With increased lung cancer screening, early-stage diagnoses and recurrences are expected to rise. Identifying the ~20% of patients with early-stage non-small cell lung cancer (NSCLC), including lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), who relapse after curative-intent surgery remains a major clinical challenge. Here, we identify a COX-2-associated pro-tumorigenic inflammatory signature (PTI) in resected tumors as an independent predictor of disease relapse in both LUAD and LUSC, with particular utility within one year after surgery in stage I NSCLC. We developed a clinically compatible workflow for PTI scoring in tumor resections and validated its predictive performance in real-world samples from routine care and screening programs. Spatial immune profiling revealed that PTIhigh tumors, which swiftly recur, exhibit markedly reduced tumor cell content alongside expanded neutrophil-rich immune-stromal compartments. These findings link COX-2-driven inflammation to early post-surgical recurrence in NSCLC and indicate that PTI may serve as a biomarker for risk stratification to guide imaging surveillance and adjuvant therapy decisions.

Background and objective: Evidence on the cost effectiveness of decision aids to guide management decisions for men with prostate cancer is limited. We examined the cost utility of the Navigate online decision aid for men with prostate cancer in comparison to usual care (no decision aid). Methods: A Markov model with a 10-yr time horizon was constructed from a government health care perspective. Data from the Navigate trial (n = 302) and relevant published studies were used for model inputs. Incremental costs and quality-adjusted life-years (QALYs) were calculated for the two strategies. One-way and probabilistic sensitivity analyses were undertaken to address model uncertainty. Key findings and limitations: On average, the Navigate strategy was estimated to cost AU$8899 (95% uncertainty interval [UI] AU$7509-AU$10 438) and produce 7.08 QALYs (95% UI 6.73-7.36) in comparison to AU$9559 (95% UI AU$8177-AU$11 017) and 7.03 QALYs (95% UI 6.67-7.31) or usual care. The Navigate strategy dominated usual care as it produced cost-savings and higher QALYs, although differences for both outcomes were small over 10 yr. The likelihood of Navigate being cost effective at a conventionally acceptable threshold of AU$50 000 per QALY gained was 99.7%. This study is limited by the availability, quality, and choice of the data used in the model. Conclusions and clinical implications: Use of an online decision aid for men with pros-tate cancer appears to be cost effective relative to usual care in Australia, driven by the higher acceptance and uptake of active surveillance. Wider implementation of deci-sion aids may better inform men diagnosed with prostate cancer about their manage-ment options. Patient summary: We looked at the cost effectiveness of an online decision aid for guid-ing Australian men with prostate cancer in choosing a management option. We found that this decision aid was cost effective, mainly because more men chose active surveil-lance. Decision aids that inform patients about their management options should be more widely used in health care. (c) 2024 European Association of Urology. Published by Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

ObjectivesTo construct and externally calibrate a predictive model for early biochemical recurrence (BCR) after radical prostatectomy (RP) incorporating clinical and modern imaging characteristics of the primary tumour.Patients and MethodsPatients who underwent RP following multiparametric magnetic resonance imaging, prostate biopsy and prostate‐specific membrane antigen‐positron emission tomography/computed tomography (PSMA‐PET/CT), from two centres in Australia and the Netherlands. The primary outcome was biochemical recurrence‐free survival (BRFS), where BCR was defined as a rising PSA level of ≥0.2 ng/mL or initiation of postoperative treatment per clinician discretion. Proportional hazards models to predict time to event were developed in the Australian sample using relevant pre‐ and post‐surgical parameters and primary tumour maximum standardised uptake value (SUVmax) on diagnostic PSMA‐PET/CT. Calibration was assessed in an external dataset from the Netherlands with the same inclusion criteria.ResultsData from 846 patients were used to develop the models. Tumour SUVmax was associated with worse predicted 3‐year BRFS for both pre‐ and post‐surgical models. SUVmax change from 4 to 16 lessened the predicted 3‐year BRFS from 66% to 42% for a patient aged 65 years with typical pre‐surgical parameters (PSA level 8 ng/mL, Prostate Imaging‐Reporting and Data System score 4/5 and biopsy Gleason score ≥4 + 5). Considering post‐surgical variables, a patient with the same age and PSA level but pathological stage pT3a, RP Gleason score ≥4 + 5 and negative margins, SUVmax change from 4 to 16 lessened the predicted 3‐year BRFS from 76% to 61%. Calibration on an external sample (n = 464) showed reasonable performance; however, a tendency to overestimate survival in patients with good prognostic factors was observed.ConclusionTumour SUVmax on diagnostic PSMA‐PET/CT has utility additional to commonly recognised variables for prediction of BRFS after RP.

Background: Preoperative assessment of the probability of pelvic lymph-node meta-static disease (pN1) is required to identify patients with prostate cancer (PCa) who are candidates for extended pelvic lymph-node dissection (ePLND).Objective: To develop a novel intuitive prognostic nomogram for predicting pathological lymph-node (pN) status in contemporary patients with primary diagnosed localized PCa, using preoperative clinical and histopathological parameters, magnetic resonance imaging (MRI), and prostate-specific membrane antigen (PSMA) positron emission tomography (PET).Design, setting, and participants: In total, 700 eligible patients who underwent robot -assisted radical prostatectomy and ePLND were included in the model-building cohort. The external validation cohort consisted of 305 surgically treated patients. Logistic regression with backward elimination was used to select variables for the Amsterdam-Brisbane-Sydney nomogram.Outcome measurements and statistical analysis: Performance of the final model was evaluated using the area under the receiver operating characteristic curve (AUC), calibration plots, and decision-curve analyses. Models were subsequently validated in an external population.Results and limitations: The Amsterdam-Brisbane-Sydney nomogram included initial prostate-specific antigen value, MRI T stage, highest biopsy grade group (GG), biopsy technique, percentage of systematic cores with clinically significant PCa (GG >= 2), and lymph-node status on PSMA-PET. The AUC for predicting pN status was 0.81 (95% confidence interval [CI] 0.78-0.85) for the final model. On external validation, the Amsterdam-Brisbane-Sydney nomogram showed superior discriminative ability to the Briganti-2017 and Memorial Sloan Kettering Cancer Center (MSKCC) nomograms (AUC 0.75 [95% CI 0.69-0.81] vs 0.67 [95% CI 0.61-0.74] and 0.65 [95% CI 0.58-0.72], respectively; p < 0.05), and similar discriminative ability to the Briganti-2019 nomogram (AUC 0.78 [95% CI 0.71-0.86] vs 0.80 [95% CI 0.73-0.86]; p = 0.76). The Amsterdam-Brisbane -Sydney nomogram showed excellent calibration on external validation, with an increased net benefit at a threshold probability of >= 4%.Conclusions: The validated Amsterdam-Brisbane-Sydney nomogram performs superior to the Briganti-2017 and MSKCC nomograms, and similar to the Briganti-2019 nomogram. Furthermore, it is applicable in all patients with newly diagnosed unfavorable intermediate-and high-risk PCa.Patient summary: We developed and validated the Amsterdam-Brisbane-Sydney nomogram for the prediction of prostate cancer spread to lymph nodes before surgery. This nomogram performs similar or superior to all presently available nomograms.(c) 2023 The Author(s). Published by Elsevier B.V. on behalf of European Association of Urology.

PURPOSE:The Prostate Imaging Reporting and Data System (PI-RADS) score is standard of care for clinically significant prostate cancer (csPCa) diagnosis. The PRIMARY score (prostate-specific membrane antigen [PSMA]-positron emission tomography [PET]/CT) also has high diagnostic accuracy for csPCa. This study aimed to develop an easily calculated combined (P) score for csPCa detection (International Society of Urological Pathology [ISUP] ≥2) incorporating separately read PI-RADS and PRIMARY scores, with external validation. MATERIALS AND METHODS:Two datasets of men with suspected PCa, no prior biopsy, recent MRI and 68Ga-PSMA-11-PET/CT, and subsequent transperineal biopsy were evaluated. These included the development sample (n = 291, 56% csPCa) a prospective trial and the validation sample (n = 227, 67% csPCa) a multicenter retrospective database. Primary outcome was detection of csPCa (ISUP ≥2), with ISUP ≥ 3 cancer detection a secondary outcome. Score performance was evaluated by area under the curve, sensitivity, specificity, and decision curve analysis. RESULTS:The 5-point combined (P) score was developed in a prospective dataset. In the validation dataset, csPCa was identified in 0%, 20%, 52%, 96%, and 100% for P score 1 to 5. The area under the curve was 0.93 (95% CI: 0.90-0.96), higher than PI-RADS 0.89 (95% CI: 0.85-0.93, P = .039) and PRIMARY score alone 0.84 (95% CI: 0.79-0.89, P < .001). Splitting scores at 1/2 (negative) vs 3/4/5 (positive), P score sensitivity was 94% (95% CI: 89-97) compared to PI-RADS 89% (95% CI: 83-93) and PRIMARY score 86% (95% CI: 79-91). For ISUP ≥ 3, P score sensitivity was 99% (95% CI: 95-100) vs 94% (95% CI: 88-98) and 92% (95% CI: 85-97) for PI-RADS and PRIMARY scores respectively. A maximum standardized uptake value > 12 (P score 5) was ISUP ≥ 2 in all cases with 93% ISUP ≥ 3. CONCLUSIONS:The P score is easily calculated and improves accuracy for csPCa over both PI-RADS and PRIMARY scores. It should be considered when PSMA-PET is undertaken for diagnosis.

Objective: To conduct a systematic literature review on urethral calculi in a contemporary cohort describing etiology, investigation, and management patterns. Methods: A systematic search of MEDLINE and Cochrane Central Register of Controlled Trials (CENTRAL) databases was performed. Articles, including case reports and case series on urethral calculi published between January 2000 and December 2019, were included. Full-text manuscripts were reviewed for clinical parameters including symptomatology, etiology, medical history, investigations, treatment, and outcomes. Data were collated and analyzed with univariate methods. Results: Seventy-four publications met inclusion criteria, reporting on 95 cases. Voiding symptoms (41.1%), pain (40.0%), and acute urinary retention (32.6%) were common presenting features. Urethral calculi were most often initially investigated using plain X-ray (63.2%), with almost all radio-opaque (98.3%). Urethral calculi were frequently associated with coexistent bladder or upper urinary tract calculi (16.8%) and underlying urethral pathology (53.7%) including diverticulum (33.7%) or stricture (13.7%). Urethral calculi were most commonly managed with external urethrolithotomy (31.6%), retrograde manipulation (22.1%), and endoscopic in situ lithotripsy (17.9%). Conclusion: This unique systematic review of urethral calculi provided a summary of clinical features and treatment trends with a suggested treatment algorithm. Management in contemporary urological practice should be according to calculus size, shape, anatomical location, and presence of urethral pathology.

Testicular loss or absence can present for a range of reasons including congenital absence of testis to orchidectomy. Men undergo orchidectomy for numerous reasons including testicular cancer, cryptorchidism, and chronic orchialgia. In 2020, 74 500 men were diagnosed with testicular cancer globally leading to a potential significant role for testicular prostheses [1]. Although under-utilised, testicular prostheses, commonly silicone or saline filled, can appear like normal testicles within the scrotum, which may help restore normal physical appearance and improve quality of life for patients missing one or two testes [2]. Qualitative studies found that men were generally satisfied with testicular prostheses and do not regret inserting them; however, they are generally too firm and do not feel similarly to healthy human testicles [3]. Given there is a recommended volume range for fluid-filled testicular prostheses, this work tested the hardness of fluid-filled prostheses and determined the optimal fill volume that most closely mimics the human testicle stiffness. This study was exempted from institutional ethical approval given there was no human testing or participation, and all testing was performed on samples of testicular prostheses provided by the company in bench-top laboratory testing. Nine Torosa® (Coloplast Corp., Minneapolis, MN, USA) fluid-filled testicular prostheses were acquired for hardness testing. The nine prostheses were broken down to three samples per size: small (S), medium (M), and large (L). The saline fill procedure followed the manufacturer's guidelines regarding technique, maximum number of punctures, and the fill volume level was controlled within the guideline range per prosthesis size (Torosa Saline-Filled Testicular Prosthesis – Filling Procedure). Testing was conducted at empty, minimum, middle, and maximum recommended fill volumes for all sizes. The recommended fill volume ranges were 8–9 mL for S, 11–12 mL for M, and 15–16 mL for L. Empty was 0 mL across all sizes; minimum volume was 8 mL (S), 11 mL (M), and 15 mL (L); middle volume was 8.5 mL (S), 11.5 mL (M), and 15.5 mL (L); and maximum volume was 9 mL (S), 12 mL (M), and 16 mL (L). Hardness testing was conducted using the Shore Hardness Scale, as this method has been shown to be an effective method of measuring skin hardness by measuring the resistance of a material to indentation using a device with a spring-loaded indenter [6]. A Shore OO durometer (DSD, Starr Instruments, Auckland, New Zealand) was calibrated and tested for accuracy prior to carrying out the hardness testing (Fig. 1). Hardness testing was carried out vertically ('bottom') at the injection site opposite from the suture site, and horizontally ('side') in the middle of the implant and 90 ° from side ('90s') (Fig. 1). Both 'side' and '90s' were tested as there was a material seam that was remnant from the manufacturing process. Testing was repeated on 'bottom', 'side', and '90s' for each prosthesis three times and an average value was calculated for each prosthesis at 'bottom', 'side', and '90s'. Two-tailed t-test demonstrated no statistical difference for hardness values between 'side' and '90s' for all testicular prostheses in all fill volumes (P > 0.20), therefore only results for 'side' are reported further. Skewes et al. [4] converted the human testicle E-modulus values determined by shear-wave elastography to the Shore OO Hardness Scale resulting in interpreted Shore OO values between 10 and 20. This study uses this conversion to compare the hardness of fluid-filled prostheses measured here using Shore Hardness testing to the human testicular stiffness values reported in literature (mean [SD] 28 [6] kPa) [5] in order to provide guidance on optimal fill volumes. In all nine testicular prostheses, regardless of prosthesis size and fill volume, the vertical testing was harder than the horizontal testing, which is likely due to the increased thickness of both the injection site and the opposite suture site. The mean (SD) Shore Hardness value for 'bottom' testing did not vary across the sizes and measured 78 (6) (n = 108 total tests), with the L-size being the hardest at 81 (3). The 'side' testing was expectedly variable across different fill volumes. A two-way analysis of variance was conducted between all fill volumes with alpha set to 0.05. There was a significant difference in hardness across all volumes where minimum (mean [SD] 23.1 [6.7]) was less hard than middle (mean [SD] 31.4 [8.7], P = 0.04), which in turn was less hard than maximum (mean [SD] 46.1 [6.4], P < 0.001). The minimum recommended fill volume was not statistically different from the baseline empty prosthesis (mean [SD] 15.9 [4.6], P = 0.10). However, there were some data discrepancies: the linear hardness increase with increasing fill volumes was not seen at all levels for the M-size (Fig. 1, right) and one of the L-size protheses was harder than the rest across all fill volumes. For all prostheses, no fill volume was able to achieve the range of a human testicle. All sizes and fill levels were too hard with the recommended minimum fill volume providing a hardness most similar to that of a human testicle (mean [SD] 23.1 [6.7] for minimum vs 10–20 of human testicle, Fig. 1). However, there was a dimple noted in the prostheses (Fig. 1, middle), most prominent in the S- and M-size, at the minimal recommended fill volume and it was unavoidable to regain the shape of the prosthesis without introducing air bubbles. To avoid the dimple in the prosthesis without introducing any air bubbles, injecting an extra 0.2 mL above minimum recommended fill appeared sufficient to regain the shape of the prosthesis. Achieving better prosthesis satisfaction may prove challenging given current implant design parameters such as material and sizing. Current silicone prostheses available in Australia include solid silicone N&S implant by Promedon (Promedon GmbH, Kolbermoor, Germany) and both solid and gel-filled silicone implants by Polytech (POLYTECH Health & Aesthetics GmbH, Dieburg, Germany) [6]. Gel-filled silicone implants have been reported to more closely resemble the hardness of a human testicle while solid silicone implants and fluid-filled implants measured harder than a human testicle [4]. As fluid-filled prostheses measured harder, the knowledge of their optimal fill volume is timely. Achieving an appropriate prosthesis size may affect patient satisfaction in terms of feel and visualisation. However, appropriate sizing is made more difficult because there are currently no standardised sizes between prostheses companies. Readily available orchidometers from companies or standard sizing, such as the French sizing system, could enable more standardised testicular implant sizing. Although there is a recommended fill range, which is specific to the prosthesis size, this study demonstrates that the minimal end of the recommended fill range is most similar to the human testicle hardness. Given that dissatisfaction with current testicular prostheses can be because they are generally too firm and do not feel similar to human testicles [3], injecting the minimal fill volume possible without creating a dimple is likely to improve patient satisfaction with the prosthesis given it most closely resembles the hardness of a human testicle. This study's findings are consistent with Hayon et al. [3] who recommend a lower fill volume, within the range set by the manufacture, based on qualitative assessment. In fluid-filled testicular prostheses, the lowest fill achievable without creating a dimple within the recommended fill volume range was measured to be the most optimal fill to best mimic the hardness of a human testicle. This work has been supported by Metro North Health through Herston Biofabrication Institute, and The University of Queensland. Matthew Roberts is supported by a Clinician Research Fellowship from the Metro North Office of Research, Queensland Health and Research Support Package from The University of Queensland. The Torosa® testicular prostheses were kindly supplied by Coloplast (Minneapolis, MN, USA) for research purposes, but they were not involved in the study design or result interpretation. Open access publishing facilitated by The University of Queensland, as part of the Wiley - The University of Queensland agreement via the Council of Australian University Librarians. None.

Objective This study aimed to quantify the out-of-pocket (OOP) costs and perceived financial burden among Australian men with localised prostate cancer in the first 6 months after diagnosis, by primary management option.Methods This cost-analysis quantified OOP costs using administrative claims data and self-reported survey data. Financial burden was assessed using the COmprehensive Score for financial Toxicity-Functional Assessment of Chronic Illness Therapy (COST-FACIT) tool. Participants were recruited into a randomised control trial from public or private treatment centres in Victoria and Queensland. Generalised linear models were used to predict OOP costs and COST-FACIT scores.Results Median total OOP costs within 6 months of diagnosis for 256 Australian patients with localised prostate cancer was A$1172 (A$343-2548). Up to 50% of the sample reported A$0 costs for most medical services. Compared with those managed with active surveillance, men having active treatment had 6.4 (95% CI: 3.2-12.7) times greater total OOP costs. Management option, higher Gleason score at diagnosis and having multiple comorbidities were significant predictors of higher OOP costs. Overall high scores on the COST-FACIT indicated low levels of financial burden for the entire sample.Conclusion Largely attributable to being managed with active surveillance, Australian men diagnosed with localised prostate cancer reported relatively low OOP costs and financial burden in the first 6 months post-diagnosis. Together with clinical outcomes, clinicians can use this up to date evidence on costs and perceived financial burdens to assist localised prostate cancer patients and their families make informed decisions about their preferred management option. What is known about the topic? International evidence suggests that men with low-risk prostate cancer managed with active surveillance initially incur lower out-of-pocket costs than those managed with active treatment. What does this paper add? Australian men with low-risk prostate cancer report low out-of-pocket costs and financial burden in the first 6 months post-diagnosis. Compared with those managed with active surveillance, men having active treatment had 6-7 times greater out-of-pocket expenses. What are the implications for practitioners? Being managed by active surveillance as the primary management option for low-risk prostate cancer reduces the financial burdens associated with a cancer diagnosis.

Abstract Lung cancer is the most common cause of cancer-related deaths with Non-Small Cell Lung Cancer (NSCLC) accounting for ~85% of cases. Patients with early-stage NSCLC (stages I-IIIA) undergo surgery with curative intent but up to 30% relapse. Identification of biomarkers that predict outcome at the point of surgery could inform patient management. Here, we explored whether a COX-2-based pro-tumourigenic inflammatory gene signature (PTI), measured in surgically resected samples from early-stage NSCLC patients, can predict patient outcome. Gene expression analysis was performed on 30 formalin fixed paraffin embedded surgical tumour samples from early-stage NSCLC patients with 36-63 months follow-up, using a custom code-set on the NanoString nCounter® platform. Additionally, in silico analysis of early-stage NSCLC data from The Cancer Genome Atlas (TCGA) was undertaken. The PTI gene signature and a published signature associated with T cell-inflamed tumours measuring IFNγ activity (IFNG)1 were assessed in both datasets and correlated with patient outcome. NanoString gene expression data was robust, displaying good correlations with immunohistochemistry (IHC) expression for key proteins such as CD8 and COX-2, R=0.88, p<1 × 10−6 and R=0.83, p<1 × 10−6, respectively. The IFNG signature score, widely reported to associate with response to checkpoint inhibitors2, did not correlate with outcome and consistent with this observation neither did CD8 protein expression (by IHC). In contrast, patients with LUSC (n=16) with the highest (upper quartile) PTI score showed significantly worse overall survival (p<0.01). Median overall survival for these PTIhigh patients was <6 months vs 4.5 years for LUSC patients with PTIlow scores. Analysis of TCGA data from stage I-IIIA LUAD/LUSC cases confirmed these contrasting findings for the PTI compared with the IFNG signature. A multiplexed IHC panel for immune contexture analysis was successfully transferred from the Coussens Laboratory Oregon to CRUK Manchester3 and with inclusion of COX-2 in this panel and adaptation of the pipeline for use with the HALO image analysis platform, analysis of the immune contexture in PTI high versus low tumours is underway. Transcriptional profiling of early-stage NSCLC samples revealed that COX-2-associated inflammation predicts patient outcome following surgery. These data highlight the importance of pro-tumourigenic inflammation in early-stage NSCLC. Findings are under validation in a larger cohort, including early-stage NSCLC samples from Manchester’s early-detection screening studies and mapping of the immune contexture of PTI high versus low tumours is underway. 1: Ayers, M., et al., J Clin Invest., 2017 2: Danaher, P., et al., J Immunother Cancer., 2018 3: Banik, G., et al., Methods Enzymol., 2020 Citation Format: Victoria Fife, Matthew Roberts, Christian P. Bromley, Derrick Morgan, Sophie Atkinson, Cong Zhou, Anshuman Chaturvedi, Steven Bagley, Garry Ashton, Lisa M. Coussens, Philip A. Crosbie, Caroline Dive, Elaine Kilgour, Santiago Zelenay. A COX-2-based pro-tumourigenic inflammatory signature predicts poor outcome in early-stage non-small cell lung cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5572.

Background:Prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) can detect multiparametric magnetic resonance imaging (mpMRI)-invisible prostate tumours and improve the sensitivity of detection of prostate cancer (PCa) in comparison to mpMRI alone. Numerous risk calculators have been validated as tools for stratification of men at risk of being diagnosed with clinically significant (cs)PCa. Objective:To develop a novel risk calculator using clinical parameters and imaging parameters from mpMRI and PSMA PET/CT in a cohort of patients undergoing mpMRI and PSMA PET/CT before biopsy. Design setting and participants:A total of 291 men from the PRIMARY prospective trial underwent mpMRI and PSMA PET/CT before transperineal prostate biopsy with sampling of systematic and targeted cores. Outcome measurements and statistical analysis:Novel risk calculators were developed using multivariable logistic regression analysis to predict detection of overall PCa (International Society of Urological Pathology grade group [GG] ≥1) and csPCa (GG ≥2). The risk calculators were then compared with the European Randomised Study of Screening for Prostate Cancer risk calculator incorporating mpMRI (ERSPC-MRI). Resampling methods were used to evaluate the discrimination and calibration of the risk calculators and to perform decision curve analysis. Results and limitations:Age, prostate-specific antigen, prostate volume, and mpMRI Prostate Imaging-Reporting and Data System scores were included in the MRI risk calculator, resulting in area under the receiver operating characteristic curve (AUC) values of 0.791 for overall PCa (GG ≥1) and 0.812 for csPCa (GG ≥2). Addition of the maximum standardised uptake value (SUVmax) on PSMA PET/CT for the prostate lesion, and of SUVmax for the mpMRI lesions for the MRI-PSMA risk calculator resulted in AUCs of 0.831 for overall PCa and 0.876 for csPCa (≥ISUP2).The ERSPC-MRI risk calculator had AUCs of 0.758 (p = 0.02) for overall PCa and 0.805 (p = 0.001) for csPCa. Both the MRI and MRI-PSMA risk calculators were superior to the ERSPC-MRI for both overall PCa and csPCa. Conclusions:These novel risk calculators incorporate clinical and radiological parameters for stratification of men at risk of csPCa. The risk calculator including PSMA PET/CT data is superior to a calculator incorporating mpMRI data alone. Patient summary:We evaluated a new risk calculator that uses clinical information and results from two types of scan to predict the risk of clinically significant prostate cancer on prostate biopsy. This risk model can guide patients and clinicians in shared decision-making and may help in avoiding unnecessary prostate biopsies.

BJU InternationalVolume 132, Issue 2 p. 146-148 Comment Treatment de-intensification for low-risk biochemical recurrence after radical prostatectomy: rational or risky? Matthew J. Roberts, Corresponding Author Matthew J. Roberts [email protected] orcid.org/0000-0003-0552-7402 Department of Urology, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia Faculty of Medicine, University of Queensland Centre for Clinical Research, Brisbane, Queensland, Australia Correspondence: Matthew Roberts, Department of Urology, Royal Brisbane and Women's Hospital, Brisbane, Queensland 4006, Australia. e-mail: [email protected]Search for more papers by this authorGeorge Hruby, George Hruby Department of Radiation Oncology, Royal North Shore Hospital, Sydney, New South Wales, Australia Genesis Cancer Care, Sydney, New South Wales, AustraliaSearch for more papers by this authorAndrew Kneebone, Andrew Kneebone Department of Radiation Oncology, Royal North Shore Hospital, Sydney, New South Wales, Australia Genesis Cancer Care, Sydney, New South Wales, AustraliaSearch for more papers by this authorJarad M. Martin, Jarad M. Martin Department of Radiation Oncology, Calvary Mater Newcastle, Waratah, New South Wales, Australia Genesis Care, Maitland, Metford, New South Wales, AustraliaSearch for more papers by this authorScott G. Williams, Scott G. Williams Sir Peter MacCallum Department of Oncology, Melbourne University, Parkville, Victoria, Australia Prostate Cancer Theranostics and Imaging Centre of Excellence, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia Division of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, AustraliaSearch for more papers by this authorMark Frydenberg, Mark Frydenberg Department of Surgery, Department of Anatomy and Developmental Biology, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Victoria, Australia Cabrini Research, Cabrini Health, Melbourne, Victoria, AustraliaSearch for more papers by this authorDeclan G. Murphy, Declan G. Murphy orcid.org/0000-0002-7500-5899 Sir Peter MacCallum Department of Oncology, Melbourne University, Parkville, Victoria, Australia Prostate Cancer Theranostics and Imaging Centre of Excellence, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, Victoria, AustraliaSearch for more papers by this authorBen Namdarian, Ben Namdarian St Vincent's Hospital, Darlinghurst, Sydney, New South Wales, AustraliaSearch for more papers by this authorJohn W. Yaxley, John W. Yaxley Department of Urology, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia Faculty of Medicine, University of Queensland Centre for Clinical Research, Brisbane, Queensland, AustraliaSearch for more papers by this authorMichael S. Hofman, Michael S. Hofman orcid.org/0000-0001-8622-159X Sir Peter MacCallum Department of Oncology, Melbourne University, Parkville, Victoria, Australia Prostate Cancer Theranostics and Imaging Centre of Excellence, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia Molecular Imaging and Therapeutic Nuclear Medicine, Peter MacCallum Cancer Centre, Victoria, Melbourne, AustraliaSearch for more papers by this authorIan D. Davis, Ian D. Davis Eastern Health Clinical School, Monash University, Victoria, Melbourne, Australia Department of Cancer Services, Eastern Health, Melbourne, Victoria, AustraliaSearch for more papers by this authorLouise Emmett, Louise Emmett Department of Theranostics and Nuclear Medicine, St. Vincent's Hospital Sydney, Darlinghurst, New South Wales, Australia Faculty of Medicine, University of New South Wales, Sydney, New South Wales, AustraliaSearch for more papers by this author Matthew J. Roberts, Corresponding Author Matthew J. Roberts [email protected] orcid.org/0000-0003-0552-7402 Department of Urology, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia Faculty of Medicine, University of Queensland Centre for Clinical Research, Brisbane, Queensland, Australia Correspondence: Matthew Roberts, Department of Urology, Royal Brisbane and Women's Hospital, Brisbane, Queensland 4006, Australia. e-mail: [email protected]Search for more papers by this authorGeorge Hruby, George Hruby Department of Radiation Oncology, Royal North Shore Hospital, Sydney, New South Wales, Australia Genesis Cancer Care, Sydney, New South Wales, AustraliaSearch for more papers by this authorAndrew Kneebone, Andrew Kneebone Department of Radiation Oncology, Royal North Shore Hospital, Sydney, New South Wales, Australia Genesis Cancer Care, Sydney, New South Wales, AustraliaSearch for more papers by this authorJarad M. Martin, Jarad M. Martin Department of Radiation Oncology, Calvary Mater Newcastle, Waratah, New South Wales, Australia Genesis Care, Maitland, Metford, New South Wales, AustraliaSearch for more papers by this authorScott G. Williams, Scott G. Williams Sir Peter MacCallum Department of Oncology, Melbourne University, Parkville, Victoria, Australia Prostate Cancer Theranostics and Imaging Centre of Excellence, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia Division of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, AustraliaSearch for more papers by this authorMark Frydenberg, Mark Frydenberg Department of Surgery, Department of Anatomy and Developmental Biology, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Victoria, Australia Cabrini Research, Cabrini Health, Melbourne, Victoria, AustraliaSearch for more papers by this authorDeclan G. Murphy, Declan G. Murphy orcid.org/0000-0002-7500-5899 Sir Peter MacCallum Department of Oncology, Melbourne University, Parkville, Victoria, Australia Prostate Cancer Theranostics and Imaging Centre of Excellence, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, Victoria, AustraliaSearch for more papers by this authorBen Namdarian, Ben Namdarian St Vincent's Hospital, Darlinghurst, Sydney, New South Wales, AustraliaSearch for more papers by this authorJohn W. Yaxley, John W. Yaxley Department of Urology, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia Faculty of Medicine, University of Queensland Centre for Clinical Research, Brisbane, Queensland, AustraliaSearch for more papers by this authorMichael S. Hofman, Michael S. Hofman orcid.org/0000-0001-8622-159X Sir Peter MacCallum Department of Oncology, Melbourne University, Parkville, Victoria, Australia Prostate Cancer Theranostics and Imaging Centre of Excellence, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia Molecular Imaging and Therapeutic Nuclear Medicine, Peter MacCallum Cancer Centre, Victoria, Melbourne, AustraliaSearch for more papers by this authorIan D. Davis, Ian D. Davis Eastern Health Clinical School, Monash University, Victoria, Melbourne, Australia Department of Cancer Services, Eastern Health, Melbourne, Victoria, AustraliaSearch for more papers by this authorLouise Emmett, Louise Emmett Department of Theranostics and Nuclear Medicine, St. Vincent's Hospital Sydney, Darlinghurst, New South Wales, Australia Faculty of Medicine, University of New South Wales, Sydney, New South Wales, AustraliaSearch for more papers by this author First published: 22 May 2023 https://doi.org/10.1111/bju.16086Citations: 1Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat No abstract is available for this article. References 1Mottet N, Bellmunt J, Briers E et al. EAU – ESTRO – ESUR – SIOG Guidelines on Prostate Cancer. Arnhem, The Netherlands: EAU Guidelines Office, 2022 2Adam M, Tennstedt P, Lanwehr D et al. Functional outcomes and quality of life after radical prostatectomy only versus a combination of prostatectomy with radiation and hormonal therapy. Eur Urol 2017; 71: 330–6 3Fendler WP, Calais J, Eiber M et al. Assessment of 68Ga-PSMA-11 PET accuracy in localizing recurrent prostate cancer: A prospective single-arm clinical trial. JAMA Oncol 2019; 5: 856–63 4Emmett L, Tang R, Nandurkar R et al. 3-year freedom from progression after (68)Ga-PSMA PET/CT-triaged Management in men with biochemical recurrence after radical prostatectomy: Results of a prospective multicenter trial. J Nucl Med 2020; 61: 866–72 5Roberts MJ, Chatfield MD, Hruby G et al. Event-free survival after radical prostatectomy according to prostate-specific membrane antigen-positron emission tomography and European Association of Urology biochemical recurrence risk groups. BJU Int 2022; 130(Suppl 3): 32–9 6Jani AB, Schreibmann E, Goyal S et al. 18F-fluciclovine-PET/CT imaging versus conventional imaging alone to guide postprostatectomy salvage radiotherapy for prostate cancer (EMPIRE-1): A single Centre, open-label, phase 2/3 randomised controlled trial. Lancet 2021; 397: 1895–904 Citing Literature Volume132, Issue2August 2023Pages 146-148 ReferencesRelatedInformation

BACKGROUND:Multiparametric magnetic resonance imaging (mpMRI) has an established role for the diagnosis of clinically significant prostate cancer (sPCa). The PRIMARY trial demonstrated that [68Ga]Ga-PSMA-11 positron emission tomography/computed tomography (PET/CT) was associated with a significant improvement in sensitivity and negative predictive value for sPCa detection. OBJECTIVE:To demonstrate that addition of prostate-specific membrane antigen (PSMA) radioligand PET/CT will enable some men to avoid transperineal prostate biopsy without missing sPCa, and will facilitate biopsy targeting of PSMA-avid sites. DESIGN, SETTING, AND PARTICIPANTS:This multicentre, two-arm, phase 3, randomised controlled trial will recruit 660 participants scheduled to undergo biopsy. Eligible participants will have clinical suspicion of sPCa with a Prostate Imaging-Reporting and Data System (PI-RADS) score of 2 and red flags, or a PI-RADS score of 3 on mpMRI (PI-RADS v2). Participants will be randomised at a 1:1 ratio in permuted blocks stratified by centre. The trial is registered on ClinicalTrials.gov as NCT05154162. INTERVENTION:In the experimental arm, participants will undergo pelvic PSMA PET/CT. Local and central reviewers will interpret scans independently using the PRIMARY score. Participants with a positive result will undergo targeted transperineal prostate biopsies, whereas those with a negative result will undergo prostate-specific antigen monitoring alone. In the control arm, all participants undergo template transperineal prostate biopsies. Participants will be followed for subsequent clinical care for up to 2 yr after randomisation. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:sPCa is defined as Gleason score 3 + 4 (≥10%) = 7 disease (grade group 2) or higher on transperineal prostate biopsy. Avoidance of transperineal prostate biopsy will be measured at 6 mo from randomisation. The primary endpoints will be analysed on an intention-to-treat basis. CONCLUSIONS:Patient enrolment began in March 2022, with recruitment expected to take 36 mo. PATIENT SUMMARY:For patients with suspected prostate cancer who have nonsuspicious or unclear MRI (magnetic resonance imaging) scan findings, a different type of scan (called PSMA PET/CT; prostate-specific membrane antigen positron emission tomography/computed tomography) may identify men who could avoid an invasive prostate biopsy. This type of scan could also help urologists in better targeting of samples from suspicious lesions during prostate biopsies.

Background/objectives Inadequate movement, excess adiposity, and insulin resistance augment cardiometabolic risk. This study examined the associations of objectively measured moderate-to-vigorous intensity physical activity (MVPA), sedentary time and cardiorespiratory fitness (CRF), with adipose tissue insulin resistance and ectopic fat. Methods Data were combined from two previous experimental studies with community volunteers ( n = 141, male = 60%, median (interquartile range) age = 37 (19) years, body mass index (BMI) = 26.1 (6.3) kg·m -2 ). Adipose tissue insulin resistance was assessed using the adipose tissue insulin resistance index (Adipo-IR); whilst magnetic resonance imaging (MRI) was used to measure liver, visceral (VAT) and subcutaneous abdominal adipose tissue (ScAT). Sedentary time and MVPA were measured via an ActiGraph GT3X+ accelerometer. Generalized linear models examined the association of CRF, MVPA, and sedentary time with Adipo-IR and fat depots. Interaction terms explored the moderating influence of age, sex, BMI and CRF. Results After controlling for BMI and cardiometabolic variables, sedentary time was positively associated with Adipo-IR (β = 0.68 AU [95%CI = 0.27 to 1.10], P < 0.001). The association between sedentary time and Adipo-IR was moderated by age, CRF and BMI; such that it was stronger in individuals who were older, had lower CRF and had a higher BMI. Sedentary time was also positively associated with VAT (β = 0.05 L [95%CI = 0.01 to 0.08], P = 0.005) with the relationship being stronger in females than males. CRF was inversely associated with VAT (β = −0.02 L [95%CI = −0.04 to −0.01], P = 0.003) and ScAT (β = −0.10 L [95%CI = −0.13 to −0.06], P < 0.001); with sex and BMI moderating the strength of associations with VAT and ScAT, respectively. Conclusions Sedentary time is positively associated with adipose tissue insulin resistance which regulates lipogenesis and lipolysis. CRF is independently related to central fat storage which is a key risk factor for cardiometabolic disease.

The objective of this study is to determine if there was a difference in rate of post-transplantation urinary tract infection (UTI) in patients who have an indwelling catheter inserted using sterile versus clean technique. UTI is the most common nosocomial infection in the post-transplantation period. We aim to describe risk factors associated with postoperative UTI in our institution and determine if there was a difference between those who have an indwelling catheter inserted using sterile versus clean technique. Risk factors for UTIs can be divided into recipient, donor, and procedure related factors. While an indwelling urinary catheter increases the risk of infection, it is vital for post-operative fluid balance monitoring. Given the morbidity of UTIs in transplant recipients, a number of studies have investigated modifiable risk factors; however, investigation of the technique of indwelling catheter insertion at the time of renal transplantation is yet to be examined. A retrospective analysis of a contemporaneously maintained database was performed of renal transplant recipients over a 2-year period from 2019-2021. Patients were divided into sterile versus clean technique, defined as the use of sterile gloves, gown and fenestrated drape following a surgical scrub, or sterile gloves alone following the use of alcohol-based hand sanitiser respectively. A p value of <0.05 was considered statistically significant. One hundred sixty-nine patients were included in analysis, with 31 UTIs (18.3%) within 30 days of renal transplantation. Female gender and autosomal dominant polycystic kidney disease were associated with a higher rate of UTI. One hundred twenty-three patients had a catheter inserted via sterile technique, and 46 with clean technique, with no significant difference in rate of post-operative UTI (p = 0.52). Inserting an indwelling catheter either by sterile or clean technique at the time of renal transplantation was not associated with the rate of postoperative UTI within 30 days.

Perioperative immune checkpoint inhibitor (ICI) trials for intermediate high-risk clear cell renal cell carcinoma (ccRCC) have failed to consistently demonstrate improved patient outcomes. These unsuccessful ICI trials suggest that the tumour infiltrating immunophenotypes, termed here as the immune cell types, states and their spatial location within the tumour microenvironment (TME), were unfavourable for ICI treatment. Defining the tumour infiltrating immune cells may assist with the identification of predictive immunophenotypes within the TME that are favourable for ICI treatment. To define the immunophenotypes within the ccRCC TME, fresh para-tumour (pTME, n = 2), low-grade (LG, n = 4, G1-G2) and high-grade (HG, n = 4, G3-G4) tissue samples from six patients with ccRCC presenting at a tertiary referral hospital underwent spatial transcriptomics sequencing (ST-seq). Within the generated ST-seq datasets, immune cell types and states, termed here as exhausted/pro-tumour state or non-exhausted/anti-tumour state, were identified using multiple publicly available single-cell RNA and T-cell receptor sequencing datasets as references. HG TMEs revealed abundant exhausted/pro-tumour immune cells with no consistent increase in expression of PD-1, PD-L1 and CTLA4 checkpoints and angiogenic genes. Additional HG TME immunophenotype characteristics included: pro-tumour tissue-resident monocytes with consistently increased expression of HAVCR2 and LAG3 checkpoints; an exhausted CD8+ T cells sub-population with stem-like progenitor gene expression; and pro-tumour tumour-associated macrophages and monocytes within the recurrent TME with the expression of TREM2. Whilst limited by a modest sample size, this study represents the largest ST-seq dataset on human ccRCC. Our study reveals that high-risk ccRCC TMEs are infiltrated by exhausted/pro-tumour immunophenotypes lacking specific checkpoint gene expression confirming that HG ccRCC TME are immunogenic but not ICI favourable.

Combined magnetic resonance imaging (MRI) and positron emission tomography/computed tomography (PET/CT) may enhance diagnosis, aid surgical planning and intra-operative orientation for prostate biopsy and radical prostatectomy. Although PET-MRI may provide these benefits, PET-MRI machines are not widely available. Image fusion of Prostate specific membrane antigen PET/CT and MRI acquired separately may be a suitable clinical alternative. This study compares CT-MR registration algorithms for urological prostate cancer care. Paired whole-pelvis MR and CT scan data were used (n = 20). A manual prostate CTV contour was performed independently on each patients MR and CT image. A semi-automated rigid-, automated rigid- and automated non-rigid registration technique was applied to align the MR and CT data. Dice Similarity Index (DSI), 95% Hausdorff distance (95%HD) and average surface distance (ASD) measures were used to assess the closeness of the manual and registered contours. The automated non-rigid approach had a significantly improved performance compared to the automated rigid- and semi-automated rigid-registration, having better average scores and decreased spread for the DSI, 95%HD and ASD (all p < 0.001). Additionally, the automated rigid approach had similar significantly improved performance compared to the semi-automated rigid registration across all accuracy metrics observed (all p < 0.001). Overall, all registration techniques studied here demonstrated sufficient accuracy for exploring their clinical use. While the fully automated non-rigid registration algorithm in the present study provided the most accurate registration, the semi-automated rigid registration is a quick, feasible, and accessible method to perform image registration for prostate cancer care by urologists and radiation oncologists now.