James Edward Thompson

Purpose: This case series describes the experiences and outcomes of multiple Australian surgeons performing robotic-assisted bladder diverticulectomy (RABD), highlighting the procedural effectiveness and safety, for both benign and malignant indications for diverticulectomy. Methods: Outcomes were analyzed from 13 experienced Australian urologists who performed RABD between 2016 and 2023. Retrospective analysis was performed on prospectively collected data, which included patient demographics, diverticulum characteristics, surgical approaches, and post-operative outcomes. Surgical techniques included the extravesical and intravesical approaches, with the focus on maintaining oncological principles in cases of malignancy. Results: A total of 28 patients underwent RABD, with the majority being male and a mean age of 63.9 years. All surgeons utilized a four-port transperitoneal approach and opted for the extravesical dissection of the diverticular neck; one case utilized both an extravesical and a trans-diverticular approach. Functional outcomes demonstrated symptomatic resolution in patients with nonmalignant diverticula, whereas oncological outcomes indicated clear margins in 90% of malignant cases. The average length of the procedure was 106 minutes, with minimal blood loss and a mean hospital stay of 2.67 days. Early complications occurred in 14% with the majority Clavien–Dindo grade II. Conclusion: Robotic bladder diverticulectomy, predominantly via the transperitoneal extravesical approach, has emerged as a safe, effective, and reliable surgical intervention for both malignant and nonmalignant bladder diverticula. The consistent surgical approach and excellent outcomes demonstrated in this case series reinforce the procedure’s potential as a safe option, even in the setting of malignancy within a diverticulum.

Objectives: To prospectively compare systemic anti‐tumour immune responses induced by irreversible electroporation (IRE) and robot‐assisted radical prostatectomy (RARP) in patients with localised intermediate‐risk prostate cancer (PCa). Patients and Methods: Between February 2021 and June 2022, before and after treatment (at 5, 14 and 30 days) peripheral blood samples of 30 patients with localised PCa were prospectively collected. Patient inclusion criteria were: International Society of Urological Pathologists Grade 2–3, clinical cancer stage ≤T2c, prostate‐specific antigen level n = 20) or RARP ( n = 10). Frequency and activation status of lymphocytic and myeloid immune cell subsets were determined using flow cytometry. PCa‐specific T‐cell responses to prostatic acid phosphatase (PSAP) and cancer testis antigen (New York oesophageal squamous cell carcinoma 1 [NY‐ESO‐1]) were determined by interferon‐γ enzyme‐linked immunospot assay (ELISpot). Repeated‐measures analysis of variance and two‐sided Student's t ‐tests were used to compare immune responses over time and between treatment cohorts. Results: Patient and tumour characteristics were similar between the cohorts except for age (median 68 years [IRE] and 62 years [RARP], P = 0.01). IRE induced depletion of systemic regulatory T cells ( P = 0.0001) and a simultaneous increase in activated cytotoxic T‐lymphocyte antigen 4 (CTLA‐4) ⁺ cluster of differentiation (CD)4 ⁺ ( P < 0.001) and CD8 ⁺ ( P = 0.032) T cells, consistent with reduction of systemic immune suppression allowing for effector T‐cell activation, peaking 14 days after IRE. Effects were positively correlated with tumour volume/ablation size. Accordingly, IRE induced expansion of PSAP and/or NY‐ESO‐1 specific T‐cell responses in four of the eight immune competent patients. Temporarily increased activated myeloid derived suppressor cell frequencies ( P = 0.047) were consistent with transient immunosuppression after RARP. Conclusions: Irreversible electroporation induces a PCa‐specific systemic immune response in patients with localised PCa, aiding conversion of the tumour microenvironment into a more immune permissive state. Therapeutic efficacy might be further enhanced by combination with CTLA‐4 checkpoint inhibition, potentially opening up a new synergistic treatment paradigm for high‐risk localised or (oligo)metastatic disease.

Objective: To evaluate the additional value of prostate‐specific membrane antigen positron emission tomography (PSMA‐PET) to conventional diagnostic tools to select patients for hemi‐ablative focal therapy (FT). Patients and Methods: We performed a retrospective analysis on a multicentre cohort (private and institutional) of 138 patients who underwent multiparametric magnetic resonance imaging (mpMRI), PSMA‐PET, and systematic biopsies prior to radical prostatectomy between January 2011 and July 2021. Patients were eligible when they met the consensus criteria for FT: PSA 0.5 mm or seminal vesicle involvement at final histopathology. The diagnostic accuracy of mpMRI, systematic biopsies and PSMA‐PET for csPCa (separate and combined) was calculated within a four‐quadrant prostate model by receiver‐operating characteristic and 2 × 2 contingency analysis. Additionally, we assessed whether the diagnostic tools correctly identified patients suitable for hemi‐ablative FT. Results: In total 552 prostate quadrants were analysed and 272 (49%) contained csPCa on final histopathology. The area under the curve, sensitivity, specificity, positive predictive value and negative predictive value for csPCa were 0.79, 75%, 83%, 81% and 77%, respectively, for combined mpMRI and systematic biopsies, and improved after addition of PSMA‐PET to 0.84, 87%, 80%, 81% and 86%, respectively ( P < 0.001). On final histopathology 46/138 patients (33%) were not suitable for hemi‐ablative FT. Addition of PSMA‐PET correctly identified 26/46 (57%) non‐suitable patients and resulted in 4/138 (3%) false‐positive exclusions. Conclusions: Addition of PSMA‐PET to the conventional work‐up by mpMRI and systematic biopsies could improve selection for hemi‐ablative FT and guide exclusion of patients for whom whole‐gland treatments might be a more suitable treatment option.

Objectives: To prospectively assess the safety, functional‐ and oncological‐outcomes of irreversible electroporation (IRE) as salvage therapy for radio‐recurrent focal prostate cancer in a multicenter setting. Patients and methods: Men with focal recurrent PCa after external beam radiation or brachytherapy without metastatic disease on staging imaging and co‐registration between mpMRI and biopsies were prospectively included in this multicenter trial. Adverse events were reported following the Clavien‐Dindo classification. Validated questionnaires were used for patient‐reported functional outcomes. Follow‐up consisted of 3 monthly prostate specific antigen (PSA) levels, a 6‐month mpMRI and standardised transperineal template mapping biopsies at 12‐months. Thereafter follow‐up was guided by MRI and/or PSMA‐PET/CT and PSA. Local recurrence was defined as any ISUP score ≥2 on biopsies. Results: 37 patients were analysed with a median (interquartile range (IQR)) follow up of 29 (22–43) months. Median age was 71 (53–83), median PSA was 3.5 ng/mL (2.7–6.1). 28 (75.5%) patients harboured intermediate risk and 9 patients (24.5%) high risk PCa. Seven patients (19%) reported self‐limiting urgency, frequency, or hematuria (grade 1–2). Seven patients (19%) developed a grade 3 AE; urethral sludge requiring transurethral resection. At 12 months post treatment 93% of patients remained continent and erectile function sufficient for intercourse deteriorated from 35% to 15% (4/27). Local control was achieved in 29 patients (78%) and 27 patients (73%) were clear of local and systemic disease. Four (11%) patients had local recurrence only. Six (16%) patients developed metastatic disease with a median time to metastasis of 8 months. Conclusion: The FIRE trial shows that salvage IRE after failed radiation therapy for localised PCa is safe with minimal toxicity, and promising functional and oncological outcomes. Salvage IRE can offer a possible solution for notoriously difficult to manage radio recurrent prostate tumours.

Objectives: To evaluate the safety, and short to mid‐term oncological and quality‐of‐life (QoL) outcomes of focal irreversible electroporation (IRE) for radio‐recurrent prostate cancer (PCa) at a median follow‐up of 4 years. Patients and Methods: This was a single‐centre series of men with biopsy‐proven radio‐recurrent PCa treated with IRE between December 2013 and February 2022, with a minimum follow‐up of 6 months. Follow‐up included magnetic resonance imaging at 6 months, and standard transperineal saturation template biopsies at 12 months. Further biopsies were guided by suspicion on serial imaging or prostate‐specific antigen (PSA) levels. Validated questionnaires were used to measure functional outcomes. Significant local recurrence was defined as any International Society of Urological Pathology (ISUP) score ≥ 2 on biopsies. Progression‐free survival was defined as no signs of local or systemic disease on either imaging or template biopsies, or according to the Phoenix criteria for biochemical recurrence. Results: Final analysis was performed on 74 men with radio‐recurrent PCa (median age 69 years, median PSA level 5.4 ng/mL, 76% ISUP score 2/3). The median (range) follow‐up was 48 (27–68) months. One rectal fistula occurred, and eight patients developed urethral sloughing that resolved with transurethral resection. Among patients who returned questionnaires (30/74, 41%), 93% (28/30) had preserved urinary continence and 23% (7/30) had sustained erectile function at 12‐month follow‐up. Local control was achieved in 57 patients (77%), who needed no further treatment. Biopsy diagnosed 41(55%) patients received follow up template biopsies, in‐field recurrences occurred in 7% (3/41), and out‐field recurrences occurred in 15% of patients (6/41). The metastasis‐free survival rate was 91% (67/74), with a median (interquartile range) time to metastases of 8 (5–27) months. The Kaplan–Meier estimated 5‐year progression‐free survival rate was 60%. Conclusions: These short‐ to mid‐term safety, oncological and QoL outcome data endorse results from smaller series and show the ability of salvage focal IRE to safely achieve oncological control in patients with radio‐recurrent PCa.

Objectives: To evaluate longer‐term oncological and functional outcomes of focal irreversible electroporation (IRE) as primary treatment for localised clinically significant prostate cancer (csPCa) at a median follow‐up of 5 years (up to 10 years). Patients and Methods: All patients that underwent focal IRE as primary treatment for localised PCa between February 2013 and August 2021 with a minimum 12 months of follow‐up were analysed. Follow‐up included 6‐month magnetic resonance imaging (MRI) and standardised transperineal saturation template ± targeted biopsies at 12 months, and further biopsies in the case of clinical suspicion on serial imaging and/or prostate‐specific antigen (PSA) levels. Failure‐free survival (FFS) was defined as no progression to radical treatment or nodal/distant disease. Local recurrence was defined as any International Society of Urological Pathology Grade of ≥2 on biopsy. Results: A total of 229 patients were analysed with a median (interquartile range [IQR]) follow‐up of 60 (40–80) months. The median (IQR) age was 68 (64–74) years, the median (IQR) PSA level was 5.9 (4.1–8.2) ng/mL, and 86% harboured intermediate‐risk disease and 7% high‐risk disease. In all, 38 patients progressed to radical treatment (17%), at a median (IQR) of 35 (17–53) months after IRE. Kaplan–Meier FFS rates were 91% at 3 years, 84% at 5 years and 69% at 8 years. Metastasis‐free survival was 99.6% (228/229), PCa‐specific and overall survival were 100% (229/229). Residual csPCa was found in 24% (45/190) during follow‐up biopsy and MRI showed a complete ablation in 82% (186/226). Short‐term urinary continence was preserved (98%, three of 144 at baseline, 99%, one of 131 at 12 months) and erections sufficient for intercourse decreased by 13% compared to baseline (71% to 58%). Conclusion: Longer‐term follow‐up confirms our earlier findings that focal IRE provides acceptable local and distant oncological control in selected men with less urinary and sexual toxicity than radical treatment. Long‐term follow‐up and external validation of these findings, is required to establish this new treatment paradigm as a valid treatment option.

Objectives: To identify whether synchronous reading of multiparametric magnetic resonance imaging (mpMRI) and ⁶⁸ Ga‐PSMA‐11 positron emission tomography (PET)/computed tomography (prostate‐specific membrane antigen [PSMA‐PET]) images can improve diagnostic performance and certainty compared with mpMRI/PSMA‐PET reported independently and synthesized, while also assessing concordance between imaging modalities and agreement with histopathology. Methods: This was a retrospective analysis of 100 patients randomly selected from the PRIMARY trial, a prospective Phase II multicentre imaging trial. Three dual‐trained radiologist/nuclear medicine physicians re‐reported the mpMRI and PSMA‐PET both independently and synchronously for the same patients in random order, blinded to previous results. Diagnostic performance was assessed for mpMRI/PSMA‐PET images read synchronously or independently and then synthesized. Agreement between imaging results and histopathology was examined. ‘Concordance’ between imaging modalities was defined as overlapping lesions. Reporting certainty was evaluated by the individual reporters for each modality. Results: International Society of Urological Pathology Grade Group ≥2 cancer was present in 60% of patients on biopsy. Synchronous reading of mpMRI/PSMA‐PET increased sensitivity compared to mpMRI or PSMA‐PET alone (93% vs 80% vs 88%, respectively), although specificity was not improved (63% vs 58% vs 78%, respectively). No significant difference in diagnostic performance was noted between mpMRI/PSMA‐PET read synchronously and mpMRI or PSMA‐PET reported independently and then synthesized. Most patients had concordant imaging (60%), while others had discordant lesions only (28%) or a mixture (concordant and discordant lesions; 12%). When mpMRI/PSMA‐PET findings were concordant and positive, 95% of patients had clinically significant prostate cancer (csPCa). When PSMA‐PET alone was compared to synchronous PSMA‐PET/MRI reads, there was an improvement in reader certainty in 20% of scans. Conclusion: Synchronous mpMRI/PSMA‐PET reading improves reader certainty and sensitivity for csPCa compared to mpMRI or PSMA‐PET alone. However, synthesizing the results of independently read PSMA‐PET and mpMRI reports provided similar diagnostic performance to synchronous PSMA‐PET/MRI reads. This may provide greater flexibility for urologists in terms of referral patterns, reducing healthcare system costs and improving efficiencies in prostate cancer diagnosis.

Bladder cancer is one of the top ten most common cancers and top ten causes of cancer death globally. 5-year survival rates have decreased in Australia from 66% to 55% in the past three decades. The current gold standard for diagnosis is cystoscopy. However, cystoscopies are an invasive and health-resource intensive procedure which has sub-optimal sensitivity for flat lesions such as CIS (carcinoma in situ) and low specificity for differentiating inflammation from cancer - hence requiring biopsies under anesthesia. Frequent and life-long surveillance cystoscopy is required for most patients since there are high rates of progression and local recurrence in high-risk non-muscle invasive cancer (NMIBC) as well as poor outcomes associated with delayed detection of muscle-invasive bladder cancer (MIBC). There is an unmet need for a non-invasive test to provide better discrimination and risk-stratification of bladder cancer which could aid clinicians by improving patient selection for cystoscopy; enhanced risk stratification methods may guide the frequency of surveillance cystoscopies and inform treatment choices. Exosomes, which are nano-sized extracellular vesicles containing genetic material and proteins, have been shown to have functional roles in the development and progression of bladder cancer. Exosomes have also been demonstrated to be a robust source of potential biomarkers for bladder cancer diagnosis and prognosis and may also have roles as therapeutic agents. In this review, we summarize the latest evidence of biological roles of exosomes in bladder cancer and highlight their clinical significance in bladder cancer diagnosis, surveillance and treatment.