Pre-Referral Primary Care Blood Tests and Symptom Presentation before Cancer Diagnosis: National Cancer Diagnosis Audit Data.

BACKGROUND: Blood tests can support the diagnostic process in primary care. Understanding how symptomatic presentations are associated with blood test use in patients subsequently diagnosed with cancer can help to benchmark current practices and guide interventions. METHODS: English National Cancer Diagnosis Audit data on 39,751 patients with incident cancer in 2018 were analysed. The frequency of four generic (full blood count, urea and electrolytes, liver function tests, and inflammatory markers) and five organ-specific (cancer biomarkers (PSA or CA125), serum protein electrophoresis, ferritin, bone profile, and amylase) blood tests was described for a total of 83 presenting symptoms. The adjusted analysis explored variation in blood test use by the symptom-positive predictive value (PPV) group. RESULTS: There was a large variation in generic blood test use by presenting symptoms, being higher in patients subsequently diagnosed with cancer who presented with nonspecific symptoms (e.g., fatigue 81% or loss of appetite 79%), and lower in those who presented with alarm symptoms (e.g., breast lump 3% or skin lesion 1%). Serum protein electrophoresis (reflecting suspicion of multiple myeloma) was most frequently used in cancer patients who presented with back pain (18%), and amylase measurement (reflecting suspicion of pancreatic cancer) was used in those who presented with upper abdominal pain (14%). Prostate-specific antigen (PSA) use was greatest in men with cancer who presented with lower urinary tract symptoms (88%), and CA125 in women with cancer who presented with abdominal distention (53%). Symptoms with PPV values between 2.00-2.99% were associated with greater test use (64%) compared with 52% and 51% in symptoms with PPVs in the 0.01-0.99 or 1.00-1.99% range and compared with 42% and 31% in symptoms with PPVs in either the 3.00-4.99 or ≥5% range (p < 0.001). CONCLUSIONS: Generic blood test use reflects the PPV of presenting symptoms, and the use of organ-specific tests is greater in patients with symptomatic presentations with known associations with certain cancer sites. There are opportunities for greater blood test use in patients presenting with symptoms that do not meet referral thresholds (i.e., <3% PPV for cancer) where information gain to support referral decisions is likely greatest. The findings benchmark blood test use in cancer patients, highlighting opportunities for increasing use.

National Cancer Diagnosis Audits for England 2018 versus 2014: a comparative analysis.

BACKGROUND: Timely diagnosis of cancer in patients who present with symptoms in primary care is a quality-improvement priority. AIM: To examine possible changes to aspects of the diagnostic process, and its timeliness, before and after publication of the National Institute for Health and Care Excellence's (2015) guidance on the referral of suspected cancer in primary care. DESIGN AND SETTING: Comparison of findings from population-based clinical audits of cancer diagnosis in general practices in England for patients diagnosed in 2018 or 2014. METHOD: GPs in 1878 (2018) and 439 (2014) practices collected primary care information on the diagnostic pathway of cancer patients. Key measures including patient characteristics, place of presentation, number of pre-referral consultations, use of primary care investigations, and referral type were compared between the two audits by descriptive analysis and regression models. RESULTS: Among 64 489 (2018) and 17 042 (2014) records of a new cancer diagnosis, the percentage of patients with same-day referral (denoted by a primary care interval of 0 days) was higher in 2018 (42.7% versus 37.7%) than in 2014, with similar improvements in median diagnostic interval (36 days versus 40 days). Compared with 2014, in 2018: fewer patients had ≥3 pre-referral consultations (18.8% versus 26.2%); use of primary care investigations increased (47.9% versus 45.4%); urgent cancer referrals increased (54.8% versus 51.8%); emergency referrals decreased (13.4% versus 16.5%); and recorded use of safety netting decreased (40.0% versus 44.4%). CONCLUSION: In the 5-year period, including the year when national guidelines were updated (that is, 2015), there were substantial improvements to the diagnostic process of patients who present to general practice in England with symptoms of a subsequently diagnosed cancer.

Predictors of the experience of a Cytosponge test: analysis of patient survey data from the BEST3 trial.

BACKGROUND: The Cytosponge is a cell-collection device, which, coupled with a test for trefoil factor 3 (TFF3), can be used to diagnose Barrett's oesophagus, a precursor condition to oesophageal adenocarcinoma. BEST3, a large pragmatic, randomised, controlled trial, investigated whether offering the Cytosponge-TFF3 test would increase detection of Barrett's. Overall, participants reported mostly positive experiences. This study reports the factors associated with the least positive experience. METHODS: Patient experience was assessed using the Inventory to Assess Patient Satisfaction (IAPS), a 22-item questionnaire, completed 7-14 days after the Cytosponge test. STUDY COHORT: All BEST3 participants who answered ≥ 15 items of the IAPS (N = 1458). STATISTICAL ANALYSIS: A mean IAPS score between 1 and 5 (5 indicates most negative experience) was calculated for each individual. 'Least positive' experience was defined according to the 90th percentile. 167 (11.4%) individuals with a mean IAPS score of ≥ 2.32 were included in the 'least positive' category and compared with the rest of the cohort. Eleven patient characteristics and one procedure-specific factor were assessed as potential predictors of the least positive experience. Multivariable logistic regression analysis using backwards selection was conducted to identify factors independently associated with the least positive experience and with failed swallow at first attempt, one of the strongest predictors of least positive experience. RESULTS: The majority of responders had a positive experience, with an overall median IAPS score of 1.7 (IQR 1.5-2.1). High (OR = 3.01, 95% CI 2.03-4.46, p < 0.001) or very high (OR = 4.56, 95% CI 2.71-7.66, p < 0.001) anxiety (relative to low/normal anxiety) and a failed swallow at the first attempt (OR = 3.37, 95% CI 2.14-5.30, p < 0.001) were highly significant predictors of the least positive patient experience in multivariable analyses. Additionally, sex (p = 0.036), height (p = 0.032), alcohol intake (p = 0.011) and education level (p = 0.036) were identified as statistically significant predictors. CONCLUSION: We have identified factors which predict patient experience. Identifying anxiety ahead of the procedure and discussing particular concerns with patients or giving them tips to help with swallowing the capsule might help improve their experience. Trial registration ISRCTN68382401.

Primary care blood tests before cancer diagnosis: National Cancer Diagnosis Audit data.

BACKGROUND: Blood tests can support the diagnostic process in patients with cancer but how often they are used is unclear. AIM: To explore use of common blood tests before cancer diagnosis in primary care. DESIGN AND SETTING: English National Cancer Diagnosis Audit data on 39 752 patients with cancer diagnosed in 2018. METHOD: Common blood test use (full blood count [FBC], urea and electrolytes [U&E], and liver function tests [LFTs]), variation by patient and symptom group, and associations with the primary care interval and the diagnostic interval were assessed. RESULTS: At least one common blood test was used in 41% (n = 16 427/39 752) of patients subsequently diagnosed with cancer. Among tested patients, (n = 16 427), FBC was used in 95% (n = 15 540), U&E in 89% (n = 14 555), and LFTs in 76% (n = 12 414). Blood testing was less common in females (adjusted odds ratio versus males: 0.92, 95% confidence interval [CI] = 0.87 to 0.98) and Black and minority ethnic patients (0.89, 95% CI = 0.82 to 0.97 versus White), and more common in older patients (1.12, 95% CI = 1.06 to 1.18 for ≥70 years versus 50-69 years). Test use varied greatly by cancer site (melanoma 2% [ n = 55/2297]; leukaemia 84% [ n = 552/661]). Fewer patients presenting with alarm symptoms alone were tested (24% [ n = 3341/13 778]) than those with non-alarm symptoms alone (50% [ n = 8223/16 487]). Median primary care interval and diagnostic interval were longer in tested than non-tested patients (primary care interval: 10 versus 0 days; diagnostic interval: 49 versus 32 days, respectively, P<0.001 for both), including among tested patients with alarm symptoms (primary care interval: 4 versus 0 days; diagnostic interval: 41 versus 22 days). CONCLUSION: Two-fifths of patients subsequently diagnosed with cancer have primary care blood tests as part of their diagnostic process. Given variable test use, research is needed on the clinical context in which blood tests are ordered.

The evolution and co-evolution of a primary care cancer research network: From academic social connection to research collaboration.

Academic networks are expected to enhance scientific collaboration and thereby increase research outputs. However, little is known about whether and how the initial steps of getting to know other researchers translates into effective collaborations. In this paper, we investigate the evolution and co-evolution of an academic social network and a collaborative research network (using co-authorship as a proxy measure of the latter), and simultaneously examine the effect of individual researcher characteristics (e.g. gender, seniority or workplace) on their evolving relationships. We used longitudinal data from an international network in primary care cancer research: the CanTest Collaborative (CanTest). Surveys were distributed amongst CanTest researchers to map who knows who (the 'academic social network'). Co-authorship relations were derived from Scopus (the 'collaborative network'). Stochastic actor-oriented models were employed to investigate the evolution and co-evolution of both networks. Visualizing the development of the CanTest network revealed that researchers within CanTest get to know each other quickly and also start collaborating over time (evolution of the academic social network and collaborative network respectively). Results point to a stable and solid academic social network that is particularly encouraging towards more junior researchers; yet differing for male and female researchers (the effect of individual researcher characteristics). Moreover, although the academic social network and the research collaborations do not grow at the same pace, the benefit of creating academic social relationships to stimulate effective research collaboration is clearly demonstrated (co-evolution of both networks).

Patient-reported experiences and views on the Cytosponge test: a mixed-methods analysis from the BEST3 trial.

OBJECTIVES: The BEST3 trial demonstrated the efficacy and safety of the Cytosponge-trefoil factor 3, a cell collection device coupled with the biomarker trefoil factor 3, as a tool for detecting Barrett's oesophagus, a precursor of oesophageal adenocarcinoma (OAC), in primary care. In this nested study, our aim was to understand patient experiences. DESIGN: Mixed-methods using questionnaires (including Inventory to Assess Patient Satisfaction, Spielberger State-Trait Anxiety Inventory-6 and two-item perceived risk) and interviews. OUTCOME MEASURES: Participant satisfaction, anxiety and perceived risk of developing OAC. SETTING: General practices in England. PARTICIPANTS: Patients with acid reflux enrolled in the intervention arm of the BEST3 trial and attending the Cytosponge appointment (N=1750). RESULTS: 1488 patients successfully swallowing the Cytosponge completed the follow-up questionnaires, while 30 were interviewed, including some with an unsuccessful swallow.Overall, participants were satisfied with the Cytosponge test. Several items showed positive ratings, in particular convenience and accessibility, staff's interpersonal skills and perceived technical competence. The most discomfort was reported during the Cytosponge removal, with more than 60% of participants experiencing gagging. Nevertheless, about 80% were willing to have the procedure again or to recommend it to friends; this was true even for participants experiencing discomfort, as confirmed in the interviews.Median anxiety scores were below the predefined level of clinically significant anxiety and slightly decreased between baseline and follow-up (p < 0.001). Interviews revealed concerns around the ability to swallow, participating in a clinical trial, and waiting for test results.The perceived risk of OAC increased following the Cytosponge appointment (p<0.001). Moreover, interviews suggested that some participants had trouble conceptualising risk and did not understand the relationships between test results, gastro-oesophageal reflux and risk of Barrett's oesophagus and OAC. CONCLUSIONS: When delivered during a trial in primary care, the Cytosponge is well accepted and causes little anxiety. TRIAL REGISTRATION NUMBER: ISRCTN68382401.

Factors determining development of researchers within a research network on cancer diagnosis in primary care (CanTest): an interview study.

OBJECTIVES: Developing connections with other researchers in a network, learning informally through these connections and using them to reach goals, is expected to increase research capacity and strengthen performance. So far, this has not been empirically demonstrated. We assessed what and how network collaboration adds to development of researchers. DESIGN: Exploratory qualitative study using semistructured online interviews, analysed by inductive and deductive methods. For the deductive analysis, an existing value creation framework to study informal learning in networks was used and adjusted to our context. SETTING: The CanTest Collaborative-an international team of primary care cancer researchers working on early detection and diagnosis of cancer. PARTICIPANTS: Sixteen primary care cancer researchers. RESULTS: Connections with other researchers in an international network created diverse value cycles, where most outcomes were in the potential value cycle, acquiring knowledge, skills, social capital, resources and ideas. Not all potential value will be applied but many interviewees described realised as well as transformational value. In our context, the transformational value from the framework appeared to be related to other perspectives on the research process. Advancement of the network depends on opportunities, timing, role models and connections between different perspectives. CONCLUSIONS: Focus on the factors that are relevant for network advancement will support researchers in early detection and diagnosis of cancer research patients who participate in an international network and bring sustainable change in this domain. When, subsequently, researchers in the CanTest network bring about more realised and transformational learning outcomes, this will contribute to capacity development.

Recruitment to a large scale randomised controlled clinical trial in primary care: the Helicobacter Eradication Aspirin Trial (HEAT).

BACKGROUND: The Helicobacter Eradication Aspirin Trial (HEAT) is a multicentre, double blind, randomised controlled trial investigating whether Helicobacter (H.) pylori eradication reduces hospitalisation for peptic ulcer bleeding. Recruited participants were aged 60 and over and taking aspirin (≤325 mg daily) for at least four months prior to consent. Based on results of a pilot study, a sample size calculation predicted 6600 H. pylori-positive randomised participants would be required, from 33,000 volunteers, recruited from 170,000 invited patients. Methodology was therefore designed for recruitment of large numbers of patients from primary care using a novel electronic search tool, automated mail-out and electronic follow-up. Recruitment started in 2012 and completed in 2017. METHODS: All participants were recruited from GP practices, with assistance from the UK Clinical Research Network (UKCRN). H. pylori-positive participants were randomised to one week of eradication treatment or placebo. Recruitment was managed using a bespoke web-based database that communicated directly with a programmed search tool downloaded at participating practices. The primary endpoint is hospitalisation due to peptic ulcer bleeding. The trial will end when 87 adjudicated events have occurred, identified from searches of GP databases, review of secondary care admission data and mortality data, and reported events from randomised participants and GPs. RESULTS: HEAT has recruited participants from 1208 GP practices across the UK. Of the 188,875 invitation letters sent, 38,771 returned expressions of interest. Of these, 30,166 patients were consented to the trial, of whom 5355 H. pylori-positive participants (17.8% of those consented) were randomised. Mean age at consent was 73.1 ± 6.9 (SD) years and 72.2% of participants were male. Of the randomised (H. pylori-positive) participants, 531 have died (as of 17 Sep 2020); none of the deaths was due to trial treatment. CONCLUSION: The HEAT trial methodology has demonstrated that recruitment of large numbers of patients from primary care is attainable, with the assistance of the UKCRN, and could be applied to other clinical outcomes studies. TRIAL REGISTRATION: ClinicalTrials.gov ; registration number NCT01506986 . Registered on 10 Jan 2012.

Morbidity and measures of the diagnostic process in primary care for patients subsequently diagnosed with cancer.

BACKGROUND: There is uncertainty regarding how pre-existing conditions (morbidities) may influence the primary care investigation and management of individuals subsequently diagnosed with cancer. METHODS: We identified morbidities using information from both primary and secondary care records among 11,716 patients included in the English National Cancer Diagnosis Audit (NCDA) 2014. We examined variation in 5 measures of the diagnostic process (the primary care interval, diagnostic interval, number of pre-referral consultations, use of primary care-led investigations, and referral type) by both primary care- and hospital records-derived measures of morbidity. RESULTS: Morbidity prevalence recorded before cancer diagnosis was almost threefold greater using the primary care (75%) vs secondary care-derived measure (28%). After adjustment, there was limited variation in the primary care interval and the number of pre-referral consultations by either definition of morbidity. Patients with more severe morbidities were less likely to have had a primary care-led investigation before cancer diagnosis compared with those without any morbidity (adjusted odds ratio, OR [95% confidence interval]: 0.72 [0.60-0.86] for Charlson score 3+ vs 0; joint P < 0.001). Patients with multiple primary care-recorded conditions or a Charlson score of 3+ were more likely to have diagnostic intervals exceeding 60 days (aOR: 1.26 [1.10-1.45] and 1.19 [>1.00-1.41], respectively), and more likely to receive an emergency referral (aOR: 1.60 [1.26-2.02] and 1.61 [1.26-2.06], respectively). CONCLUSION: Among cancer cases with up to 2 morbidities, there was no evidence of differences in diagnostic processes and intervals in primary care but higher morbidity burden was associated with longer time to diagnosis and higher likelihood of emergency referral.

Individuals with pre-existing long-term conditions (morbidities) may have a different pathways leading to their cancer diagnosis compared with those without such conditions but detailed evidence is limited. We aimed to investigate how morbidities were associated with a range of measures of the diagnostic process in primary care. We examined morbidity in 2 ways, using information from a primary care audit and hospital records. We found that three-quarters of patients were living with 1 or more conditions according to primary care-based information, while the prevalence was almost threefold lower when estimated using hospital records. There was little difference in the time from first primary care appointment to specialist referral and the number of appointments before specialist referral by morbidity, particularly when comparing patients with 1 or 2 conditions vs those without. However, patients with multiple conditions or more serious diseases experienced lower likelihood of investigation, greater likelihood of being sent to the hospital as an emergency, and longer time to diagnosis. We did not find evidence of substantial differences in primary care-based diagnostic processes by morbidity. However, once an initial referral has been made, multiple or more severe conditions appear to influence the time taken to reach a diagnosis.

Barriers to Early Presentation amongst Rural Residents Experiencing Symptoms of Colorectal Cancer: A Qualitative Interview Study.

Rural cancer inequalities are evident internationally, with rural cancer patients 5% less likely to survive than their urban counterparts. There is evidence to suggest that diagnostic delays prior to entry into secondary care may be contributing to these poorer rural cancer outcomes. This study explores the symptom appraisal and help-seeking decision-making of people experiencing symptoms of colorectal cancer in rural areas of England. Patients were randomly invited from 4 rural practices, serving diverse communities. Semi-structured interviews were undertaken with 40 people who had experienced symptoms of colorectal cancer in the preceding 8 weeks. Four key themes were identified as influential in participants' willingness and timeliness of consultation: a desire to rule out cancer (facilitator of help-seeking); stoicism and self-reliance (barrier to help-seeking); time scarcity (barrier to help-seeking); and GP/patient relationship (barrier or facilitator, depending on perceived strength of the relationship). Self-employed, and "native" rural residents most commonly reported experiencing time scarcity and poor GP/patient relationships as a barrier to (re-)consultation. Targeted, active safety-netting approaches, and increased continuity of care, may be particularly beneficial to expedite timely diagnoses and minimise cancer inequalities for rural populations.

Electronic clinical decision support tool for assessing stomach symptoms in primary care (ECASS): a feasibility study.

OBJECTIVE: To determine the feasibility of a definitive trial in primary care of electronic clinical decision support (eCDS) for possible oesophago-gastric (O-G) cancer. DESIGN AND SETTING: Feasibility study in 42 general practices in two regions of England, cluster randomised controlled trial design without blinding, nested qualitative and health economic evaluation. PARTICIPANTS: Patients aged 55 years or older, presenting to their general practitioner (GP) with symptoms associated with O-G cancer. 530 patients (mean age 68 years, 58% female) participated. INTERVENTION: Practices randomised 1:1 to usual care (control) or to receive a previously piloted eCDS tool for suspected cancer (intervention), for use at the discretion of the GPs, supported by a theory-based implementation package and ongoing support. We conducted semistructured interviews with GPs in intervention practices. Recruitment lasted 22 months. OUTCOMES: Patient participation rate, use of eCDS, referrals and route to diagnosis, O-G cancer diagnoses; acceptability to GPs; cost-effectiveness. Participants followed up 6 months after index encounter. RESULTS: From control and intervention practices, we screened 3841 and 1303 patients, respectively; 1189 and 434 were eligible, 392 and 138 consented to participate. Ten patients (1.9%) had O-G cancer. eCDS was used eight times in total by five unique users. GPs experienced interoperability problems between the eCDS tool and their clinical system and also found it did not fit with their workflow. Unexpected restrictions on software installation caused major problems with implementation. CONCLUSIONS: The conduct of this study was hampered by technical limitations not evident during an earlier pilot of the eCDS tool, and by regulatory controls on software installation introduced by primary care trusts early in the study. This eCDS tool needed to integrate better with clinical workflow; even then, its use for suspected cancer may be infrequent. Any definitive trial of eCDS for cancer diagnosis should only proceed after addressing these constraints. TRIAL REGISTRATION NUMBER: ISRCTN125595588.

Measuring patient experience of diagnostic care and acceptability of testing.

A positive patient experience has been long recognised as a key feature of a high-quality health service, however, often assessment of patient experience excludes diagnostic care. Experience of diagnostic services and the acceptability of diagnostic tests are often conflated, with lack of clarity about when and how either should be measured. These problems contrast with the growth in the development and marketing of new tests and investigation strategies. Building on the appraisal of current practice, we propose that the experience of diagnostic services and the acceptability of tests should be assessed separately, and describe distinct components of each. Such evaluations will enhance the delivery of patient-centred care, and facilitate patient choice.

Conceptual Framework to Guide Early Diagnosis Programs for Symptomatic Cancer as Part of Global Cancer Control.

Diagnosing cancer earlier can enable timely treatment and optimize outcomes. Worldwide, national cancer control plans increasingly encompass early diagnosis programs for symptomatic patients, commonly comprising awareness campaigns to encourage prompt help-seeking for possible cancer symptoms and health system policies to support prompt diagnostic assessment and access to treatment. By their nature, early diagnosis programs involve complex public health interventions aiming to address unmet health needs by acting on patient, clinical, and system factors. However, there is uncertainty regarding how to optimize the design and evaluation of such interventions. We propose that decisions about early diagnosis programs should consider four interrelated components: first, the conduct of a needs assessment (based on cancer-site-specific statistics) to identify the cancers that may benefit most from early diagnosis in the target population; second, the consideration of symptom epidemiology to inform prioritization within an intervention; third, the identification of factors influencing prompt help-seeking at individual and system level to support the design and evaluation of interventions; and finally, the evaluation of factors influencing the health systems' capacity to promptly assess patients. This conceptual framework can be used by public health researchers and policy makers to identify the greatest evidence gaps and guide the design and evaluation of local early diagnosis programs as part of broader cancer control strategies.

The prevalence of chronic conditions in patients diagnosed with one of 29 common and rarer cancers: A cross-sectional study using primary care data.

BACKGROUND: Pre-existing chronic conditions (morbidities) influence the diagnosis and management of cancer. The prevalence of specific morbidities in patients diagnosed with common and rarer cancers is inadequately described. METHODS: Using data from the English National Cancer Diagnosis Audit 2014, we studied 11 pre-existing morbidities recorded as yes/no items by participating general practitioners based on information included in primary care records. We examined the number and type of morbidities across socio-demographic and cancer site strata, and subsequently estimated observed and age/sex standardised prevalence of each morbidity by cancer. RESULTS: Over three-quarters (77 %; 11,429/14,774) of non-screen-detected patients had at least one chronic condition before diagnosis, while nearly half (47 %) had two or more. Hypertension (39 %) and physical disability (2%) were the most and least common conditions. Male, older and more socio-economically deprived patients were more likely to have at least one morbidity (p < 0.001 for all between variable group comparisons). For most morbidities, the standardised prevalence was similar across different cancers with a few exceptions, including respiratory disease prevalence being greatest among lung cancer patients and diabetes prevalence being greatest among liver, pancreatic, and endometrial cancer patients. CONCLUSIONS: Most cancer patients have at least one morbidity, while almost one in two have two or more. The findings highlight the need to take certain morbidity- and cancer-site combinations into account when examining associations between morbidity and cancer outcomes.

Cytosponge-trefoil factor 3 versus usual care to identify Barrett's oesophagus in a primary care setting: a multicentre, pragmatic, randomised controlled trial.

BACKGROUND: Treatment of dysplastic Barrett's oesophagus prevents progression to adenocarcinoma; however, the optimal diagnostic strategy for Barrett's oesophagus is unclear. The Cytosponge-trefoil factor 3 (TFF3) is a non-endoscopic test for Barrett's oesophagus. The aim of this study was to investigate whether offering this test to patients on medication for gastro-oesophageal reflux would increase the detection of Barrett's oesophagus compared with standard management. METHODS: This multicentre, pragmatic, randomised controlled trial was done in 109 socio-demographically diverse general practice clinics in England. Randomisation was done both at the general practice clinic level (cluster randomisation) and at the individual patient level, and the results for each type of randomisation were analysed separately before being combined. Patients were eligible if they were aged 50 years or older, had been taking acid-suppressants for symptoms of gastro-oesophageal reflux for more than 6 months, and had not undergone an endoscopy procedure within the past 5 years. General practice clinics were selected by the local clinical research network and invited to participate in the trial. For cluster randomisation, clinics were randomly assigned (1:1) by the trial statistician using a computer-generated randomisation sequence; for individual patient-level randomisation, patients were randomly assigned (1:1) by the general practice clinics using a centrally prepared computer-generated randomisation sequence. After randomisation, participants received either standard management of gastro-oesophageal reflux (usual care group), in which participants only received an endoscopy if required by their general practitioner, or usual care plus an offer of the Cytosponge-TFF3 procedure, with a subsequent endoscopy if the procedure identified TFF3-positive cells (intervention group). The primary outcome was the diagnosis of Barrett's oesophagus at 12 months after enrolment, expressed as a rate per 1000 person-years, in all participants in the intervention group (regardless of whether they had accepted the offer of the Cytosponge-TFF3 procedure) compared with all participants in the usual care group. Analyses were intention-to-treat. The trial is registered with the ISRCTN registry, ISRCTN68382401, and is completed. FINDINGS: Between March 20, 2017, and March 21, 2019, 113 general practice clinics were enrolled, but four clinics dropped out shortly after randomisation. Using an automated search of the electronic prescribing records of the remaining 109 clinics, we identified 13 657 eligible patients who were sent an introductory letter with 14 days to opt out. 13 514 of these patients were randomly assigned (per practice or at the individual patient level) to the usual care group (n=6531) or the intervention group (n=6983). Following randomisation, 149 (2%) of 6983 participants in the intervention group and 143 (2%) of 6531 participants in the usual care group, on further scrutiny, did not meet all eligibility criteria or withdrew from the study. Of the remaining 6834 participants in the intervention group, 2679 (39%) expressed an interest in undergoing the Cytosponge-TFF3 procedure. Of these, 1750 (65%) met all of the eligibility criteria on telephone screening and underwent the procedure. Most of these participants (1654 [95%]; median age 69 years) swallowed the Cytosponge successfully and produced a sample. 231 (3%) of 6834 participants had a positive Cytosponge-TFF3 result and were referred for an endoscopy. Patients who declined the offer of the Cytosponge-TFF3 procedure and all participants in the usual care group only had an endoscopy if deemed necessary by their general practitioner. During an average of 12 months of follow-up, 140 (2%) of 6834 participants in the intervention group and 13 (<1%) of 6388 participants in the usual care group were diagnosed with Barrett's oesophagus (absolute difference 18·3 per 1000 person-years [95% CI 14·8-21·8]; rate ratio adjusted for cluster randomisation 10·6 [95% CI 6·0-18·8], p<0·0001). Nine (<1%) of 6834 participants were diagnosed with dysplastic Barrett's oesophagus (n=4) or stage I oesophago-gastric cancer (n=5) in the intervention group, whereas no participants were diagnosed with dysplastic Barrett's oesophagus or stage I gastro-oesophageal junction cancer in the usual care group. Among 1654 participants in the intervention group who swallowed the Cytosponge device successfully, 221 (13%) underwent endoscopy after testing positive for TFF3 and 131 (8%, corresponding to 59% of those having an endoscopy) were diagnosed with Barrett's oesophagus or cancer. One patient had a detachment of the Cytosponge from the thread requiring endoscopic removal, and the most common side-effect was a sore throat in 63 (4%) of 1654 participants. INTERPRETATION: In patients with gastro-oesophageal reflux, the offer of Cytosponge-TFF3 testing results in improved detection of Barrett's oesophagus. Cytosponge-TFF3 testing could also lead to the diagnosis of treatable dysplasia and early cancer. This strategy will lead to additional endoscopies with some false positive results. FUNDING: Cancer Research UK, National Institute for Health Research, the UK National Health Service, Medtronic, and the Medical Research Council.

Reconceptualising Rural Cancer Inequalities: Time for a New Research Agenda.

Evidence has shown for over 20 years that patients residing in rural areas face poorer outcomes for cancer. The inequalities in survival that rural cancer patients face are observed throughout the developed world, yet this issue remains under-examined and unexplained. There is evidence to suggest that rural patients are more likely to be diagnosed as a result of an emergency presentation and that rural patients may take longer to seek help for symptoms. However, research to date has been predominantly epidemiological, providing us with an understanding of what is occurring in these populations, yet failing to explain why. In this paper we outline the problems inherent in current research approaches to rural cancer inequalities, namely how 'cancer symptoms' are conceived of and examined, and the propensity towards a reductionist approach to rural environments and populations, which fails to account for their heterogeneity. We advocate for a revised rural cancer inequalities research agenda, built upon in-depth, community-based examinations of rural patients' experiences across the cancer pathway, which takes into account both the micro and macro factors which exert influence on these experiences, in order to develop meaningful interventions to improve cancer outcomes for rural populations.

Patient symptom experience prior to a diagnosis of oesophageal or gastric cancer: a multi-methods study.

BACKGROUND: Late stage diagnosis of oesophageal and gastric cancer is common, which limits treatment options and contributes to poor survival. AIM: To explore patients' understanding, experience and presentation of symptoms before a diagnosis of oesophageal or gastric cancer. DESIGN & SETTING: Between May 2016 and October 2017, all patients newly diagnosed with oesophageal or gastric cancer were identified at weekly multidisciplinary team meetings at two large hospitals in England. A total of 321 patients were invited to participate in a survey and secondary care medical record review; 127 (40%) participants responded (102 patients had oesophageal cancer and 25 had gastric cancer). Of these, 26 participated in an additional face-to-face interview. METHOD: Survey and medical record data were analysed descriptively. Interviews were analysed using thematic analysis, informed by the Model of Pathways to Treatment. RESULTS: Participants experienced multiple symptoms before diagnosis. The most common symptom associated with oesophageal cancer was dysphagia (n = 66, 65%); for gastric cancer, fatigue or tiredness (n = 20, 80%) was the most common symptom. Understanding of heartburn, reflux and indigestion, and associated symptoms differed between participants and often contrasted with clinical perspectives. Bodily changes attributed to personal and/or lifestyle factors were self-managed, with presentation to primary care prompted when symptoms persisted, worsened, or impacted daily life, or were notably severe or unusual. Participants rarely presented all symptoms at the initial consultation. CONCLUSION: The patient interval may be lengthened by misinterpretation of key terms, such as heartburn, or misattribution or non-recognition of important bodily changes. Clearly defined symptom awareness messages may encourage earlier help-seeking, while eliciting symptom experience and meanings in primary care consultations could prompt earlier referral and diagnosis.

Cross-sectional study using primary care and cancer registration data to investigate patients with cancer presenting with non-specific symptoms.

INTRODUCTION: Patients presenting to primary care with site-specific alarm symptoms can be referred onto urgent suspected cancer pathways, whereas those with non-specific symptoms currently have no dedicated referral routes leading to delays in cancer diagnosis and poorer outcomes. Pilot Multidisciplinary Diagnostic Centres (MDCs) provide a referral route for such patients in England. OBJECTIVES: This work aimed to use linked primary care and cancer registration data to describe diagnostic pathways for patients similar to those being referred into MDCs and compare them to patients presenting with more specific symptoms. METHODS: This cross-sectional study linked primary care data from the National Cancer Diagnosis Audit (NCDA) to national cancer registration and Route to Diagnosis records. Patient symptoms recorded in the NCDA were used to allocate patients to one of two groups - those presenting with symptoms mirroring referral criteria of MDCs (non-specific but concerning symptoms (NSCS)) and those with at least one site-specific alarm symptom (non-NSCS). Descriptive analyses compared the two groups and regression analysis by group investigated associations with long primary care intervals (PCIs). RESULTS: Patients with NSCS were more likely to be diagnosed at later stage (32% stage 4, compared with 21% in non-NSCS) and via an emergency presentation (34% vs 16%). These patients also had more multiple pre-referral general practitioner consultations (59% vs 43%) and primary care-led diagnostics (blood tests: 57% vs 35%). Patients with NSCS had higher odds of having longer PCIs (adjusted OR: 1.24 (1.11 to 1.36)). Patients with lung and urological cancers also had higher odds of longer PCIs overall and in both groups. CONCLUSIONS: Differences in the diagnostic pathway show that patients with symptoms mirroring the MDC referral criteria could benefit from a new referral pathway.