Colorectal cancer risk stratification using a polygenic risk score in symptomatic primary care patients-a UK Biobank retrospective cohort study.

Colorectal cancer (CRC) is a leading cause of cancer mortality worldwide. Accurate cancer risk assessment approaches could increase rates of early CRC diagnosis, improve health outcomes for patients and reduce pressure on diagnostic services. The faecal immunochemical test (FIT) for blood in stool is widely used in primary care to identify symptomatic patients with likely CRC. However, there is a 6-16% noncompliance rate with FIT in clinic and ~90% of patients over the symptomatic 10 µg/g test threshold do not have CRC. A polygenic risk score (PRS) quantifies an individual's genetic risk of a condition based on many common variants. Existing PRS for CRC have so far been used to stratify asymptomatic populations. We conducted a retrospective cohort study of 50,387 UK Biobank participants with a CRC symptom in their primary care record at age 40+. A PRS based on 201 variants, 5 genetic principal components and 22 other risk factors and markers for CRC were assessed for association with CRC diagnosis within 2 years of first symptom presentation using logistic regression. Associated variables were included in an integrated risk model and trained in 80% of the cohort to predict CRC diagnosis within 2 years. An integrated risk model combining PRS, age, sex, and patient-reported symptoms was predictive of CRC development in a testing cohort (receiver operating characteristic area under the curve, ROCAUC: 0.76, 95% confidence interval: 0.71-0.81). This model has the potential to improve early diagnosis of CRC, particularly in cases of patient noncompliance with FIT.

The diagnostic performance of CA-125 for the detection of ovarian cancer in women from different ethnic groups: a cohort study of English primary care data.

BACKGROUND: CA-125 testing is a recommended first line investigation for women presenting with possible symptoms of ovarian cancer in English primary care, to help determine whether further investigation for ovarian cancer is needed. It is currently not known how well the CA-125 test performs in ovarian cancer detection for patients from different ethnic groups. METHODS: A retrospective cohort study utilising English primary care data linked to the national cancer registry was undertaken. Women aged ≥ 40 years with a CA-125 test between 2010 and 2017 were included. Logistic regression predicted one-year ovarian cancer incidence by ethnicity, adjusting for age, deprivation status, and comorbidity score. The estimated incidence of ovarian cancer by CA-125 level was modelled for each ethnic group using restricted cubic splines. RESULTS: The diagnostic performance of CA-125 differed for women from different ethnicities. In an unadjusted analysis, predicted CA-125 levels for Asian and Black women were higher than White women at corresponding probabilities of ovarian cancer. The higher PPVs for White women compared to Asian or Black women were eliminated by inclusion of covariates. CONCLUSION: The introduction of ethnicity-specific thresholds may increase the specificity and PPVs of CA-125 in ovarian cancer detection at the expense of sensitivity, particularly for Asian and Black women. As such, we cannot recommend the use of ethnicity-specific thresholds for CA-125.

Clinical decision-making on lung cancer investigations in primary care: a vignette study.

OBJECTIVES: To investigate the role of comorbid chronic obstructive pulmonary disease (COPD) and symptom type on general practitioners' (GP's) symptom attribution and clinical decision-making in relation to lung cancer diagnosis. DESIGN: Vignette survey with a 2×2 mixed factorial design. SETTING: A nationwide online survey exploring clinical decision-making in primary care. PARTICIPANTS: 109 GPs based in the United Kingdom (UK) who were registered as responders on Dynata (an online survey platform). INTERVENTIONS: GPs were presented with four vignettes which described a patient aged 75 with a smoking history presenting with worsening symptoms (either general or respiratory) and with or without a pre-existing diagnosis of COPD. PRIMARY AND SECONDARY OUTCOME MEASURES: GPs indicated the three most likely diagnoses (free-text) and selected four management approaches (20 pre-coded options). Attribution of symptoms to lung cancer and referral for urgent chest X-ray were primary outcomes. Alternative diagnoses and management approaches were explored as secondary outcomes. Multivariable mixed-effects logistic regression was used, including random intercepts for individual GPs. RESULTS: 422 vignettes were completed. There was no evidence for COPD status as a predictor of lung cancer attribution (OR=1.1, 95% CI=0.5-2.4, p=0.914). There was no evidence for COPD status as a predictor of urgent chest X-ray referral (OR=0.6, 95% CI=0.3-1.2, p=0.12) or as a predictor when in combination with symptom type (OR=0.9, 95% CI=0.5-1.8, p=0.767). CONCLUSIONS: Lung cancer was identified as a possible diagnosis for persistent respiratory by only one out of five GPs, irrespective of the patients' COPD status. Increasing awareness among GPs of the link between COPD and lung cancer may increase the propensity for performing chest X-rays and referral for diagnostic testing for symptomatic patients.

Patient safety in actioning and communicating blood test results in primary care: a UK wide audit using the Primary care Academic CollaboraTive (PACT).

BACKGROUND: Errors associated with failures in filing, actioning and communicating blood test results can lead to delayed and missed diagnoses and patient harm. This study aimed to audit how blood tests in primary care are filed, actioned and communicated in primary care, to identify areas for patient safety improvements. METHODS: UK primary care clinicians were recruited through the Primary Care Academic CollaboraTive (PACT). PACT members audited 50 recent sets of blood tests from their practice and retrospectively extracted data on blood test result coding, actioning and communication. PACT members received a practice report, showing their own results, benchmarked against other participating practices. RESULTS: PACT members from 57 general practices across all four UK nations collected data on 2572 patients who had blood tests in April 2021. In 89.9% (n=2311) they agreed with the initial clinician's actioning of blood tests; 10.1% disagreed, either partially (7.1%) or fully (3.0%).In 44% of patients (n=1132) an action (eg, 'make an appointment') was specified by the filing clinician. This action was carried out in 89.7% (n=1015/1132) of cases; in 6.8% (n=77) the action was not carried out, in 3.5% (n=40) it was unclear. In the 117 cases where the test result had not been actioned 38% (n=45) were felt to be at low risk of harm, 1.7% (n=2) were at high risk of harm, 0.85% (n=1) came to harm.Overall, in 47% (n=1210) of patients there was no evidence in the electronic health records that results had been communicated. Out of 1176 patients with one or more abnormal results there was no evidence of test communication in 30.6% (n=360). There were large variations between practices in rates of actioning and communicating tests. CONCLUSION: This research demonstrates variation in the way blood test results are actioned and communicated, with important patient safety implications.

Optimising the use of the prostate- specific antigen blood test in asymptomatic men for early prostate cancer detection in primary care: report from a UK clinical consensus.

BACKGROUND: Screening is not recommended for prostate cancer in the UK. Asymptomatic men aged ≥50 years can request a prostate-specific antigen (PSA) test following counselling on potential harms and benefits. There are areas of clinical uncertainty among GPs, resulting in the content and quality of counselling varying. AIM: To produce a consensus that can influence guidelines for UK primary care on the optimal use of the PSA test in asymptomatic men for early prostate cancer detection. DESIGN AND SETTING: Prostate Cancer UK facilitated a RAND/UCLA consensus. METHOD: Statements covering five topics were developed with a subgroup of experts. A panel of 15 experts in prostate cancer scored (round one) statements on a scale of one (strongly disagree) to nine (strongly agree). Panellists met to discuss statements before rescoring (round two). A lived experience panel of seven men scored a subset of statements with outcomes fed into the main panel. RESULTS: Of the initial 94 statements reviewed by the expert panel, a final 48/85 (56%) achieved consensus. In the absence of screening, there was consensus on proactive approaches to initiate discussions about the PSA test with men who were at higher-than-average risk. CONCLUSION: Improvements in the prostate cancer diagnostic pathway may have reduced some of the harms associated with PSA testing; however, several areas of uncertainty remain in relation to screening, including optimal PSA thresholds for referral and intervals for retesting. There is consensus on proactive approaches to testing in higher-than-average risk groups. This should prompt a review of current guidelines.

What helps or hinders the communication of poor prognosis between secondary and primary care? A systematic review with narrative synthesis.

Introduction The communication of poor prognosis from secondary to primary care helps to ensure that patients with life-limiting illness receive appropriate, coordinated care in line with their preferences. However, little is known about this information-sharing process. Aim To determine how poor prognosis is communicated from secondary care to primary care. Design and setting Systematic literature review and narrative synthesis. Method Four electronic databases were searched from 1st January 2000 to 17th May 2021, supplemented by hand-searching key journals. One quarter of titles and abstracts were independently screened by a second reviewer. Two reviewers undertook data extraction and quality appraisal, independently using the Mixed-Methods Appraisal Tool. Data were analysed using narrative synthesis. Reporting follows PRISMA guidance. Results Searches identified 23,853 unique studies of which 30 met the inclusion criteria. Few studies had a focus on the interprofessional communication of poor prognosis. Information about prognosis was not commonly communicated from secondary to primary care and was more likely to occur if death was imminent. Lack of identification of poor prognosis by secondary care teams was a barrier. Facilitators included shared electronic records and direct clinician-clinician contact. GPs welcomed this information from secondary care and felt it was vital for continuity of care. Conclusion Although the communication of poor prognosis from secondary to primary care is highly valued, it is rare and associated with cultural and systemic challenges. Further research is necessary to understand the information needs of GPs and to explore the challenges facing secondary care clinicians initiating this communication.

Exploring ethnic differences in the distribution of blood test results in healthy adult populations to inform earlier cancer detection: a systematic review.

BACKGROUND: In primary care, health professionals use blood tests to investigate nonspecific presentations to inform referral decisions. Reference ranges for the commonly used blood tests in western countries were developed in predominately White populations, and so may perform differently when applied to non-White populations. Knowledge of ethnic variation in blood test results in healthy/general populations could help address ethnic inequalities in cancer referral for diagnosis and outcomes. OBJECTIVE: This systematic review explored evidence of ethnic differences in the distribution of selected blood test results among healthy/general populations to inform future research aimed at addressing inequalities in cancer diagnosis. METHODS: We searched PubMed and EMBASE to identify studies reporting measures of haemoglobin, MCV, calcium, albumin, platelet count, and CRP in nondiseased adults from at least 2 different ethnic groups. Two reviewers independently screened studies, completed data extraction and quality assessment using an adapted Newcastle-Ottawa scale. Participants were stratified into White, Black, Asian, Mixed, and Other groups. Data were synthesised narratively and meta-analyses were conducted where possible. RESULTS: A total of 47 papers were included. Black men and women have lower average values of haemoglobin, MCV, and albumin, and higher average values of CRP relative to their White counterparts. Additionally, Black men have lower average haemoglobin than Asian men, whereas Asian women have lower average CRP values when compared with White women. CONCLUSIONS: There is evidence of ethnic differences in average values of haemoglobin, MCV, CRP, and albumin in healthy/general populations. Further research is needed to explore the reasons for these differences. Systematic review registration: CRD42021274580.

Acceptability of magnetic resonance imaging for prostate cancer diagnosis with patients and GPs: a qualitative interview study.

BACKGROUND: Magnetic resonance imaging (MRI) of the prostate is a new, more accurate, non-invasive test for prostate cancer diagnosis. AIM: To understand the acceptability of MRI for patients and GPs for prostate cancer diagnosis. DESIGN AND SETTING: Qualitative study of men who had undergone a prostate MRI for possible prostate cancer, and GPs who had referred at least one man for possible prostate cancer in the previous 12 months in West London and Devon. METHOD: Semi-structured interviews, conducted in person or via telephone, were audio-recorded and transcribed verbatim. Deductive thematic analysis was undertaken using Sekhon's Theoretical Framework of Acceptability, retrospectively for patients and prospectively for GPs. RESULTS: Twenty-two men (12 from Devon, age range 47-80 years), two patients' partners, and 10 GPs (6 female, age range 36-55 years) were interviewed. Prostate MRI was broadly acceptable for most patient participants, and they reported that it was not a significant undertaking to complete the scan. GPs were more varied in their views on prostate MRI, with a broad spectrum of knowledge and understanding of prostate MRI. Some GPs expressed concerns about additional clinical responsibility and local availability of MRI if direct access to prostate MRI in primary care were to be introduced. CONCLUSION: Prostate MRI appears to be acceptable to patients. Some differences were found between patients in London and Devon, mainly around burden of testing and opportunity costs. Further exploration of GPs' knowledge and understanding of prostate MRI could inform future initiatives to widen access to diagnostic testing in primary care.

Association between patient ethnicity and prostate cancer diagnosis following a prostate-specific antigen test: a cohort study of 730,000 men in primary care in the UK.

BACKGROUND: Black men have higher prostate-specific antigen (PSA) levels and higher prostate cancer incidence and mortality than White men, while Asian men tend to have lower prostate cancer incidence and mortality than White men. Much of the evidence comes from the USA, and information from UK populations is limited. METHODS: This retrospective cohort study used data on patients registered at general practices in England contributing to the Clinical Practice Research Datalink (CPRD) Aurum dataset. Those eligible were men aged 40 and over with a record of ethnicity and a PSA test result recorded between 2010 and 2017 with no prior cancer diagnosis. The aim was to assess the incidence of prostate cancer following a raised PSA test result in men from different ethnic groups. Additionally, incidence of advanced prostate cancer was investigated. Cancer incidence was estimated from multi-level logistic regression models adjusting for potential confounding factors. RESULTS: 730,515 men with a PSA test were included (88.9% White). Black men and men with mixed ethnicity had higher PSA values, particularly for those aged above 60 years. In the year following a raised PSA result (using age-specific thresholds), Black men had the highest prostate cancer incidence at 24.7% (95% CI 23.3%, 26.2%); Asian men had the lowest at 13.4% (12.2%, 14.7%); incidence for White men was 19.8% (19.4%, 20.2%). The peak incidence of prostate cancer for all groups was in men aged 70-79. Incidence of prostate cancer diagnosed at an advanced stage was similar between Black and White men. CONCLUSIONS: More prostate cancer was diagnosed in Black men with a raised PSA result, but rates of advanced prostate cancer were not higher in this group. In this large primary care-based cohort, the incidence of prostate cancer in men with elevated PSA levels increases with increasing age, even when using age-adjusted thresholds, with Black men significantly more likely to be diagnosed compared to White or Asian men. The incidence of advanced stage prostate cancer at diagnosis was similar for Black and White men with a raised PSA result, but lower for Asian men.

Learning from new colorectal cancers: a qualitative synthesis of significant event reports.

BACKGROUND: Colorectal cancer is the second leading cause of cancer-related mortality in the UK and a significant contributor to morbidity and mortality worldwide. Early diagnosis provides opportunities for intervention and improved survival. Significant event analysis (SEA) is a well-established quality improvement method for learning from new cancer diagnoses. AIM: To provide additional insights into diagnostic processes for colorectal cancer and to identify areas for improvement in patient care pathways. DESIGN & SETTING: Fifty-three general practices across Pennine Lancashire, England, submitted one or more SEA reports as part of an incentivised scheme. METHOD: A standardised data collection form was used to collate learning points and recommendations for improvements. In total, 161 reports were analysed using an inductive framework analysis approach. RESULTS: There was an overarching theme of building vigilance and collaboration between and within general practices and secondary care. The following four main sub-themes were also identified: education; individualised and flexible care; ownership and continuity; and communication. CONCLUSION: These findings provide additional insights into colorectal cancer pathways from a primary care perspective. Practices should be supported in developing protocols for assessment and follow-up of patients with varying presentations. Screening and access to investigations are paramount for improving early diagnosis; however, a flexible diagnostic approach is required according to the individual circumstances of each patient.

Exploration of reasons for primary care testing (the Why Test study): a UK-wide audit using the Primary care Academic CollaboraTive.

BACKGROUND: Rates of blood testing have increased over the past two decades. Reasons for testing cannot easily be extracted from electronic health record databases. AIM: To explore who requests blood tests and why, and what the outcomes of testing are in UK primary care. DESIGN AND SETTING: A retrospective audit of electronic health records in general practices in England, Wales, Scotland, and Northern Ireland was undertaken. METHOD: Fifty-seven clinicians from the Primary care Academic CollaboraTive (PACT) each reviewed the electronic health records of 50 patients who had blood tests in April 2021. Anonymised data were extracted including patient characteristics, who requested the tests, reasons for testing, test results, and outcomes of testing. RESULTS: Data were collected from 2572 patients across 57 GP practices. The commonest reasons for testing in primary care were investigation of symptoms (43.2%), monitoring of existing disease (30.1%), monitoring of existing medications (10.1%), and follow up of previous abnormalities (6.8%); patient requested testing was rare in this study (1.5%). Abnormal and borderline results were common, with 26.6% of patients having completely normal test results. Around one-quarter of tests were thought to be partially or fully unnecessary when reviewed retrospectively by a clinical colleague. Overall, 6.2% of tests in primary care led to a new diagnosis or confirmation of a diagnosis. CONCLUSION: The utilisation of a national collaborative model (PACT) has enabled a unique exploration of the rationale and outcomes of blood testing in primary care, highlighting areas for future research and optimisation.

Clinical trials in cancer screening, prevention and early diagnosis (SPED): a systematic mapping review.

BACKGROUND: Global annual cancer incidence is forecast to rise to 27.5 M by 2040, a 62% increase from 2018. For most cancers, prevention and early detection are the most effective ways of reducing mortality. This study maps trials in cancer screening, prevention, and early diagnosis (SPED) to identify areas of unmet need and highlight research priorities. METHODS: A systematic mapping review was conducted to evaluate all clinical trials focused on cancer SPED, irrespective of tumour type. The National Cancer Research Institute (NCRI) portfolio, EMBASE, PubMed and Medline were searched for relevant papers published between 01/01/2007 and 01/04/2020. References were exported into Covidence software and double-screened. Data were extracted and mapped according to tumour site, geographical location, and intervention type. RESULTS: One hundred seventeen thousand seven hundred one abstracts were screened, 5157 full texts reviewed, and 2888 studies included. 1184 (52%) trials focussed on screening, 554 (24%) prevention, 442 (20%) early diagnosis, and 85 (4%) a combination. Colorectal, breast, and cervical cancer comprised 61% of all studies compared with 6.4% in lung and 1.8% in liver cancer. The latter two are responsible for 26.3% of global cancer deaths compared with 19.3% for the former three. Number of studies varied markedly according to geographical location; 88% were based in North America, Europe, or Asia. CONCLUSIONS: This study shows clear disparities in the volume of research conducted across different tumour types and according to geographical location. These findings will help drive future research effort so that resources can be directed towards major challenges in cancer SPED.

Using the Primary care Academic CollaboraTive to explore the characteristics and healthcare use of older housebound patients in England: protocol for a retrospective observational study and clinician survey (the CHiP study).

BACKGROUND: Older housebound people are an under-researched group for whom achieving good primary health care can be resource intensive. AIMS: To describe the characteristics and healthcare use of older (≥65 years) housebound people; explore clinician views on delivery of care to housebound people; and assess the feasibility of using a new network of healthcare professionals to deliver high quality research. DESIGN & SETTING: Retrospective observational study of electronic GP records and clinician survey in England. METHOD: Clinical members of a new UK research network called the Primary care Academic CollaboraTive (PACT) will collect the data. For part A, around 20 GP practices will be recruited and clinicians will identify 20 housebound and 20 non-housebound people, matched by age and gender (around 400 total in each group). Anonymised data will be collected on characteristics (age, gender, ethnicity, deprivation decile), long-term conditions, prescribed medicines, quality of healthcare (via Quality Outcomes Framework targets), and continuity of care. Reports with benchmarked practice-level data will be provided to practices to identify areas for quality improvement and to enhance engagement. For part B, 2-4 clinicians will be recruited from around 50 practices in England (around 150 clinicians) to complete a survey about delivery of healthcare for housebound people. For part C, data will be collected to assess the feasibility of using the PACT network to deliver primary care research. CONCLUSION: Older housebound people are a neglected group both in terms of research and clinical care. Understanding the characteristics and use of primary healthcare of housebound people will help identify how to improve their care.

Systematic Review and Narrative Synthesis of Economic Evaluations of Prostate Cancer Diagnostic Pathways Incorporating Prebiopsy Magnetic Resonance Imaging.

Context: Prebiopsy magnetic resonance imaging (MRI) of the prostate has been shown to increase the accuracy of the diagnosis of clinically significant prostate cancer. However, evidence is still evolving about how best to integrate prebiopsy MRI into the diagnostic pathway and for which patients, and whether MRI-based pathways are cost effective. Objective: This systematic review aimed to assess the evidence for the cost effectiveness of prebiopsy MRI-based prostate cancer diagnostic pathways. Evidence acquisition: INTERTASC search strategies were adapted and combined with terms for prostate cancer and MRI, and used to search a wide range of databases and registries covering medicine, allied health, clinical trials, and health economics. No limits were set on country, setting, or publication year. Included studies were full economic evaluations of prostate cancer diagnostic pathways with at least one strategy including prebiopsy MRI. Model-based studies were assessed using the Philips framework, and trial-based studies were assessed using the Critical Appraisal Skills Programme checklist. Evidence synthesis: A total of 6593 records were screened after removing duplicates, and eight full-text papers, reporting on seven studies (two model based) were included in this review. Included studies were judged to have a low-to-moderate risk of bias. All studies reported cost-effectiveness analyses based in high-income countries but had significant heterogeneity in diagnostic strategies, patient populations, treatment strategies, and model characteristics. Prebiopsy MRI-based pathways were cost effective compared with pathways relying on ultrasound-guided biopsy in all eight studies. Conclusions: Incorporation of prebiopsy MRI into prostate cancer diagnostic pathways is likely to be more cost effective in than that into pathways relying on prostate-specific antigen and ultrasound-guided biopsy. The optimal prostate cancer diagnostic pathway design and method of integrating prebiopsy MRI are not yet known. Variations between health care systems and diagnostic approaches necessitate further evaluation for a particular country or setting to know how best to apply prebiopsy MRI. Patient summary: In this report, we looked at studies that measured the health care costs and benefits and harms to patients of using prostate magnetic resonance imaging (MRI), to decide whether men need a prostate biopsy for possible prostate cancer. We found that using prostate MRI before biopsy is likely to be less costly for health care services and probably has better outcomes for patients being investigated for prostate cancer. It is still unclear what the best way to use prostate MRI is.

Best Current Practice and Research Priorities in Active Surveillance for Prostate Cancer-A Report of a Movember International Consensus Meeting.

BACKGROUND: Active surveillance (AS) is recommended for low-risk and some intermediate-risk prostate cancer. Uptake and practice of AS vary significantly across different settings, as does the experience of surveillance-from which tests are offered, and to the levels of psychological support. OBJECTIVE: To explore the current best practice and determine the most important research priorities in AS for prostate cancer. DESIGN, SETTING, AND PARTICIPANTS: A formal consensus process was followed, with an international expert panel of purposively sampled participants across a range of health care professionals and researchers, and those with lived experience of prostate cancer. Statements regarding the practice of AS and potential research priorities spanning the patient journey from surveillance to initiating treatment were developed. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Panel members scored each statement on a Likert scale. The group median score and measure of consensus were presented to participants prior to discussion and rescoring at panel meetings. Current best practice and future research priorities were identified, agreed upon, and finally ranked by panel members. RESULTS AND LIMITATIONS: There was consensus agreement that best practice includes the use of high-quality magnetic resonance imaging (MRI), which allows digital rectal examination (DRE) to be omitted, that repeat standard biopsy can be omitted when MRI and prostate-specific antigen (PSA) kinetics are stable, and that changes in PSA or DRE should prompt MRI ± biopsy rather than immediate active treatment. The highest ranked research priority was a dynamic, risk-adjusted AS approach, reducing testing for those at the least risk of progression. Improving the tests used in surveillance, ensuring equity of access and experience across different patients and settings, and improving information and communication between and within clinicians and patients were also high priorities. Limitations include the use of a limited number of panel members for practical reasons. CONCLUSIONS: The current best practice in AS includes the use of high-quality MRI to avoid DRE and as the first assessment for changes in PSA, with omission of repeat standard biopsy when PSA and MRI are stable. Development of a robust, dynamic, risk-adapted approach to surveillance is the highest research priority in AS for prostate cancer. PATIENT SUMMARY: A diverse group of experts in active surveillance, including a broad range of health care professionals and researchers and those with lived experience of prostate cancer, agreed that best practice includes the use of high-quality magnetic resonance imaging, which can allow digital rectal examination and some biopsies to be omitted. The highest research priority in active surveillance research was identified as the development of a dynamic, risk-adjusted approach.