Epidemiology and screening for renal cancer.

PURPOSE: The widespread use of abdominal imaging has affected the epidemiology of renal cell carcinoma (RCC). Despite this, over 25% of individuals with RCC have evidence of metastases at presentation. Screening for RCC has the potential to downstage the disease. METHODS: We performed a literature review on the epidemiology of RCC and evidence base regarding screening. Furthermore, contemporary RCC epidemiology data was obtained for the United Kingdom and trends in age-standardised rates of incidence and mortality were analysed by annual percentage change statistics and joinpoint regression. RESULTS: The incidence of RCC in the UK increased by 3.1% annually from 1993 through 2014. Urinary dipstick is an inadequate screening tool due to low sensitivity and specificity. It is unlikely that CT would be recommended for population screening due to cost, radiation dose and increased potential for other incidental findings. Screening ultrasound has a sensitivity and specificity of 82-83% and 98-99%, respectively; however, accuracy is dependent on tumour size. No clinically validated urinary nor serum biomarkers have been identified. Major barriers to population screening include the relatively low prevalence of the disease, the potential for false positives and over-diagnosis of slow-growing RCCs. Individual patient risk-stratification based on a combination of risk factors may improve screening efficiency and minimise harms by identifying a group at high risk of RCC. CONCLUSION: The incidence of RCC is increasing. The optimal screening modality and target population remain to be elucidated. An analysis of the benefits and harms of screening for patients and society is warranted

Models predicting survival to guide treatment decision-making in newly diagnosed primary non-metastatic prostate cancer: a systematic review.

OBJECTIVES: Men diagnosed with non-metastatic prostate cancer require standardised and robust long-term prognostic information to help them decide on management. Most currently-used tools use short-term and surrogate outcomes. We explored the evidence base in the literature on available pre-treatment, prognostic models built around long-term survival and assess the accuracy, generalisability and clinical availability of these models. DESIGN: Systematic literature review, pre-specified and registered on PROSPERO (CRD42018086394). DATA SOURCES: MEDLINE, Embase and The Cochrane Library were searched from January 2000 through February 2018, using previously-tested search terms. ELIGIBILITY CRITERIA: Inclusion required a multivariable model prognostic model for non-metastatic prostate cancer, using long-term survival data (defined as ≥5 years), which was not treatment-specific and usable at the point of diagnosis. DATA EXTRACTION AND SYNTHESIS: Title, abstract and full-text screening were sequentially performed by three reviewers. Data extraction was performed for items in the CHecklist for critical Appraisal and data extraction for systematic Reviews of prediction Modelling Studies checklist. Individual studies were assessed using the new Prediction model Risk Of Bias ASsessment Tool. RESULTS: Database searches yielded 6581 studies after deduplication. Twelve studies were included in the final review. Nine were model development studies using data from over 231 888 men. However, only six of the nine studies included any conservatively managed cases and only three of the nine included treatment as a predictor variable. Every included study had at least one parameter for which there was high risk of bias, with failure to report accuracy, and inadequate reporting of missing data common failings. Three external validation studies were included, reporting two available models: The University of California San Francisco (UCSF) Cancer of the Prostate Risk Assessment score and the Cambridge Prognostic Groups. Neither included treatment effect, and both had potential flaws in design, but represent the most robust and usable prognostic models currently available. CONCLUSION: Few long-term prognostic models exist to inform decision-making at diagnosis of non-metastatic prostate cancer. Improved models are required to inform management and avoid undertreatment and overtreatment of non-metastatic prostate cancer.The Urology Foundation - Research Scholarship

XMM-Newton observations of the black hole X-ray transient XTE J1650-500 in quiescence

We report the result of an XMM-Newton observation of the black-hole X-ray transient XTE J1650-500 in quiescence. The source was not detected and we set upper limits on the 0.5-10 keV luminosity of 0.9e31-1.0e31 erg/s (for a newly derived distance of 2.6 kpc). These limits are in line with the quiescent luminosities of black-hole X-ray binaries with similar orbital periods (~7-8 hr)Comment: 3 pages. Accepted for publication in MNRA

Public attitudes towards screening for kidney cancer: an online survey

Funder: Kidney Cancer UKFunder: The Urology FoundationAbstract: Background: Kidney cancer is often asymptomatic, leading to proposals for a screening programme. The views of the public towards introducing a new screening programme for kidney cancer are unknown. The aim of this study was to explore attitudes towards kidney cancer screening and factors influencing intention to attend a future screening programme. Methods: We conducted an online population-based survey of 1021 adults aged 45–77 years. The main outcome measure was intention to attend four possible screening tests (urine, blood, ultrasound scan, low-dose CT) as well as extended low-dose CT scans within lung cancer screening programmes. We used multivariable regression to examine the association between intention and each screening test. Results: Most participants stated that they would be ‘very likely’ or ‘likely’ to undergo each of the screening tests [urine test: n = 961 (94.1%); blood test: n = 922 (90.3%); ultrasound: n = 914 (89.5%); low-dose CT: n = 804 (78.8%); lung CT: n = 962 (95.2%)]. Greater intention to attend was associated with higher general cancer worry and less perceived burden/inconvenience about the screening tests. Less worry about the screening test was also associated with higher intention to attend, but only in those with low general cancer worry (cancer worry scale ≤ 5). Compared with intention to take up screening with a urine test, participants were half as likely to report that they intended to undergo blood [OR 0.56 (0.43–0.73)] or ultrasound [OR 0.50 (0.38–0.67)] testing, and half as likely again to report that they intended to take part in a screening programme featuring a low dose CT scan for kidney cancer screening alone [OR 0.19 (0.14–0.27)]. Conclusion: Participants in this study expressed high levels of intention to accept an invitation to screening for kidney cancer, both within a kidney cancer specific screening programme and in conjunction with lung cancer screening. The choice of screening test is likely to influence uptake. Together these findings support on-going research into kidney cancer screening tests and the potential for combining kidney cancer screening with existing or new screening programmes

High frequency quasi-periodic oscillations in the black hole X-ray transient XTE J1650-500

We report the detection of high frequency variability in the black hole X-ray transient XTE J1650-500. A quasi-periodic oscillation (QPO) was found at 250 Hz during a transition from the hard to the soft state. We also detected less coherent variability around 50 Hz, that disappeared when the 250 Hz QPO showed up. There are indications that when the energy spectrum hardened the QPO frequency increased from ~110 Hz to ~270 Hz, although the observed frequencies are also consistent with being 1:2:3 harmonics of each other. Interpreting the 250 Hz as the orbital frequency at the innermost stable orbit around a Schwarzschild black hole leads to a mass estimate of 8.2 Msun. The spectral results by Miller et al.(2002, ApJ, 570, L69), which suggest considerable black hole spin, would imply a higher mass.Comment: Submitted to ApJ, 12 pages including 2 figure

Urine proteomics in the diagnosis of stable angina.

BACKGROUND: We have previously described a panel of 238 urinary polypeptides specific for established severe coronary artery disease (CAD). Here we studied this polypeptide panel in patients with a wider range of CAD severity. METHODS: We recruited 60 patients who underwent elective coronary angiography for investigation of stable angina. Patients were selected for either having angiographic evidence of CAD or not (NCA) following coronary angiography (n = 30/30; age, 55 ± 6 vs. 56 ± 7 years, P = 0.539) to cover the extremes of the CAD spectrum. A further 66 patients with severe CAD (age, 64 ± 9 years) prior to surgical coronary revascularization were added for correlation studies. The Gensini score was calculated from coronary angiograms as a measure of CAD severity. Urinary proteomic analyses were performed using capillary electrophoresis coupled online to micro time-of-flight mass spectrometry. The urinary polypeptide pattern was classified using a predefined algorithm and resulting in the CAD238 score, which expresses the pattern quantitatively. RESULTS: In the whole cohort of patients with CAD (Gensini score 60 [40; 98]) we found a close correlation between Gensini scores and CAD238 (ρ = 0.465, P < 0.001). After adjustment for age (β = 0.144; P = 0.135) the CAD238 score remained a significant predictor of the Gensini score (β =0.418; P < 0.001). In those with less severe CAD (Gensini score 40 [25; 61]), however, we could not detect a difference in CAD238 compared to patients with NCA (-0.487 ± 0.341 vs. -0.612 ± 0.269, P = 0.119). CONCLUSIONS: In conclusion the urinary polypeptide CAD238 score is associated with CAD burden and has potential as a new cardiovascular biomarker

Kidney Cancer Screening and Epidemiology

The incidence of renal cell carcinoma (RCC) has risen worldwide over the past few decades, and this has been associated with a stage shift. Survival outcomes of RCC depend largely on the stage at diagnosis. Although overall mortality has stabilized or declined in most countries, survival remains poor in late-stage disease, suggesting early detection may improve overall survival outcomes. A number of potential candidate screening tools have been considered (including urinary dipstick, blood- and urine-based biomarkers, ultrasound, and computed tomography [CT]), though it may be that a combination of these approaches may be optimal. Ultimately, the sensitivity and specificity of the chosen screening tool will determine the rate of false positives and false negatives, which must be minimized. One of the key challenges is the relatively low prevalence of the disease, which might be overcome by performing risk-stratified screening or screening for more than one condition (such as combined lung and kidney cancer screening). Both approaches have been shown to be acceptable to the general public, and they may maximize the efficiency of screening while reducing harms. Indeed, quantifying benefits and harms of screening is key (including the impact on overdiagnosis and quality of life). Whether screening for RCC will lead to a stage shift and the impact on survival are the decisive missing pieces of information that will determine whether the screening program might be adopted into clinical practice (along with feasibility, acceptability, and cost-effectiveness)

Validation and public health modelling of risk prediction models for kidney cancer using the UK Biobank

Funder: Kidney Cancer UKFunder: Yorkshire Cancer ResearchFunder: Mark Foundation For Cancer Research; Id: http://dx.doi.org/10.13039/100014599Funder: The Rosetrees TrustFunder: Urology Foundation; Id: http://dx.doi.org/10.13039/501100007568Objectives: To externally validate risk models for the detection of kidney cancer, as early detection of kidney cancer improves survival and stratifying the population using risk models could enable an individually tailored screening programme. Methods: We validated the performance of 30 existing phenotypic models predicting the risk of kidney cancer in the UK Biobank cohort (n = 450 687). We compared the discrimination and calibration of models for men, women, and a mixed‐sex cohort. Population level data were used to estimate model performance in a screening scenario for a range of risk thresholds (6‐year risk: 0.1–1.0%). Results: In all, 10 models had reasonable discrimination (area under the receiver‐operating characteristic curve >0.60), although some had poor calibration. Modelling demonstrated similar performance of the best models over a range of thresholds. The models showed an improvement in ability to identify cases compared to age‐ and sex‐based screening. All the models performed less well in women than men. Conclusions: The present study is the first comprehensive external validation of risk models for kidney cancer. The best‐performing models are better at identifying individuals at high risk of kidney cancer than age and sex alone; however, the benefits are relatively small. Feasibility studies are required to determine applicability to a screening programme

Acceptability and potential impact on uptake of using different risk stratification approaches to determine eligibility for screening: A population‐based survey

Funder: Kidney Cancer UKFunder: Renal Cancer Research FundAbstract: Background: Using risk stratification approaches to determine eligibility has the potential to improve efficiency of screening. Objectives: To compare the public acceptability and potential impact on uptake of using different approaches to determine eligibility for screening. Design: An online population‐based survey of 668 adults in the UK aged 45‐79 including a series of scenarios in the context of a potential kidney cancer screening programme in which eligibility was determined by age, sex, age and sex combined, a simple risk score (age, sex, body mass index, smoking status), a complex risk score additionally incorporating family history and lifestyle, or a genetic risk score. Outcome measures: We used multi‐level ordinal logistic regression to compare acceptability and potential uptake within individuals and multivariable ordinal logistic regression differences between individuals. Results: Using sex, age and sex, or the simple risk score were less acceptable than age (P < .0001). All approaches were less acceptable to women than men. Over 70% were comfortable waiting until they were older if the complex risk score or genetics indicated a low risk. If told they were high risk, 85% would be more likely to take up screening. Being told they were low risk had no overall influence on uptake. Conclusions: Varying the starting age of screening based on estimated risk from models incorporating phenotypic or genetic risk factors would be acceptable to most individuals and may increase uptake. Patient or Public Contribution: Two members of the public contributed to the development of the survey and have commented on this paper

Prostate cancer detection through unbiased capture of methylated cell-free DNA

Funding: Cancer Research UK, CRUK Career Development Fellowship, University of Cambridge W.D. Armstrong Trust Fund, John Black Prostate Cancer Foundation Young Investigator Award. This research was also supported by the NIHR Cambridge Biomedical Research Centre (BRC-1215-20014).Prostate cancer screening using prostate-specific antigen (PSA) has been shown to reduce mortality but with substantial overdiagnosis, leading to unnecessary biopsies. The identification of a highly specific biomarker using liquid biopsies, represents an unmet need in the diagnostic pathway for prostate cancer. In this study, we employed a method that enriches for methylated cell-free DNA fragments coupled with a machine learning algorithm which enabled the detection of metastatic and localized cancers with AUCs of 0.96 and 0.74, respectively. The model also detected 51.8% (14/27) of localized and 88.7% (79/89) of patients with metastatic cancer in an external dataset. Furthermore, we show that the differentially methylated regions reflect epigenetic and transcriptomic changes at the tissue level. Notably, these regions are significantly enriched for biologically relevant pathways associated with the regulation of cellular proliferation and TGF-beta signaling. This demonstrates the potential of circulating tumor DNA methylation for prostate cancer detection and prognostication.Peer reviewe