Prabhakar Rajan

Objectives: To evaluate the impact of 5‐alpha reductase inhibitor (5‐ARI) exposure on multiparametric MRI (mpMRI) diagnostic performance for clinically significant prostate cancer (csPCa) and to assess whether standard prostate‐specific antigen density (PSAD)‐gated biopsy thresholds remain safe in this population. Subjects/patients and methods: A systematic review followed PRISMA 2020 (PROSPERO: CRD420251050507). PubMed/MEDLINE, EMBASE and the Cochrane Library were searched from January 2015 to December 2024. Eligible studies reported PI‐RADS, PSAD or lesion‐level apparent diffusion coefficient (ADC) data by exposure status, biopsy‐verified csPCa (ISUP grade group ≥2) and an unexposed comparator (≥100 patients). Risk of bias was assessed using QUADAS‐2 and ROBINS‐I; heterogeneity precluded meta‐analysis. Results: Seven comparative studies met inclusion criteria. Patient‐level csPCa diagnostic accuracy was largely maintained: Sensitivity at a PI‐RADS ≥3 threshold was 93.8% in exposed versus 96.1% in unexposed men, csPCa detection was 39.1% versus 39.3% (p = 0.9), and 5‐ARI exposure was not an independent negative predictor of detection. On blinded matched review, peripheral zone lesion ADC was higher in exposed men (869 vs. 765 mm ² /s, p = 0.04) with lower conspicuity (1.59 vs. 1.78, p = 0.03); that cohort also reported lower adjusted per‐lesion yield (OR 0.32, 95% CI 0.18–0.57), confined to the peripheral zone. A PSAD threshold of >0.15 ng/ml/cc avoided biopsy in 37.0% of exposed versus 30.3% of unexposed men, with missed csPCa in 12.3% and 11.0%, respectively. Conclusion: Across seven heterogeneous observational studies, patient‐level mpMRI performance for csPCa appears largely preserved in men receiving 5‐ARIs, though this lacks pooled support and was not reproduced in the one lesion‐level, zone‐stratified analysis. Standard PSAD‐gated thresholds, evidenced by a single cohort, may perform comparably across populations. Prospective validation is required.

Objectives: To examine the association between the nerve‐sparing (NS) technique applied during radical prostatectomy (RP) and early oncological and continence outcomes in patients with Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy (STAMPEDE)‐defined high‐risk prostate cancer (PCa) undergoing robot‐assisted RP (RARP) within a structured patient‐specific surgical planning (PSSP) pathway. Patients and Methods: A retrospective single‐centre cohort study of 1385 patients who underwent primary RARP between 2021 and 2022 was conducted in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement. Patients were stratified into three groups according to the number of STAMPEDE‐defined high‐risk factors: none, one, and two or more. Outcomes were compared across these cohorts and between NS‐ and non‐NS (nNS)‐ RARP, within each risk stratum. Results: Overall, NS‐RARP was performed in 75.4% of patients (1044/1385). In the STAMPEDE‐defined high‐risk cohort (two or more high‐risk criteria) 57.3% (150/262) of patients underwent some sort of NS. Among those with at least two STAMPEDE‐defined risk factors, oncological outcomes were similar between NS and nNS surgery (positive surgical margin rate 21.3% vs 23.2%, P = 0.72; 12‐month biochemical recurrence rate 6.7% vs 5.4%, P = 0.9), and urinary continence rates at 3 and 12 months were also similar ( P = 0.2 and P = 0.5, respectively). However, high‐risk patients undergoing NS‐RARP used significantly fewer pads at 12 months ( P = 0.03). Conclusion: In a contemporary RARP cohort within a PSSP pathway, NS was feasible in over half of high‐risk patients and was not associated with worse short‐term oncological outcomes. Although pad‐free continence rates were similar between NS and nNS groups, patients undergoing NS‐RARP used significantly fewer pads at 12 months, suggesting a potential functional benefit that warrants further prospective evaluation of NS strategies in selected cases.

Summary: In this feasibility study, plasma cfRNA transcriptomes from 64 men with prostate cancer on active surveillance revealed differences between stable disease and progression to radical prostatectomy and suggested a predominantly non-tumour origin of circulating RNA. These findings demonstrate the feasibility of cfRNA transcriptomic analysis in this setting and support its further investigation as a minimally invasive adjunct for personalised risk stratification and monitoring.

Background: Prostate-specific antigen (PSA)-based prostate cancer (PCa) screening risks overdiagnosis and overtreatment. PCa disproportionately affects Black men, those with a family history (FH) of the disease, and BRCA1/2 gene variant carriers. Risk-adapted approaches are gaining interest but are underexplored. Aim: To assess the feasibility of PSA-based Targeted Prostate Health Checks (TPHCs) for men at high PCa risk, compare invitation methods, and assess sociodemographic variations. Design & setting: Prospective feasibility cohort study in four primary care networks (PCNs) in North East London. Method: Men aged 45–69 years from Black ethnic group, or with a positive PCa FH, were identified via primary care records and invited by the PCN to one of two TPHCs: (i) telephone-first (phone consultation followed by hospital-based PSA testing); or (ii) test-first (community-based PSA testing followed by phone consultation). Elevated PSA prompted multiparametric magnetic resonance imaging (mpMRI), and prostate biopsy if malignancy was suspected. Results: Of 2400 invitees, 398 (16.6%) attended. Attendance was higher with the test-first than telephone-first TPHC (22.9% versus 11.2%, P n = 22), with five PCa diagnoses (1.4%). Conclusion: Identification of men at high PCa risk is feasible using age and ethnicity primary care data, but FH coding is unreliable. Test-first invitations improved engagement. Disparities affecting Black men highlight the need for tailored outreach, and better coding of risk factors will facilitate risk-adapted screening.

Objective: To examine contemporary evidence supporting non‐surgical interventions for patients with early prostate cancer (PCa) on active surveillance (AS). Methods: A literature search was conducted using the databases PubMed, Medline, and Embase in January 2024 to identify relevant articles published from 2011 onwards. Randomised controlled trials (RCTs) and cohort studies reporting on interventions in patients with PCa on AS were included. Results: Several studies have investigated a range of non‐surgical interventions, from exercise and food supplements to androgen receptor pathway inhibitors (ARPIs). The largest RCTs of ARPIs have shown the greatest effect in delaying disease progression to aggressive PCa, however, concerns exist around toxicity, long‐term oncological safety, and mortality benefit. Nutraceuticals, dietary modifications, and exercise appear to be well tolerated, but evidence of oncological benefit from large‐scale RCTs is lacking. A major challenge is the lack of consensus on criteria for entry to and exit from AS as pre‐biopsy magnetic resonance imaging reduces diagnosis of the lowest‐risk disease. Molecular and imaging biomarkers may help refine baseline risk stratification and guide monitoring during surveillance. Conclusion: Current evidence supporting interventions for patients on AS remains largely based on small prospective cohort studies or open‐label phase II trials. There is growing interest in short‐term ARPIs for patients at higher risk of disease progression, while nutraceuticals, diet and exercise may have a role for long‐term use in lower‐risk patients. Large, well‐powered RCTs with long‐term outcomes testing different interventions and incorporating molecular and imaging biomarkers are warranted.

Introduction: Prostate cancer (PCa) is the second most common cancer in men globally, with a rising incidence. Early detection through population‐based screening by Prostate Specific Antigen (PSA) testing improves survival outcomes, at the expense of overdiagnosis and overtreatment of clinically insignificant disease. Here, we explore emerging tools for more effective PCa early detection and evaluate their potential roles for PCa screening.Materials and Methods: Key articles on emerging adjuncts and alternatives to PSA for PCa early detection were identified.Results: Multiparametric MRI (mpMRI) remains the gold standard modality for identifying clinically significant PCa and has been evaluated for screening. Newer imaging strategies incorporating biparametric MRI (bpMRI) or multiparametric ultrasound (mpUS) potentially offer similar accuracy to mpMRI. Saliva‐derived polygenic risk scores (PRS) hold potential as a non‐invasive screening tool to identify at‐risk patient groups. Blood‐based biomarker tests can improve risk stratification, reducing unnecessary biopsies while maintaining detection of clinically significant cancers compared to PSA alone. Urine‐based biomarker tests have been examined for the early detection and risk stratification of clinically significant disease as adjuncts to PSA testing.Conclusion: PSA is commonly used to detect early PCa, but its lack of specificity and associated overdiagnosis risk has led to controversy over its use for population‐based screening. Imaging modalities such as mpMRI have reduced detection of clinically insignificant PCa, and emerging cost‐effective alternatives, such as bpMRI and mpUS, show promise. Molecular biomarkers and PRS for risk stratification may help target imaging‐based early detection more effectively to at‐risk populations. Prospective randomised clinical trials are urgently needed to evaluate the performance of different modalities for population‐wide screening. Future developments may involve technologies such as artificial intelligence and diagnostic tests that incorporate circulating tumour markers.

Background: Standard of care (SOC) treatments for International Germ Cell Cancer Collaborative Group (IGCCCG) good prognosis stage II germ cell tumours (GCT) involve primary orchidectomy followed by combination chemotherapy for both seminoma and non‐seminomatous germ cell tumours (NSGCT). Alternatively, external beam radiotherapy may be used for seminoma and retroperitoneal lymph node dissection (RPLND) for NSGCT. While these treatments achieve high cure rates, they are associated with significant toxicities. De‐escalation strategies including three cycles of Carboplatin AUC10 or robotic RPLND with or without adjuvant chemotherapy have demonstrated potential to reduce treatment‐related toxicity in stage II seminoma while preserving oncological efficacy. However, these approaches are not widely adopted due to limited prospective comparative trials.Study Design: The THERATEST trial is a prospective multicentre observational feasibility study evaluating participants receiving SOC treatments for good prognosis stage II seminoma and NSGCT or de‐escalated treatments for stage II seminoma.Endpoints: The primary endpoints are to assess feasibility of recruitment and retention. Secondary endpoints include assessing health‐related quality of life (HRQOL), sexual function and satisfaction, progression‐free survival (PFS), overall survival (OS) and safety and treatment‐related complications.Patients and Methods: Thirty participants with good prognosis stage II seminoma or NSGCTs will be recruited over 18 months into two cohorts: de‐escalation arm and SOC arm. The de‐escalation cohort will receive either Carboplatin AUC10 or robotic RPLND with or without adjuvant therapy depending on institutional SOC. Participants who decline or are ineligible for de‐escalation will receive SOC treatment: combination chemotherapy or radiotherapy for seminoma and combination chemotherapy for NSGCT. All participants will be followed for two years post‐treatment or until withdrawal. Data collection includes recruitment and retention rates, disease status, surgical outcomes, adverse events and patient‐reported outcomes using validated questionnaire: EORTC QLQ‐TC26, EORTC QLQ‐C30, Brief Male Sexual Function Inventory (BMSFI) and additional enquiries on anejaculation.Coordinating Centre: THERATEST Trial Coordinator, Centre for Experimental Cancer Medicine, Barts Cancer Institute, Queen Mary University of London, Old Anatomy Building, Charterhouse Square, London, EC1M 6BQ|T: 0207882 8497|E: bci-theratest@qmul.ac.ukTrial registration number: ISRCTN61007118.

Objectives: The objective of this study is to identify healthcare inequities in referrals and diagnoses of suspected prostate cancer (PCa) in an ethnically diverse and socially deprived large urban region.Methods: Retrospective cohort study of 2‐Week Wait (2WW) suspected PCa patients (n = 12 947) referred to two acute NHS Trusts in North East London (NEL) from February 2019 to August 2023. Sociodemographics, diagnosis and pretreatment staging data were collected from patient records. We examined referral and diagnosis statistics, age at referral, radiological T‐stage at diagnosis, levels of deprivation by ethnicity and the impact of COVID‐19 pandemic lockdowns on proportion of referrals and diagnoses by ethnicity and T‐stage at diagnosis. Uni‐ and multivariable logistic regression was performed to identify predictors of locally advanced (T‐stage ≥T3) disease.Results: Of all referrals, 22% were diagnosed with PCa. There were no statistically significant differences in referrals, diagnoses or T‐stage of PCa by ethnicity during COVID lockdown versus non‐lockdown periods (p > 0.05). Compared to men from any other ethnicity, Black men (from Black British, Black African and Black Caribbean ethnic groups) were diagnosed at a younger age (mean = 65 years), had the highest age‐adjusted PCa incidence rate of 149 per 100 000 person‐years, were from the most deprived backgrounds, and were diagnosed with the highest proportion of localised PCa (74%). Multivariable analysis of a patient subgroup revealed age bands 71–80 years (OR 2.01, 95% CI 1.31–3.07) and >80 (OR 4.27, 95% CI 2.25–8.08) as independent positive predictors of locally advanced PCa, and Black ethnicity as an independent predictor of localised disease (OR 0.66, 95% CI 0.43–1.00). Limitations of this study include the exclusion of PCa cases diagnosed outside the 2WW pathway, as well as missing data on Prostate‐Specific Antigen (PSA) levels, distant radiological staging and histopathological findings.Conclusion: We identify disparities in PCa incidence, stage and age at presentation, as well as socio‐economic deprivation among Black men in NEL. Targeted efforts are needed to mitigate these healthcare inequities.

Background: Understanding sex‐specific factors contributing to advanced‐stage diagnosis can guide interventions to reduce sex inequality in patients with urological cancers.Method: We used linked primary care and cancer registry data to examine associations between symptoms and advanced‐stage in 1151 bladder cancer and 440 renal cancer patients diagnosed between January 2012 and December 2015 in England. We performed logistic regression, adjusting for sex, age, deprivation and routes to diagnosis, including interaction terms between symptoms and sex and symptoms and age.Results: Female sex (OR vs. men 1.89 [1.28–2.79]; p = 0.001) and patients presenting with urinary tract infections (OR 2.22 [1.34–3.69]) and abdominal symptoms (OR 2.19 [1.30–3.70]) were associated with increased odds of advanced‐stage bladder cancer (vs. haematuria, p = 0.016 for both). Women with haematuria and men with abdominal symptoms (compared with the opposite sex with the same presenting symptom) were more likely to have advanced‐stage bladder cancer. Neither sex nor symptom associations were observed for renal cancer.Conclusion: Non‐haematuria symptoms are associated with higher risk of advanced‐stage bladder cancer. Greater risk of advanced‐stage bladder cancer in women may reflect biological differences in haematuria onset and sex differences during diagnostic process. Identifying higher risk women with haematuria may reduce sex inequalities in bladder cancer outcomes.