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Epidemiologic studies suggest that diet can alter prostate cancer risk. This study aimed to establish the feasibility and acceptability of dietary modification in men at increased risk of prostate cancer. Men were invited with a PSA level of 2.0–2.95 ng/mL or 3.0–19.95 ng/mL with negative prostate biopsies. Randomization (3 × 3 factorial design) to daily green tea and lycopene: green tea drink (3 cups, unblinded) or capsules [blinded, 600 mg flavan-3-ol ()-epigallocatechin-3-gallate (EGCG) or placebo] and lycopene-rich foods (unblinded) or capsules (blinded, 15 mg lycopene or placebo) for 6 months. Primary endpoints were randomization rates and intervention adherence (blinded assessment of metabolites) at 6 months with secondary endpoints of acceptability (from interviews), safety, weight, blood pressure, and PSA. A total of 133 of 469 (28.4%) men approached agreed to be randomized and 132 were followed-up (99.2%). Mean lycopene was 1.28 [95% confidence intervals (CI), 1.09–1.50, P = 0.003] times higher in the lycopene capsule group and 1.42 (95% CI, 1.21–1.66; P < 0.001) times higher in the lycopene-enriched diet group compared with placebo capsules. Median EGCG was 10.7 nmol/L (95% CI, 7.0–32.0) higher in in the active capsule group and 20.0 nmol/L (95% CI, 0.0–19.0) higher in the green tea drink group compared with placebo capsules (both P < 0.001). All interventions were acceptable and well tolerated although men preferred the capsules. Dietary prevention is acceptable to men at risk of prostate cancer. This intervention trial demonstrates that a chemoprevention clinical trial is feasible. Cancer Prev Res; 11(11); 687–96. ©2018 AACR.

Figure of changes in lycopene and green tea intake over 6 months

BACKGROUND Long-term patient-reported outcomes are needed to inform treatment decisions for localized prostate cancer. METHODS Patient-reported outcomes of 1643 randomly assigned participants in the ProtecT (Prostate Testing for Cancer and Treatment) trial were evaluated to assess the functional and quality-of-life impacts of prostatectomy, radiotherapy with neoadjuvant androgen deprivation, and active monitoring. This article focuses on the outcomes of the randomly assigned participants from 7 to 12 years using mixed effects linear and logistic models. RESULTS Response rates exceeded 80% for most measures. Among the randomized groups over 7 to 12 years, generic quality-of-life scores were similar. Among those in the prostatectomy group, urinary leakage requiring pads occurred in 18 to 24% of patients over 7 to 12 years, compared with 9 to 11% in the active monitoring group and 3 to 8% in the radiotherapy group. In the prostatectomy group, 18% reported erections sufficient for intercourse at 7 years, compared with 30% in the active monitoring and 27% in the radiotherapy groups; all converged to low levels of potency by year 12. Nocturia (voiding at least twice per night) occurred in 34% in the prostatectomy group compared with 48% in the radiotherapy group and 47% in the active monitoring group at 12 years. Fecal leakage affected 12% in the radiotherapy group compared with 6% in the other groups by year 12. The active monitoring group experienced gradual age-related declines in sexual and urinary function, avoiding radical treatment effects unless they changed management. CONCLUSIONS ProtecT provides robust evidence about continued impacts of treatments in the long term. These data allow patients newly diagnosed with localized prostate cancer and their clinicians to assess the trade-offs between treatment harms and benefits and enable better informed and prudent treatment decisions. (Funded by the UK National Institute for Health and Care Research Health Technology Assessment Programme projects 96/20/06 and 96/20/99; ISRCTN number, ISRCTN20141297; ClinicalTrials.gov number, NCT02044172.)

BACKGROUND: To determine differences in cancer detection rates (CDRs) of regions of interest (ROI) on magnetic resonance imaging (MRI) with robotic-assisted (RA) targeted biopsies (RA-TB) compared to cognitive targeted biopsies (C-TB). METHODS: In a two-centre, retrospective outcome study, a total of 92 consecutive men who had a pre-biopsy MRI, were biopsy naïve and had a transperineal (TP) prostate biopsy between 9/2015 and 7/2017 were included. The primary analysis consists of 39 men who had C-TB and 53 men who had RA-TB. Outcomes from targeted biopsies were reported as CDR for clinically significant prostate cancer (csPC) and for any cancer. RESULTS: Targeted csCDR was higher in RA-TB vs. C-TB (32.1% vs. 10.3%, P=0.014). Targeted CDR of any cancer with Prostate Imaging Reporting and Data System (PI-RADS) 3–5 ROIs was also significantly higher in RA-TB compared to C-TB (47.2% vs. 12.8%, P=0.001). On multivariable analysis significant factors which affected the CDR for csPC was prostate volume only [odds ratio (OR) 1.04, 95% confidence interval (CI): 1.01–1.07]. For any cancer, the CDR was related to prostate volume (OR 1.03, 95% CI: 1.01–1.06) and RA-TB (OR 5.97, 95% CI: 1.69–21.07). RA biopsy results in less acute urinary retention (1.9% vs. 12.8%, P=0.03), less prolonged haematuria (7.5% vs. 38.5%, P

Improved medical care throughout childhood and adolescence has enabled patients with complex urological abnormalities to live longer into adulthood. These patients are now at risk of developing common, age-related, urological conditions. This review aims to review existing data and make recommendations in areas where expert opinion is currently lacking METHODS: This review represents the joint SIU-ICUD (Société Internationale d'Urologie-International Consultation on Urological Disease) consultation on congenital lifelong urology. The results of this analysis were first presented at a joint consultation of the ICUD and SIU at the 2018 SIU annual conference in Seoul, South Korea.BPH may present differently in patients with neurogenic bladder. Thorough assessment of neurological status, bladder and sphincter function is required before offering any bladder outlet surgery. Prostate specific antigen screening should be offered to men aged 50-69 with neurogenic bladders if they have good life expectancy. Multi-parametric MRI and transperineal biopsy would be the investigations of choice if feasible. Surgery for localized disease should only be done by surgeons with the relevant expertise. Bladder cancer in this patient group is more likely to present at a later stage and have a worse prognosis. Parenthood is achievable for most, but often requires assistance with conception. Pregnant women who have had previous urogenital reconstructive surgery should be managed in appropriate obstetric units with the involvement of a reconstructive urologist.Most evidence regarding complex urogenital abnormalities comes from the pediatric population. Evidence regarding common, age-related urological issues is generally from the 'normal' adult population. As patients with complex congenital urological conditions live longer, more data will become available to assess the long-term benefits of intervention.

There are mixed reports on the role that IGFBP-2 plays in cancer progression, with some indicating a tumour suppressive role and others showing that IGFBP-2 may act as an oncogene. These apparent contradictions may be context and tissue specific. In this study we determined the role that IGFBP-2 played on the phenotype and chemosensitivity of a selection of bladder cancer cell lines and investigated how the abundance of IGFBP-2 was regulated. We found that IGFBP-2 was more abundant in the epithelial bladder cancer cells, RT4 and UMUC3 and absent in the more mesenchymal T24 and TCCSUP cells. Silencing IGFBP-2 using siRNA in epithelial RT4 cells promoted cell proliferation, invasion, colony formation, resulted in a reduction in epithelial (E-cadherin) and an increase in mesenchymal (N-cadherin) markers and increased sensitivity to cisplatin-induced cell death. Conversely, we observed the opposite effects when adding exogenous IGFBP-2 to the mesenchymal T24 cells. We determined that IGFBP-2 was epigenetically silenced via DNA methylation as the cells adopted a mesenchymal phenotype. Collectively these data suggest that IGFBP-2 acts as a tumour suppressor and marker of chemosensitivity in epithelial bladder cancer cells and that IGFBP-2 is epigenetically silenced by methylation to promote bladder cancer progression.

Objective\ud \ud To investigate the functional and quality of life (QoL) outcomes of treatments for localised prostate cancer and inform treatment decision-making.\ud \ud \ud \ud Patients and Methods\ud \ud Men aged 50–69 years diagnosed with localised prostate cancer by prostate-specific antigen testing and biopsies at nine UK centres in the Prostate Testing for Cancer and Treatment (ProtecT) trial were randomised to, or chose one of, three treatments. Of 2565 participants, 1135 men received active monitoring (AM), 750 a radical prostatectomy (RP), 603 external-beam radiotherapy (EBRT) with concurrent androgen-deprivation therapy (ADT) and 77 low-dose-rate brachytherapy (BT, not a randomised treatment). Patient-reported outcome measures (PROMs) completed annually for 6 years were analysed by initial treatment and censored for subsequent treatments. Mixed effects models were adjusted for baseline characteristics using propensity scores.\ud \ud \ud \ud Results\ud \ud Treatment-received analyses revealed different impacts of treatments over 6 years. Men remaining on AM experienced gradual declines in sexual and urinary function with age (e.g., increases in erectile dysfunction from 35% of men at baseline to 53% at 6 years and nocturia similarly from 20% to 38%). Radical treatment impacts were immediate and continued over 6 years. After RP, 95% of men reported erectile dysfunction persisting for 85% at 6 years, and after EBRT this was reported by 69% and 74%, respectively (P

IntroductionActive surveillance (AS) for patients with prostate cancer (PC) with low risk of PC death is an alternative to radical treatment. A major drawback of AS is the uncertainty whether a patient truly has low risk PC based on biopsy alone. Multiparametric MRI scan together with biopsy, appears useful in separating patients who need curative therapy from those for whom AS may be safe. Two small clinical trials have shown short-term high-dose vitamin D supplementation may prevent PC progression. There is no substantial evidence for its long-term safety and efficacy, hence its use in the care of men with PC on AS needs assessment. This protocol describes the ProsD clinical trial which aims to determine if oral high-dose vitamin D supplementation taken monthly for 2 years can prevent PC progression in cases with low-to-intermediate risk of progression.Method and analysisThis is an Australian national multicentre, 2:1 double-blinded placebo-controlled phase II randomised controlled trial of monthly oral high-dose vitamin D supplementation (50 000 IU cholecalciferol), in men diagnosed with localised PC who have low-to-intermediate risk of disease progression and are being managed by AS. This trial will assess the feasibility, efficacy and safety of supplementing men with an initial oral loading dose of 500 000 IU cholecalciferol, followed by a monthly oral dose of 50 000 IU during the 24 months of AS. The primary trial outcome is the commencement of active therapy for clinical or non-clinical reason, within 2 years of AS.Ethics and disseminationThis trial is approved by Bellberry Ethics Committee (2016-06-459). All results will be reported in peer-reviewed journals.Trial registration numberACTRN12616001707459.

Background: Salvage radical prostatectomy (sRP) historically yields poor functional outcomes and high complication rates. However, recent reports on robotic sRP show improved results. Our objectives were to evaluate sRP oncological outcomes and predictors of positive margins and biochemical recurrence (BCR). Methods: We retrospectively collected data of sRP for recurrent prostate cancer after local nonsurgical treatment at 18 tertiary referral centers in United States, Australia and Europe, from 2000 to 2016. SM and BCR were evaluated in a univariate and multivariable analysis. Overall and cancer-specific survival were also assessed. Results: We included 414 cases, 63.5% of them performed after radiotherapy. Before sRP the majority of patients had biopsy Gleason score (GS) = 9 27.6%), with 52.9% having >= pT3 disease and 16% pN+. SM was positive in 29.7%. Five years BCR-Free, cancer-specific survival and OS were 56.7%, 97.7% and 92.1%, respectively. On multivariable analysis pathological T (pT3a odds ratio [OR] 2.939, 95% confidence interval [CI] 1.469-5.879; >= pT3b OR 2.428-95% CI 1.333-4.423) and N stage (pN1 OR 2.871, 95% CI 1.503-5.897) were independent predictors of positive margins. Pathological T stage >= T3b (OR 2.348 95% CI 1.338-4.117) and GS (up to OR 7.183, 95% CI 1.906-27.068 for GS > 8) were independent predictors for BCR. Limitations include the retrospective nature of the study and limited follow-up. Conclusions: In a contemporary series, sRP showed promising oncological control in the medium term despite aggressive pathological features. BCR risk increased in case of locally advanced disease and higher GS. Future studies are needed to confirm our findings. (C) 2020 Published by Elsevier Inc.

OBJECTIVES To investigate whether anti-glypican-1 antibody Miltuximab conjugated with near-infrared dye IRDye800CW can be used for in vivo fluorescence imaging of urothelial carcinoma. METHODS The conjugate, Miltuximab-IRDye800CW, was produced and characterized by size exclusion chromatography and flow cytometry with glypican-1-expressing cells. Balb/c nude mice bearing subcutaneous urothelial carcinoma xenografts were intravenously injected with Miltuximab-IRDye800CW or control IgG-IRDye800CW and imaged daily by fluorescence imaging. After 10 days, tumors and major organs were collected for ex vivo study of the conjugate biodistribution, including its accumulation in the tumor. RESULTS The intravenous injection of Miltuximab-IRDye800CW to tumor-bearing mice showed its specific accumulation in the tumors with the tumor-to-background ratio of 12.7 ± 2.4, which was significantly higher than that in the control group (4.6 ± 0.9, P

ObjectivesActive surveillance (AS) enables men with low risk, localised prostate cancer (PCa) to avoid radical treatment unless progression occurs; lack of reliable AS protocols to determine progression leaves uncertainties for men and clinicians. This study investigated men’s strategies for coping with the uncertainties of active monitoring (AM, a surveillance strategy within the Prostate testing for cancer and Treatment, ProtecT trial) over the longer term and implications for optimising supportive care.DesignLongitudinal serial in-depth qualitative interviews every 2–3 years for a median 7 (range 6–14) years following diagnosis.SettingFour centres within the UK Protect trial.ParticipantsPurposive sample of 20 men with localised PCa: median age at diagnosis 64 years (range 52–68); 15 (75%) had low-risk PCa; 12 randomly allocated to, 8 choosing AM. Eleven men continued with AM throughout the study period (median 7 years). Nine received radical treatment after a median 4 years (range 0.8–13.8 years).InterventionAM: 3-monthly serum prostate-specific antigen (PSA)-level assessment (year 1), 6–12 monthly thereafter; increase in PSA ≥50% during previous 12 months or patient/clinician concern triggered review.Main outcomesThematic analysis of 73 interviews identified strategies to accommodate uncertainty and anxiety of living with untreated cancer; implications for patient care.ResultsMen sought clarity, control or reassurance, with contextual factors mediating individual responses. Trust in the clinical team was critical for men in balancing anxiety and facilitating successful management change/continued monitoring. Only men from ProtecT were included; men outside ProtecT may have different experiences.ConclusionMen looked to clinicians for clarity, control and reassurance. Where provided, men felt comfortable continuing AM or having radical treatments when indicated. Clinicians build patient trust by clearly describing uncertainties, allowing patients control wherever possible and being aware of how context influences individual responses. Insights indicate need for supportive services to build trust and patient engagement over the long term.Trial registration numberISRCTN20141297; Pre-results.

Background Prostate cancer is the most common cancer among men in the UK. Prostate-specific antigen testing followed by biopsy leads to overdetection, overtreatment as well as undertreatment of the disease. Evidence of treatment effectiveness has lacked because of the paucity of randomised controlled trials comparing conventional treatments. Objectives To evaluate the effectiveness of conventional treatments for localised prostate cancer (active monitoring, radical prostatectomy and radical radiotherapy) in men aged 50–69 years. Design A prospective, multicentre prostate-specific antigen testing programme followed by a randomised trial of treatment, with a comprehensive cohort follow-up. Setting Prostate-specific antigen testing in primary care and treatment in nine urology departments in the UK. Participants Between 2001 and 2009, 228,966 men aged 50–69 years received an invitation to attend an appointment for information about the Prostate testing for cancer and Treatment (ProtecT) study and a prostate-specific antigen test; 82,429 men were tested, 2664 were diagnosed with localised prostate cancer, 1643 agreed to randomisation to active monitoring (n = 545), radical prostatectomy (n = 553) or radical radiotherapy (n = 545) and 997 chose a treatment. Interventions The interventions were active monitoring, radical prostatectomy and radical radiotherapy. Trial primary outcome measure Definite or probable disease-specific mortality at the 10-year median follow-up in randomised participants. Secondary outcome measures Overall mortality, metastases, disease progression, treatment complications, resource utilisation and patient-reported outcomes. Results There were no statistically significant differences between the groups for 17 prostate cancer-specific (p = 0.48) and 169 all-cause (p = 0.87) deaths. Eight men died of prostate cancer in the active monitoring group (1.5 per 1000 person-years, 95% confidence interval 0.7 to 3.0); five died of prostate cancer in the radical prostatectomy group (0.9 per 1000 person-years, 95% confidence interval 0.4 to 2.2 per 1000 person years) and four died of prostate cancer in the radical radiotherapy group (0.7 per 1000 person-years, 95% confidence interval 0.3 to 2.0 per 1000 person years). More men developed metastases in the active monitoring group than in the radical prostatectomy and radical radiotherapy groups: active monitoring, n = 33 (6.3 per 1000 person-years, 95% confidence interval 4.5 to 8.8); radical prostatectomy, n = 13 (2.4 per 1000 person-years, 95% confidence interval 1.4 to 4.2 per 1000 person years); and radical radiotherapy, n = 16 (3.0 per 1000 person-years, 95% confidence interval 1.9 to 4.9 per 1000 person-years; p = 0.004). There were higher rates of disease progression in the active monitoring group than in the radical prostatectomy and radical radiotherapy groups: active monitoring (n = 112; 22.9 per 1000 person-years, 95% confidence interval 19.0 to 27.5 per 1000 person years); radical prostatectomy (n = 46; 8.9 per 1000 person-years, 95% confidence interval 6.7 to 11.9 per 1000 person-years); and radical radiotherapy (n = 46; 9.0 per 1000 person-years, 95% confidence interval 6.7 to 12.0 per 1000 person years; p Limitations A single prostate-specific antigen test and transrectal ultrasound biopsies were used. There were very few non-white men in the trial. The majority of men had low- and intermediate-risk disease. Longer follow-up is needed. Conclusions At a median follow-up point of 10 years, prostate cancer-specific mortality was low, irrespective of the assigned treatment. Radical prostatectomy and radical radiotherapy reduced disease progression and metastases, but with side effects. Further work is needed to follow up participants at a median of 15 years. Trial registration Current Controlled Trials ISRCTN20141297. Funding This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 37. See the National Institute for Health Research Journals Library website for further project information.

Objectives:Recruitment to pragmatic trials is often difficult, and little is known about factors associated with key participation and treatment decisions. These were explored in the Prostate cancer testing and Treatment (ProtecT) study. Study Design and Setting:Baseline sociodemographic, patient-reported outcome, clinical history, and prostate cancer biopsy data were collected for all patients eligible to take part in the ProtecT trial, in a comprehensive cohort design. Men who rejected randomization specified a preferred option and were followed up identically to the randomized cohort. Factors associated with participation decisions, patient preferences, and reasons for changing treatment were explored. Results:Of 2,664 men with clinically localized prostate cancer, 997 (37%) rejected randomization. Their treatment preferences and subsequent treatment choices/changes in both randomized and treatment choice cohorts were strongly associated with prostate cancer risk features: toward active monitoring for low-risk disease and toward radical options with higher risk prostate cancer. Among many factors measured, only a small number of weak associations were found for occupation groups and some patient symptoms. Similar percentages changed from the random allocation and initially stated preference. Conclusion:The comprehensive cohort design provided new insights into trial recruitment and participation decisions. Opportunities to improve recruitment by supporting recruiters with equipoise and patient preferences were identified.

Background Photoimmunotherapy (PIT) is an emerging method of cancer treatment based on the use of a photosensitizer near-infrared dye IRDye700DX (IR700) conjugated to a monoclonal antibody. The antibody selectively delivers IR700 to cancer cells, which can then be killed after photoexcitation. Glypican-1 (GPC-1) is a novel target expressed specifically in malignant tumors. We aimed to investigate whether anti-GPC-1 antibody Miltuximab® (Glytherix Ltd., Sydney, Australia) can be conjugated with IR700 for PIT of solid tumors. Methods The dye IR700 was conjugated with Miltuximab® and characterized by spectrophotometry and flow cytometry. Miltuximab®-IR700-mediated PIT was tested in prostate (DU-145), bladder (C3 and T-24), brain (U-87 and U-251) and ovarian (SKOV-3) cancer cell lines. After 1 h incubation with Miltuximab®-IR700, the cells were washed by PBS and illuminated using a 690-nm light-emitting diode. The viability of the cells was assessed by a CCK-8 viability kit 24 h later. Results Miltuximab®-IR700-mediated PIT caused 67.3–92.3% reduction in viability of cells with medium-high GPC-1 expression and did not affect the viability of GPC-1-low cells. Cytotoxicity was attributed to the targeted binding of the conjugate with subsequent photoactivation, as the conjugate or light exposure alone had no effect on the cell viability. Miltuximab®-IR700 did not induce cytotoxicity in cells blocked by unconjugated Miltuximab®. Conclusions PIT with Miltuximab®-IR700 appears to be highly specific and effective against GPC-1-expressing cancer cells, indicating that it holds promise for an effective and safe treatment of early stage solid tumors or as adjuvant therapy following surgical resection. These findings necessitate further investigation of PIT with Miltuximab®-IR700 in other GPC-1-expressing cancer cell lines in vitro and in vivo in xenograft tumor models.

INTRODUCTION AND OBJECTIVE:Men with biochemical recurrence (BCR) after primary treatment can be managed with curative intent by salvage radical prostatectomy (sRP). Historical series show high comp...

229 Background: Clinicians want a more accurate diagnostic test to identify patients for prostate biopsy. We have previously described the development of a Luminex based test for aggressive prostate cancer (MiCheck). To facilitate widespread deployment of MiCheck on standard clinical chemistry analysers such as Roche Cobas and Abbott ARCHITECT/Alinity systems, we have performed additional analytical validation and model development using the MiCheck-01 clinical samples. A novel algorithm, termed MiCheck Prostate, was developed to differentiate aggressive prostate cancer (Gleason 3+4 or above) from non-aggressive (GS3+3) or no cancer patients. Methods: Serum protein biomarkers were measured in 317 samples from the MiCheck-01 clinical trial using either Luminex Multiplex kits, Abbott ARCHITECT or Beckmann Coulter systems. Logistic regression models were used to select best analytes, then Monte Carlo cross-validation was applied to avoid overfitting. A final model was selected from the cross-validation models with best test specificity at 95% sensitivity. The MiCheck-01 samples were later all measured on a standard Abbott ARCHITECT system using commercial ARCHITECT IVD tests. The best cross-validated model was developed and the results compared to those obtained from the mixed analyte platforms using ROC curve analysis. Results: The MiCheck Prostate algorithm was developed to maximise discrimination between aggressive prostate cancer and no cancer or non-aggressive cancer. The MiCheck Prostate algorithm reports a percentage risk of aggressive prostate cancer on biopsy. MiCheck Prostate is a logistic regression algorithm that combines three serum protein markers and one clinical factor and was derived using data from the MiCheck-01 trial. The algorithm gave an AUC of 0.82, with a 48% specificity at a 95% sensitivity cutpoint, with a negative predictive value of 94% for GS3+4 and higher cancers. The samples were later re-measured using all ARCHITECT immunoassays. Good correlations of each analyte across different measurement platforms was observed (Pearson’s R > 0.9). The algorithm was revalidated using the new set of analyte values. AUC of 0.82 for the detection of aggressive CaP, and sensitivity of 95%, specificity of 47% were obtained for the best model, showing no statistical difference to the previous best model derived from the mixed platforms. NPV of 94% for GS3+4 or higher cancers was maintained. Conclusions: The MiCheck Prostate test shows high sensitivity, specificity and NPV for the detection of aggressive prostate cancer. It uses analytes widely available on standard clinical chemistry analysers such as Abbott Architect and Roche Cobas, hence is simple to deploy in the laboratory setting. Studies are ongoing to confirm the MiCheck Prostate algorithm performance using additional clinical sample cohorts.

During the last decade, isolation of circulating tumour cells via blood liquid biopsy of prostate cancer (PCa) has attracted significant attention as an alternative, or substitute, to conventional diagnostic tests. However, it was previously determined that localised forms of PCa shed a small number of cancer cells into the bloodstream, and a large volume of blood is required just for a single test, which is impractical. To address this issue, urine has been used as an alternative to blood for liquid biopsy as a truly non-invasive, patient-friendly test. To this end, we developed a spiral microfluidic chip capable of isolating PCa cells from the urine of PCa patients. Potential clinical utility of the chip was demonstrated using anti-Glypican-1 (GPC-1) antibody as a model of the primary antibody in immunofluorescent assay for identification and detection of the collected tumour cells. The microchannel device was first evaluated using DU-145 cells in a diluted Dulbecco&rsquo, s phosphate-buffered saline sample, where it demonstrated &gt, 85 (&plusmn, 6) % efficiency. The microchannel proved to be functional in at least 79% of cases for capturing GPC1+ putative tumour cells from the urine of patients with localised PCa. More importantly, a correlation was found between the amount of the captured GPC1+ cells and crucial diagnostic and prognostic parameter of localised PCa&mdash, Gleason score. Thus, the technique demonstrated promise for further assessment of its diagnostic value in PCa detection, diagnosis, and prognosis.

Bladder cancer is the ninth most common cancer worldwide. Due to a high risk of recurrence and progression of bladder cancer, every patient needs long-term surveillance, which includes regular cystoscopy, sometimes followed by a biopsy of suspicious lesions or resections of recurring tumours. This study addresses the development of novel biohybrid nanocomplexes representing upconversion nanoparticles (UCNP) coupled to antibodies for photoluminescent (PL) detection of bladder cancer cells. Carrying specific antibodies, these nanoconjugates selectively bind to urothelial carcinoma cells and make them visible by emitting visible PL upon excitation with deeply penetrating near-infrared light. UCNP were coated with a silica layer and linked to anti-Glypican-1 antibody MIL38 via silica-specific solid-binding peptide. Conjugates have been shown to specifically attach to urothelial carcinoma cells with high expression of Glypican-1. This result highlights the potential of produced conjugates and conjugation technology for further studies of their application in the tumour detection and fluorescence-guided resection.

Objectives\ud \ud Randomized controlled trials (RCTs) deliver robust internally valid evidence but generalizability is often neglected. Design features built into the Prostate testing for cancer and Treatment (ProtecT) RCT of treatments for localized prostate cancer (PCa) provided insights into its generalizability.\ud \ud \ud Study Design and Setting\ud \ud Population-based cluster randomization created a prospective study of prostate-specific antigen (PSA) testing and a comprehensive-cohort study including groups choosing treatment or excluded from the RCT, as well as those randomized. Baseline information assessed selection and response during RCT conduct.\ud \ud \ud Results\ud \ud The prospective study (82,430 PSA-tested men) represented healthy men likely to respond to a screening invitation. The extended comprehensive cohort comprised 1,643 randomized, 997 choosing treatment, and 557 excluded with advanced cancer/comorbidities. Men choosing treatment were very similar to randomized men except for having more professional/managerial occupations. Excluded men were similar to the randomized socio-demographically but different clinically, representing less healthy men with more advanced PCa.\ud \ud \ud Conclusion\ud The design features of the ProtecT RCT provided data to assess the representativeness of the prospective cohort and generalizability of the findings of the RCT. Greater attention to collecting data at the design stage of pragmatic trials would better support later judgments by clinicians/policy-makers about the generalizability of RCT findings in clinical practice.

Male Stress Urinary Incontinence is a complication post robotic radical prostatectomy. This is a major problem that needs to be solved, since it has great impact on quality of life affecting the patient's physical activity and social well-being. A systematic review relating to literature on impact of preoperative PFE on continence outcomes for patients undergoing prostatectomy was conducted. The search strategy aimed to identify all references related to pelvic floor exercises and post-prostatectomy. Search terms used were as follows: (Pelvic floor exercises) AND (incontinence) AND (prostatectomy). The following databases were screened from 2000 to September 2017: CINAHL, MEDLINE (NHS Evidence), Cochrane, AMed, EMBASE, PsychINFO, SCOPUS, Web of Science. In addition, searches using Medical Subject Headings (MeSH) and keywords were conducted using Cochrane databases. Two UK-based experts in prostate cancer and robotic surgery were consulted to identify any additional studies. In the 6 months following surgery, the continence rates, as defined by the use of one pad or less per day, were 94% (44 of 47) and 96% (48 of 50) in the PFE and biofeedback groups and control groups (PFE alone), respectively (P = 0.596) (Bales et al. in Urology 56: 627-630, 2000). This demonstrates preoperative PFE may improve early continence after RP. Geraerts et al. (Eur Urol 64:766-772, 2013) demonstrated the "incontinence impact" was in favour of a group with PFE at 3 and 6 months after surgery. This demonstrates again the advantage of preoperative PFE. Cornel et al. [World J Urol 23:353-355, 2005] determined the benefit of starting pelvic floor muscle exercise (PFE) 30 days before RP and of continuing PFE postoperatively for early recovery of continence as part of a randomised, prospective study (Moher quality A). This demonstrated preoperative PFE may improve early continence and QoL outcomes after RP. Post-prostatectomy incontinence is a bothersome complication of radical prostatectomy [Chughtai et al. in Rev Urol 15:61-66, 2013]. Weak pelvic floor muscles compromised normal pelvic floor function and led to urinary incontinence and erectile dysfunction. Strengthening the pelvic floor muscles was shown to significantly improve post-prostatectomy urinary continence, post-micturition dribble and erectile function. It would be prudent for all men to exercise their pelvic floor muscles to maintain normal pelvic floor function and start prior to surgery.

Objective: The formation of multidisciplinary teams (MDTs) was formalised for urological cancer services by the National Institute for Health and Care Excellence (NICE) in the 2002 Improving Outcomes in Urological Cancer guidance. This project aimed to assess the variability of MDT recommendations when presented with the same patient. It covered the type and grade of tumour, recorded stage, treatment recommendations and whether clinical trials were considered. Materials and methods: Anonymised details of 10 patients were sent to South West Trust MDTs in two tranches. Details included age, clinical history, haematology and biochemistry results, digital radiology, and pathology text. A panel of representative urologists and urological oncologists from the region decided on optimal treatment and key points of management decisions. Results: The MDTs were not consistent in decision making. This agrees with a previous survey of urologists which also showed inconsistent decision making, and under-use of clinical cues. Some decisions contradicted NICE guidelines in force at the time. Conclusions: MDTs are now an instrumental, integrated part of cancer management. It is vital for assurance of best patient care and best outcomes that the MDT considering and planning treatment is fully functional and well informed on the evidence base, with effective communications. This audit suggests that this is not the case. The Oxford Centre for Evidence-based Medicine – Levels of Evidence is not applicable to this study.

Salvage radical prostatectomy has historically yielded a poor functional outcome and a high complication rate. However, recent reports of robotic salvage radical prostatectomy have demonstrated improved results. In this study we assessed salvage radical prostatectomy functional outcomes and complications when comparing robotic and open approaches.We retrospectively collected data on salvage radical prostatectomy for recurrent prostate cancer after local nonsurgical treatment at 18 tertiary referral centers from 2000 to 2016. The Clavien-Dindo classification was applied to classify complications. Complications and functional outcomes were evaluated by univariable and multivariable analysis.We included 395 salvage radical prostatectomies, of which 186 were open and 209 were robotic. Robotic salvage radical prostatectomy yielded lower blood loss and a shorter hospital stay (each p0.0001). No significant difference emerged in the incidence of major and overall complications (10.1%, p=0.16, and 34.9%, p=0.67), including an overall low risk of rectal injury and fistula (1.58% and 2.02%, respectively). However, anastomotic stricture was more frequent for open salvage radical prostatectomy (16.57% vs 7.66%, p0.01). Overall 24.6% of patients had had severe incontinence, defined as 3 or more pads per day, for 12 or 6 months. On multivariable analysis robotic salvage radical prostatectomy was an independent predictor of continence preservation (OR 0.411, 95% CI 0.232-0.727, p=0.022). Limitations include the retrospective nature of the study and the absence of a standardized surgical technique.In this contemporary series to our knowledge salvage radical prostatectomy showed a low risk of major complications and better functional outcomes than previously reported. Robotic salvage radical prostatectomy may reduce anastomotic stricture, blood loss and hospital stay, and improve continence outcomes.

INTRODUCTION AND OBJECTIVES:Salvage radical prostatectomy (sRP) has been associated with high complication rates and poor functional outcomes in the past, while latest sRP series have shown a subst...

INTRODUCTION AND OBJECTIVES:A curative option in men with biochemical recurrence (BCR) after primary treatment is represented by salvage radical prostatectomy (sRP). To enhance cancer control and b...

Inguinal hernia is a known sequel of radical prostatectomy which contributes to patient morbidity and health care expenditure. In this systematic review we evaluated the incidence of inguinal hernia associated with minimally invasive radical prostatectomy, in addition to predictive factors and preventive measures.We searched PubMed® and Embase® between 2000 and February 2018 using the search terms inguinal hernia and radical prostatectomy.In concordance with search terms and selection criteria we identified a total of 155 reports with 27 studies eligible for inclusion. Collated results demonstrated a variable prevalence of inguinal hernia after laparoscopic radical prostatectomy and robotic assisted radical prostatectomy ranging from 4.3% to 8.3% and from 3% to 19.4 %, respectively. There was a higher mean prevalence of inguinal hernia after robotic assisted prostatectomy. Factors predicting inguinal hernia following minimally invasive radical prostatectomy included low body mass index, poor stream and straining prior to prostatectomy detected on symptom score instruments, a patent processus vaginalis or an intraoperative incidental inguinal hernia. Herniotomy or herniorrhaphy with onlay mesh repair was the most commonly reported intraoperative repair technique at the time of minimally invasive radical prostatectomy. Recurrence of repaired incidental hernia is rare.Inguinal hernia is common after minimally invasive radical prostatectomy. There is a lack of high level evidence to clarify risk factors and preventive strategies for inguinal hernia after minimally invasive radical prostatectomy. There is a justification for randomized controlled trials to further evaluate this under recognized clinical problem.

Background Osseointegration, an approach for direct skeletal attachment of a prosthesis to an amputated limb, may address many of the problems associated with socket prostheses. The safety of osseointegration remains uncertain. The aim of this study was to summarize evidence on functional and clinical outcomes, as well as adverse effects of osseointegration for patients with a limb amputation. Methods MEDLINE, Embase, Web of Science and the Cochrane Library were searched to April 2018. Eligible studies were observational, case and qualitative studies, and RCTs conducted in patients with a limb amputation, who were managed with osseointegrated prostheses and had follow-up data. Results Twenty-two eligible articles comprising 13 unique studies were included. No RCT was identified. Apart from three case reports that comprised one to five patients, the sample size of studies ranged from 11 to 100 participants. All relevant studies reported improvement in functional outcomes (walking ability, prosthetic use and mobility), satisfaction and quality of life following osseointegration, compared with their preoperative status or when using a conventional socket prosthesis. Infection rates ranged from 1 (95 per cent c.i. 0 to 5) to 77 (59 to 88) per cent. The majority of infections were described as low-grade soft tissue or superficial infections related to the skin–implant interface, and were treated effectively with antibiotics. None of the studies reported additional amputation or death as a result of osseointegration. Conclusion Osseointegration after limb amputation improves prosthetic use, comfort when sitting, walking ability, mobility, gait and quality of life. However, it is associated with an increased risk of soft tissue infection.

Aims: The treatment of prostate cancer has evolved markedly over the last 40 years, including radiotherapy, notably with escalated dose and targeting. However, the optimal treatment for localised disease has not been established in comparative randomised trials. The aim of this article is to describe the history ofprostate radiotherapy trials, including their quality assurance processes, and to compare these with the ProtecT trial.Materials and methods: The UK ProtecT randomised trial compares external beam conformal radiotherapy, surgery and active monitoring for clinically localized prostate cancer and will report on the primary outcome (disease-specific mortality) in 2016 following recruitment between 1999 and 2009. The embedded quality assurance programme consists of on-site machine dosimetry at the nine trial centres, a retrospective review of outlining and adherence to dose constraints based on the trial protocol in 54 participants (randomly selected, around 10% of the total randomised to radiotherapy, n ¼ 545). These quality assurance processes and results were compared with prostate radiotherapy trials of a comparable era.Results: There has been an increasingly sophisticated quality assurance programme in UK prostate radiotherapy trials over the last 15 years, reflecting dose escalation and treatment complexity. In ProtecT, machine dosimetry results were comparable between trial centres and with the UK RT01 trial. The outliningreview showed that most deviations were clinically acceptable, although three (1.4%) may have been of clinical significance and were related to outlining of theprostate. Seminal vesicle outlining varied, possibly due to several prostate trials running concurrently with different protocols. Adherence to dose constraints inProtecT was considered acceptable, with 80% of randomised participants having two or less deviations and planning target volume coverage was excellent.Conclusion: The ProtecT trial quality assurance results were satisfactory and comparable with trials of its era. Future trials should aim to standardise treatment protocols and quality assurance programmes where possible to reduce complexities for centres involved in multiple trials. 2016 Published by Elsevier Ltd on behalf of The Royal College of Radiologists.

Radiation therapy (RT) is one of the most important strategies in cancer treatment. Radioresistance (the failure to RT) results in locoregional recurrence and metastasis. Therefore, it is critically important to investigate the mechanisms leading to cancer radioresistance to overcome this problem and increase patients' survival. Currently, the majority of the radioresistance-associated researches have focused on preclinical studies. Although the exact mechanisms of cancer radioresistance have not been fully uncovered, accumulating evidence supports that cancer stem cells (CSCs) and different signaling pathways play important roles in regulating radiation response and radioresistance. Therefore, targeting CSCs or signaling pathway proteins may hold promise for developing novel combination modalities and overcoming radioresistance. The present review focuses on the key evidence of CSC markers and several important signaling pathways in cancer radioresistance and explores innovative approaches for future radiation treatment.

Introduction and Objectives: Up to 50% of patients with non-muscle invasive bladder cancer suffer from recurrence or progression into a muscle-invasive disease despite multiple resections and long-term chemo and immunotherapy. Possible reasons for that are incomplete resection and reimplantation of cancer cells, which could be prevented by early detection and improved resection of tumor margins. Fluorescence-guided surgery is beneficial in some patients with flat tumors; however, it is currently based on metabolic differences of cancer cells and lacks specificity in many cases. Molecular imaging could improve the specificity of fluorescence-guided surgery since it can target biomarkers expressed by individual tumors. We aimed to select a biomarker and develop a probe for molecular imaging of urothelial carcinoma (UC). Methods: One of the biomarkers present in UC is a heparan sulphate proteoglycan Glypican-1 (GPC-1). The anti-GPC-1 monoclonal antibody Miltuximab (Glytherix Ltd. Sydney, Australia) was used to analyze the expression of GPC-1 in UC cell lines T24 and UM-UC-6. Miltuximab was then labelled by a fluorescent dye IRDye800CW and tested in vivo. Luciferase-transfected UM-UC-6 cells were injected subcutaneously into the hind leg of ten nude mice. When the tumors reached 1000 mm3 in volume, the mice were intravenously injected with 5.7 mg/kg Miltuximab-IRDye800 or isotype IgG-IRDye800. They were then imaged daily for ten days and sacrificed for ex vivo imaging to study the distribution of Miltuximab within the body and its accumulation in the tumors. Results: Flow cytometry and Western blotting demonstrated high expression of GPC-1 in cells UM-UC-6 and T24. UM-UC-6 cells formed subcutaneous tumors that were histologically representative of tumors of human bladder in all animals. From one to ten days after the intravenous injection of the fluorescently labeled Miltuximab, we detected its high accumulation in the tumors by in vivo and ex vivo imaging. One day after the injection, tumors could be visualized in both groups with tumor-to-noise (T/N) ratio of 2. On the 5th day, this value went up to 6.7 for Miltuximab and 3.5 for the Isotype IgG group. By day 10, non-bound antibody molecules further cleared from the mice, resulting in T/N ratio of 14.1 in the mice injected with Miltuximab, while in the control group the value reached only 4.8. Conclusions: Overexpression of GPC-1 in UC shows its high potential as a target for molecular imaging. The animal model developed in this study demonstrated accumulation of the antibody in the tumor and its strong visualization, which could be helpful in tumor detection and resection. Another advantage of this platform is its high potential for clinical translation. IRDye800 can be visualized by existing equipment for indocyanine green imaging and has been proven to be safe in several clinical trials. The antibody Miltuximab has also been used in clinic and has an excellent safety profile. Citation Format: Dmitry Polikarpov, Douglas Campbell, Lucinda McRobb, Alexander Zaslavsky, Andrei Zvyagin, Bradley Walsh, Ganesh Palapattu, David Gillatt. Application of Miltuximab®-IRDye800 for near-infrared fluorescence imaging of urothelial carcinoma in vivo [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2019 May 18-21; Denver, CO. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(15_Suppl):Abstract nr A08.

Introduction and Objectives: Despite multiple resections and long-term chemo and immunotherapy, most non-muscle invasive bladder cancer patients suffer from recurrence or progression leading to cystectomy and a less favorable outcome. Possible reasons for that are incomplete resection and reimplantation of cancer cells, which could be prevented by improved resection and adjuvant therapy. Our objective was to develop a targeted drug for detection, fluorescence-guided resection, and deep-penetrating adjuvant photodynamic therapy of urothelial carcinoma (UC). The agent was based on upconversion nanoparticles (UCNP), which can carry a photosensitizer and can transform deep-penetrating near-infrared light into high-energy visible light, demanded for tumor visualization and for production of reactive oxygen species in the photosensitizer. At this stage, we aimed to select an antibody that could be attached to UCNPs to deliver them to UC cells. Methods: We produced silica-coated UCNP of the composition NaYF4:Yb,Er amenable for conjugation with biomolecules. An anti-Glypican-1 (GPC-1) monoclonal antibody MIL-38 (Glytherix Ltd., Sydney, Australia), was chosen for targeted delivery of the nanoparticles as it had previously demonstrated affinity towards bladder cancer. UCNPs were conjugated with MIL-38 by using a fusion protein Linker-Protein G (LPG). Finally, to investigate targeted binding and molecular specificity of these nanoconjugates, we incubated them with GPC-1 positive and GPC-1 negative cells. The role of MIL-38 in targeted delivery of nanoconjugates was also validated by incubation of GPC-1 positive T24 cells with nanoparticles coupled to an isotype control antibody and without an antibody. Results: Targeted upconversion nanoconjugates UCNP-LPG-MIL-38 labeled almost 90% of T24 cells with high expression of GPC-1 and only 23.2% of C3 cells with low expression of this antigen, demonstrating high molecular selectivity and specificity. Incubation of T24 cells with nanoconjugates linked with a control antibody and without antibody resulted in labeling of 19.8% and 26.2%, respectively, demonstrating the role of MIL-38 in targeted delivery of these nanoconjugates. As a result of the labeling, mean photoluminescence of cells in targeted group was from five to eight times stronger than in control groups, allowing for easy identification of positive cells with low background autofluorescence. Conclusions: These results highlight the potential of these nanoconjugates for the diagnosis and therapy of UC, as they can bind to Glypican-1-positive BC cells and cause their bright photoluminescence, which could be used for detection of tumors and activation of photosensitizers. It was also confirmed that monoclonal antibody MIL-38 has high potential to be applied in experimental diagnosis, drug delivery, and targeted therapy of UC, as it mediated targeted binding of upconversion photoluminescent nanoconjugates to Glypican-1-positive UC cells. Citation Format: Liuen Liang, Andrew Care, Anwar Sunna, Douglas Campbell, Bradley Walsh, Andrei Zvyagin, David Gillatt, Dmitry Polikarpov. Photoluminescent nanoconjugates for molecular imaging of bladder cancer [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2019 May 18-21; Denver, CO. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(15_Suppl):Abstract nr B27.

Background A clinical need exists for a biomarker test to accurately delineate aggressive prostate cancer (AgCaP), and thus better assist clinicians and patients decision-making on whether to proceed to prostate biopsy. Objectives To develop a blood test for AgCaP and compare to PSA, %free PSA, proPSA, and prostate health index (PHI) tests. Design, settings and participants Patient samples from the MiCheck-01 trial were used for development of the MiCheck test. Methods Serum analyte concentrations for cellular growth factors were determined using a custom-made Luminex-based R&D Systems multianalyte kit. Outcome measurements and statistical analysis Bayesian model averaging and random forest approaches were used to identify clinical factors and growth factors able to distinguish between men with AgCaP (Gleason Score [GS] ≥3+4) from those with non-AgCaP (GS 3+3). Logistic regression and Monte Carlo cross-validation identified variable combinations in order to able to maximize differentiation of AgCaP from non-AgCaP. Results The MiCheck logistic regression model was developed and comprises the following variables: serum prostate-specific antigen (PSA), patient age, Digital Rectal Exam (DRE) status, Leptin, IL-7, vascular endothelial growth factor, and Glypican-1. The model differentiated AgCaP from non-AgCaP with an area under the curve of 0.83 and was superior to PSA, %free PSA and PHI in all patient groups, regardless of PSA range. Applying the MiCheck test to all evaluable biopsy patients from the MiCheck-01 study demonstrated that up to 30% of biopsies could be avoided while delaying diagnosis of only 6.8% of GS ≥3+4 cancers, 5% of GS ≥4+3 cancers and no cancers of GS 8 or higher. Conclusions The MiCheck test outperforms PSA, %free PSA and PHI tests in differentiating AgCaP vs. non-AgCaP patients. The MiCheck test could result in a significant number of biopsies being avoided with a low number of patients experiencing a delayed diagnosis.

Glioblastoma (GBM) is one of the most aggressive tumors and its 5-year survival is approximately 5%. Fluorescence-guided surgery (FGS) improves the extent of resection and leads to better prognosis. Molecular near-infrared (NIR) imaging appears to outperform conventional FGS, however, novel molecular targets need to be identified in GBM. Proteoglycan glypican-1 (GPC-1) is believed to be such a target as it is highly expressed in GBM and is associated with poor prognosis. We hypothesize that an anti-GPC-1 antibody, Miltuximab&reg, conjugated with the NIR dye, IRDye800CW (IR800), can specifically accumulate in a GBM xenograft and provide high-contrast in vivo fluorescent imaging in rodents following systemic administration. Miltuximab&reg, was conjugated with IR800 and intravenously administered to BALB/c nude mice bearing a subcutaneous U-87 GBM hind leg xenograft. Specific accumulation of Miltuximab&reg, IR800 in subcutaneous xenograft tumor was detected 24 h later using an in vivo fluorescence imager. The conjugate did not cause any adverse events in mice and caused strong fluorescence of the tumor with tumor-to-background ratio (TBR) reaching 10.1 &plusmn, 2.8. The average TBR over the 10-day period was 5.8 &plusmn, 0.6 in mice injected with Miltuximab&reg, IR800 versus 2.4 &plusmn, 0.1 for the control group injected with IgG-IR800 (p = 0.001). Ex vivo assessment of Miltuximab&reg, IR800 biodistribution confirmed its highly specific accumulation in the tumor. The results of this study confirm that Miltuximab&reg, IR800 holds promise for intraoperative fluorescence molecular imaging of GBM and warrants further studies.

Epidemiologic studies suggest that diet can alter prostate cancer risk. This study aimed to establish the feasibility and acceptability of dietary modification in men at increased risk of prostate cancer. Men were invited with a PSA level of 2.0–2.95 ng/mL or 3.0–19.95 ng/mL with negative prostate biopsies. Randomization (3 × 3 factorial design) to daily green tea and lycopene: green tea drink (3 cups, unblinded) or capsules [blinded, 600 mg flavan-3-ol ()-epigallocatechin-3-gallate (EGCG) or placebo] and lycopene-rich foods (unblinded) or capsules (blinded, 15 mg lycopene or placebo) for 6 months. Primary endpoints were randomization rates and intervention adherence (blinded assessment of metabolites) at 6 months with secondary endpoints of acceptability (from interviews), safety, weight, blood pressure, and PSA. A total of 133 of 469 (28.4%) men approached agreed to be randomized and 132 were followed-up (99.2%). Mean lycopene was 1.28 [95% confidence intervals (CI), 1.09–1.50, P = 0.003] times higher in the lycopene capsule group and 1.42 (95% CI, 1.21–1.66; P < 0.001) times higher in the lycopene-enriched diet group compared with placebo capsules. Median EGCG was 10.7 nmol/L (95% CI, 7.0–32.0) higher in in the active capsule group and 20.0 nmol/L (95% CI, 0.0–19.0) higher in the green tea drink group compared with placebo capsules (both P < 0.001). All interventions were acceptable and well tolerated although men preferred the capsules. Dietary prevention is acceptable to men at risk of prostate cancer. This intervention trial demonstrates that a chemoprevention clinical trial is feasible. Cancer Prev Res; 11(11); 687–96. ©2018 AACR.

Objectives: Men diagnosed with low‐risk prostate cancer are typically eligible for active surveillance of their cancer, involving monitoring for cancer progression and making judgements about the risks of prostate cancer against those of active inter‐ vention. Our study examined how risk for prostate cancer is perceived and expe‐ rienced by patients undergoing active surveillance with their clinicians, how risk is communicated in clinical consultations, and the implications for treatment and care. Method: Participants were nine patients and three clinicians from a university hos‐ pital urology clinic. A staged, qualitative, multi‐method data collection approach was undertaken, comprising: observations of consultations; patient and clinician in‐ terviews; and patient surveys. The three data sets were analysed separately using thematic analysis and then integrated to give a comprehensive view of patient and clinician views. Results: Thirty data points (eight patient surveys; 10 observations of consultations between patients and clinicians; 10 patient interviews; and two clinician interviews) combined to create a detailed picture of how patients perceived and appraised risk, in three themes of "Making sense of risk", "Talking about risk" and "Responding to risk". Conclusion: Effective risk communication needs to be finely tuned and timed to in‐ dividual patient's priorities and information requirements. A structured information exchange process that identifies patients’ priorities, and details key moments in risk assessment, so that complexities of risk are discussed in ways that are meaningful to patients, may benefit patient care. These findings could inform the development of patient‐centric risk assessment procedures and service delivery models in prostate cancer care more broadly.

Objective To determine the contemporary survival outcomes from a whole population and identify significant predictors of survival, as contemporary population-based survival outcomes after radical cystectomy (RC) for the treatment of bladder cancer (BC) are sparse. Reports suggest a large disparity between population outcomes and those of centres of excellence. Patients and Methods All invasive BC cases diagnosed between 2001 and 2007 in New South Wales, Australia, were identified from the Central Cancer Registry. Records of treatment and death were electronically linked. All patients who underwent RC between 2001 and 2009 were selected for this study (804 patients). Follow-up was to the end of 2009. Outcomes assessed were disease-specific survival (DSS) and overall survival (OS). Multivariable Cox regression and log-rank analysis were used to model and compare survival within groups. Results Of 804 patients diagnosed during the study period 420 (52.2%) died during follow-up. The 5-year DSS and OS for all patients was 59.6% and 53.2%, respectively. The 5-year DSS for patients with localised, regional and distant disease, undergoing RC was 72%, 51% and 10%, respectively. Age (P < 0.001) and stage (P < 0.001) were associated with 5-year DSS and OS after adjusting for all other variables. High-volume centres had significantly better 5-year DSS compared with low-volume centres (P < 0.05). The 30-day mortality for high- vs low-volume centres was 1.8% and 3.6%, respectively. Perioperative mortality improved over time for high- and moderate-volume centres but not for low-volume centres. Conclusion Contemporary survival outcomes after RC are much improved compared with older studies and appear close to results from academic centres of excellence. High-volume centres report better 5-year DSS outcomes than lower volume centres.