New therapies are needed for patients who experience primary or secondary resistance to renal cell cancer (RCC) treatment. Pre-clinical data suggests PARP inhibitors may be effective for RCC in combination with VEGF inhibitors. Neoadjuvant clinical trials offer an opportunity to understand the mechanisms of new therapies by comparing tumour and blood before and after treatment. WIRE is a window of opportunity, phase II, multi-centre, multi-arm, non-randomised, neoadjuvant clinical trial platform (NCT03741426). Arms 1-3 comprised: 1. cediranib (VEGF inhibitor), 2. cediranib + olaparib (PARP inhibitor), 3. olaparib. Eligible patients (pts) have cT1b+, cN0/1, cM0/1 clear cell RCC, planned for surgery, with no contraindication to IMP. A Bayesian adaptive design optimises recruitment to arms based on interim analyses of treatment effects. Pts receive 14-28 days of IMP to fit with the planned surgery date. Primary endpoint for arms 1-3 is a ≥30% reduction in DCE-MRI assessed capillary permeability (median Ktrans) post-treatment compared to baseline. Secondary endpoints include RECIST v1.1 primary tumour response and adverse events. Translational analysis will include blood profiling and multi-region tissue analysis by transcriptomics and digital pathology. 29 pts were recruited (arm 1=6, arm 2=16, arm 3=7), 28/29 were male, median age 61y (range 48-75y). All pts were treatment naïve with ECOG PS of 0 or 1. 8/29 pts had M1 disease. All surgeries were completed within the planned window. 3/29 pts were not evaluable for the primary endpoint due to inadequate dose of IMP. The numbers of evaluable pts which met the primary endpoint were arm 1: 4/6 (67%), arm 2: 4/14 (29%), arm 3: 0/6 (0%). Table 1 shows changes in Ktrans, RECIST response and adverse events. Plasma angiogenic factors were significantly induced on treatment in the combination therapy arm 2. There was no correlation between angiogenic factor induction and Ktrans change. Positive responses in median Ktrans were observed in both the cediranib monotherapy and cediranib and olaparib combination therapy arms. Therapy was well tolerated, with no substantial toxicity or delays to surgery. Greater induction of angiogenic factors in the combination arm indicates possible synergy between cediranib and olaparib. Ongoing translational analysis of tissue and blood samples will investigate the mechanisms of response to these agents. James O. Jones, Ines Horvat Menih, Martin Thomas, Helen Mossop, Rebecca Wray, Maria Aquino, James Armitage, Harriet Baker, Carley Batley, James Blackmur, Sarah Burge, Anita Chhabra, Farhana Easita, Tim Eisen, Kate Fife, Angela Godoy, Richard Goodwin, Will Ince, Rose John, Alexander Laird, Natalia Lukashchuk, Athena Matakidou, Thomas J. Mitchell, Andrew N. Priest, Andrew Protheroe, Sreenidhi Ranjit, Anthony Riddick, Sulekha Said, Jamal Sipple, Amy Strong, Helen Su, Mark Sullivan, Silvia Tarantino, Gemma Tsang-Pells, Stephan Ursprung, Balaji Venugopal, Lauren Wallis, Anne Y. Warren, James Wason, Sarah J. Welsh, Younghwa Kim, John Stone, Mireia Crispin-Ortuzar, Ferdia A. Gallagher, Brent O'Carrigan, Grant D. Stewart, on behalf of the WIRE Trial Group. Neoadjuvant olaparib and cediranib in renal cancer: Outcomes of the WIndow-of-opportunity in REnal cancer (WIRE) Trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr CT175.

Here, in a multi-ancestry genome-wide association study meta-analysis of kidney cancer (29,020 cases and 835,670 controls), we identified 63 susceptibility regions (50 novel) containing 108 independent risk loci. In analyses stratified by subtype, 52 regions (78 loci) were associated with clear cell renal cell carcinoma (RCC) and 6 regions (7 loci) with papillary RCC. Notably, we report a variant common in African ancestry individuals (rs7629500) in the 3' untranslated region of VHL, nearly tripling clear cell RCC risk (odds ratio 2.72, 95% confidence interval 2.23-3.30). In cis-expression quantitative trait locus analyses, 48 variants from 34 regions point toward 83 candidate genes. Enrichment of hypoxia-inducible factor-binding sites underscores the importance of hypoxia-related mechanisms in kidney cancer. Our results advance understanding of the genetic architecture of kidney cancer, provide clues for functional investigation and enable generation of a validated polygenic risk score with an estimated area under the curve of 0.65 (0.74 including risk factors) among European ancestry individuals.

OBJECTIVES:To report the NHS Digital (NHSD) data for patients diagnosed with kidney cancer (KC) in England. We explore the incidence, route to diagnosis (RTD), treatment, and survival patterns from 2013 to 2019. MATERIALS AND METHODS:Data was extracted from the Cancer Data NHSD portal for International Classification of Diseases, 10th edition coded KC; this included Cancer Registry data, Hospital Episode Statistics, and cancer waiting times data. RESULTS:Registrations included 66 696 individuals with KC. Incidence of new KC diagnoses increased (8998 in 2013, to 10 232 in 2019), but the age-standardised rates were stable (18.7-19.4/100 000 population). Almost half of patients (30 340 [45.5%]) were aged 0-70 years and the cohort were most frequently diagnosed with Stage 1-2 KC (n = 26 297 [39.4%]). Most patients were diagnosed through non-urgent general practitioner referrals (n = 16 814 [30.4%]), followed by 2-week-wait (n = 15 472 [28.0%]) and emergency routes (n = 11 796 [21.3%]), with older patients (aged ≥70 years), Stage 4 KCs, and patients with non-specified renal cell carcinoma being significantly more likely to present through the emergency route (all P < 0.001). Invasive treatment (surgery or ablation), radiotherapy, or systemic anti-cancer therapy use varied with disease stage, patient factors, and treatment network (Cancer Alliance). Survival outcomes differed by Stage, histological subtype, and social deprivation class (P < 0.001). Age-standardised mortality rates did not change over the study duration, although immunotherapy usage is likely not captured in this study timeline. CONCLUSION:The NHSD resource provides useful insight about the incidence, diagnostic pathways, treatment, and survival of patients with KC in England and a useful benchmark for the upcoming commissioned National Kidney Cancer Audit. The RTD data may be limited by incidental diagnoses, which could confound the high proportion of 'emergency' diagnoses. Importantly, survival outcomes remained relatively unchanged.

Aaron Leiblich , Stefanos Gorgoraptis , Alexandra Shaw, Farhan Ahmad, Angus Campbell, Steven Foley, Oliver Flossmann, Peter Dimitrov, Venkatesha Udupa, Sanjay Sinha and Mark E. Sullivan Department of Urology, Churchill Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, Department of Radiology, Department of Urology, Department of Nephrology, Royal Berkshire Hospital, Royal Berkshire NHS Foundation Trust, Reading, Department of Anaesthesia, and Oxford Transplant Centre, Churchill Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, UK

Background: In this article we share our experience of creating a digital pathology (DP) supraregional germ cell tumour service, including full digitisation of the central laboratory. Methods: DP infrastructure (Philips) was deployed across our hospital network to allow full central digitisation with partial digitisation of two peripheral sites in the supraregional testis germ cell tumour network. We used a survey-based approach to capture the quantitative and qualitative experiences of the multidisciplinary teams involved. Results: The deployment enabled case sharing for the purposes of diagnostic reporting, second opinion, and supraregional review. DP was seen as a positive step forward for the departments involved, and for the wider germ cell tumour network, and was completed without significant issues. Whilst there were challenges, the transition to DP was regarded as worthwhile, and examples of benefits to patients are already recognised. Conclusion: Pathology networks, including highly specialised services, such as in this study, are ideally suited to be digitised. We highlight many of the benefits but also the challenges that must be overcome for such clinical transformation. Overall, from the survey, the change was seen as universally positive for our service and highlights the importance of engagement of the whole team to achieve success.

Background Window-of-opportunity trials, evaluating the engagement of drugs with their biological target in the time period between diagnosis and standard-of-care treatment, can help prioritise promising new systemic treatments for later-phase clinical trials. Renal cell carcinoma (RCC), the 7 th commonest solid cancer in the UK, exhibits targets for multiple new systemic anti-cancer agents including DNA damage response inhibitors, agents targeting vascular pathways and immune checkpoint inhibitors. Here we present the trial protocol for the WIndow-of-opportunity clinical trial platform for evaluation of novel treatment strategies in REnal cell cancer (WIRE). Methods WIRE is a Phase II, multi-arm, multi-centre, non-randomised, proof-of-mechanism (single and combination investigational medicinal product [IMP]), platform trial using a Bayesian adaptive design. The Bayesian adaptive design leverages outcome information from initial participants during pre-specified interim analyses to determine and minimise the number of participants required to demonstrate efficacy or futility. Patients with biopsy-proven, surgically resectable, cT1b+, cN0–1, cM0–1 clear cell RCC and no contraindications to the IMPs are eligible to participate. Participants undergo diagnostic staging CT and renal mass biopsy followed by treatment in one of the treatment arms for at least 14 days. Initially, the trial includes five treatment arms with cediranib, cediranib + olaparib, olaparib, durvalumab and durvalumab + olaparib. Participants undergo a multiparametric MRI before and after treatment. Vascularised and de-vascularised tissue is collected at surgery. A ≥ 30% increase in CD8+ T-cells on immunohistochemistry between the screening and nephrectomy is the primary endpoint for durvalumab-containing arms. Meanwhile, a reduction in tumour vascular permeability measured by K trans on dynamic contrast-enhanced MRI by ≥30% is the primary endpoint for other arms. Secondary outcomes include adverse events and tumour size change. Exploratory outcomes include biomarkers of drug mechanism and treatment effects in blood, urine, tissue and imaging. Discussion WIRE is the first trial using a window-of-opportunity design to demonstrate pharmacological activity of novel single and combination treatments in RCC in the pre-surgical space. It will provide rationale for prioritising promising treatments for later phase trials and support the development of new biomarkers of treatment effect with its extensive translational agenda. Trial registration ClinicalTrials.gov: NCT03741426 / EudraCT: 2018–003056-21 .

The management trend of low-risk kidney cancer over the last decade has been from treatment with radical nephrectomy, to use of nephron sparing procedures of partial nephrectomy and ablation, as well as the option of active surveillance (AS). This narrative review aims to summarise the available guidelines related to AS and review the published descriptions of regional practices on the management of low-risk kidney cancer worldwide. A search of PubMed, Google Scholar and Cochrane Library databases for studies published 2010 to June 2020 identified 15 studies, performed between 2000 and 2019, which investigated 13 different cohorts of low-risk kidney cancer patients on AS. Although international guidelines show a level of agreement in their recommendation on how AS is conducted, in terms of patient selection, surveillance strategy and triggers for intervention, cohort studies show distinct differences in worldwide practice of AS. Prospective studies showed general agreement in their predefined selection criteria for entry into AS. Retrospective studies showed that patients who were older, with greater comorbidities, worse performance status and smaller tumours were more likely to be managed with AS. The rate of percutaneous renal mass biopsy varied between studies from 2% to 56%. The surveillance protocol was different across all studies in terms of recommended modality and frequency of imaging. Of the 6 studies which had set indications for intervention, these were broadly in agreement. Despite clear criteria for intervention, patient or surgeon preference was still the reason in 11-71% of cases of delayed intervention across 5 studies. This review shows that AS is being applied in a variety of centres worldwide and that key areas of patient selection criteria and surveillance strategy have large similarities. However, the rate of renal mass biopsy and of delayed intervention varies significantly between studies, suggesting the process of diagnosing malignant SRM and decision making whilst on AS are varying in practice. Further research is needed on the diagnosis and characterisation of incidentally found small renal masses (SRM), using imaging and histology, and the natural history of these SRM in order to develop evidence-based active surveillance protocols.

This chapter covers techniques, indications, and useful guides for common urological skills and equipment. It has topics on catheters, including techniques for urethral and suprapubic catheterization, and how to deal with complications, stents, lasers and diathermy, sterilization, urological incisions, and small bowel surgery. Highly illustrated, it serves as a useful primer.

A male factor alone is responsible for infertility in 20% of couples and is contributory in another 30%. Evaluation of both partners is an essential part of the assessment of any infertile couple. After describing the aetiology and evaluation of male infertility, the chapter goes over surgical management techniques and approaches. It also has topics on testicular semen retrieval techniques, epididymal biopsy, and varicocele repair.

Purpose: The purpose of this article is to present the first reported case of a renal tumour classified as tuberous sclerosis complex-associated renal cell carcinoma in the UK and discuss its clinical implications. Case report: A female, aged 65 years, with tuberous sclerosis complex was found on surveillance imaging to have interval growth of multiple right renal tumours up to 19 mm. Right partial nephrectomy was performed. Histology showed multiple tiny angiomyolipomas and a 20 mm tumour classified as tuberous sclerosis complex-associated renal cell carcinoma. These tumour cells showed abundant clear cytoplasm with a branched elongated arrangement encircled in dense smooth muscle stroma. Literature review: Renal cell carcinoma in patients with tuberous sclerosis complex is rare, occurring in approximately 4% of cases. Tuberous sclerosis complex-associated renal cell carcinoma is a relatively new histological entity, having previously been described as clear cell or chromophobe-like, with only one published case series from the USA. These tumours have three histological entities which are distinct from all other renal cell carcinoma classifications. Based on case series, tuberous sclerosis complex-associated renal cell carcinoma tends to occur more often in females, present at a younger age, have multiple tumours, and tend to show an indolent course, although metastases have been reported. Learning points: Patients with tuberous sclerosis complex can develop renal cell carcinoma, though the risk is thought to be no higher than for sporadic renal cell carcinoma. Given the limited literature, more evidence is required to help predict the future behaviour of these tumours. Level of evidence: 5

Objectives To describe the frequency and nature of symptoms in patients presenting with suspected renal cell carcinoma (RCC) and examine their reliability in achieving early diagnosis. Design Multicentre prospective observational cohort study. Setting and participants Eleven UK centres recruiting patients presenting with suspected newly diagnosed RCC. Symptoms reported by patients were recorded and reviewed. Comprehensive clinico-pathological and outcome data were also collected. Outcomes Type and frequency of reported symptoms, incidental diagnosis rate, metastasis-free survival and cancer-specific survival. Results Of 706 patients recruited between 2011 and 2014, 608 patients with a confirmed RCC formed the primary study population. The majority (60%) of patients were diagnosed incidentally. 87% of patients with stage Ia and 36% with stage III or IV disease presented incidentally. Visible haematuria was reported in 23% of patients and was commonly associated with advanced disease (49% had stage III or IV disease). Symptomatic presentation was associated with poorer outcomes, likely reflecting the presence of higher stage disease. Symptom patterns among the 54 patients subsequently found to have a benign renal mass were similar to those with a confirmed RCC. Conclusions Raising public awareness of RCC-related symptoms as a strategy to improve early detection rates is limited by the fact that related symptoms are relatively uncommon and often associated with advanced disease. Greater attention must be paid to the feasibility of screening strategies and the identification of circulating diagnostic biomarkers.

This chapter begins by covering the physiology of erections and ejaculation. It provides ways of evaluating erectile dysfunction and then surgical interventions, including vascular surgery and penile prosthesis. Finally, surgical treatment for Peyronie’s disease is covered.

You have accessJournal of UrologyKidney Cancer: Epidemiology & Evaluation/Staging/Surveillance III (MP80)1 Apr 2020MP80-18 ACTIVE SURVEILLANCE OF SMALL RENAL MASSES IN AN OLDER POPULATION OFFERS LONG-TERM ONCOLOGICAL EFFICACY EQUIVALENT TO PARTIAL OR RADICAL NEPHRECTOMY Mark Sullivan*, Nilay Patel, Sarah Brown, Chris Blick, Aaron Leiblich, Andrew Protheroe, David Cranston, and Richard Bryant Mark Sullivan*Mark Sullivan* More articles by this author , Nilay PatelNilay Patel More articles by this author , Sarah BrownSarah Brown More articles by this author , Chris BlickChris Blick More articles by this author , Aaron LeiblichAaron Leiblich More articles by this author , Andrew ProtheroeAndrew Protheroe More articles by this author , David CranstonDavid Cranston More articles by this author , and Richard BryantRichard Bryant More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000972.018AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Presently active surveillance (AS) is the recommended management of small renal masses (SRM’s) in elderly patients with multiple co-morbidities, or for those who decline surgery/ablation (EAU guidelines 2018, AUA guidelines 2017). We have previously reported the short-term oncological and overall outcomes of AS compared against partial nephrectomy (PN) or radical nephrectomy (RN) in the management of T1a SRMs (Patel et al, BJUI, 2012). We now provide an update at a median of 9.4 years follow-up for the AS management of this cohort compared with PN or RN. METHODS: We have retrospectively updated the pre-2012 cohort of patients with T1a SRMs managed with AS, PN or RN in our institution. Data was collected from electronic patient records with survival data and cause of death cross-referenced with the Oxford Cancer Intelligence Unit. RESULTS: A total of 208 patients with 212 T1a SRMs (solid or Bosniak IV) were identified in the cohort. 76 patients were managed with AS, 93 with PN and 39 with RN. Mean tumour size was 23mm (AS) and 27mm (PN and RN). Over a median follow-up of 9.4 years the mean growth rate of SRMs managed by AS was 0.9 mm/year, with 55% of these SRMs showing zero/negative growth. 14 (18%) AS patients underwent intervention due to tumour growth or patient choice. 7.8% of AS patients developed metastatic disease, versus 12.9% (PN) and 10.3% (RN). A tumour growth rate >5mm/year on AS approached statistical significance for development of metastases (p=0.066). No statistically significant difference was observed in overall (OS) and cancer-specific (CSS) survival for AS, PN and RN (AS-CSS 97.1.%, AS-OS 52.9%; PN-CSS 90.3%, PN-OS 75.3%; RN-CSS 89.7%, RN-OS 41%). CONCLUSIONS: AS of SRMs in older patients offers oncological efficacy equivalent to surgery in the long term. 47.1% of AS patients died from other causes at prolonged follow-up, further justifying this approach to management. Source of Funding: No funding. © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e1233-e1233 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Mark Sullivan* More articles by this author Nilay Patel More articles by this author Sarah Brown More articles by this author Chris Blick More articles by this author Aaron Leiblich More articles by this author Andrew Protheroe More articles by this author David Cranston More articles by this author Richard Bryant More articles by this author Expand All Advertisement PDF downloadLoading ...

Adult congenital heart disease (ACHD) presents diagnostic and management dilemmas. We present a patient with oxygen-refractory hypoxemia and outline an approach to her care. A 60 year old female with history of tetralogy of Fallot repair, pulmonary artery aneurysm and pulmonic stenosis presents

This chapter covers various surgical procedures for dealing with different urological cancers. For each method, it takes the reader through diagnosis, indications for the procedure, assessment and staging, patient preparation, and surgical approaches, then closure, and any other potential issues. Each topic is highly illustrated, to aid understanding for unfamiliar procedures.

This chapter covers female stress urinary incontinence and its management, including assessment, non-operative management, urethral bulking agents, artificial urinary sphincters, and different types of sling. It also describes modes of management for male stress urinary incontinence, pelvic organ prolapse, female urethral diverticulum, and the repair of vesicovaginal fistula.