Surgery (St Vincent's) - Research Publications
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ItemDistant Nodes Seen on PSMA PET-CT Staging Predicts Post-Treatment Progression in Men with Newly Diagnosed Prostate Cancer-A Prospective Cohort Study(MDPI, 2022-12)PSMA PET-CT scans are now recommended in international urological guidelines for primary staging and re-staging of prostate cancer. However, there is little published literature on the clinical outcomes for patients after treatment decisions made using PSMA PET-CT results. This is a multisite, prospective cohort study investigating the clinical outcomes of men who received treatment plans based on PSMA PET-CT results for primary staging. Men with biopsy proven prostate cancer received a PSMA PET-CT scan for primary staging. Treatment plans were recommended by multidisciplinary teams (MDT). After treatment, these men were followed with 6 monthly PSA tests and imaging or biopsies if recommended by MDT. The primary outcome was treatment progression defined as the addition or change of any treatment modalities such as androgen deprivation therapy, radiation therapy or chemotherapy. In total, 80% of men did not have any treatment progression after enactment of treatment based on PSMA PET-CT primary staging results at 29 months of follow up. Men who had distant nodes seen on PSMA PET-CT had a 5 times increased risk of treatment progression. Larger studies with longer follow up are needed to validate our results and optimise the way clinicians use PSMA PET-CT results to guide management.
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ItemPEDAL protocol: a prospective single-arm paired comparison of multiparametric MRI and 18F-DCPFyl PSMA PET/CT to diagnose prostate cancer(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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ItemNovel Germline Mutations in a Cohort of Men with Familial Prostate Cancer(MDPI, 2022-08)Background: Germline mutations in BRCA2 are associated with aggressive prostate cancer. Additional information regarding the clinical phenotype of germline pathogenic variants in other prostate cancer predisposition genes is required. Clinical testing has been limited by evidence, further restricting knowledge of variants that contribute to prostate cancer development. Objective: Prostate cancer patients who were first- and second-degree relatives from multi-case prostate cancer families underwent a gene panel screen to identify novel (non-BRCA) germline pathogenic variants in cancer predisposition genes and define clinical phenotypes associated with each gene. Methods: The germline genomic DNA (gDNA) of 94 index cases with verified prostate cancer from families with a minimum of two verified prostate cancer cases was screened with an 84-cancer-gene panel. Families were recruited for multi-case breast/ovarian cancer (n = 66), or multi-case prostate cancer (n = 28). Prostate cancer characteristics associated with each gene were compared with prostate cancer cases of confirmed non-mutation carriers (BRCAX), also from multi-case prostate cancer families (n = 111), and with data from the Prostate Cancer Outcomes Registry (PCOR). Results: Ninety-four prostate cancer index cases underwent gene panel testing; twenty-two index cases (22/94; 23%) were found to carry a class 4-5 (C4/5) variant. Six of twenty-two (27%) variants were not clinically notifiable, and seven of twenty-two (31.8%) variants were in BRCA1/2 genes. Nine of twenty-two (40.9%) index cases had variants identified in ATM (n = 4), CHEK2 (n = 2) and HOXB13G84 (n = 3); gDNA for all relatives of these nine cases was screened for the corresponding familial variant. The final cohort comprised 15 confirmed germline mutation carriers with prostate cancer (ATM n = 9, CHEK2 n = 2, HOXB13G84 n = 4). ATM and CHEK2-associated cancers were D'Amico intermediate or high risk, comparable to our previously published BRCA2 and BRCAX prostate cancer cohort. HOXB13G84 carriers demonstrated low- to intermediate-risk prostate cancer. In the BRCAX cohort, 53.2% of subjects demonstrated high-risk disease compared with 25% of the PCOR cohort. Conclusions:ATM and CHEK2 germline mutation carriers and the BRCAX (confirmed non-mutation carriers) cohort demonstrated high risk disease compared with the general population. Targeted genetic testing will help identify men at greater risk of prostate-cancer-specific mortality. Data correlating rare variants with clinical phenotype and familial predisposition will strengthen the clinical validity and utility of these results and establish these variants as significant in prostate cancer detection and management.
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ItemTumor immune microenvironment of primary prostate cancer with and without germline mutations in homologous recombination repair genes(BMJ PUBLISHING GROUP, 2022-06)BACKGROUND: Aberrations in homologous recombination repair (HRR) genes are emerging as important biomarkers for personalized treatment in prostate cancer (PCa). HRR deficiency (HRD) could affect the tumor immune microenvironment (TIME), potentially contributing to differential responses to poly ADP-ribose polymerase (PARP) inhibitors and immune checkpoint inhibitors. Spatial distribution of immune cells in a range of cancers identifies novel disease subtypes and is related to prognosis. In this study we aimed to determine the differences in the TIME of PCa with and without germline (g) HRR mutations. METHODS: We performed gene expression analysis, multiplex immunohistochemistry of T and B cells and quantitative spatial analysis of PCa samples from 36 patients with gHRD and 26 patients with sporadic PCa. Samples were archival tumor tissue from radical prostatectomies with the exception of one biopsy. Results were validated in several independent cohorts. RESULTS: Although the composition of the T cell and B cells was similar in the tumor areas of gHRD-mutated and sporadic tumors, the spatial profiles differed between these cohorts. We describe two T-cell spatial profiles across primary PCa, a clustered immune spatial (CIS) profile characterized by dense clusters of CD4+ T cells closely interacting with PD-L1+ cells, and a free immune spatial (FIS) profile of CD8+ cells in close proximity to tumor cells. gHRD tumors had a more T-cell inflamed microenvironment than sporadic tumors. The CIS profile was mainly observed in sporadic tumors, whereas a FIS profile was enriched in gHRD tumors. A FIS profile was associated with lower Gleason scores, smaller tumors and longer time to biochemical recurrence and metastasis. CONCLUSIONS: gHRD-mutated tumors have a distinct immune microenvironment compared with sporadic tumors. Spatial profiling of T-cells provides additional information beyond T-cell density and is associated with time to biochemical recurrence, time to metastasis, tumor size and Gleason scores.
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ItemPSMA PET-CT Imaging Predicts Treatment Progression in Men with Biochemically Recurrent Prostate Cancer-A Prospective Study of Men with 3 Year Follow Up(MDPI, 2022-06)Prostate-specific membrane antigen (PSMA) positron emission tomography-computed tomography (PET-CT) is a novel imaging modality used to stage recurrent prostate cancer. It has the potential to improve prognostication and ultimately guide the timing of treatment for men with recurrent prostate cancer. This study aims to assess the clinical impact of PSMA PET-CT by analyzing its predictive value of treatment progression after 3 years of follow-up. In this prospective cohort study of 100 men, patients received a PSMA PET-CT for restaging of their disease which was used by a multi-disciplinary team to make a treatment decision. The primary endpoint was treatment progression. This was defined as the addition or change of any treatment modalities such as androgen deprivation therapy (ADT), radiation therapy or chemotherapy. The median follow-up time was 36 months (IQR 24-40 months). No treatment progression was found in 72 (75%) men and therefore 24 (25%) patients were found to have treatment progression. In men with a negative PSMA PET-CT result, 5/33 (15.1%) had treatment progression and 28/33 (84.8%) had no treatment progression. In conclusion, clinical decisions made with PSMA PET-CT results led to 75% of men having no treatment progression at 3 years of follow-up. In men with negative PSMA PET-CT results, this increased to 85% of men.
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ItemUreteric orifice obstruction by catheter balloon Post-TURP: A rare cause of obstructive uropathy(ELSEVIER SCIENCE INC, 2022-01)A 50-year-old male underwent small volume TURP for median lobe prostatic hypertrophy. Post-procedure, a 3-way urethral catheter was placed. He subsequently developed flank pain, anuria and creatinine rise. CT demonstrated bilateral obstructive uropathy. In the absence of obstructing lesions, it was suspected that the catheter balloon may have caused obstruction of bilateral ureteric orifices. Balloon deflation (from 30 to 10 mL) and catheter repositioning resulted in rapid resolution of pain and resumption of urine output. Urologists should consider the catheter balloon as a cause of obstructive uropathy, especially after procedures where normal trigonal anatomy is disrupted.
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ItemReview of the use of prophylactic drain tubes post-robotic radical prostatectomy: Dogma or decent practice?(WILEY, 2020-09)OBJECTIVE: To assess the necessity of routine prophylactic drain tube use following robot-assisted radical prostatectomy (RARP). METHOD: We performed a literature review using the Medline, Scopus, and Web of Science databases with no restriction of language from January 1900 to January 2020. The following terms we used in the literature search: prostatectomy, radical prostatectomy, robot assisted, drainage, and drain tube. RESULTS: We identified six studies that examined the use of routine prophylactic drain tubes following RARP. One of these studies was a randomized study that included 189 patients, with 97 in the pelvic drain (PD) arm and 92 in the no pelvic drain (ND) arm. This non-inferiority showed an early (90-day) complication rate of 17.4% in the ND arm versus 26.8% in the PD arm (P < .001). Another non-inferiority randomized control trial (RCT) showed a complication rate of 28.9% in the PD group versus 20.4% in the ND group (P = .254). Similarly, the other studies found no benefit of routine use of prophylactic drain tube after RARP. CONCLUSION: Drain tubes play a role during robotic-assisted radical prostatectomy, however, following a review of the current available literature, they can be safely omitted and we suggest that clinicians may be selective in their use.
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ItemWhich has more complications?-Shockwave lithotripsy versus endoscopic treatment of renal calculi with 1-year follow-up in an Australian population(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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ItemWhat 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(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.