Surgery (St Vincent's) - Research Publications

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    Pathological predictors of 18F-DCFPyL prostate-specific membrane antigen-positive recurrence after radical prostatectomy
    Perry, E ; Talwar, A ; Taubman, K ; Ng, M ; Wong, L-M ; Sutherland, TR (WILEY, 2022-06)
    OBJECTIVES: To assess the correlation of pathological radical prostatectomy (RP) specimen features and prostate-specific antigen (PSA) characteristics to imaging findings on subsequent 18 F-DCFPyL positron emission tomography/computed tomography (PET/CT) in patients with biochemical failure (BF). PATIENTS AND METHODS: Retrospective analysis of combined 18 F-DCFPyL PET/CT database of patients from centres in Australia and New Zealand was performed. A total of 205 patients presenting with BF after RP were included in this study. Imaging findings on 18 F-DCFPyL PET/CT were recorded and correlated with the PSA characteristics at BF and pathological features of the original tumour. RESULTS: Of the 205 patients, 120 (58.5%) had evidence of abnormal prostate-specific membrane antigen (PSMA) expression compatible with recurrent prostate cancer. Increasing PSA velocity (P = 0.01), International Society of Urological Pathology (ISUP) Grade Group (P = 0.02), lymphovascular invasion (P = 0.05) and nodal positivity (P = 0.02) at the time of RP were more likely to demonstrate PSMA positivity. Multivariable logistic regression revealed a higher PSA level prior to PSMA PET/CT (P < 0.01), adjuvant radiotherapy (P = 0.09), Gleason score ≥8 (P < 0.01) and nodal positivity (P = 0.05) were all predictive of PSMA positivity. CONCLUSION: 18 F-DCFPyL PET/CT positivity, both generally and site specific, correlates with PSA and RP pathological factors. Our results echo cohorts focussing on post-RP patients, those imaged with 68 Ga-PSMA and those concerning biochemical persistence. Nomograms that include risk factors for 'PSMA-positive recurrence' in the BF population may increase the catchment of patients with disease confined to the prostate bed or pelvis who have a greater probability of prolonged disease-free survival.
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    PEDAL protocol: a prospective single-arm paired comparison of multiparametric MRI and 18F-DCPFyl PSMA PET/CT to diagnose prostate cancer
    Tran, V ; Hong, A ; Sutherland, T ; Taubman, K ; Lee, S-F ; Lenaghan, D ; Sethi, K ; Corcoran, NM ; Lawrentschuk, N ; Woo, H ; Tarlinton, L ; Bolton, D ; Spelman, T ; Thomas, L ; Booth, R ; Hegarty, J ; Perry, E ; Wong, L-M (BMJ PUBLISHING GROUP, 2022-09)
    INTRODUCTION: Prostate-specific membrane antigen positron emission tomography (PSMA-PET) has emerged as valuable imaging to assessing metastatic disease in prostate malignancy. However, there has been limited studies exploring the utility PSMA-PET as primary imaging assessing for index lesions prior to biopsy. The primary objective of this study is to compare the diagnostic accuracy of 18-fluorine PSMA (18F DCFPyL PSMA) PET scans to multiparametric MRI (mpMRI) to detect primary prostate cancer at prostate biopsy. METHODS AND ANALYSIS: The PEDAL trial is a multicentre, prospective, single-arm, paired comparison, non-randomised phase III trial in subjects considered for diagnostic prostate biopsy. Subjects who are eligible for a diagnostic mpMRI prostate will undergo additional same-day 18 F DCFPyl PSMA PET/CT of the chest, abdomen and pelvis. Software coregistration of the mpMRI and PSMA-PET/CT images will be performed. The reporting of the mpMRI prostate, PSMA-PET/CT and PSMA PET/MRI coregistration will be performed blinded. The diagnostic accuracy of PSMA PET/CT alone, and in combination with mpMRI, to detect prostate cancer will be assessed. Histopathology at prostate biopsy will be used as the reference standard. Sample size calculations estimate that 240 subjects will need to be recruited to demonstrate 20% superiority of PSMA-PET/CT. The sensitivity, specificity, positive predictive value and negative predictive value of the combination of mpMRI prostate and PSMA PET/CT compared with targeted and systematic prostate biopsy will be evaluated. It is hypothesised that PSMA PET/CT combined with mpMRI prostate will have improved diagnostic accuracy compared with mpMRI prostate alone for detection of prostate cancer in biopsy-naïve men, resulting in a significant impact on patient management. ETHICS AND DISSEMINATION: This study was approved by the independent Human Research Ethics Committee. Results will be published in peer-reviewed medical journals with eligible investigators will significantly contribute. TRIAL REGISTRATION NUMBER: ACTRN12620000261910.
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    Combination of MRI prostate and 18F-DCFPyl PSMA PET/CT detects all clinically significant prostate cancers in treatment-naive patients: An international multicentre retrospective study
    Parathithasan, N ; Perry, E ; Taubman, K ; Hegarty, J ; Talwar, A ; Wong, L-M ; Sutherland, T (WILEY, 2022-10)
    INTRODUCTION: Clinical and biochemical assessment and biopsies can miss clinically significant prostate cancers (csPCa) in up to 20% of patients and diagnose clinically insignificant tumours leading to overtreatment. This retrospective study analyses the accuracy of 18 F-DCFPyL PET/CT in detecting csPCa as a primary diagnostic tool and directly compares it with mpMRI prostate in treatment-naive patients. The two modalities are then correlated to determine whether they are better in combination, than either alone. METHODS: This is a retrospective dual-institution study of patients who underwent contemporaneous MRI and PSMA-PET between January 2017 and March 2020 with histologic confirmation. The images were re-reviewed and concordance between modalities assessed. Results were compared with histopathology to determine the ability of MRI and PSMA-PET to detect csPCA. RESULTS: MRI and PSMA-PET detected the same index lesion in 90.8% of cases with a kappa of 0.82. PET detected an additional 6.2% of index lesions which were MRI occult. MRI detected an additional 3.1% which were PET occult. No additional csPCa was identified on pathology which was not seen on imaging. The sensitivity of PSMA-PET in detecting csPCa is 96.7% and that of MRI is 93.4% with no statistically significant difference between the two (P = 0.232). Both modalities detected all four cases of non-csPCa with these being considered false positives. CONCLUSION: Both mpMRI and 18F-DCFPyL-PSMA-PET/CT have high sensitivity for detecting csPCa with high agreement between modalities. There were no synchronous csPCa lesions detected on pathology that were not detected on imaging too.
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    Non-prostate cancer tumours: incidence on 18F-DCFPyL PSMA PET/CT and uptake characteristics in 1445 patients
    Perry, E ; Talwar, A ; Sharma, S ; O'Connor, D ; Wong, L-M ; Taubman, K ; Sutherland, TR (SPRINGER, 2022-07)
    PURPOSE: With increasing use of PSMA PET/CT in the staging and restaging of prostate cancer (PCa), the identification of non-prostate cancer tumours (NPCaT) has become an increasing clinical dilemma. Atypical presentations of PSMA expression in prostate cancer and expression in NPCaT are not well established. Understanding the normal and abnormal distribution of PSMA expression is essential in preparing clinically relevant reports and in guiding multidisciplinary discussion and decisions. METHODS: Retrospective review of 1445 consecutive 18F-DCFPyL PSMA PET/CT studies by experienced radiologists and nuclear medicine physicians. Lesions indeterminate for PCa were identified. Correlation was made with patient records, biopsy results, and dedicated imaging. Lesions were then categorized into four groups: 1. Confirmed prostate cancer, metastases, 2. NPCaT 3. Benign, and 4. Indeterminate lesions. RESULTS: 68/1445 patients had lesions atypical for prostate cancer metastases. These comprised 8/68 (11.8%) atypical prostate cancer metastases, 17/68 (25.0%) NPCaT, 29/68 (42.6%) indeterminate, and 14/68 (20.6%) benign. In the context of the entire cohort, these are adjusted to 8/1445 (0.6%), 17/1445 (1.2%), 29/1445 (2.0%), and 14/1445 (1.0%) respectively. With the exception of Renal Cell Carcinoma (RCC), NPCaT demonstrated no or low PSMA expression. A similar trend was also observed for indeterminate and benign lesions. Conversely, most atypical PCa metastases demonstrated intermediate or high PSMA expression. CONCLUSION: 18F-DCFPyL PSMA PET/CT detection of NPCaT is low. Lesions demonstrating intermediate to high PSMA expression were exclusively prostate cancer metastases, aside from RCC, and lesions detected in organs with high background expression.
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    Feasibility for active surveillance in biopsy Gleason 3+4 prostate cancer: an Australian radical prostatectomy cohort
    Wong, L-M ; Tang, V ; Peters, J ; Costello, A ; Corcoran, N (WILEY, 2016-04)
    OBJECTIVE: To examine the feasibility of active surveillance for low volume Gleason sum (GS) 3 + 4 disease compared to GS 3 + 3 disease. PATIENTS AND METHODS: Retrospective review of 929 patients, with biopsy proven GS 3 + 3 and 3 + 4 PCa, undergoing upfront radical prostatectomy (RP) was performed. Suitability for AS was adapted from protocols by Royal Marsden Hospital, University of Toronto, and PRIAS by allowing Gleason 3 + 4 disease. The outcomes assessed were adverse pathology at RP (upgrading ≥GS 4 + 3 and/or upstaging ≥pT3) and biochemical recurrence (BCR) after RP. RESULTS: Adverse pathology at RP was compared between GS 3 + 3 vs 3 + 4 groups. When selecting patients using Royal Marsden (n = 714) or University of Toronto (n = 699) protocols, there was statistically significantly more adverse pathology at RP in GS 3 + 4 group (21% vs 31%, P = 0.0028 and 19% vs 33%, P=<0.001 respectively). Using the more stringent PRIAS protocol (n = 198), there was no statistical significant difference in groups. There was no difference in BCR survival between biopsy GS 3 + 3 and 3 + 4 groups, regardless of which AS protocol assessed. Pre-operative PSA and clinical staging were the predictors for BCR. CONCLUSION: Presence of Gleason 3 + 4 at biopsy, when compared to 3 + 3, increases the risk of adverse pathology being present at radical prostatectomy for less stringent selection criteria. When considering AS, a stricter protocol such as PRIAS, limiting PSA density and number of positive cores to ≤2, appears to decrease the risk of adverse pathology. No differences in BCR were seen between biopsy 3 + 3 and 3 + 4 disease, regardless of AS selection criteria.
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    PSMA PET/CT to guide salvage treatment post prostatectomy: The IMPPORT trial
    Koschel, S ; Guerrieri, M ; Chao, M ; Foo, M ; Sutherland, T ; Taubman, K ; Yap, K ; Schlicht, S ; Booth, R ; Gyomber, D ; Lenaghan, D ; Wong, L ; Ng, M (Elsevier BV, 2020-07)
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    Which has more complications?-Shockwave lithotripsy versus endoscopic treatment of renal calculi with 1-year follow-up in an Australian population
    Farag, M ; Jack, GS ; Papa, N ; Wong, L-M ; Bolton, DM ; Lenaghan, D (WILEY, 2021-07)
    INTRODUCTION AND OBJECTIVES: Renal calculi are a common medical problem with incidence rates calculated to be approximately 6%-9% in men & 3%-4% in women worldwide. Incidence appears to be increasing. This study compares emergency presentations and unplanned readmissions between extracorporeal shock wave lithotripsy (SWL) and pyeloscopic stone treatment in the population of Victoria, Australia after 1-year follow-up. METHODS: This is a population study comparing all patients with renal calculi electively treated with SWL to those initially treated with flexible ureteroscopy (URS) in Victoria, Australia. We used data linkage across the state of Victoria to follow patients treated with either modality in a 12 months period (with no urological surgery in the prior 12 months). Each patient's emergency presentations and subsequent re-admissions were followed up for 1 year after their index treatment to assess for stone complications. We assessed for selection bias between the two patient groups by comparing age, gender, insurance status, geographical location, and comorbidity scores. RESULTS: We report stone-related complications for 739 flexible URS and 1317 SWL procedures undertaken across public and private hospitals in Victoria over 12 months. Unplanned emergency presentations within 60-days of surgery were (22/739) 2.98% for flexible URS patients and (83/1317) 6.30% for SWL patients (P = .001); however, at 12 months, this became 16.23% (120/739) for flexible URS patients and 12.83% (169/1317) for SWL patients (P = .034). Flexible URS patients were more likely than SWL patients to be admitted with 71.76% of flexible URS versus 53.97% of SWL patients requiring an admission at any given emergency presentation (P ≤ .001) within 12 months. On multivariate analysis, both flexible URS ([OR] 1.67, CI 1.23-2.26, P = .001) and being a public patient ([OR] 3.06, CI 2.24-4.18, P < .001) significantly increased the likelihood that patients required an unplanned re-admission within 12 months. CONCLUSIONS: There is work needed to reduce emergency presentations and unplanned re-admissions after both SWL and flexible URS. At 12-months follow-up, unplanned emergency visits and re-admission rates were significantly more after flexible URS. Symptoms at emergency presentation indicate that better education regarding stent management is needed, especially in the public health care system.
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    Prostate magnetic resonance imaging and the value of experience: An intrareader variability study
    Whish-Wilson, T ; Tan, J-L ; Cross, W ; Wong, L-M ; Sutherland, T (ELSEVIER SINGAPORE PTE LTD, 2023-10)
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    What is the best way to manage ureteric calculi in the time of COVID‐19? A comparison of extracorporeal shockwave lithotripsy (SWL) and ureteroscopy (URS) in an Australian health‐care setting
    Farag, M ; Jack, GS ; Wong, L ; Bolton, DM ; Lenaghan, D (Wiley, 2021-03)
    OBJECTIVES: To determine the best way to intervene for ureteric stones which still require treatment during the COVID-19 pandemic, with respect to infection control. In this setting, in which resources are constrained, extracorporeal shockwave lithotripsy (SWL) has prima facie advantages over ureteroscopy (URS). It is also necessary to also consider posttreatment resource consumption in regards to complications and repeat procedures. SUBJECTS AND METHODS: The ideal ureteric stone treatment during a pandemic such as COVID-19 would involve minimum resource consumption and a minimum number of patient attendances. We compared all patients initially treated with SWL to those initially treated with URS for acute ureteral colic within the state of Victoria, Australia in 2017. RESULTS: A total of 2724 ureteric stones were analyzed, a cumulative "3-month exposure and burden on the healthcare system" was calculated for each patient by their initial procedure type. The readmission rate for URS was significantly higher than for SWL, 0.92 readmissions/patient for URS versus 0.54 readmissions/patient for SWL (P < .001). The cumulative hospital stay per patient for these two procedures was 2.35 days for SWL versus 3.21 days for URS (P < .001). The number of procedures per patient was 1.52 for SWL versus 1.89 for URS (P = .0213). CONCLUSIONS: Patients with ureteric stones treated initially by SWL have shorter length of stay with fewer overall attendances and procedures at 3 months than those treated with URS. During a pandemic such as COVID-19, SWL may have benefits in preserving hospital resources and limiting opportunity for virus transmission, compared to URS.