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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    Feasibility of biology-guided radiotherapy using PSMA-PET to boost to dominant intraprostatic tumour
    Gaudreault, M ; Chang, D ; Hardcastle, N ; Jackson, P ; Kron, T ; Hofman, MS ; Siva, S (ELSEVIER IRELAND LTD, 2022-07-01)
    Background: Biology-guided radiotherapy (BgRT) delivers dose to tumours triggered from positron emission tomography (PET) detection. Prostate specific membrane antigen (PSMA) PET uptake is abundant in the dominant intraprostatic lesion (DIL). This study investigates the feasibility of BgRT to PSMA-avid subvolume in the prostate region. Methods: Patients enrolled in the prospective randomized trial ProPSMA at our institution were included (ID: ANZCTR12617000005358). Gross tumour volumes (GTVs) were delineated on the PET component of a PET/CT scan from a standardized uptake value (SUV) threshold technique. Suitability for BgRT requires a strong signal-to-background ratio with a surrounding tissue free of significant PSMA uptake. The signal-to-background ratio was quantified from the calculation of the normalized SUV (nSUV), defined as the ratio between SUVmax within the GTV and SUVmean inside a 3D margin expansion of the GTV. The PSMA distribution surrounding the tumour was quantified as a function of the distance from the GTV. Results: In this cohort of 84 patients, 83 primary tumours were included. Prostate volume ranged from 19 cm3 to 148 cm3 (median = 52 cm3; IQR = 39 cm3 - 63 cm3). SUVmax inside the prostate was between 2 and 125 (median = 19; IQR = 11 - 30). More than 50% of GTVs generated with threshold between 25%SUVmax (median volume = 10.0 cm3; IQR = 4.5 cm3 - 20.0 cm3) and 50%SUVmax (median volume = 1.9 cm3; IQR = 1.1 cm3 - 3.8 cm3) were suitable for BgRT by using nSUV ≥ 3 and a margin expansion of 5 mm. Conclusions: It is feasible to identify GTVs suitable for BgRT in the prostate. These GTVs are characterized by a strong signal-to-background ratio and a surrounding tissue free of PSMA uptake.
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    High prostate-specific membrane antigen (PSMA) positron emission tomography (PET) maximum standardized uptake value in men with PI-RADS score 4 or 5 confers a high probability of significant prostate cancer
    Ptasznik, G ; Papa, N ; Kelly, BD ; Thompson, J ; Stricker, P ; Roberts, MJ ; Hofman, MS ; Buteau, J ; Murphy, DG ; Emmett, L ; Moon, D (WILEY, 2022-04-20)
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    Utility of Biology-Guided Radiotherapy to De Novo Metastases Diagnosed During Staging of High-Risk Biopsy-Proven Prostate Cancer
    Gaudreault, M ; Chang, D ; Hardcastle, N ; Jackson, P ; Kron, T ; Hanna, GG ; Hofman, MS ; Siva, S (FRONTIERS MEDIA SA, 2022-04-12)
    Background: Biology-guided radiotherapy (BgRT) uses real-time functional imaging to guide radiation therapy treatment. Positron emission tomography (PET) tracers targeting prostate-specific membrane antigen (PSMA) are superior for prostate cancer detection than conventional imaging. This study aims at describing nodal and distant metastasis distribution from prostate cancer and at determining the proportion of metastatic lesions suitable for BgRT. Methods: A single-institution patient subset from the ProPSMA trial (ID ACTRN12617000005358) was analysed. Gross tumour volumes (GTV) were delineated on the CT component of a PSMA PET/CT scan. To determine the suitability of BgRT tracking zones, the normalized SUV (nSUV) was calculated as the ratio of SUVmax inside the GTV to the SUVmean of adjacent three-dimensional shells of thickness 5 mm/10 mm/20 mm as a measure of signal to background contrast. Targets were suitable for BgRT if (1) nSUV was larger than an nSUV threshold and (2) non-tumour tissue inside adjacent shell was free of PET-avid uptake. Results: Of this cohort of 84 patients, 24 had at least one pelvic node or metastatic site disease, 1 to 13 lesions per patient, with a total of 98 lesions (60 pelvic nodes/38 extra-pelvic nodal diseases and haematogenous metastases). Target volumes ranged from 0.08 to 9.6 cm3 while SUVmax ranged from 2.1 to 55.0. nSUV ranged from 1.9 to 15.7/2.4 to 25.7/2.5 to 34.5 for the 5 mm/10 mm/20 mm shell expansion. Furthermore, 74%/68%/34% of the lesions had nSUV ≥ 3 and were free of PSMA PET uptake inside the GTV outer shell margin expansion of 5 mm/10 mm/20 mm. Adjacent avid organs were another lesion, bladder, bowel, ureter, prostate, and liver. Conclusions: The majority of PSMA PET/CT-defined radiotherapy targets would be suitable for BgRT by using a 10-mm tracking zone in prostate cancer. A subset of lesions had adjacent non-tumour uptake, mainly due to the proximity of ureter or bladder, and may require exclusion from emission tracking during BgRT.
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    Quantitative assessment of ventilation-perfusion relationships with gallium-68 positron emission tomography/computed tomography imaging in lung cancer patients.
    Li, Z ; Le Roux, P-Y ; Callahan, J ; Hardcastle, N ; Hofman, MS ; Siva, S ; Yamamoto, T (Elsevier BV, 2022-04)
    Pulmonary functional imaging has demonstrated potential to improve thoracic radiotherapy. The purpose of this study was twofold: 1) to quantify ventilation/perfusion relationships in lung cancer patients using a new functional imaging approach, gallium-68 (68Ga)-positron emission tomography/computed tomography (PET/CT); and 2) to compare ventilation/perfusion matching with diffusing capacity of the lung for carbon monoxide (DLCO). Voxel-wise correlations between ventilation and perfusion varied widely among 19 patients (range: 0.26-0.88). 68Ga-PET/CT-measured percent gas exchanging lung volume was moderately correlated with DLCO (≤0.59). Our findings suggested that 68Ga-PET/CT ventilation/perfusion imaging provided complementary information and a reasonable surrogate for gas exchange in lung cancer patients.
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    Chimeric Antigen Receptor T-Cell Therapy in Metastatic Castrate-Resistant Prostate Cancer
    Perera, MPJ ; Thomas, PB ; Risbridger, GP ; Taylor, R ; Azad, A ; Hofman, MS ; Williams, ED ; Vela, I (MDPI, 2022-02-01)
    Prostate cancer is the most commonly diagnosed solid-organ cancer amongst males worldwide. Metastatic castrate-resistant prostate cancer (mCRPC) is a rapidly fatal end-sequelae of prostate cancer. Therapeutic options for men with mCRPC are limited and are not curative in nature. The recent development of chimeric antigen receptor T-cell (CAR-T) therapy has revolutionised the treatment of treatment-resistant haematological malignancies, and several studies are underway investigating the utility of this technology in the treatment of solid tumours. In this review, we evaluate the current treatment options for men with mCRPC as well as the current landscape of preclinical and clinical trials of CAR-T cell therapy against prostate cancer. We also appraise the various prostate cancer-specific tumour-associated antigens that may be targeted by CAR-T cell technology. Finally, we examine the potential translational barriers of CAR-T cell therapy in solid tumours. Despite preclinical success, preliminary clinical trials in men with prostate cancer have had limited efficacy. Therefore, further clinically translatable preclinical models are required to enhance the understanding of the role of this investigational therapeutic in men with mCRPC. In the era of precision medicine, tailored immunotherapy administered to men in a tumour-agnostic approach provides hope to a group of men who otherwise have few treatment options available.
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    The role of F-18-FDG PET/CT in retroperitoneal sarcomas-A multicenter retrospective study
    Subramaniam, S ; Callahan, J ; Bressel, M ; Hofman, MS ; Mitchell, C ; Hendry, S ; Vissers, FL ; Van Der Hiel, B ; Patel, D ; Van Houdt, WJ ; Tseng, WW ; Gyorki, DE (WILEY, 2021-01-14)
    BACKGROUND: The role of 18 F-fluorodeoxyglucose positron emission tomography/computed tomography (18 F-FDG PET/CT) in the evaluation of retroperitoneal sarcomas is poorly defined. We evaluated the correlation of maximum standardized uptake value (SUVmax) with pathologic tumor grade in the surgical specimen of primary retroperitoneal dedifferentiated liposarcoma (DDLPS) and leiomyosarcoma (LMS). METHODS: Patients with the above histological subtypes in three participating institutions with preoperative 18 F-FDG PET/CT scan and histopathological specimen available for review were included. The association between SUVmax and pathological grade was assessed. Correlation between SUVmax and relapse-free survival (RFS) and overall survival (OS) were also studied. RESULTS: Of the total 58 patients, final pathological subtype was DDLPS in 44 (75.9%) patients and LMS in 14 (24.1%) patients. The mean SUVmax was 8.7 with a median 7.1 (range, 2.2-33.9). The tumors were graded I, II, III in 6 (10.3%), 35 (60.3%), and 17 (29.3%) patients, respectively. There was an association of higher histological grade with higher SUVmax (rs  = 0.40, p = .002). Increasing SUVmax was associated with worse RFS (p = .003) and OS (p = .003). CONCLUSION: There is a correlation between SUVmax and pathologic tumor grade; increasing SUVmax was associated with worse OS and RFS, providing a preoperative noninvasive surrogate marker of tumor grade and biological behavior.
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    PSMA targeting in metastatic castration-resistant prostate cancer: where are we and where are we going?
    Giraudet, A-L ; Kryza, D ; Hofman, M ; Moreau, A ; Fizazi, K ; Flechon, A ; Hicks, RJ ; Tran, B (SAGE PUBLICATIONS LTD, 2021-10-01)
    Prostate-specific membrane antigen (PSMA) is highly expressed on the membrane of most prostate cancer cells and to a lesser extent in normal tissues. Many vectors targeting this protein have been created over the past decade and numerous clinical studies have positively demonstrated the tolerance and efficacy of radiolabeled prostate-specific membrane antigen ligands for PSMA radioligand therapy (PRLT). Preliminary results are encouraging that PRLT will become an important addition to the current therapeutic options in a number of settings. Improvement in radiopharmaceutical targeting and combination with other oncological agents are under investigation to further improve its therapeutic efficacy. These encouraging results have led to the development of other therapies using PSMA as a target, such as PSMA-targeted chimeric antigen receptor T-cells, PSMA-targeted antibody drug conjugates, and PSMA-targeted bi-specific T-cell-directed therapy. This narrative review details the current state and advancements in prostate-specific membrane antigen targeting in prostate cancer treatment.