Risk-stratified screening for the early detection of kidney cancer.

Earlier detection and screening for kidney cancer has been identified as a key research priority, however the low prevalence of the disease in unselected populations limits the cost-effectiveness of screening. Risk-stratified screening for kidney cancer may improve early detection by targeting high-risk individuals whilst limiting harms in low-risk individuals, potentially increasing the cost-effectiveness of screening. A number of models have been identified which estimate kidney cancer risk based on both phenotypic and genetic data, and while several of the former have been shown to identify individuals at high-risk of developing kidney cancer with reasonable accuracy, current evidence does not support including a genetic component. Combined screening for lung cancer and kidney cancer has been proposed, as the two malignancies share some common risk factors. A modelling study estimated that using lung cancer risk models (currently used for risk-stratified lung cancer screening) could capture 25% of patients with kidney cancer, which is only slightly lower than using the best performing kidney cancer-specific risk models based on phenotypic data (27%-33%). Additionally, risk-stratified screening for kidney cancer has been shown to be acceptable to the public. The following review summarises existing evidence regarding risk-stratified screening for kidney cancer, highlighting the risks and benefits, as well as exploring the management of potential harms and further research needs.

Short-term psychosocial outcomes of adding a non-contrast abdominal computed tomography (CT) scan to the thoracic CT within lung cancer screening.

OBJECTIVES: To evaluate psychological, social, and financial outcomes amongst individuals undergoing a non-contrast abdominal computed tomography (CT) scan to screen for kidney cancer and other abdominal malignancies alongside the thoracic CT within lung cancer screening. SUBJECTS AND METHODS: The Yorkshire Kidney Screening Trial (YKST) is a feasibility study of adding a non-contrast abdominal CT scan to the thoracic CT within lung cancer screening. A total of 500 participants within the YKST, comprising all who had an abnormal CT scan and a random sample of one-third of those with a normal scan between 14/03/2022 and 24/08/2022 were sent a questionnaire at 3 and 6 months. Outcomes included the Psychological Consequences Questionnaire (PCQ), the short-form of the Spielberger State-Trait Anxiety Inventory, and the EuroQoL five Dimensions five Levels scale (EQ-5D-5L). Data were analysed using regression adjusting for participant age, sex, socioeconomic status, education, baseline quality of life (EQ-5D-5L), and ethnicity. RESULTS: A total of 380 (76%) participants returned questionnaires at 3 months and 328 (66%) at 6 months. There was no difference in any outcomes between participants with a normal scan and those with abnormal scans requiring no further action. Individuals requiring initial further investigations or referral had higher scores on the negative PCQ than those with normal scans at 3 months (standardised mean difference 0.28 sd, 95% confidence interval 0.01-0.54; P = 0.044). The difference was greater in those with anxiety or depression at baseline. No differences were seen at 6 months. CONCLUSION: Screening for kidney cancer and other abdominal malignancies using abdominal CT alongside the thoracic CT within lung cancer screening is unlikely to cause significant lasting psychosocial or financial harm to participants with incidental findings.

Estimating the Effectiveness of Kidney Cancer Screening Within Lung Cancer Screening Programmes: A Validation in UK Biobank.

In the absence of population-based screening, addition of screening for kidney cancer to lung cancer screening could provide an efficient and low-resource means to improve early detection. In this study, we used the UK Biobank cohort (n = 442 865) to determine the performance of the Yorkshire Lung Cancer Screening Trial (YLST) eligibility criteria for selecting individuals for kidney cancer screening. We measured the performance of two models widely used to determine eligibility for lung cancer screening (PLCO[m2012] and the Liverpool-Lung-Project-v2) and the performance of the combined YLST criteria. We found that the lung cancer models have discrimination (area under the receiver operating curve) between 0.60 and 0.68 for kidney cancer. In the UK, one in four cases (25%) of kidney cancer cases is expected to occur in those eligible for lung cancer screening, and one case of kidney cancer detected for every 200 people invited to lung cancer screening. These results suggest that adding kidney cancer screening to lung cancer screening would be an effective strategy to improve early detection rates of kidney cancer. However, most kidney cancers would not be picked up by this approach. This analysis does not address other important considerations about kidney cancer screening, such as overdiagnosis. PATIENT SUMMARY: It has been proposed that adding-on kidney cancer screening to lung cancer screening (both carried out by a computed tomography scan of the chest/abdomen) would be an easy and low-cost way of detecting cases of kidney cancer earlier, when these can be treated more easily. Lung cancer screening is usually targeted at people who are at a high risk (eg, older smokers); therefore, here we look at whether the same group of people are also at a high risk of kidney cancer. Our analysis shows that one in four people later diagnosed with kidney cancer are also at a high risk of lung cancer; hence, a combined screening programme could detect up to a quarter of kidney cancers.

Public Preferences for Determining Eligibility for Screening in Risk-Stratified Cancer Screening Programs: A Discrete Choice Experiment.

BACKGROUND: Risk stratification has been proposed to improve the efficiency of population-level cancer screening. We aimed to describe and quantify the relative importance of different attributes of potential screening programs among the public, focusing on stratifying eligibility. METHODS: We conducted a discrete choice experiment in which respondents selected between 2 hypothetical screening programs in a series of 9 questions. We presented the risk factors used to determine eligibility (age, sex, or lifestyle or genetic risk scores) and anticipated outcomes based on eligibility criteria with different sensitivity and specificity levels. We performed conditional logit regression models and used the results to estimate preferences for different approaches. We also analyzed free-text comments on respondents' views on the programs. RESULTS: A total of 1,172 respondents completed the survey. Sensitivity was the most important attribute (7 and 11 times more important than specificity and risk factors, respectively). Eligibility criteria based on age and sex or genetics were preferred over age alone and lifestyle risk scores. Phenotypic and polygenic risk prediction models would be more acceptable than screening everyone aged 55 to 70 y if they had high discrimination (area under the receiver-operating characteristic curve ≥0.75 and 0.80, respectively). LIMITATIONS: Although our sample was representative with respect to age, sex, and ethnicity, it may not be representative of the UK population regarding other important characteristics. Also, some respondents may have not understood all the information provided to inform decision making. CONCLUSIONS: The public prioritized lives saved from cancer over reductions in numbers screened or experiencing unnecessary follow-up. Incorporating personal-level risk factors into screening eligibility criteria is acceptable to the public if it increases sensitivity; therefore, maximizing sensitivity in model development and communication could increase uptake. HIGHLIGHTS: The public prioritized lives saved when considering changing from age-based eligibility criteria to risk-stratified cancer screening over reductions in numbers of people being screened or experiencing unnecessary follow-up.The risk stratification strategy used to do this was the least important component, although age plus sex or genetics were relatively preferable to using age alone and lifestyle risk scores.Communication strategies that emphasize improvements in the numbers of cancers detected or not missed across the population are more likely to be salient than reductions in unnecessary investigations or follow-up among some groups.Future research should focus on developing implementation strategies that maximize gains in sensitivity within the context of resource constraints and how to present attributes relating to specificity to facilitate understanding and informed decision making.

Dynamic partitioning of branched-chain amino acids-derived nitrogen supports renal cancer progression.

Metabolic reprogramming is critical for tumor initiation and progression. However, the exact impact of specific metabolic changes on cancer progression is poorly understood. Here, we integrate multimodal analyses of primary and metastatic clonally-related clear cell renal cancer cells (ccRCC) grown in physiological media to identify key stage-specific metabolic vulnerabilities. We show that a VHL loss-dependent reprogramming of branched-chain amino acid catabolism sustains the de novo biosynthesis of aspartate and arginine enabling tumor cells with the flexibility of partitioning the nitrogen of the amino acids depending on their needs. Importantly, we identify the epigenetic reactivation of argininosuccinate synthase (ASS1), a urea cycle enzyme suppressed in primary ccRCC, as a crucial event for metastatic renal cancer cells to acquire the capability to generate arginine, invade in vitro and metastasize in vivo. Overall, our study uncovers a mechanism of metabolic flexibility occurring during ccRCC progression, paving the way for the development of novel stage-specific therapies.

Accurate detection of benign and malignant renal tumor subtypes with MethylBoostER: An epigenetic marker-driven learning framework.

Current gold standard diagnostic strategies are unable to accurately differentiate malignant from benign small renal masses preoperatively; consequently, 20% of patients undergo unnecessary surgery. Devising a more confident presurgical diagnosis is key to improving treatment decision-making. We therefore developed MethylBoostER, a machine learning model leveraging DNA methylation data from 1228 tissue samples, to classify pathological subtypes of renal tumors (benign oncocytoma, clear cell, papillary, and chromophobe RCC) and normal kidney. The prediction accuracy in the testing set was 0.960, with class-wise ROC AUCs >0.988 for all classes. External validation was performed on >500 samples from four independent datasets, achieving AUCs >0.89 for all classes and average accuracies of 0.824, 0.703, 0.875, and 0.894 for the four datasets. Furthermore, consistent classification of multiregion samples (N = 185) from the same patient demonstrates that methylation heterogeneity does not limit model applicability. Following further clinical studies, MethylBoostER could facilitate a more confident presurgical diagnosis to guide treatment decision-making in the future.

The Yorkshire Kidney Screening Trial (YKST): protocol for a feasibility study of adding non-contrast abdominal CT scanning to screen for kidney cancer and other abdominal pathology within a trial of community-based CT screening for lung cancer.

INTRODUCTION: Kidney cancer (renal cell cancer (RCC)) is the seventh most common cancer in the UK. As RCC is largely curable if detected at an early stage and most patients have no symptoms, there is international interest in evaluating a screening programme for RCC. The Yorkshire Kidney Screening Trial (YKST) will assess the feasibility of adding non-contrast abdominal CT scanning to screen for RCC and other abdominal pathology within the Yorkshire Lung Screening Trial (YLST), a randomised trial of community-based CT screening for lung cancer. METHODS AND ANALYSIS: In YLST, ever-smokers aged 55-80 years registered with a general practice in Leeds have been randomised to a Lung Health Check assessment, including a thoracic low-dose CT (LDCT) for those at high risk of lung cancer, or routine care. YLST participants randomised to the Lung Health Check arm who attend for the second round of screening at 2 years without a history of RCC or abdominal CT scan within the previous 6 months will be invited to take part in YKST. We anticipate inviting 4700 participants. Those who consent will have an abdominal CT immediately following their YLST thoracic LDCT. A subset of participants and the healthcare workers involved will be invited to take part in a qualitative interview. Primary objectives are to quantify the uptake of the abdominal CT, assess the acceptability of the combined screening approach and pilot the majority of procedures for a subsequent randomised controlled trial of RCC screening within lung cancer screening. ETHICS AND DISSEMINATION: YKST was approved by the North West-Preston Research Ethics Committee (21/NW/0021), and the Health Research Authority on 3 February 2021. Trial results will be disseminated at clinical meetings, in peer-reviewed journals and to policy-makers. Findings will be made available to participants via the study website (www.YKST.org). TRIAL REGISTRATION NUMBERS: NCT05005195 and ISRCTN18055040.

A community jury study exploring the public acceptability of using risk stratification to determine eligibility for cancer screening.

INTRODUCTION: Using risk stratification to determine eligibility for cancer screening is likely to improve the efficiency of screening programmes by targeting resources towards those most likely to benefit. We aimed to explore the implications of this approach from a societal perspective by understanding public views on the most acceptable stratification strategies. METHODS: We conducted three online community juries with 9 or 10 participants in each. Participants were purposefully sampled by age (40-79 years), sex, ethnicity, social grade and English region. On the first day, participants were informed of the potential benefits and harms of cancer screening and the implications of different ways of introducing stratification using scenarios based on phenotypic and genetic risk scores. On the second day, participants deliberated to reach a verdict on the research question, 'Which approach(es) to inviting people to screening are acceptable, and under what circumstances?' Deliberations and feedback were recorded and analysed using thematic analysis. RESULTS: Across the juries, the principle of risk stratification was generally considered to be an acceptable approach for determining eligibility for screening. Disregarding increasing capacity, the participants considered it to enable efficient resource allocation to high-risk individuals and could see how it might help to save lives. However, there were concerns regarding fair implementation, particularly how the risk assessment would be performed at scale and how people at low risk would be managed. Some favoured using the most accurate risk prediction model whereas others thought that certain risk factors should be prioritized (particularly factors considered as non-modifiable and relatively stable, such as genetics and family history). Transparently justifying the programme and public education about cancer risk emerged as important contributors to acceptability. CONCLUSION: Using risk stratification to determine eligibility for cancer screening was acceptable to informed members of the public, particularly if it included risk factors they considered fair and when communicated transparently. PATIENT OR PUBLIC CONTRIBUTION: Two patient and public involvement representatives were involved throughout this study. They were not involved in synthesizing the results but contributed to producing study materials, co-facilitated the community juries and commented on the interpretation of the findings and final report.

The current state of genetic risk models for the development of kidney cancer: a review and validation.

OBJECTIVE: To review the current state of genetic risk models for predicting the development of kidney cancer, by identifying and comparing the performance of published models. METHODS: Risk models were identified from a recent systematic review and the Cancer-PRS web directory. A narrative synthesis of the models, previous validation studies and related genome-wide association studies (GWAS) was carried out. The discrimination and calibration of the identified models was then assessed and compared in the UK Biobank (UKB) cohort (cases, 452; controls, 487 925). RESULTS: A total of 39 genetic models predicting the development of kidney cancer were identified and 31 were validated in the UKB. Several of the genetic-only models (seven of 25) and most of the mixed genetic-phenotypic models (five of six) had some discriminatory ability (area under the receiver operating characteristic curve >0.5) in this cohort. In general, models containing a larger number of genetic variants identified in GWAS performed better than models containing a small number of variants associated with known causal pathways. However, the performance of the included models was consistently poorer than genetic risk models for other cancers. CONCLUSIONS: Although there is potential for genetic models to identify those at highest risk of developing kidney cancer, their performance is poorer than the best genetic risk models for other cancers. This may be due to the comparatively small number of genetic variants associated with kidney cancer identified in GWAS to date. The development of improved genetic risk models for kidney cancer is dependent on the identification of more variants associated with this disease. Whether these will have utility within future kidney cancer screening pathways is yet to determined.

Early detection of kidney cancer using urinary proteins: a truly non-invasive strategy.

OBJECTIVES: To review urinary protein biomarkers as potential non-invasive, easily obtainable, early diagnostic tools in renal cell carcinoma (RCC). METHODS: A PubMed database search was performed up to the year 2020 to identify primary studies reporting potential urinary protein biomarkers for RCC. Separate searches were conducted to identify studies describing appropriate methods of developing cancer screening programmes and detection of cancer biomarkers. RESULTS: Several urinary protein biomarkers are under validation for RCC diagnostics, e.g. aquaporin-1, perilipin-2, carbonic anhydrase-9, Raf-kinase inhibitory protein, nuclear matrix protein-22, 14-3-3 Protein ß/α and neutrophil gelatinase-associated lipocalin. However, none has yet been validated or approved for clinical use due to low sensitivity or specificity, inconsistencies in appropriate study design, or lack of external validation. CONCLUSIONS: Evaluation of biomarkers' feasibility, sample preparation and storage, biomarker validation, and the application of novel technologies may provide a solution that maximises the potential for a truly non-invasive biomarker in early RCC diagnostics.

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

OBJECTIVES: 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.

Risk models for recurrence and survival after kidney cancer: a systematic review.

OBJECTIVE: To systematically identify and compare the performance of prognostic models providing estimates of survival or recurrence of localized renal cell cancer (RCC) in patients treated with surgery with curative intent. MATERIALS AND METHODS: We performed a systematic review (PROSPERO CRD42019162349). We searched Medline, EMBASE and the Cochrane Library from 1 January 2000 to 12 December 2019 to identify studies reporting the performance of one or more prognostic model(s) that predict recurrence-free survival (RFS), cancer-specific survival (CSS) or overall survival (OS) in patients who have undergone surgical resection for localized RCC. For each outcome we summarized the discrimination of each model using the C-statistic and performed multivariate random-effects meta-analysis of the logit transformed C-statistic to rank the models. RESULTS: Of a total of 13 549 articles, 57 included data on the performance of 22 models in external populations. C-statistics ranged from 0.59 to 0.90. Several risk models were assessed in two or more external populations and had similarly high discriminative performance. For RFS, these were the Sorbellini, Karakiewicz, Leibovich and Kattan models, with the UCLA Integrated Staging System model also having similar performance in European/US populations. All had C-statistics ≥0.75 in at least half of the validations. For CSS, they the models with the highest discriminative performance in two or more external validation studies were the Zisman, Stage, Size, Grade and Necrosis (SSIGN), Karakiewicz, Leibovich and Sorbellini models (C-statistic ≥0.80 in at least half of the validations), and for OS they were the Leibovich, Karakiewicz, Sorbellini and SSIGN models. For all outcomes, the models based on clinical features at presentation alone (Cindolo and Yaycioglu) had consistently lower discrimination. Estimates of model calibration were only infrequently included but most underestimated survival. CONCLUSION: Several models had good discriminative ability, with there being no single 'best' model. The choice from these models for each setting should be informed by both the comparative performance and availability of factors included in the models. All would need recalibration if used to provide absolute survival estimates.

Risk prediction models for symptomatic patients with bladder and kidney cancer: a systematic review.

BACKGROUND: Timely diagnosis of bladder and kidney cancer is key to improving clinical outcomes. Given the challenges of early diagnosis, models incorporating clinical symptoms and signs may be helpful to primary care clinicians when triaging at-risk patients. AIM: To identify and compare published models that use clinical signs and symptoms to predict the risk of undiagnosed prevalent bladder or kidney cancer. DESIGN AND SETTING: Systematic review. METHOD: A search identified primary research reporting or validating models predicting the risk of bladder or kidney cancer in MEDLINE and EMBASE. After screening identified studies for inclusion, data were extracted onto a standardised form. The risk models were classified using TRIPOD guidelines and evaluated using the PROBAST assessment tool. RESULTS: The search identified 20 661 articles. Twenty studies (29 models) were identified through screening. All the models included haematuria (visible, non-visible, or unspecified), and seven included additional signs and symptoms (such as abdominal pain). The models combined clinical features with other factors (including demographic factors and urinary biomarkers) to predict the risk of undiagnosed prevalent cancer. Several models (n = 13) with good discrimination (area under the receiver operating curve >0.8) were identified; however, only eight had been externally validated. All of the studies had either high or unclear risk of bias. CONCLUSION: Models were identified that could be used in primary care to guide referrals, with potential to identify lower-risk patients with visible haematuria and to stratify individuals who present with non-visible haematuria. However, before application in general practice, external validations in appropriate populations are required.

Reasons for intending to accept or decline kidney cancer screening: thematic analysis of free text from an online survey.

OBJECTIVES: Kidney cancer has been identified as a disease for which screening might provide significant benefit for patients. The aim of this study was to understand in detail the facilitators and barriers towards uptake of a future kidney cancer screening programme, and to compare these across four proposed screening modalities. DESIGN: An online survey including free-text responses. SETTING: UK PARTICIPANTS: 668 adults PRIMARY AND SECONDARY OUTCOME MEASURES: The survey assessed participants' self-reported intention to take-up kidney cancer screening with four different test methods (urine test, blood test, ultrasound scan and low-dose CT). We conducted thematic analysis of 2559 free-text comments made within the survey using an inductive approach. RESULTS: We identified five overarching themes that influenced screening intention: 'personal health beliefs', 'practicalities', 'opinions of the test', 'attitudes towards screening' and 'cancer apprehension'. Overall, participants considered the tests presented as simple to complete and the benefits of early detection to outweigh any drawbacks to screening. Dominant facilitators and barriers varied with patterns of intention to take up screening across the four tests. Most intended to take up screening by all four tests, and for these participants, screening was seen as a positive health behaviour. A significant minority were driven by practicalities and the risks of the tests offered. A smaller proportion intended to reject all forms of screening offered, often due to fear or worry about results and unnecessary medical intervention or a general negative view of screening. CONCLUSIONS: Most individuals would accept kidney cancer screening by any of the four test options presented because of strong positive attitudes towards screening in general and the perceived simplicity of the tests. Providing information about the rationale for screening in general and the potential benefits of early detection will be important to optimise uptake among uncertain individuals.

A Decision Analysis Evaluating Screening for Kidney Cancer Using Focused Renal Ultrasound.

BACKGROUND: Screening for renal cell carcinoma (RCC) has been identified as a key research priority; however, no randomised control trials have been performed. Value of information analysis can determine whether further research on this topic is of value. OBJECTIVE: To determine (1) whether current evidence suggests that screening is potentially cost-effective and, if so, (2) in which age/sex groups, (3) identify evidence gaps, and (4) estimate the value of further research to close those gaps. DESIGN, SETTING, AND PARTICIPANTS: A decision model was developed evaluating screening in asymptomatic individuals in the UK. A National Health Service perspective was adopted. INTERVENTION: A single focused renal ultrasound scan compared with standard of care (no screening). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Expected lifetime costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER), discounted at 3.5% per annum. RESULTS AND LIMITATIONS: Given a prevalence of RCC of 0.34% (0.18-0.54%), screening 60-yr-old men resulted in an ICER of £18 092/QALY (€22 843/QALY). Given a prevalence of RCC of 0.16% (0.08-0.25%), screening 60-yr-old women resulted in an ICER of £37327/QALY (€47 129/QALY). In the one-way sensitivity analysis, the ICER was <£30000/QALY as long as the prevalence of RCC was ≥0.25% for men and ≥0.2% for women at age 60yr. Given the willingness to pay a threshold of £30000/QALY (€37 878/QALY), the population-expected values of perfect information were £194 million (€244 million) and £97 million (€123 million) for 60-yr-old men and women, respectively. The expected value of perfect parameter information suggests that the prevalence of RCC and stage shift associated with screening are key research priorities. CONCLUSIONS: Current evidence suggests that one-off screening of 60-yr-old men is potentially cost-effective and that further research into this topic would be of value to society. PATIENT SUMMARY: Economic modelling suggests that screening 60-yr-old men for kidney cancer using ultrasound may be a good use of resources and that further research on this topic should be performed.

Risk Prediction Models for Kidney Cancer: A Systematic Review.

CONTEXT: Early detection of kidney cancer improves survival; however, low prevalence means that population-wide screening may be inefficient. Stratification of the population into risk categories could allow for the introduction of a screening programme tailored to individuals. OBJECTIVE: This review will identify and compare published models that predict the risk of developing kidney cancer in the general population. EVIDENCE ACQUISITION: A search identified primary research reporting or validating models predicting the risk of kidney cancer in Medline and EMBASE. After screening identified studies for inclusion, we extracted data onto a standardised form. The risk models were classified using the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) guidelines and evaluated using the PROBAST assessment tool. EVIDENCE SYNTHESIS: The search identified 15 281 articles. Sixty-two satisfied the inclusion criteria; performance measures were provided for 11 models. Some models predicted the risk of prevalent undiagnosed disease and others future incident disease. Six of the models had been validated, two using external populations. The most commonly included risk factors were age, smoking status, and body mass index. Most of the models had acceptable-to-good discrimination (area under the receiver-operating curve >0.7) in development and validation. Many models also had high specificity; however, several had low sensitivity. The highest performance was seen for the models using only biomarkers to detect kidney cancer; however, these were developed and validated in small case-control studies. CONCLUSIONS: We identified a small number of risk models that could be used to stratify the population according to the risk of kidney cancer. Most exhibit reasonable discrimination, but a few have been validated externally in population-based studies. PATIENT SUMMARY: In this review, we looked at mathematical models predicting the likelihood of an individual developing kidney cancer. We found several suitable models, using a range of risk factors (such as age and smoking) to predict the risk for individuals. Most of the models identified require further testing in the general population to confirm their usefulness.

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

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.

Public attitudes towards screening for kidney cancer: an online survey.

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.

Current evidence on screening for renal cancer.

Renal cell carcinoma (RCC) incidence is increasing worldwide. A high proportion of individuals are asymptomatic at diagnosis, but RCC has a high mortality rate. These facts suggest that RCC meets some of the criteria for screening, and a new analysis shows that screening for RCC could potentially be cost-effective. Targeted screening of high-risk individuals is likely to be the most cost-effective strategy to maximize the benefits and reduce the harms of screening. However, the size of the benefit of earlier initiation of treatment and the overall cost-effectiveness of screening remains uncertain. The optimal screening modality and target population is also unclear, and uncertainties exist regarding the specification and implementation of a screening programme. Before moving to a fully powered trial of screening, future work should focus on the following: developing and validating accurate risk prediction models; developing non-invasive methods of early RCC detection; establishing the feasibility, public acceptability and potential uptake of screening; establishing the prevalence of RCC and stage distribution of RCC detected by screening; and evaluating the potential harms of screening, including the impact on quality of life, overdiagnosis and over-treatment.