Prostate cancer is now the most frequently diagnosed cancer in UK men. Faster diagnostic pathways form a key component of the NHS Cancer Programme's strategic approach to improving patient outcomes. The Prostate cancer diagnostic pathway involves a number of stages which create potential areas of delay. We describe how data has been synthesised and used in the South West region through an innovation called the South West Prostate Dashboard to improve patient pathways.

OBJECTIVE:To characterise contemporary practice patterns in female radical cystectomy (RC) across the UK and Ireland, focusing on preoperative counselling, operative strategies, and postoperative care. SUBJECTS AND METHODS:A 36-item survey was distributed to consultant urologists performing RC, identified via the British Association of Urological Surgeons (BAUS) and Cancer Alliances. The questionnaire addressed surgeon demographics, preoperative assessment and counselling, operative decision-making including organ- and nerve-sparing techniques, and survivorship care. Responses were analysed descriptively; group comparisons were made using the Wilcoxon rank-sum and Fisher's exact tests. RESULTS:A total of 64 surgeons responded (56.1% [64/114]), representing 41 cystectomy centres (70.7% [41/58]). Preoperative assessment of sexual activity (68.8%) and menopausal status (78.1%) was common, whereas sexual orientation (15.6%) and prolapse (26.6%) were rarely addressed. Female surgeons were significantly more likely to enquire about menopausal status (P = 0.025). Counselling on sexual dysfunction (98.4%) and vaginal shortening (96.9%) was routine, but other complications, including prolapse (68.8%), menopause (82.8%), or fistula (6.3%), were inconsistently discussed. Organ-sparing practice varied: 28.1% rarely or never performed organ preservation, citing oncological concerns. High-volume centres were more likely to offer organ-sparing RC (P = 0.013). Over half reported inadequate access to female-specific rehabilitation services, with most centres lacking formal pathways for vaginal complications. CONCLUSIONS:Female RC practice across the UK and Ireland is heterogeneous, with clear gaps in preoperative counselling, uptake of organ-sparing techniques, and survivorship care. There is an urgent need for standardised, evidence-based pathways and consensus guidance to optimise outcomes for female patients.

BACKGROUND:Bladder cancer (BC) symptoms often overlap with benign conditions, while no routine screening exists for general population. We aim to develop a machine learning (ML)-based screening pipeline for early BC detection using electronic-health-records (EHRs) in primary care. METHODS:A multi-centred case-control cohort (1995-2018; n = 64,884) was created for model training and testing. We further validated the model prospectively on an independent cohort (2019-2020; n = 4,569). We proposed the Parsimony driven REweighting for Calibrated Input-based Screening for Early detection-Adjustable Grey Zone (PRECISE-AGZ), which identified influential features from 48,261 candidates and developed a calibrated logistic regression screening model with optimised grey-zone thresholds. RESULTS:We finally identified 38 features, achieving an AUC (area under the curve) of 0.789 (95% CI: 0.780-0.798) on testing set. Neurological disorders (e.g., Parkinson's disease, OR: 0.86, 95% CI: 0.79-0.92) and medications (e.g., Tamoxifen, OR: 1.13, 95% CI: 1.07-1.20) emerged as novel predictors for BC screening. The screening model stratified the population into three risk categories based on predicted probability: low-risk (0.55), achieving a sensitivity of 0.852, F1-score of 0.799, and screening population coverage (SPC) of 34.5%. Applied to the prospective validation cohort, model performance varied by months before BC diagnosis, with sensitivities ranging from 0.872 (F1-score: 0.714, SPC: 29.9%) at the first month to 0.667 (F1-score: 0.690, SPC: 12.7%) at the twelfth month. CONCLUSION:The PRECISE-AGZ pipeline efficiently identified clinical signals from EHRs for early BC detection, offering promising potential for implementing population-based BC screening.

IntroductionGonadotropin-releasing hormone (GnRH) agonists are the most commonly used form of androgen deprivation therapy (ADT) for advanced prostate cancer, often prescribed with radiotherapy or chemotherapy. This study examined national trends in the prescribing of injectable GnRH agonists in England from 2015 to 2024, by formulation type and demographic factors (age, ethnicity, and deprivation). We hypothesised that the use of longer-acting formulations has been increasing over time, specifically during the COVID-19 pandemic when access to face-to-face appointments was limited, and that variation over time and by demographics could inform future service delivery.MethodsWith the approval of NHS England, we conducted a cohort study using the OpenSAFELY-TPP database of 24 million adults. Monthly prescription counts and rates (per 100,000 men with prostate cancer) were visualised over time. Generalised linear models were used to estimate the impact of the COVID-19 pandemic.ResultsThe cohort included 390,265 men with prostate cancer (mean age 69.8 years, SD 13.5). Overall, 1,535,725 prescriptions were issued to 208,010 participants (53%). Monthly prescription counts increased by 40%, from 11,787 in 2015 to 16,697 in 2024, while rates declined from 8453 to 7721. During 2020-2021, prescribing of 1- and 3-monthly formulations decreased, whereas 6-monthly formulations increased from 437 per month (245 per 100,000 men) in 2019 to 755 (349 per 100,000 men) in 2024, an excess of 29%.ConclusionsBefore the pandemic, 6-monthly formulations were rarely prescribed. Their uptake during the pandemic suggested a shift towards longer-acting formulations, reducing treatment burden. Declining GnRH rates may reflect earlier diagnosis and evolving treatment guidelines. Divergence between prescription counts and rates, and variation by demographic factors, reflected challenges faced by healthcare systems.

OBJECTIVES:Malignant upper urinary tract obstruction (MUUTO) is caused by advanced cancer. Developing MUUTO is often associated with approaching the end of life. Percutaneous nephrostomy (PCN) and retrograde ureteric stent insertion (RUS) are common interventions to treat patients with MUUTO, although neither intervention is likely to extend overall survival significantly. Little is known about patient, carer and healthcare professional (HCP) views of the MUUTO management pathway, the benefits and harms of the procedure and the treatment decision-making process. This study investigated the experiences, decision-making and priorities of patients admitted to hospital for MUUTO, and their carers, along with HCPs involved in providing care for this patient group. DESIGN:Qualitative, using semi-structured interviews. SETTING:This study was conducted across two NHS trusts in England. PARTICIPANTS:12 patients, 8 carers and 14 HCPs were interviewed. Patients were interviewed in hospital during their admission and, where possible, follow-up interviews took place 2-3 weeks later at their homes. In total, 18 patient interviews were conducted. Interviews were analysed thematically by cohort and systematically cross-referenced for areas of congruence and divergence of priorities and views. Ethical approval was obtained before study commencement. RESULTS:Most patients were admitted as emergencies and received PCNs to relieve severe pain and distress. Patients reported having little choice in the decision-making around intervention due to their symptoms and frequently described the PCN procedure as being painful. HCPs considered the availability of further cancer treatment options a rationale to support intervening for MUUTO. However, HCPs reported decision-making was often complicated by unclear prognosis and the need to address the emergency nature of patient circumstances. A lack of compassionate communication, disrespect and indignity, traumatic hospital admission and premature discharge, in addition to practical administrative difficulties caused patient and carer distress. CONCLUSIONS:Emergency admissions for MUUTO are associated with significant patient and carer distress and are complex for HCPs to manage. MUUTO patients would benefit from a specific pathway to avoid emergency admissions and to facilitate timely advance care planning discussions so that patients' wishes and HCP views can be shared and incorporated into decision-making about the appropriateness and value of PCN and RUS interventions.

Objective: To characterise contemporary United Kingdom (UK) practice for suspected testicular cancer referrals and benchmark performance against the NHS Faster Diagnosis Standard (FDS). Materials and Methods: EMPAST (Evaluating the Management Pathway for Suspected Testicular Cancer) is a British Association of Urological Surgeons (BAUS)-affiliated national retrospective audit. It comprised a unit-level questionnaire and two anonymised cohorts: patients referred with suspected testicular cancer (June-July 2025) and confirmed cancer undergoing orchidectomy (April 2023-March 2024). Timeliness to consultation and outcome communication was assessed against 14-day and 28-day (FDS proxy) standards. Analyses used descriptive statistics and logistic regression. Results: Across 107 centres, 1818 submissions were analysed (773 diagnostic; 947 confirmed cancer). Median referral-to-consultation time was 7.5 days (IQR 5-14), with 79% seen within 14 days. Median referral-to-outcome communication was 14 days (IQR 8-25), and 81% achieved the FDS proxy. Pre-referral ultrasound (PRUS) occurred in 18.6% of cases and was associated with a higher proportion of cancer diagnoses in the referred cohort (60% vs 9.7%) and higher FDS proxy achievement (OR 1.10, 95% CI 1.06-1.84, p < 0.01). Median referral-to-orchidectomy time was 23 days (IQR 15-35). Conclusions: UK suspected testicular cancer pathways demonstrate good diagnostic timeliness but variation in pathway configuration between units highlights opportunities for optimisation. Level of evidence: 4

Abstract Objectives To investigate the potential of the Haematuria Cancer Risk Score (HCRS) to improve the real‐world investigation pathway for suspected bladder cancer. Materials and methods Data were retrospectively analysed for all consecutive patients referred with suspected urinary tract cancer on a faster diagnostic pathway to five UK institutions between January and April 2025. The HCRS cut‐off score of ≥82 was used to define a ‘HCRS high risk’ population. The co‐primary outcomes were the ability to calculate HCRS in the referred population from the information provided by primary care and the cancer detection rate. Results In total, 1944 referrals were received, median age of 71 years (IQR 61–78), 1186/1944 (61%) were male, and 1586/1944 (82%) had sufficient information to calculate the HCRS. Of the cohort with HCRS scores, overall 165/1586 (10%) had bladder cancer. The HCRS was ≥82 in 176/437 (40%) of those with non‐visible haematuria (NVH); in total, 6/176 (3%) had bladder cancer; and using HCRS in the NVH group alone, no case of muscle‐invasive bladder cancer (MIBC) would have been missed. The HCRS was ≥82 in 1062/1149 (92%) with visible haematuria (VH), of whom 150/1062 (14%) had bladder cancer. Adopting a strategy of using HCRS and upper tract imaging in combination for the whole cohort would have resulted in two cases of NMIBC being missed for the NVH cohort and one case of NMIBC being missed for the VH cohort. No cases of MIBC or upper tract urothelial cancer would have been missed. Conclusion HCRS is a simple innovation, which demonstrates clear potential when combined with upper tract imaging to improve current UK risk stratification to determine which patients referred with haematuria need flexible cystoscopy.

To develop and retrospectively validate an artificial intelligence-based decision support system (AI-DSS) for optimising prostate biopsy decisions and improving benefit-to-harm ratios. This retrospective, multicentre, multiscanner study used data from 1022 patients. An AI-DSS integrating PI-RADS scores, automated prostate-specific antigen density (PSAd), and deep-learning imaging risk scores was developed on 770 cases and validated on an independent cohort of 252 men from six UK centres. The AI-DSS performance was benchmarked against the real-world clinical decisions (reference standard) using grade selectivity, biopsy efficiency, and selective biopsy avoidance as outcome measures. Biopsy-proven detection of grade group (GG) ≥ 2 disease was the reference standard. In the validation cohort of 252 patients (mean age, 67.3 years), 137 underwent biopsy and 79 (31

Prospective evidence on clinical utility of AI in histopathology is limited. We conducted a prospective study across three National Health Service specialist centres in England to evaluate a commercially available AI system for assistance in prostate biopsy reporting. Of 1613 cases, 1049 were reported with AI-assistance. Endpoints evaluated diagnostic impact, clinical impact and workflow. Staged AI assistance (second-read) prompted case review and changed the initial diagnosis or Grade Group of 21/386(5.4%) patients, 5 of these (1.3%) potentially affecting clinical management. AI-assisted workflows showed significantly reduced mean turnaround time with concurrent-read compared to unassisted-read by 30.1 h (p < 0.0001) at one site with significant reductions in cases requiring immunohistochemistry in all sites (Odds Ratios 0.50,0.43,0.33, p < 0.0001, p = 0.01, p = 0.001). This first prospective, multi-centric evaluation demonstrates AI can enhance diagnostic accuracy, shorten turnaround times and reduce unnecessary testing. Scaled across the NHS, such improvements could improve patient care, deliver faster diagnoses and optimise laboratory efficiency, supporting adoption.

Abstract Objectives This study aimed to understand clinical pathways for patients with high‐risk non‐muscle‐invasive bladder cancer (HR‐NMIBC) from diagnosis to follow‐up and to identify opportunities to improve care. Materials and Methods A cross‐sectional survey was conducted via structured online interviews with consented NHS healthcare professionals (HCPs) from the United Kingdom (UK) between June and September 2025. Topics surveyed included MDT structures/roles, diagnostic timelines, adjuvant treatment, radical cystectomy (RC) decision making, current bladder‐sparing treatment and clinical trial access. Quantitative data were analysed descriptively. Qualitative responses were analysed thematically. Results Seventy HCPs were included and reported that typically; 88.5% of patients achieve diagnosis within 6–8 weeks of referral, and 11.4% reported delays beyond 8 weeks. BCG maintenance duration and completion rates varied. Following BCG induction, a median (IQR) of 20.0% (5.0–32.5%) and 60.0% (40.0–70.0%) of patients completed ≥2 or ≤1 years of maintenance, respectively; 1.0% (1.0–2.0%) failed to complete induction. For BCG‐unresponsive HR‐NMIBC, HCPs reported that a mean ( SD ) proportion of 53.4 (18.1)% of patients tend to be eligible for and consent to RC, 22.0 (12.6)% tend to be eligible but decline RC and 24.6 (14.9)% tend to be ineligible. Bladder‐sparing options remain limited, with 60% of HCPs regarding further BCG as the most appropriate option. All respondents agreed that adherence to quality performance indicators (QPIs) and a national bladder cancer audit would be beneficial. Insufficient specialist nurse capacity to meet foreseeable demands of HR‐NMIBC patient care was reported by 70% ( n = 49) of HCPs. Conclusion Results reveal variability in real‐world HR‐NMIBC care within the NHS. Delays in diagnosis, inconsistent BCG maintenance duration, lack of evidence‐based alternatives to BCG and a lack of bladder‐sparing treatment and trial options in the BCG‐unresponsive setting were identified. Findings highlight unmet needs in relation to MDT resourcing, diagnostic efficiency, trial access, QPI adherence and a national bladder cancer audit.

OBJECTIVES:To evaluate diagnostic practices in the United Kingdom (UK) prior to radical nephroureterectomy (RNU) for suspected upper tract urothelial carcinoma (UTUC) and assess their impact on early oncological outcomes. The audit examined compliance post-operative intravesical Mitomycin C (MMC) instillation and adjuvant chemotherapy for ≥pT2 disease. MATERIALS AND METHODS:This national audit, by the British Association of Urological Surgeons (BAUS), invited all NHS hospitals performing RNU for non-metastatic UTUC. Retrospective anonymised data were collected. Outcomes included time from imaging to RNU, use of MMC, adjuvant chemotherapy, bladder recurrence, surgical margins, extravesical metastasis, and final histology. Statistical analysis used Mann-Whitney U, Chi-square/Fisher's exact test, and multivariate logistic regression. RESULTS:A total of 877 patients who underwent RNU across 70 hospitals were analysed (median 10 cases per hospital). Diagnostic ureteroscopy (d-URS) was performed in 61.3% of cases, delaying RNU by a median of 53 days (130 vs 77 days; P < 0.01). Voided urine cytology was recorded in 34.3%. Among patients with high-grade and/or ≥ pT1 disease, 89% had positive cytology. MMC was administered in 45.1% of ≥pT2 cases and adjuvant chemotherapy in 46%. Bladder recurrence was significantly higher in patients undergoing d-URS (26.6% vs 12.3%; P < 0.01), as were positive margins in ≥pT2 tumours (24% vs 14%; P = 0.03). Although not statistically significant, d-URS was associated with more metastases (27.2% vs 19.2%) and fewer non-UTUC diagnoses (5.5% vs 8.6%). Multivariate analysis showed that d-URS independently predicted bladder recurrence and margin positivity in ≥pT2 disease. CONCLUSIONS:Our audit showed that d-URS is associated with significant treatment delays, increased rates of metachronous bladder cancer recurrence, and higher surgical positive margin rates in patients with ≥pT2 disease. Compliance with MMC therapy and adjuvant chemotherapy was low. This national audit highlights the need for risk-stratified diagnostic pathways, multidisciplinary expertise, and establishment of quality performance indicators to improve care and outcomes in UTUC management in the UK.

Objective:To investigate the added value of systematic biopsies in men referred with suspected PCa undergoing visual registration targeted local anaesthetic transperineal prostate biopsies (LATPB) as their first biopsy for MRI-P visible lesions (MRI Score≥3) in a real-world setting. Patients and methods:The outcomes of 2611 biopsy naïve men with MRI Score≥3 who underwent visual registration combined targeted and systematic LATPB at 5 hospitals between 2021 and 2024 were studied. The primary outcome was the clinically significant PCa (csPCa [Gleason≥ 3 + 4 = 7])) cancer detection rate at targeted prostate biopsy without upgrading contributed by the systematic component of the biopsies. Results:Overall, PCa was diagnosed in 2079/2611 (80%) patients. The targeted biopsy csPCa detection rate in MRI Score 3,4 and 5 lesions was 108/534 (20%), 461/940 (49%) and 865/1137 (76%), respectively. The csPCa detection rate for combined biopsies in MRI Score 3, 4 and 5 lesions was 150/534 (28%), 579/940 (62%) and 959/1137 (84%). The NPV for targeted biopsies for MRI scores 3,4 and 5 lesions were 81.7%, 95% CI = (78.0%, 84.9%), 68.4%, 95% CI = (63.5%, 73.0%) and 55.7%, 95% CI = (48.0%, 63.1%), respectively. Increasing PSA-D was strongly associated with increased detection of csPCa at targeted prostate biopsy irrespective of MRI score (chi-square test p < 0.001). Conclusions:An MRI-P and targeted prostate biopsy-only approach should be considered in all biopsy naïve men with MRI score 5 lesions and MRI score 4 lesions with a PSA Density greater than 0.15. Patient summary:We looked at the difference between sampling a specific area of interest identified by prostate MRI compared to sampling the area of interest and additionally the prostate zones. In our study, we concluded that sampling the area of interest guided by the MRI scan alone can be more beneficial with less risk of missing out on clinically important prostate cancer in real-life practice.

This manuscript summarizes the first part of the proceedings of the 2023 Dublin ISUP Consensus Conference encompassing the best practice recommendations on the pathology of neoplasms of urachal origin. The rationale for convening this consensus conference was the lack of structured and consented histopathologic recommendations in these rare tumors. Consensus among the meeting participants (n=80) was reached on the following statements: (1) combination of gross, histologic, clinical and imaging findings with exclusion of secondary tumor metastasis are to be used in the diagnosis of urachal carcinoma; (2) the 2022 World Health Organization (WHO) separate criteria for the diagnosis of urachal adenocarcinoma and for nonglandular carcinoma should be applied; (3) specific elements are to be evaluated and recorded in the gross examination of resection specimens containing urachal tumors; (4) sampling considerations for resection specimens containing urachal tumors are advised; (5) participants are against using 5% or 10% cutoff for the extent of intraepithelial carcinoma in urachal mucinous cystic tumor of low malignant potential; (6) use of immunohistochemical markers for the differential diagnosis of urachal adenocarcinomas in transurethral resection (TUR) specimen is considered optional; (7) similar tumor classificatory (nosology) rules for carcinomas arising from bladder mucosa (eg, urothelial carcinoma, squamous cell carcinoma, and neuroendocrine carcinoma) should be applied for nonglandular urachal carcinomas; (8) a new staging approach other than the previously proposed systems should be designed for urachal carcinoma; (9) a system modifying the current Tumor-Node-Metastasis (TNM)/American Joint Committee on Cancer (AJCC) staging system for urinary bladder cancer is considered appropriate for a study in urachal carcinoma; and (10) several histologic elements are to be reported when diagnosing urachal carcinoma in TUR and resection specimens. This report from the Dublin ISUP consensus conference will serve as a practice recommendation for pathologists and as a guide for future standardized reporting protocols and research regarding urachal tumors. In addition, an international database for urachal cancers under the guidance of ISUP is being planned to be established to address pertinent issues in the pathology of urachal cancers.

Multi-centre, multi-vendor validation of artificial intelligence (AI) software to detect clinically significant prostate cancer (PCa) using multiparametric magnetic resonance imaging (MRI) is lacking. We compared a new AI solution, validated on a separate dataset from different UK hospitals, to the original multidisciplinary team (MDT)-supported radiologist’s interpretations. A Conformité Européenne (CE)-marked deep-learning (DL) computer-aided detection (CAD) medical device (Pi) was trained to detect Gleason Grade Group (GG) ≥ 2 cancer using retrospective data from the PROSTATEx dataset and five UK hospitals (793 patients). Our separate validation dataset was on six machines from two manufacturers across six sites (252 patients). Data included in the study were from MRI scans performed between August 2018 to October 2022. Patients with a negative MRI who did not undergo biopsy were assumed to be negative (90.4

The Dublin ISUP Consensus Conference covered the proceedings on the best practice recommendations on nonurachal glandular lesions of the urinary bladder, bladder diverticular cancers, and molecular features of bladder and urachal glandular lesions. The conference proceedings on urachal neoplasms (except for their molecular features) are published elsewhere. The rationale for convening this conference was the lack of structured and consented pathologic recommendations in these rare lesions. Consensus by participants was reached on the following statements: (1) intestinal metaplasia with dysplasia is considered to be a precursor to primary bladder adenocarcinoma; (2) dysplasia arising from cystitis glandularis should be reported in terms of focality (focal or nonfocal) and grade (low or high); (3) the term "adenocarcinoma" should only be used for carcinomas showing pure (nonurothelial) morphology and should not be used interchangeably in urothelial carcinoma with "glandular differentiation" because of the pathobiological differences and management implications; (4) the different histologic subtypes of bladder adenocarcinoma should be specified in the report; (5) immunohistochemistry has an ancillary role in the work up of bladder adenocarcinoma versus gastrointestinal or Müllerian-type adenocarcinomas; (6) lymphovascular invasion should be included as a parameter when reporting bladder adenocarcinoma; (7) representative or targeted sampling will be sufficient for bladder diverticulum resection specimens; and (8) molecular analysis in genomic profiling should be performed only in advanced or metastatic bladder and urachal adenocarcinomas for targetable therapy. This report on glandular (nonurachal) lesions of the bladder from the Dublin ISUP consensus conference will serve as a best practice recommendation and as a guide for future research on these relatively rare lesions.

Moderate to vigorous physical activity and metformin are associated in epidemiological studies with reduced biochemical recurrence and mortality in men with prostate cancer. This study assessed the feasibility of a home-based physical activity and/or metformin intervention in men with non-metastatic prostate cancer following radical treatment (surgery or radiotherapy) or active surveillance. A 2 × 2 factorial design randomised men into one of four groups for 6 months: (1) physical activity (defined as brisk walking ≥ 30 min for ≥ 5 days per week, aiming for ≥ 10,000 steps a day); (2) metformin (one 500 mg slow-release tablet daily); (3) physical activity and metformin; and (4) control. Men were recruited from a single tertiary referral centre in the South West of England, UK, (September 2018–March 2020 which terminated slightly early due to the COVID-19 pandemic). Co-primary outcomes were rates of randomisation and adherence which was defined as men brisk walking ≥30 minutes on at least 5 days with 10,000 steps daily (measured over one week 6-months after randomisation) with ≥ 60 https://www.isrctn.com/ISRCTN13543667

OBJECTIVE:The rising incidence and mortality in bladder cancer (BC) underscore the importance of identifying asscociated features. Current reliance on haematuria as a primary indicator for BC proves inadequate. While mining electronic health records (EHRs) offer potential of identifying BC-related signals, traditional data-driven methods struggle with high-dimensional datasets. This study aims to uncover novel BC-associated clinical signals by developing Parsimony-driven cAtegory-balaNced binary Signal extractor for Primary Care EHRs (PanSPICE) tailored to extremely high-dimensional data linked from multi-centres. METHODS:We collected BC cases and control patients (n = 64,884) linked at patient-level from Welsh nationwide databases, yielding 48,261 features in primary care settings. The PanSPICE approach begins with information gain to pre-rank features, then applies Retentive Stickiness Binary Particle Swarm Optimisation (RSBPSO) combined with C5.0 classification tree to overcome computational barriers in feature selection. A two-layer optimisation treated clinical signals in care processes (POC), diagnoses (DIAG), and medications (MED) separately to prevent feature masking. A tailored fitness function for RSBPSO to simultaneously optimise model performance and feature sparsity. Associations of the selected features were interpreted using logistic regression models adjusted for deprivation indices. RESULTS:The PanSPICE identified 38 optimal features (AUC (area under the curve) = 0.81, 95 % CI: 0.80-0.82), including urinary tract infections (OR = 2.19, 95 % CI: 2.05-2.14) and inverse associations with stroke (OR = 0.64, 95 % CI: 0.54-0.74) and dementia (OR = 0.25, 95 % CI: 0.17-0.35). Gender stratification revealed female-specific urine glucose testing association (OR = 1.24, 95 % CI: 1.08-1.43). Certain medications, such as trimethoprim, were positively associated with BC, while others, including ramipril and prednisolone, showed protective effects. CONCLUSION:The PanSPICE enables efficient high-dimensional EHR analysis, revealing under-recognised potential BC risk profiles and protective comorbidities. Gender-specific differences in BC associations highlight the importance of gender-stratified analyses, while computational advances provide a template for EHR-based clinical discovery. Findings warrant further mechanistic research into neurological protective pathways.