Development and Implementation of a Digital Quality Measure of Emergency Cancer Diagnosis.

PURPOSE: Missed and delayed cancer diagnoses are common, harmful, and often preventable. Automated measures of quality of cancer diagnosis are lacking but could identify gaps and guide interventions. We developed and implemented a digital quality measure (dQM) of cancer emergency presentation (EP) using electronic health record databases of two health systems and characterized the measure's association with missed opportunities for diagnosis (MODs) and mortality. METHODS: On the basis of literature and expert input, we defined EP as a new cancer diagnosis within 30 days after emergency department or inpatient visit. We identified EPs for lung cancer and colorectal cancer (CRC) in the Department of Veterans Affairs (VA) and Geisinger from 2016 to 2020. We validated measure accuracy and identified preceding MODs through standardized chart review of 100 records per cancer per health system. Using VA's longitudinal encounter and mortality data, we applied logistic regression to assess EP's association with 1-year mortality, adjusting for cancer stage and demographics. RESULTS: Among 38,565 and 2,914 patients with lung cancer and 14,674 and 1,649 patients with CRCs at VA and Geisinger, respectively, our dQM identified EPs in 20.9% and 9.4% of lung cancers, and 22.4% and 7.5% of CRCs. Chart reviews revealed high positive predictive values for EPs across sites and cancer types (72%-90%), and a substantial percent represented MODs (48.8%-84.9%). EP was associated with significantly higher odds of 1-year mortality for lung cancer and CRC (adjusted odds ratio, 1.78 and 1.83, respectively, 95% CI, 1.63 to 1.86 and 1.61 to 2.07). CONCLUSION: A dQM for cancer EP was strongly associated with both mortality and MODs. The findings suggest a promising automated approach to measuring quality of cancer diagnosis in US health systems.

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.

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.

Guideline concordance for timely chest imaging after new presentations of dyspnoea or haemoptysis in primary care: a retrospective cohort study.

BACKGROUND: Guidelines recommend urgent chest X-ray for newly presenting dyspnoea or haemoptysis but there is little evidence about their implementation. METHODS: We analysed linked primary care and hospital imaging data for patients aged 30+ years newly presenting with dyspnoea or haemoptysis in primary care during April 2012 to March 2017. We examined guideline-concordant management, defined as General Practitioner-ordered chest X-ray/CT carried out within 2 weeks of symptomatic presentation, and variation by sociodemographic characteristic and relevant medical history using logistic regression. Additionally, among patients diagnosed with cancer we described time to diagnosis, diagnostic route and stage at diagnosis by guideline-concordant status. RESULTS: In total, 22 560/162 161 (13.9%) patients with dyspnoea and 4022/8120 (49.5%) patients with haemoptysis received guideline-concordant imaging within the recommended 2-week period. Patients with recent chest imaging pre-presentation were much less likely to receive imaging (adjusted OR 0.16, 95% CI 0.14-0.18 for dyspnoea, and adjusted OR 0.09, 95% CI 0.06-0.11 for haemoptysis). History of chronic obstructive pulmonary disease/asthma was also associated with lower odds of guideline concordance (dyspnoea: OR 0.234, 95% CI 0.225-0.242 and haemoptysis: 0.88, 0.79-0.97). Guideline-concordant imaging was lower among dyspnoea presenters with prior heart failure; current or ex-smokers; and those in more socioeconomically disadvantaged groups.The likelihood of lung cancer diagnosis within 12 months was greater among the guideline-concordant imaging group (dyspnoea: 1.1% vs 0.6%; haemoptysis: 3.5% vs 2.7%). CONCLUSION: The likelihood of receiving urgent imaging concords with the risk of subsequent cancer diagnosis. Nevertheless, large proportions of dyspnoea and haemoptysis presenters do not receive prompt chest imaging despite being eligible, indicating opportunities for earlier lung cancer diagnosis.

Protocol for a pragmatic cluster randomised controlled trial assessing the clinical effectiveness and cost-effectiveness of Electronic RIsk-assessment for CAncer for patients in general practice (ERICA).

INTRODUCTION: The UK has worse cancer outcomes than most comparable countries, with a large contribution attributed to diagnostic delay. Electronic risk assessment tools (eRATs) have been developed to identify primary care patients with a ≥2% risk of cancer using features recorded in the electronic record. METHODS AND ANALYSIS: This is a pragmatic cluster randomised controlled trial in English primary care. Individual general practices will be randomised in a 1:1 ratio to intervention (provision of eRATs for six common cancer sites) or to usual care. The primary outcome is cancer stage at diagnosis, dichotomised to stage 1 or 2 (early) or stage 3 or 4 (advanced) for these six cancers, assessed from National Cancer Registry data. Secondary outcomes include stage at diagnosis for a further six cancers without eRATs, use of urgent referral cancer pathways, total practice cancer diagnoses, routes to cancer diagnosis and 30-day and 1-year cancer survival. Economic and process evaluations will be performed along with service delivery modelling. The primary analysis explores the proportion of patients with early-stage cancer at diagnosis. The sample size calculation used an OR of 0.8 for a cancer being diagnosed at an advanced stage in the intervention arm compared with the control arm, equating to an absolute reduction of 4.8% as an incidence-weighted figure across the six cancers. This requires 530 practices overall, with the intervention active from April 2022 for 2 years. ETHICS AND DISSEMINATION: The trial has approval from London City and East Research Ethics Committee, reference number 19/LO/0615; protocol version 5.0, 9 May 2022. It is sponsored by the University of Exeter. Dissemination will be by journal publication, conferences, use of appropriate social media and direct sharing with cancer policymakers. TRIAL REGISTRATION NUMBER: ISRCTN22560297.

Ethnic differences in prostate-specific antigen levels in men without prostate cancer: a systematic review.

INTRODUCTION: Black men are twice as likely to be diagnosed with prostate cancer than White men. Raised prostate-specific antigen (PSA) levels can indicate an increased risk of prostate cancer, however it is not known whether PSA levels differ for men of different ethnic groups. METHODS: PubMed and Embase were searched to identify studies that reported levels of PSA for men of at least two ethnic groups without a prostate cancer diagnosis or symptoms suggestive of prostate cancer. An adaptation of the Newcastle-Ottawa scale was used to assess risk of bias and study quality. Findings were stratified into the following broad ethnic groups: White, Black, Asian, Hispanic, and Other. Data were analysed in a narrative synthesis due to the heterogeneity of reported PSA measures and methods in the included studies. RESULTS: A total of 654 197 males from 13 studies were included. By ethnicity, this included 536 201 White (82%), 38 287 Black (6%), 38 232 Asian (6%), 18 029 Pacific Island (3%), 13 614 Maori (2%), 8 885 Hispanic (1%), and 949 Other (<1%) men aged ≥40 years old. Black men had higher PSA levels than White men, and Hispanic men had similar levels to White men and lower levels than Black men. CONCLUSIONS: Black men without prostate cancer have higher PSA levels than White or Hispanic men, which reflects the higher rates of prostate cancer diagnosis in Black men. Despite that, the diagnostic accuracy of PSA for prostate cancer for men of different ethnic groups is unknown, and current guidance for PSA test interpretation does not account for ethnicity. Future research needs to determine whether Black men are diagnosed with similar rates of clinically significant prostate cancer to White men, or whether raised PSA levels are contributing to overdiagnosis of prostate cancer in Black men.

Examining methodology to identify patterns of consulting in primary care for different groups of patients before a diagnosis of cancer: An exemplar applied to oesophagogastric cancer.

BACKGROUND: Current methods for estimating the timeliness of cancer diagnosis are not robust because dates of key defining milestones, for example first presentation, are uncertain. This is exacerbated when patients have other conditions (multimorbidity), particularly those that share symptoms with cancer. Methods independent of this uncertainty are needed for accurate estimates of the timeliness of cancer diagnosis, and to understand how multimorbidity impacts the diagnostic process. METHODS: Participants were diagnosed with oesophagogastric cancer between 2010 and 2019. Controls were matched on year of birth, sex, general practice and multimorbidity burden calculated using the Cambridge Multimorbidity Score. Primary care data (Clinical Practice Research Datalink) was used to explore population-level consultation rates for up to two years before diagnosis across different multimorbidity burdens. Five approaches were compared on the timing of the consultation frequency increase, the inflection point for different multimorbidity burdens, different aggregated time-periods and sample sizes. RESULTS: We included 15,410 participants, of which 13,328 (86.5 %) had a measurable multimorbidity burden. Our new maximum likelihood estimation method found evidence that the inflection point in consultation frequency varied with multimorbidity burden, from 154 days (95 %CI 131.8-176.2) before diagnosis for patients with no multimorbidity, to 126 days (108.5-143.5) for patients with the greatest multimorbidity burden. Inflection points identified using alternative methods were closer to diagnosis for up to three burden groups. Sample size reduction and changing the aggregation period resulted in inflection points closer to diagnosis, with the smallest change for the maximum likelihood method. DISCUSSION: Existing methods to identify changes in consultation rates can introduce substantial bias which depends on sample size and aggregation period. The direct maximum likelihood method was less prone to this bias than other methods and offers a robust, population-level alternative for estimating the timeliness of cancer diagnosis.

Shared social identity and perceived social support among stroke groups during the COVID-19 pandemic: Relationship with psychosocial health.

Community-based peer support groups for stroke survivors are common in the United Kingdom and aim to support rehabilitation. This study of 260 stroke survivors across 118 groups nationally used an online survey format, completed on average 3 months into the pandemic. Analysis of both quantitative and open-ended responses provided insights into how stroke group members maintained contact during the COVID-19 pandemic and how the group processes of shared social identity and perceived social support related to psychosocial outcomes (self-esteem, well-being and loneliness). Group members adapted to the pandemic early through telephone calls (61.6% of participants) and internet-based contact (>70% of participants), although also showed a desire for greater contact with their groups. A stronger sense of shared social identity and perceptions of social support from the stroke groups were weakly associated with reductions in loneliness among members, and greater perceived social support was associated with higher self-esteem. However, having poor health and living alone were more strongly associated with more negative psychosocial outcomes. The discussion considers how barriers to contact during pandemics can be managed, including access and use of online communication, limitations imposed by stroke-related disability, and how the experience of feeling supported and social identification can be better nurtured within remote contexts.

Pre-diagnostic prescription patterns in bladder and renal cancer: a longitudinal linked data study.

BACKGROUND: Understanding pre-diagnostic prescribing activity could reveal windows during which more timely cancer investigation and detection may occur. AIM: To examine prescription patterns for common urological clinical features prior to renal and bladder cancer diagnoses. DESIGN AND SETTING: A retrospective cohort study was performed using electronic primary care and cancer registry data on patients with bladder and renal cancer, who received their diagnosis between April 2012 and December 2015 in England. METHOD: Primary care prescriptions up to 2 years pre- diagnosis were analysed for five groups of clinical features (irritative urological symptoms, obstructive symptoms, urinary tract infections [UTIs], genital infections, and atrophic vaginitis). Poisson regressions estimating the inflection point from which the rate of prescriptions increased from baseline were used to identify the start of diagnostic windows during which cancer could be detected. RESULTS: A total of 48 094 prescriptions for 5322 patients were analysed. Inflection points for an increase in UTI prescriptions were identified 9 months pre- diagnosis for renal (95% confidence interval [CI] = 5.3 to 12.7) and bladder (95% CI = 7.4 to 10.6) cancers. For bladder cancer, the change in UTI antibiotic prescription rates occurred 4 months earlier in females (11 months pre- diagnosis, 95% CI = 9.7 to 12.3) than in males (7 months pre-diagnosis, 95% CI = 5.4 to 8.6). For other clinical features, no inflection points were identified and, as such, no diagnostic windows could be defined. CONCLUSION: Prescription rates for UTIs increased 9 months before bladder and renal cancer diagnoses, indicating that there is potential to expedite diagnosis of these cancers in patients presenting with features of UTI. The greatest opportunity for more timely diagnosis may be in females with bladder cancer, who experienced the earliest increase in UTI prescription rate.

Pre-diagnostic clinical features and blood tests in patients with colorectal cancer: a retrospective linked-data study.

BACKGROUND: The majority of colorectal cancer is diagnosed in patients following symptomatic presentation in the UK. AIM: To identify windows of opportunity for timely investigations or referrals in patients presenting with colon and rectal cancer-relevant symptoms or abnormal blood tests. DESIGN AND SETTING: A retrospective cohort study was undertaken using linked primary care and cancer registry data for patients with colorectal cancer diagnosed in England between 2012 and 2015. METHOD: Monthly consultation rates for relevant clinical features (change in bowel habit, rectal bleeding, abdominal pain, abdominal mass, constitutional symptoms, and other bowel symptoms) and abnormal blood test results (low haemoglobin, high platelets, and high inflammatory markers) up to 24 months pre-diagnosis were calculated. Poisson regression adjusted for age, sex, and relevant comorbidities was used to estimate the most likely month when consultation rates increased above baseline. RESULTS: In total, 5033 patients with colon cancer and 2516 with rectal cancer were included. Consultations for all examined clinical features and abnormal blood tests increased in the year pre-diagnosis. Rectal bleeding was the earliest clinical feature to increase from the baseline rate: at 10 months (95% confidence interval [CI] = 8.3 to 11.7) pre-diagnosis for colon cancer and at 8 months (95% CI = 6.1 to 9.9) pre-diagnosis for rectal cancer. Low haemoglobin, high platelets, and high inflammatory markers increased from as early as 9 months pre-diagnosis. CONCLUSION: This study found evidence for an early increase in rates of consultation for relevant clinical features and abnormal blood tests in patients with colorectal cancer, suggesting that earlier instigation of cancer-specific investigations or referrals may be warranted in some patients who were symptomatic.

Ethnic inequalities in routes to diagnosis of cancer: a population-based UK cohort study.

BACKGROUND: UK Asian and Black ethnic groups have poorer outcomes for some cancers and are less likely to report a positive care experience than their White counterparts. This study investigated ethnic differences in the route to diagnosis (RTD) to identify areas in patients' cancer journeys where inequalities lie, and targeted intervention might have optimum impact. METHODS: We analysed data of 243,825 patients with 10 cancers (2006-2016) from the RTD project linked to primary care data. Crude and adjusted proportions of patients diagnosed via six routes (emergency, elective GP referral, two-week wait (2WW), screen-detected, hospital, and Other routes) were calculated by ethnicity. Adjusted odds ratios (including two-way interactions between cancer and age, sex, IMD, and ethnicity) determined cancer-specific differences in RTD by ethnicity. RESULTS: Across the 10 cancers studied, most patients were diagnosed via 2WW (36.4%), elective GP referral (23.2%), emergency (18.2%), hospital routes (10.3%), and screening (8.61%). Patients of Other ethnic group had the highest proportion of diagnosis via the emergency route, followed by White patients. Asian and Black group were more likely to be GP-referred, with the Black and Mixed groups also more likely to follow the 2WW route. However, there were notable cancer-specific differences in the RTD by ethnicity. CONCLUSION: Our findings suggest that, where inequalities exist, the adverse cancer outcomes among Asian and Black patients are unlikely to be arising solely from a poorer diagnostic process.

The Performance of HE4 Alone and in Combination with CA125 for the Detection of Ovarian Cancer in an Enriched Primary Care Population.

Human epididymis 4 (HE4) is a promising ovarian cancer biomarker, but it has not been evaluated in primary care. In this prospective observational study, we investigated the diagnostic accuracy of HE4 alone and in combination with CA125 for the detection of ovarian cancer in symptomatic women attending primary care. General practitioner (GP)-requested CA125 samples were tested for HE4 at a large teaching hospital in Manchester, and cancer outcomes were tracked for 12 months. We found a low incidence of ovarian cancer in primary care; thus, the cohort was enriched with pre-surgical samples from 81 ovarian cancer patients. The Risk of Ovarian Malignancy Algorithm (ROMA) was calculated using age (51) as a surrogate for menopause. Conventional diagnostic accuracy metrics were determined. A total of 1229 patients were included; 82 had ovarian cancer. Overall, ROMA performed best (AUC-0.96 (95%CI: 0.94−0.98, p = <0.001)). In women under 50 years, the combination of CA125 and HE4 (either marker positive) was superior (sensitivity: 100% (95%CI: 81.5−100.0), specificity: 80.1% (95%CI 76.7−83.1)). In women over 50, ROMA performed best (sensitivity: 84.4% (95%CI: 73.1−92.2), specificity: 87.2% (95%CI 84.1−90)). HE4 and ROMA may improve ovarian cancer detection in primary care, particularly for women under 50 years, in whom diagnosis is challenging. Validation in a larger primary care cohort is required.

Development of 2 Short Patient-Report Questionnaires of Patient Safety in Primary Care.

OBJECTIVES: The Patient Reported Experiences and Outcomes of Safety in Primary Care (PREOS-PC) is a valid and reliable instrument (61 items across 5 domains) of patients' perceptions of safety. Stakeholder feedback has supported shorter versions for improving choice and facilitating uptake of routine patient-centered evaluation. We sought to develop 2 shorter versions of PREOS-PC: one including the shortest possible scales that met established measurement performance standards and a screening version including a single item per domain. METHODS: A total of 1244 patients from 45 general practices across England completed PREOS-PC questionnaires. All scale items in PREOS-PC underwent Item Response Theory analysis, applying standard criteria for the item reduction. Cognitive debriefing from 10 patient interviews allowed for the assessment of the instruments' readability. The instruments' psychometrics properties were reassessed in a validation sample of 1557 patients in 21 English general practices. RESULTS: "PREOS-PC Compact" includes 25 items and 2 open-ended questions across the 5 domains, 44% of the length of the original instrument. "PREOS-PC Screen" consists of 6 items: the best-performing single items for 2 domains, 1 item modified from original items for each of the remaining 3 domains, and 1 open-ended question. The evaluation of the instruments confirmed they were acceptable to patients and met standards for readability; construct, convergent, and divergent validity; and reliability. CONCLUSIONS: PREOS-PC Compact meets high-performance standards while reducing patient burden for routine monitoring of patient safety in primary care. PREOS-PC Screen is a concise tool apt for incorporation into audits and to target more in-depth review as needed.

Identifying opportunities for timely diagnosis of bladder and renal cancer via abnormal blood tests: a longitudinal linked data study.

BACKGROUND: Understanding pre-diagnostic test use could reveal diagnostic windows where more timely evaluation for cancer may be indicated. AIM: To examine pre-diagnostic patterns of results of abnormal blood tests in patients with bladder and renal cancer. DESIGN AND SETTING: A retrospective cohort study using primary care and cancer registry data on patients with bladder and renal cancer who were diagnosed between April 2012 and December 2015 in England. METHOD: The rates of patients with a first abnormal result in the year before cancer diagnosis, for 'generic' (full blood count components, inflammatory markers, and calcium) and 'organ-specific' blood tests (creatinine and liver function test components) that may lead to subsequent detection of incidental cancers, were examined. Poisson regression was used to detect the month during which the cohort's rate of each abnormal test started to increase from baseline. The proportion of patients with a test found in the first half of the diagnostic window was examined, as these 'early' tests might represent opportunities where further evaluation could be initiated. RESULTS: Data from 4533 patients with bladder and renal cancer were analysed. The monthly rate of patients with a first abnormal test increased towards the time of cancer diagnosis. Abnormalities of both generic (for example, high inflammatory markers) and organ-specific tests (for example, high creatinine) started to increase from 6-8 months pre-diagnosis, with 25%-40% of these patients having an abnormal test in the 'early half' of the diagnostic window. CONCLUSION: Population-level signals of bladder and renal cancer can be observed in abnormalities in commonly performed primary care blood tests up to 8 months before diagnosis, indicating the potential for earlier diagnosis in some patients.

Evaluation of microalbuminuria as a prognostic indicator after a TIA or minor stroke in an outpatient setting: the prognostic role of microalbuminuria in TIA evolution (ProMOTE) study.

OBJECTIVE: Transient ischaemic attacks (TIA) and minor strokes are important risk factors for further vascular events. We explored the role of albumin creatinine ratio (ACR) in improving risk prediction after a first event. SETTING: Rapid access stroke clinics in the UK. PARTICIPANTS: 2202 patients attending with TIA or minor stroke diagnosed by the attending stroke physician, able to provide a urine sample to evaluate ACR using a near-patient testing device. PRIMARY AND SECONDARY OUTCOMES: Primary outcome was major adverse cardiac events (MACE: recurrent stroke, myocardial infarction or cardiovascular death) at 90 days. The key secondary outcome was to determine whether urinary ACR could contribute to a risk prediction tool for use in a clinic setting. RESULTS: 151 MACE occurred in 144 participants within 90 days. Participants with MACE had higher ACR than those without. A composite score awarding a point each for age >80 years, previous stroke/TIA and presence of microalbuminuria identified those at low risk and high risk. 90% of patients were at low risk (scoring 0 or 1). Their 90-day risk of MACE was 5.7%. Of the remaining 'high-risk' population (scoring 2 or 3) 12.4% experienced MACE over 90 days (p<0.001 compared with the low-risk population). The need for acute admission in the first 7 days was twofold elevated in the high-risk group compared with the low-risk group (3.23% vs 1.43%; p=0.05). These findings were validated in an independent historic sample. CONCLUSION: A risk score comprising age, previous stroke/TIA and microalbuminuria predicts future MACE while identifying those at low risk of a recurrent event. This tool shows promise in the risk stratification of patients to avoid the admission of low-risk patients.

A prospective cohort evaluation of the sensitivity and specificity of the chest X-ray for the detection of lung cancer in symptomatic adults.

BACKGROUND: The accuracy of the chest x-ray (CXR) in the identification of lung cancer amongst symptomatic individuals is uncertain. PURPOSE: To determine the diagnostic accuracy of the CXR for the detection of non-small cell carcinomas (NSCLC) and all primary intrathoracic malignancies. METHODS: A prospective cohort study of consecutive CXR reports obtained within a primary care open access initiative. Eligibility criteria were symptoms specified by National Institute for Clinical Excellence as indicative of possible lung cancer and age over 50-yrs. A positive test was a CXR which led directly or indirectly to investigation with CT. The reference standards were malignancies observed within a one- or two-year post-test period. RESULTS: 8,948 CXR outcomes were evaluated. 496 positive studies led to a diagnosis of 101 patients with primary intrathoracic malignancy including 80 with NSCLC. Within two-years, a cumulative total of 168 patients with primary intrathoracic malignancies including 133 NSCLC were observed. The sensitivity and specificity for NSCLC were 76% (95 %CI 68-84) and 95% (95 %CI 95-96) within 1-year and 60% (95 %CI 52-69) and 95% (95 %CI 95-96) within 2-years. The 2-yr positive and negative likelihood ratios were 12.8 and 0.4. The results did not differ for NSCLC compared to all primary malignancies. Within this symptomatic population a negative test reduced the 2-year risk of lung cancer to 0.8%. CONCLUSIONS: A positive test strongly increases the probability of malignancy whereas a negative test does not conclusively exclude the disease. The findings allow the risk of malignancy following a negative test to be estimated.

Comparison of two immunoassays for the measurement of serum HE4 for ovarian cancer.

INTRODUCTION: The use of Human Epididymis Protein 4 (HE4) as a biomarker for ovarian cancer is gaining traction, providing the impetus for development of a high throughput automated HE4 assay that is comparable to the conventional manual enzyme immunometric-assay (EIA). The aim of this study was to compare two immunoassay methods for the measurement of serum HE4. MATERIALS AND METHODS: 1348 serum samples were analysed for serum HE4 using both the EIA and the automated chemiluminescent immunoassay (CLEIA) methods. HE4 values were compared using a Passing-Bablok regression and agreement assessed using Lin's concordance correlation coefficient (CCC). The absolute and percentage bias of the CLEIA compared to EIA was determined. RESULTS: There was moderate agreement between the two methods (CCC 0.929, 95%CI 0.923-0.936). Passing-Bablok regression demonstrated an overestimation of the CLEIA [constant 4.44 (95%CI 2.96-5.68), slope 1.04 (95%CI 1.02-1.07)]. The CLEIA method had a mean percentage bias of 16.25% compared to the EIA method. CONCLUSION: The CLEIA significantly overestimated serum HE4 values compared to the EIA, which could impact clinical interpretation and patient management. Further studies are required to develop an appropriate cut-off depending on the population being investigated and the analytic method being used.

CA125 test result, test-to-diagnosis interval, and stage in ovarian cancer at diagnosis: a retrospective cohort study using electronic health records.

BACKGROUND: In the UK, the cancer antigen 125 (CA125) test is recommended as a first-line investigation in women with symptoms of possible ovarian cancer. AIM: To compare time between initial primary care CA125 test and diagnosis, tumour morphology, and stage in women with normal (<35 U/ml) and abnormal (≥35 U/ml) CA125 levels prior to ovarian cancer diagnosis. DESIGN AND SETTING: Retrospective cohort study using English primary care and cancer registry data. METHOD: Associations between CA125 test results and test-to-diagnosis interval, stage, and ovarian cancer morphology were examined. RESULTS: In total, 456 women were diagnosed with ovarian cancer in the 12 months after having a CA125 test. Of these, 351 (77%) had an abnormal, and 105 (23%) had a normal, CA125 test result. The median test-to-diagnosis interval was 35 days (interquartile range [IQR] 21-53) for those with abnormal CA125 levels, and 64 days (IQR 42-127) for normal CA125 levels. Tumour morphology differed by CA125 result: indolent borderline tumours were less common in those with abnormal CA125 levels (n = 47, 13%) than those with normal CA125 levels (n = 51, 49%) (P<0.001). Staging data were available for 304 women with abnormal, and 77 with normal, CA125 levels. Of those with abnormal CA125 levels, 35% (n = 106) were diagnosed at an early stage, compared to 86% (n = 66) of women with normal levels. The odds of being diagnosed with early-stage disease were higher in women with normal as opposed to abnormal CA125 levels (odds ratio 12.2, 95% confidence interval = 5.8 to 25.1, P<0.001). CONCLUSION: Despite longer intervals between testing and diagnosis, women with normal, compared with abnormal, CA125 levels more frequently had indolent tumours and were more commonly diagnosed at an early stage in the course of the disease. Although testing approaches that have greater sensitivity might expedite diagnosis for some women, it is not known if this would translate to earlier-stage diagnosis.

Chest X-ray sensitivity and lung cancer outcomes: a retrospective observational study.

BACKGROUND: Chest X-ray (CXR) is the first-line investigation for lung cancer in many healthcare systems. An understanding of the consequences of false-negative CXRs on time to diagnosis, stage, and survival is limited. AIM: To determine the sensitivity of CXR for lung cancer and to compare stage at diagnosis, time to diagnosis, and survival between those with CXR that detected, or did not detect, lung cancer. DESIGN AND SETTING: Retrospective observational study using routinely collected healthcare data. METHOD: All patients diagnosed with lung cancer in Leeds Teaching Hospitals NHS Trust during 2008-2015 who had a GP-requested CXR in the year before diagnosis were categorised based on the result of the earliest CXR performed in that period. The sensitivity of CXR was calculated and analyses were performed with respect to time to diagnosis, survival, and stage at diagnosis. RESULTS: CXR was negative for 17.7% of patients (n = 376/2129). Median time from initial CXR to diagnosis was 43 days for those with a positive CXR and 204 days for those with a negative CXR. Of those with a positive CXR, 29.8% (95% confidence interval [CI] = 27.9% to 31.8%) were diagnosed at stage I or II, compared with 33.5% (95% CI = 28.8% to 38.6%) with a negative CXR. CONCLUSION: GPs should consider lung cancer in patients with persistent symptoms even when CXR is negative. Despite longer duration to diagnosis for those with false-negative CXRs, there was no evidence of an adverse impact on stage at diagnosis or survival; however, this comparison is likely to be affected by confounding variables.