Evaluating the potential impact of lifestyle-based behavior change interventions delivered at the time of colorectal cancer screening.

PURPOSE: To analyze interventions implemented at the time of colorectal cancer (CRC) screening, or among individuals who have previously undergone investigation for CRC, focused on reducing CRC risk through promotion of lifestyle behavior change. Additionally, this review evaluated to what extent such interventions apply behavior change techniques (BCTs) to achieve their objectives. METHODS: Five databases were systematically searched to identify randomized control trials seeking to reduce CRC risk through behavior change. Outcomes were changes in health-related lifestyle behaviors associated with CRC risk, including changes in dietary habits, body mass index, smoking behaviors, alcohol consumption, and physical activity. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were pooled using random effects models. BCT's were coded from a published taxonomy of 93 techniques. RESULTS: Ten RCT's met the inclusion criteria. Greater increase in fruit/vegetable consumption in the intervention group were observed with respect to the control (SMD 0.13, 95% CI 0.08 to 0.18; p < 0.001). Across fiber, alcohol, fat, red meat, and multivitamin consumption, and smoking behaviors, similar positive outcomes were observed (SMD 0.09-0.57 for all, p < 0.01). However, among physical activity and body mass index, no difference between the intervention groups compared with controls were observed. A median of 7.5 BCTs were applied across included interventions. CONCLUSION: While magnitude of the observed effect sizes varied, they correspond to potentially important changes in lifestyle behaviors when considered on a population scale. Future interventions should identify avenues to maximize long-term engagement to promote sustained lifestyle behavior change.

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.

Implementation and external validation of the Cambridge Multimorbidity Score in the UK Biobank cohort.

BACKGROUND: Patients with multiple conditions present a growing challenge for healthcare provision. Measures of multimorbidity may support clinical management, healthcare resource allocation and accounting for the health of participants in purpose-designed cohorts. The recently developed Cambridge Multimorbidity scores (CMS) have the potential to achieve these aims using primary care records, however, they have not yet been validated outside of their development cohort. METHODS: The CMS, developed in the Clinical Research Practice Dataset (CPRD), were validated in UK Biobank participants whose data is not available in CPRD (the cohort used for CMS development) with available primary care records (n = 111,898). This required mapping of the 37 pre-existing conditions used in the CMS to the coding frameworks used by UK Biobank data providers. We used calibration plots and measures of discrimination to validate the CMS for two of the three outcomes used in the development study (death and primary care consultation rate) and explored variation by age and sex. We also examined the predictive ability of the CMS for the outcome of cancer diagnosis. The results were compared to an unweighted count score of the 37 pre-existing conditions. RESULTS: For all three outcomes considered, the CMS were poorly calibrated in UK Biobank. We observed a similar discriminative ability for the outcome of primary care consultation rate to that reported in the development study (C-index: 0.67 (95%CI:0.66-0.68) for both, 5-year follow-up); however, we report lower discrimination for the outcome of death than the development study (0.69 (0.68-0.70) and 0.89 (0.88-0.90) respectively). Discrimination for cancer diagnosis was adequate (0.64 (0.63-0.65)). The CMS performs favourably to the unweighted count score for death, but not for the outcomes of primary care consultation rate or cancer diagnosis. CONCLUSIONS: In the UK Biobank, CMS discriminates reasonably for the outcomes of death, primary care consultation rate and cancer diagnosis and may be a valuable resource for clinicians, public health professionals and data scientists. However, recalibration will be required to make accurate predictions when cohort composition and risk levels differ substantially from the development cohort. The generated resources (including codelists for the conditions and code for CMS implementation in UK Biobank) are available online.

Understanding the Preferences and Considerations of the Public Towards Risk-Stratified Screening for Colorectal Cancer: Insights From Think-Aloud Interviews Based on a Discrete Choice Experiment.

CONTEXT: Risk stratification has been suggested as a strategy for improving cancer screening. Any changes to existing programmes must be acceptable to the public. OBJECTIVE: This study aimed to explore the preferences and considerations of individuals relating to the introduction of different risk-based strategies to determine eligibility for colorectal cancer (CRC) screening. STUDY DESIGN: Participants completed a discrete choice experiment (DCE) within online interviews. Nine conjoint-analysis tasks were created, each with two potential CRC screening programmes. The attributes included personal risk of CRC, screening invitation strategy and impact. Participants chose between programmes while thinking aloud and sharing their thoughts. Transcripts were analysed using codebook thematic analysis. PARTICIPANTS: Twenty participants based in England aged 40-79 years without previous cancer history or medical expertise. RESULTS: When choosing between programmes, participants first and primarily looked to prioritise saving lives. The harms associated with screening were viewed as a surprise but also felt by most to be inevitable; the benefits frequently outweighed, therefore, harms were considered less important. Risk stratification using individual characteristics was considered a nuanced approach to healthcare, which tended to be preferred over the age-alone model. Detailed personal risk information could be taken more seriously than non-personalised information to motivate behaviour change. Although it had minimal impact on decision-making, not diverting resources for screening from elsewhere was valued. Individuals who chose not to provide health information were considered irresponsible, while it was important that those with no information to provide should not lose out. CONCLUSION: Risk-stratified CRC screening is generally aligned with public preferences, with decisions between possible stratification strategies dominated by saving lives. Even if attributes including risk factors, risk stratification strategy and risk communication contributed less to the overall decision to select certain programmes, some levels more clearly fulfilled public values; therefore, all these factors should be taken into consideration when redesigning and communicating CRC screening programmes. PATIENT OR PUBLIC CONTRIBUTION: The primary data source for this study is interviews with 20 members of the public (current, past or future CRC screening invitees). Two public representatives contributed to planning this study, particularly the DCE.

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.

The association between antihypertensive treatment and serious adverse events by age and frailty: A cohort study.

BACKGROUND: Antihypertensives are effective at reducing the risk of cardiovascular disease, but limited data exist quantifying their association with serious adverse events, particularly in older people with frailty. This study aimed to examine this association using nationally representative electronic health record data. METHODS AND FINDINGS: This was a retrospective cohort study utilising linked data from 1,256 general practices across England held within the Clinical Practice Research Datalink between 1998 and 2018. Included patients were aged 40+ years, with a systolic blood pressure reading between 130 and 179 mm Hg, and not previously prescribed antihypertensive treatment. The main exposure was defined as a first prescription of antihypertensive treatment. The primary outcome was hospitalisation or death within 10 years from falls. Secondary outcomes were hypotension, syncope, fractures, acute kidney injury, electrolyte abnormalities, and primary care attendance with gout. The association between treatment and these serious adverse events was examined by Cox regression adjusted for propensity score. This propensity score was generated from a multivariable logistic regression model with patient characteristics, medical history and medication prescriptions as covariates, and new antihypertensive treatment as the outcome. Subgroup analyses were undertaken by age and frailty. Of 3,834,056 patients followed for a median of 7.1 years, 484,187 (12.6%) were prescribed new antihypertensive treatment in the 12 months before the index date (baseline). Antihypertensives were associated with an increased risk of hospitalisation or death from falls (adjusted hazard ratio [aHR] 1.23, 95% confidence interval (CI) 1.21 to 1.26), hypotension (aHR 1.32, 95% CI 1.29 to 1.35), syncope (aHR 1.20, 95% CI 1.17 to 1.22), acute kidney injury (aHR 1.44, 95% CI 1.41 to 1.47), electrolyte abnormalities (aHR 1.45, 95% CI 1.43 to 1.48), and primary care attendance with gout (aHR 1.35, 95% CI 1.32 to 1.37). The absolute risk of serious adverse events with treatment was very low, with 6 fall events per 10,000 patients treated per year. In older patients (80 to 89 years) and those with severe frailty, this absolute risk was increased, with 61 and 84 fall events per 10,000 patients treated per year (respectively). Findings were consistent in sensitivity analyses using different approaches to address confounding and taking into account the competing risk of death. A strength of this analysis is that it provides evidence regarding the association between antihypertensive treatment and serious adverse events, in a population of patients more representative than those enrolled in previous randomised controlled trials. Although treatment effect estimates fell within the 95% CIs of those from such trials, these analyses were observational in nature and so bias from unmeasured confounding cannot be ruled out. CONCLUSIONS: Antihypertensive treatment was associated with serious adverse events. Overall, the absolute risk of this harm was low, with the exception of older patients and those with moderate to severe frailty, where the risks were similar to the likelihood of benefit from treatment. In these populations, physicians may want to consider alternative approaches to management of blood pressure and refrain from prescribing new treatment.

Proactive breast cancer risk assessment in primary care: a review based on the principles of screening.

In the UK, the National Institute for Health and Care Excellence (NICE) recommends that women at moderate or high risk of breast cancer be offered risk-reducing medication and enhanced breast screening/surveillance. In June 2022, NICE withdrew a statement recommending assessment of risk in primary care only when women present with concerns. This shift to the proactive assessment of risk substantially changes the role of primary care, in effect paving the way for a primary care-based screening programme to identify those at moderate or high risk of breast cancer. In this article, we review the literature surrounding proactive breast cancer risk assessment within primary care against the consolidated framework for screening. We find that risk assessment for women under 50 years currently satisfies many of the standard principles for screening. Most notably, there are large numbers of women at moderate or high risk currently unidentified, risk models exist that can identify those women with reasonable accuracy, and management options offer the opportunity to reduce breast cancer incidence and mortality in that group. However, there remain a number of uncertainties and research gaps, particularly around the programme/system requirements, that need to be addressed before these benefits can be realised.

Patient experience of follow-up after surgery for kidney cancer: a focus group study.

OBJECTIVE: To explore patient experience of follow-up care after kidney cancer surgery and to develop recommendations for best practice. METHODS: We conducted two focus groups, including 14 participants with experience of kidney cancer follow-up after surgery, to elicit patient views on current follow-up care. Thematic analysis was used to identify unifying themes to describe the patient experience of follow-up, and the results were then used to develop a set of recommendations for best practice. RESULTS: We identified six themes (feelings of abandonment; uncertainty about the plan; anxiety about appointments; variation in care; a need for information; and a need for emotional support) that described current patient experience and areas in which current care could be improved. In particular, while most of the participants felt that their physical needs had been met, many had struggled with unmet emotional needs and a lack of information and resources. This was especially noted in the period immediately following surgery, when feelings of abandonment were common, and around follow-up scans and routine appointments, which were a source of anxiety. Our participants also described concerns about the lack of consistency between different hospitals and centres around the United Kingdom, with differences in the content and quality of follow-up care. Based on the results, we developed a list of recommendations to address some of the challenges described through relatively minor changes to the care pathway. CONCLUSIONS: We identified gaps and variability in current follow-up care after kidney cancer surgery, and have developed a set of recommendations that, if implemented, would improve the follow-up care experience for these patients.

A discrete choice experiment to understand public preferences and priorities for risk-stratified bowel cancer screening programmes in the UK.

OBJECTIVE: Public acceptability of bowel cancer screening programmes must be maintained, including if risk stratification is introduced. We aimed to describe and quantify preferences for different attributes of risk-stratified screening programmes amongst the UK population, focussing on who to invite for bowel screening. METHODS: We conducted a discrete choice experiment (DCE) including the following attributes: risk factors used to estimate bowel cancer risk (age plus/minus sex, lifestyle factors and genetics); personalisation of risk feedback; risk stratification strategy plus resource implications; default screening in the case of no risk information; number of deaths prevented by screening; and number experiencing physical harm from screening. We used the results of conditional logit regression models to estimate the importance of each attribute, willingness to trade-off between the attributes, and preferences for different programmes using contemporary risk scores and models. RESULTS: 1196 respondents completed the survey, generating 21,528 DCE observations. Deaths prevented was the most influential attribute on respondents' decision-making (contributing to 58.8% of the choice), followed by harms experienced (15.9%). For every three additional deaths prevented, respondents were willing to accept an additional screening harm per 100,000 people. Risk factors and risk stratification strategy contributed to just 11.1% and 3.6% of the choice, respectively. Although the influence on decision-making was small, respondents favoured more personalised feedback. CONCLUSIONS: Bowel cancer screening programmes that improve cancer outcomes, particularly by preventing more deaths amongst those screened, are most preferred by the public. Optimising risk prediction models, developing public communication, and readying infrastructure should be prioritised for implementation.

Enhancing the BOADICEA cancer risk prediction model to incorporate new data on RAD51C, RAD51D, BARD1 updates to tumour pathology and cancer incidence.

BACKGROUND: BOADICEA (Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm) for breast cancer and the epithelial tubo-ovarian cancer (EOC) models included in the CanRisk tool (www.canrisk.org) provide future cancer risks based on pathogenic variants in cancer-susceptibility genes, polygenic risk scores, breast density, questionnaire-based risk factors and family history. Here, we extend the models to include the effects of pathogenic variants in recently established breast cancer and EOC susceptibility genes, up-to-date age-specific pathology distributions and continuous risk factors. METHODS: BOADICEA was extended to further incorporate the associations of pathogenic variants in BARD1, RAD51C and RAD51D with breast cancer risk. The EOC model was extended to include the association of PALB2 pathogenic variants with EOC risk. Age-specific distributions of oestrogen-receptor-negative and triple-negative breast cancer status for pathogenic variant carriers in these genes and CHEK2 and ATM were also incorporated. A novel method to include continuous risk factors was developed, exemplified by including adult height as continuous. RESULTS: BARD1, RAD51C and RAD51D explain 0.31% of the breast cancer polygenic variance. When incorporated into the multifactorial model, 34%-44% of these carriers would be reclassified to the near-population and 15%-22% to the high-risk categories based on the UK National Institute for Health and Care Excellence guidelines. Under the EOC multifactorial model, 62%, 35% and 3% of PALB2 carriers have lifetime EOC risks of <5%, 5%-10% and >10%, respectively. Including height as continuous, increased the breast cancer relative risk variance from 0.002 to 0.010. CONCLUSIONS: These extensions will allow for better personalised risks for BARD1, RAD51C, RAD51D and PALB2 pathogenic variant carriers and more informed choices on screening, prevention, risk factor modification or other risk-reducing options.

Acceptability of risk stratification within population-based cancer screening from the perspective of the general public: A mixed-methods systematic review.

INTRODUCTION: Risk-stratified cancer screening has the potential to improve resource allocation and the balance of harms and benefits by targeting those most likely to benefit. Public acceptability has implications for engagement, uptake and the success of such a programme. Therefore, this review seeks to understand whether risk stratification of population-based cancer screening programmes is acceptable to the general public and in what context. METHODS: Four electronic databases were searched from January 2010 to November 2021. Qualitative, quantitative and mixed-methods papers were eligible for inclusion. The Joanna Briggs Institute convergent integrated approach was used to synthesize the findings and the quality of included literature was assessed using the Mixed Methods Appraisal Tool. The Theoretical Framework of Acceptability was used as a coding frame for thematic analysis. PROSPERO record 2021 CRD42021286667. RESULTS: The search returned 12,039 citations, 22 of which were eligible for inclusion. The majority of studies related to breast cancer screening; other cancer types included ovarian, kidney, colorectal and prostate cancer. Risk stratification was generally acceptable to the public, who considered it to be logical and of wider benefit than existing screening practices. We identified 10 priorities for implementation across four key areas: addressing public information needs; understanding communication preferences for risk estimates; mitigating barriers to accessibility to avoid exacerbating inequalities; and the role of healthcare professionals in relation to supporting reduced screening for low-risk individuals. CONCLUSION: The public generally find risk stratification of population-based cancer screening programmes to be acceptable; however, we have identified areas that would improve implementation and require further consideration. PATIENT OR PUBLIC CONTRIBUTION: This paper is a systematic review and did not formally involve patients or the public; however, three patient and public involvement members were consulted on the topic and scope before the review commenced.

Implementation of risk stratification within bowel cancer screening: a community jury study exploring public acceptability and communication needs.

BACKGROUND: Population-based cancer screening programmes are shifting away from age and/or sex-based screening criteria towards a risk-stratified approach. Any such changes must be acceptable to the public and communicated effectively. We aimed to explore the social and ethical considerations of implementing risk stratification at three different stages of the bowel cancer screening programme and to understand public requirements for communication. METHODS: We conducted two pairs of community juries, addressing risk stratification for screening eligibility or thresholds for referral to colonoscopy and screening interval. Using screening test results (where applicable), and lifestyle and genetic risk scores were suggested as potential stratification strategies. After being informed about the topic through a series of presentations and discussions including screening principles, ethical considerations and how risk stratification could be incorporated, participants deliberated over the research questions. They then reported their final verdicts on the acceptability of risk-stratified screening and what information should be shared about their preferred screening strategy. Transcripts were analysed using codebook thematic analysis. RESULTS: Risk stratification of bowel cancer screening was acceptable to the informed public. Using data within the current system (age, sex and screening results) was considered an obvious next step and collecting additional data for lifestyle and/or genetic risk assessment was also preferable to age-based screening. Participants acknowledged benefits to individuals and health services, as well as articulating concerns for people with low cancer risk, potential public misconceptions and additional complexity for the system. The need for clear and effective communication about changes to the screening programme and individual risk feedback was highlighted, including making a distinction between information that should be shared with everyone by default and additional details that are available elsewhere. CONCLUSIONS: From the perspective of public acceptability, risk stratification using current data could be implemented immediately, ahead of more complex strategies. Collecting additional data for lifestyle and/or genetic risk assessment was also considered acceptable but the practicalities of collecting such data and how the programme would be communicated require careful consideration.

Visualising health risks with medical imaging for changing recipients' health behaviours and risk factors: Systematic review with meta-analysis.

BACKGROUND: There is ongoing clinical and research interest in determining whether providing personalised risk information could motivate risk-reducing health behaviours. We aimed to assess the impact on behaviours and risk factors of feeding back to individuals' images of their bodies generated via medical imaging technologies in assessing their current disease status or risk. METHODS AND FINDINGS: A systematic review with meta-analysis was conducted using Cochrane methods. MEDLINE, Embase, PsycINFO, CINAHL, and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched up to July 28, 2021, with backward and forward citation searches up to July 29, 2021. Eligible studies were randomised controlled trials including adults who underwent medical imaging procedures assessing current health status or risk of disease, for which personal risk may be reduced by modifying behaviour. Trials included an intervention group that received the imaging procedure plus feedback of visualised results and assessed subsequent risk-reducing health behaviour. We examined 12,620 abstracts and included 21 studies, involving 9,248 randomised participants. Studies reported on 10 risk-reducing behaviours, with most data for smoking (8 studies; n = 4,308), medication use (6 studies; n = 4,539), and physical activity (4 studies; n = 1,877). Meta-analysis revealed beneficial effects of feedback of visualised medical imaging results on reduced smoking (risk ratio 1.11, 95% confidence interval [CI] 1.01 to 1.23, p = 0.04), healthier diet (standardised mean difference [SMD] 0.30, 95% CI 0.11 to 0.50, p = 0.003), increased physical activity (SMD 0.11, 95% CI 0.003 to 0.21, p = 0.04), and increased oral hygiene behaviours (SMD 0.35, 95% CI 0.13 to 0.57, p = 0.002). In addition, single studies reported increased skin self-examination and increased foot care. For other behavioural outcomes (medication use, sun protection, tanning booth use, and blood glucose testing) estimates favoured the intervention but were not statistically significant. Regarding secondary risk factor outcomes, there was clear evidence for reduced systolic blood pressure, waist circumference, and improved oral health, and some indication of reduced Framingham risk score. There was no evidence of any adverse effects, including anxiety, depression, or stress, although these were rarely assessed. A key limitation is that there were some concerns about risk of bias for all studies, with evidence for most outcomes being of low certainty. In particular, valid and precise measures of behaviour were rarely used, and there were few instances of preregistered protocols and analysis plans, increasing the likelihood of selective outcome reporting. CONCLUSIONS: In this study, we observed that feedback of medical images to individuals has the potential to motivate risk-reducing behaviours and reduce risk factors. Should this promise be corroborated through further adequately powered trials that better mitigate against risk of bias, such interventions could usefully capitalise upon the widespread and growing use of medical imaging technologies in healthcare.

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.

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.

Behavioural Challenges Associated With Risk-Adapted Cancer Screening.

Cancer screening programmes have a major role in reducing cancer incidence and mortality. Traditional internationally-adopted protocols have been to invite all 'eligible individuals' for the same test at the same frequency. However, as highlighted in Cancer Research UK's 2020 strategic vision, there are opportunities to increase effectiveness and cost-effectiveness, and reduce harms of screening programmes, by making recommendations on the basis of personalised estimates of risk. In some respects, this extends current approaches of providing more intensive levels of care outside screening programmes to individuals at very high risk due to their family history or underlying conditions. However, risk-adapted colorectal cancer screening raises a wide range of questions, not only about how best to change existing programmes but also about the psychological and behavioural effects that these changes might have. Previous studies in other settings provide some important information but remain to be tested and explored further in the context of colorectal screening. Conducting behavioural science research in parallel to clinical research will ensure that risk-adapted screening is understood and accepted by the population that it aims to serve.

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.

'Oh, I've got an appointment': A qualitative interview study exploring how to support attendance at diabetes screening after gestational diabetes.

AIMS: To explore the views of women with a history of gestational diabetes mellitus (GDM) on suggested practical approaches to support diabetes screening attendance after GDM, which is recommended but poorly attended. METHODS: We conducted semi-structured interviews with 20 participants in Cambridgeshire, UK who had been diagnosed with GDM and were 3-48 months postpartum. Interviews covered whether participants had been screened and why, plans for future screening and their views on potential interventions to facilitate attendance (at the first postpartum test and annual testing). Framework analysis was used to analyse the transcripts. The interview schedule, suggested interventions and thematic framework were based on a recent systematic review. RESULTS: Sixteen participants had undergone screening since pregnancy, explaining that they had an appointment arranged and wanted reassurance that they did not have diabetes. The participants who had not been tested were not aware that it was recommended. Only 13 had planned to attend subsequent tests at the start of the interview. Eight themes to support future attendance were discussed. The majority of the participants agreed that changing the processes for arranging tests, offering choice in test location and combining appointments would facilitate attendance. Child-friendly clinics, more opportunities to understand GDM and the role of postpartum testing, stopping self-testing and increasing their GP's awareness of their pregnancy received inconsistent feedback. The nature of the test used did not appear to influence attendance. CONCLUSIONS: The participants wanted to be screened for diabetes after GDM. We have identified interventions that could be relatively simply incorporated into routine practice to facilitate screening attendance, such as flexibility in the appointment location or time and sending invitations for tests.

Impact of achievement and change in achievement of lifestyle recommendations in middle-age on risk of the most common potentially preventable cancers.

This study aimed to assess the association between achievement, and within-person change in achievement, of lifestyle recommendations in middle-age and incidence of the most common potentially preventable cancers. We used data from 44,572 participants from the Swedish Västerbotten Intervention Programme who had attended at least two health checks 9-11 years apart. We assessed the association between the mean number of healthy lifestyle recommendations achieved (lifestyle score), and change in lifestyle score between the health checks, and risk of one or more of the eight most common potentially preventable cancers using Cox regression. Participants were followed-up for 11.0 (SD 4.9) years. A higher mean lifestyle score was associated with a lower hazard of cancer in men (HR 0.81 (95%CI 0.74-0.90) per unit increase) and women (HR 0.90 (0.84-0.96)). There was no evidence of a linear association between change in lifestyle score and risk (HR 0.93 (0.85-1.03) and HR 1.004 (0.94-1.07) per unit change for men and women respectively). When comparing those with an increase in lifestyle score of ≥2 with those who improved less or declined in achievement the HR was 0.74 (0.54-1.00) and 1.02 (0.84-1.24) for men and women respectively. These findings support the inclusion of lifestyle recommendations in cancer prevention guidelines. They further suggest that interventions to change health behaviours in middle-age may reduce risk of the most common preventable cancers in men, but this association was not observed in women. Strategies to encourage healthy lifestyles earlier in the life course may be more effective.