Lung cancer among the Elderly in Denmark - A comprehensive population-based cohort study.

OBJECTIVE: Lung cancer primarily occurs in the elderly with a median age at diagnosis in Denmark of 73 years. However, elderly patients are under-represented in clinical trials as well as in screening studies. In this study, we aim to characterize elderly patients with lung cancer and explore the diagnostic intensity, treatment patterns, and survival. METHOD: Patients diagnosed with lung cancer between 2014 and 2017 according to the Danish Cancer Registry, and with clinical information in the Danish Lung Cancer Registry were included. Patient information was linked by the unique social identification number to information from Statistics Denmark. RESULTS: We included n = 17,835 patients in this study, of whom 2,871 (16.1 %) were 80 years or older. Fewer elderly patients had lung biopsies (47 % vs 53 %) or mediastinal procedures (34 % vs 26 %), compared to the younger patients (p < 0.001). Fewer elderly patients had treatment registration (60 % vs 85 %), and fewer received treatment with curative intent (23 % vs 42 %) compared to patients younger than 80 years (p < 0.001). The elderly patients had 2.1 (CI 95 % 1.9 - 2.2) times higher odds of dying within 12 months after diagnosis than younger patients. CONCLUSION: The diagnostic intensity among lung cancer patients aged eighty years or above is lower compared to younger patients. Being elderly is associated with not undergoing surgical treatment or treatment with curative intent. Across all treatment groups, being older than eighty years of age was associated with an adverse prognosis.

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

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

Clinical activity in general practice prior to sarcoma diagnosis: Australian cohort study.

Background Increased time-to-diagnosis in sarcoma is associated with poor prognosis and patient outcomes. Research is needed to identify if opportunities to expedite the diagnosis of sarcoma in general practice (GP) exist. Aim To examine pre-diagnostic GP clinical activity prior to sarcoma diagnosis. Design and Setting An Australian retrospective cohort study using hospital registry data (Australian Comprehensive Cancer Outcomes and Research Database) linked to two primary care datasets (Patron and MedicineInsight). Method The frequency of GP healthcare utilisation events (GP attendances, prescriptions, blood test and imaging requests) were compared in 377 soft tissue sarcoma (STS) and 64 bone sarcoma (BS) patients in the year pre-diagnosis. Poisson regression models were used to calculate monthly incidence rates and rate ratios (IRR) for the 24 months pre-diagnosis and estimate inflection points for when healthcare use starts to increase from baseline. Results In the six months pre-diagnosis sarcoma patients had a median of 3-4 GP attendances, a third had a GP imaging request (33% BS and 36% STS), and one in five had multiple imaging requests (19% BS and 21% STS). GP imaging requests progressively increased up to 8-fold from 6 months prior to sarcoma diagnosis (IRR 8.43 95%CI 3.92-18.15, p<0.001) and GP attendances increased from 3 months pre-diagnosis. Conclusion Sarcoma patients have increased GP clinical activity from 6 months pre-diagnosis, indicating a diagnostic window where potential opportunities exist for earlier diagnosis. Interventions to help identify patients and promote appropriate use of imaging and direct specialist centre referrals could improve earlier diagnosis and patient outcomes.

Use of chemotherapy in patients with oesophageal, stomach, colon, rectal, liver, pancreatic, lung, and ovarian cancer: an International Cancer Benchmarking Partnership (ICBP) population-based study.

BACKGROUND: There are few data on international variation in chemotherapy use, despite it being a key treatment type for some patients with cancer. Here, we aimed to examine the presence and size of such variation. METHODS: This population-based study used data from Norway, the four UK nations (England, Northern Ireland, Scotland, and Wales), eight Canadian provinces (Alberta, British Columbia, Manitoba, Newfoundland and Labrador, Nova Scotia, Ontario, Prince Edward Island, and Saskatchewan), and two Australian states (New South Wales and Victoria). Patients aged 15-99 years diagnosed with cancer in eight different sites (oesophageal, stomach, colon, rectal, liver, pancreatic, lung, or ovarian cancer), with no other primary cancer diagnosis occurring from within the 5 years before to 1 year after the index cancer diagnosis or during the study period were included in the study. We examined variation in chemotherapy use from 31 days before to 365 days after diagnosis and time to its initiation, alongside related variation in patient group differences. Information was obtained from cancer registry records linked to clinical or patient management system data or hospital administration data. Random-effects meta-analyses quantified interjurisdictional variation using 95% prediction intervals (95% PIs). FINDINGS: Between Jan 1, 2012, and Dec 31, 2017, of 893 461 patients with a new diagnosis of one of the studied cancers, 111 569 (12·5%) did not meet the inclusion criteria, and 781 892 were included in the analysis. There was large interjurisdictional variation in chemotherapy use for all studied cancers, with wide 95% PIs: 47·5 to 81·2 (pooled estimate 66·4%) for ovarian cancer, 34·9 to 59·8 (47·2%) for oesophageal cancer, 22·3 to 62·3 (40·8%) for rectal cancer, 25·7 to 55·5 (39·6%) for stomach cancer, 17·2 to 56·3 (34·1%) for pancreatic cancer, 17·9 to 49·0 (31·4%) for lung cancer, 18·6 to 43·8 (29·7%) for colon cancer, and 3·5 to 50·7 (16·1%) for liver cancer. For patients with stage 3 colon cancer, the interjurisdictional variation was greater than that for all patients with colon cancer (95% PI 38·5 to 78·4; 60·1%). Patients aged 85-99 years had 20-times lower odds of chemotherapy use than those aged 65-74 years, with very large interjurisdictional variation in this age difference (odds ratio 0·05; 95% PI 0·01 to 0·19). There was large variation in median time to first chemotherapy (from diagnosis date) by cancer site, with substantial interjurisdictional variation, particularly for rectal cancer (95% PI -15·5 to 193·9 days; pooled estimate 89·2 days). Patients aged 85-99 years had slightly shorter median time to first chemotherapy compared with those aged 65-74 years, consistently between jurisdictions (-3·7 days, 95% PI -7·6 to 0·1). INTERPRETATION: Large variation in use and time to chemotherapy initiation were observed between the participating jurisdictions, alongside large and variable age group differences in chemotherapy use. To guide efforts to improve patient outcomes, the underlying reasons for these patterns need to be established. FUNDING: International Cancer Benchmarking Partnership (funded by the Canadian Partnership Against Cancer, Cancer Council Victoria, Cancer Institute New South Wales, Cancer Research UK, Danish Cancer Society, National Cancer Registry Ireland, The Cancer Society of New Zealand, National Health Service England, Norwegian Cancer Society, Public Health Agency Northern Ireland on behalf of the Northern Ireland Cancer Registry, DG Health and Social Care Scottish Government, Western Australia Department of Health, and Public Health Wales NHS Trust).

Use of radiotherapy in patients with oesophageal, stomach, colon, rectal, liver, pancreatic, lung, and ovarian cancer: an International Cancer Benchmarking Partnership (ICBP) population-based study.

BACKGROUND: There is little evidence on variation in radiotherapy use in different countries, although it is a key treatment modality for some patients with cancer. Here we aimed to examine such variation. METHODS: This population-based study used data from Norway, the four UK nations (England, Northern Ireland, Scotland, and Wales), nine Canadian provinces (Alberta, British Columbia, Manitoba, New Brunswick, Newfoundland and Labrador, Nova Scotia, Ontario, Prince Edward Island, and Saskatchewan), and two Australian states (New South Wales and Victoria). Patients aged 15-99 years diagnosed with cancer in eight different sites (oesophageal, stomach, colon, rectal, liver, pancreatic, lung, or ovarian cancer), with no other primary cancer diagnosis occurring within the 5 years before to 1 year after the index cancer diagnosis or during the study period were included in the study. We examined variation in radiotherapy use from 31 days before to 365 days after diagnosis and time to its initiation, alongside related variation in patient group differences. Information was obtained from cancer registry records linked to clinical or patient management system data, or hospital administration data. Random-effects meta-analyses quantified interjurisdictional variation using 95% prediction intervals (95% PIs). FINDINGS: Between Jan 1, 2012, and Dec 31, 2017, of 902 312 patients with a new diagnosis of one of the studied cancers, 115 357 (12·8%) did not meet inclusion criteria, and 786,955 were included in the analysis. There was large interjurisdictional variation in radiotherapy use, with wide 95% PIs: 17·8 to 82·4 (pooled estimate 50·2%) for oesophageal cancer, 35·5 to 55·2 (45·2%) for rectal cancer, 28·6 to 54·0 (40·6%) for lung cancer, and 4·6 to 53·6 (19·0%) for stomach cancer. For patients with stage 2-3 rectal cancer, interjurisdictional variation was greater than that for all patients with rectal cancer (95% PI 37·0 to 84·6; pooled estimate 64·2%). Radiotherapy use was infrequent but variable in patients with pancreatic (95% PI 1·7 to 16·5%), liver (1·8 to 11·2%), colon (1·6 to 5·0%), and ovarian (0·8 to 7·6%) cancer. Patients aged 85-99 years had three-times lower odds of radiotherapy use than those aged 65-74 years, with substantial interjurisdictional variation in this age difference (odds ratio [OR] 0·38; 95% PI 0·20-0·73). Women had slightly lower odds of radiotherapy use than men (OR 0·88, 95% PI 0·77-1·01). There was large variation in median time to first radiotherapy (from diagnosis date) by cancer site, with substantial interjurisdictional variation (eg, oesophageal 95% PI 11·3 days to 112·8 days; pooled estimate 62·0 days; rectal 95% PI 34·7 days to 77·3 days; pooled estimate 56·0 days). Older patients had shorter median time to radiotherapy with appreciable interjurisdictional variation (-9·5 days in patients aged 85-99 years vs 65-74 years, 95% PI -26·4 to 7·4). INTERPRETATION: Large interjurisdictional variation in both use and time to radiotherapy initiation were observed, alongside large and variable age differences. To guide efforts to improve patient outcomes, underlying reasons for these differences need to be established. FUNDING: International Cancer Benchmarking Partnership (funded by the Canadian Partnership Against Cancer, Cancer Council Victoria, Cancer Institute New South Wales, Cancer Research UK, Danish Cancer Society, National Cancer Registry Ireland, The Cancer Society of New Zealand, National Health Service England, Norwegian Cancer Society, Public Health Agency Northern Ireland on behalf of the Northern Ireland Cancer Registry, DG Health and Social Care Scottish Government, Western Australia Department of Health, and Public Health Wales NHS Trust).

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.

Phenotypes and rates of cancer-relevant symptoms and tests in the year before cancer diagnosis in UK Biobank and CPRD Gold.

Early diagnosis of cancer relies on accurate assessment of cancer risk in patients presenting with symptoms, when screening is not appropriate. But recorded symptoms in cancer patients pre-diagnosis may vary between different sources of electronic health records (EHRs), either genuinely or due to differential completeness of symptom recording. To assess possible differences, we analysed primary care EHRs in the year pre-diagnosis of cancer in UK Biobank and Clinical Practice Research Datalink (CPRD) populations linked to cancer registry data. We developed harmonised phenotypes in Read v2 and CTV3 coding systems for 21 symptoms and eight blood tests relevant to cancer diagnosis. Among 22,601 CPRD and 11,594 UK Biobank cancer patients, 54% and 36%, respectively, had at least one consultation for possible cancer symptoms recorded in the year before their diagnosis. Adjusted comparisons between datasets were made using multivariable Poisson models, comparing rates of symptoms/tests in CPRD against expected rates if cancer site-age-sex-deprivation associations were the same as in UK Biobank. UK Biobank cancer patients compared with those in CPRD had lower rates of consultation for possible cancer symptoms [RR: 0.61 (0.59-0.63)], and lower rates for any primary care consultation [RR: 0.86 (95%CI 0.85-0.87)]. Differences were larger for 'non-alarm' symptoms [RR: 0.54 (0.52-0.56)], and smaller for 'alarm' symptoms [RR: 0.80 (0.76-0.84)] and blood tests [RR: 0.93 (0.90-0.95)]. In the CPRD cohort, approximately representative of the UK population, half of cancer patients had recorded symptoms in the year before diagnosis. The frequency of non-specific presenting symptoms recorded in the year pre-diagnosis of cancer was substantially lower among UK Biobank participants. The degree to which results based on highly selected biobank cohorts are generalisable needs to be examined in disease-specific contexts.

A taxonomy of early diagnosis research to guide study design and funding prioritisation.

Researchers and research funders aiming to improve diagnosis seek to identify if, when, where, and how earlier diagnosis is possible. This has led to the propagation of research studies using a wide range of methodologies and data sources to explore diagnostic processes. Many such studies use electronic health record data and focus on cancer diagnosis. Based on this literature, we propose a taxonomy to guide the design and support the synthesis of early diagnosis research, focusing on five key questions: Do healthcare use patterns suggest earlier diagnosis could be possible? How does the diagnostic process begin? How do patients progress from presentation to diagnosis? How long does the diagnostic process take? Could anything have been done differently to reach the correct diagnosis sooner? We define families of diagnostic research study designs addressing each of these questions and appraise their unique or complementary contributions and limitations. We identify three further questions on relationships between the families and their relevance for examining patient group inequalities, supported with examples from the cancer literature. Although exemplified through cancer as a disease model, we recognise the framework is also applicable to non-neoplastic disease. The proposed framework can guide future study design and research funding prioritisation.

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.

Pre-diagnostic prescribing patterns in dyspnoea patients with as-yet-undiagnosed lung cancer: A longitudinal study of linked primary care and cancer registry data.

INTRODUCTION: Patients with as-yet undiagnosed lung cancer (LC) can present to primary care with non-specific symptoms such as dyspnoea, often in the context of pre-existing chronic obstructive pulmonary disease (COPD). Related medication prescriptions pre-diagnosis might represent opportunities for earlier diagnosis, but UK evidence is limited. Consequently, we explored prescribing patterns of relevant medications in patients who presented with dyspnoea in primary care and were subsequently diagnosed with LC. METHOD: Linked primary care (Clinical Practice Research Datalink) and National Cancer Registry data were used to identify 5434 patients with incident LC within a year of a dyspnoea presentation in primary care between 2006 and 2016. Primary care prescriptions relevant to dyspnoea management were examined: antibiotics, inhaled medications, oral steroids, and opioid analgesics. Poisson regression models estimated monthly prescribing rates during the year pre-diagnosis. Variation by COPD status (52 % pre-existing, 36 % COPD-free, 12 % new-onset) was examined. Inflection points were identified indicating when prescribing rates changed from the background rate. RESULTS: 63 % of patients received 1 or more relevant prescriptions 1-12 months pre-diagnosis. Pre-existing COPD patients were most prescribed inhaled medications. COPD-free and new-onset COPD patients were most prescribed antibiotics. Most patients received 2 or more relevant prescriptions. Monthly prescribing rates of all medications increased towards time of diagnosis in all patient groups and were highest in pre-existing COPD patients. Increases in prescribing activity were observed earliest in pre-existing COPD patients 5 months pre-diagnosis for inhaled medications, antibiotics, and steroids, CONCLUSION: Results indicate that a diagnostic window of appreciable length exists for potential earlier LC diagnosis in some patients. Lung cancer diagnosis may be delayed if early symptoms are misattributed to COPD or other benign conditions.

Are There Ethnic Differences in Recorded Features among Patients Subsequently Diagnosed with Cancer? An English Longitudinal Data-Linked Study.

We investigated ethnic differences in the presenting features recorded in primary care before cancer diagnosis. METHODS: English population-based cancer-registry-linked primary care data were analysed. We identified the coded features of six cancers (breast, lung, prostate, colorectal, oesophagogastric, and myeloma) in the year pre-diagnosis. Logistic regression models investigated ethnic differences in first-incident cancer features, adjusted for age, sex, smoking status, deprivation, and comorbidity. RESULTS: Of 130,944 patients, 92% were White. In total, 188,487 incident features were recorded in the year pre-diagnosis, with 48% (89,531) as sole features. Compared with White patients, Asian and Black patients with breast, colorectal, and prostate cancer were more likely than White patients to have multiple features; the opposite was seen for the Black and Other ethnic groups with lung or prostate cancer. The proportion with relevant recorded features was broadly similar by ethnicity, with notable cancer-specific exceptions. Asian and Black patients were more likely to have low-risk features (e.g., cough, upper abdominal pain) recorded. Non-White patients were less likely to have alarm features. CONCLUSION: The degree to which these differences reflect disease, patient or healthcare factors is unclear. Further research examining the predictive value of cancer features in ethnic minority groups and their association with cancer outcomes is needed.

Diagnostic windows in non-neoplastic diseases: a systematic review.

BACKGROUND: Investigating changes in prediagnostic healthcare utilisation can help identify how much earlier conditions could be diagnosed. Such 'diagnostic windows' are established for cancer but remain relatively unexplored for non-neoplastic conditions. AIM: To extract evidence on the presence and length of diagnostic windows for non-neoplastic conditions. DESIGN AND SETTING: A systematic review of studies of prediagnostic healthcare utilisation was carried out. METHOD: A search strategy was developed to identify relevant studies from PubMed and Connected Papers. Data were extracted on prediagnostic healthcare use, and evidence of diagnostic window presence and length was assessed. RESULTS: Of 4340 studies screened, 27 were included, covering 17 non-neoplastic conditions, including both chronic (for example, Parkinson's disease) and acute conditions (for example, stroke). Prediagnostic healthcare events included primary care encounters and presentations with relevant symptoms. For 10 conditions, sufficient evidence to determine diagnostic window presence and length was available, ranging from 28 days (herpes simplex encephalitis) to 9 years (ulcerative colitis). For the remaining conditions, diagnostic windows were likely to be present, but insufficient study duration was often a barrier to robustly determining their length, meaning that diagnostic window length may exceed 10 years for coeliac disease, for example. CONCLUSION: Evidence of changing healthcare use before diagnosis exists for many non-neoplastic conditions, establishing that early diagnosis is possible, in principle. In particular, some conditions may be detectable many years earlier than they are currently diagnosed. Further research is required to accurately estimate diagnostic windows and to determine how much earlier diagnosis may be possible, and how this might be achieved.

Improving the diagnostic process for patients with possible bladder and kidney cancer: a mixed-methods study to identify potential missed diagnostic opportunities.

BACKGROUND: Patients with bladder and kidney cancer may experience diagnostic delays. AIM: To identify patterns of suboptimal care and contributors of potential missed diagnostic opportunities (MDOs). DESIGN AND SETTING: Prospective, mixed-methods study recruiting participants from nine general practices in Eastern England between June 2018 and October 2019. METHOD: Patients with possible bladder and kidney cancer were identified using eligibility criteria based on National Institute for Health and Care Excellence (NICE) guidelines for suspected cancer. Primary care records were reviewed at recruitment and at 1 year for data on symptoms, tests, referrals, and diagnosis. Referral predictors were examined using logistic regression. Semi-structured interviews were undertaken with 15 patients to explore their experiences of the diagnostic process, and these were analysed thematically. RESULTS: Participants (n = 940) were mostly female (n = 657, 69.9%), with a median age of 71 years (interquartile range 64-77 years). In total, 268 (28.5%) received a referral and 465 (48.5%) had a final diagnosis of urinary tract infection (UTI). There were 33 (3.5%) patients who were diagnosed with cancer, including prostate (n = 17), bladder (n = 7), and upper urothelial tract (n = 1) cancers. Among referred patients, those who had a final diagnosis of UTI had the longest time to referral (median 81.5 days). Only one-third of patients with recurrent UTIs were referred despite meeting NICE referral guidelines. Qualitative findings revealed barriers during the diagnostic process, including inadequate clinical examination, female patients given repeated antibiotics without clinical reviews, and suboptimal communication of test results to patients. CONCLUSION: Older females with UTIs might be at increased risk of MDOs for cancer. Targeting barriers during the initial diagnostic assessment and follow-up might improve quality of diagnosis.

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.

Breast, Prostate, Colorectal, and Lung Cancer Incidence and Risk Factors in Women Who Have Sex with Women and Men Who Have Sex with Men: A Cross-Sectional and Longitudinal Analysis Using UK Biobank.

BACKGROUND: There is limited evidence about cancer incidence for lesbian, gay and bisexual women and men, although the prevalence of cancer risk factors may be higher. AIM: To describe cancer incidence for four common cancers (breast, lung, colorectal and prostate). METHODS: This project used UK Biobank participant data. We explored risk factor prevalence (age, deprivation, ethnicity, smoking, alcohol intake, obesity, parity, and sexual history), and calculated cancer risk, for six groups defined based on sexual history; women who have sex exclusively with men (WSEM), or women (WSEW), women who have sex with men and women (WSWM); men who have sex exclusively with women (MSEW), or men (MSEM), and men who have sex with women and men (MSWM). RESULTS: WSEW, WSWM, MSEM, and MSMW were younger, more likely to smoke, and to live in more deprived neighbourhoods. We found no evidence of an association between sexual history and breast, colorectal, or prostate cancer in age-adjusted models. Lung cancer incidence was higher for WSWM compared with WSEM, HR (95%CI) 1.78 (1.28-2.48), p = 0.0005, and MSWM compared with MSEW, 1.43 (1.03-1.99), p = 0.031; after adjustment for smoking, this difference was no longer significant. CONCLUSIONS: Sexual minority groups have a higher risk for lung cancer, due to greater exposure to smoking.

The Role of Type 2 Diabetes in Patient Symptom Attribution, Help-Seeking, and Attitudes to Investigations for Colorectal Cancer Symptoms: An Online Vignette Study.

OBJECTIVES: Type 2 diabetes is associated with a higher risk of colorectal cancer (CRC) and advanced-stage cancer diagnosis. To help diagnose cancer earlier, this study aimed at examining whether diabetes might influence patient symptom attribution, help-seeking, and willingness to undergo investigations for possible CRC symptoms. METHODS: A total of 1307 adults (340 with and 967 without diabetes) completed an online vignette survey. Participants were presented with vignettes describing new-onset red-flag CRC symptoms (rectal bleeding or a change in bowel habits), with or without additional symptoms of diabetic neuropathy. Following the vignettes, participants were asked questions on symptom attribution, intended help-seeking, and attitudes to investigations. RESULTS: Diabetes was associated with greater than two-fold higher odds of attributing changes in bowel habits to medications (OR = 2.48; 95% Cl 1.32-4.66) and of prioritising diabetes-related symptoms over the change in bowel habits during medical encounters. Cancer was rarely mentioned as a possible explanation for the change in bowel habits, especially among diabetic participants (10% among diabetics versus 16% in nondiabetics; OR = 0.55; 95% CI 0.36-0.85). Among patients with diabetes, those not attending annual check-ups were less likely to seek help for red-flag cancer symptoms (OR = 0.23; 95% Cl 0.10-0.50). CONCLUSIONS: Awareness of possible cancer symptoms was low overall. Patients with diabetes could benefit from targeted awareness campaigns emphasising the importance of discussing new symptoms such as changes in bowel habits with their doctor. Specific attention is warranted for individuals not regularly attending healthcare despite their chronic morbidity.

Underlying cancer risk among patients with fatigue and other vague symptoms: a population-based cohort study in primary care.

BACKGROUND: Presenting to primary care with fatigue is associated with slightly increased cancer risk, although it is unknown how this varies in the presence of other 'vague' symptoms. AIM: To quantify cancer risk in patients with fatigue who present with other 'vague' symptoms in the absence of 'alarm' symptoms for cancer. DESIGN AND SETTING: Cohort study of patients presenting in UK primary care with new-onset fatigue during 2007-2015, using Clinical Practice Research Datalink data linked to national cancer registration data. METHOD: Patients presenting with fatigue without co-occurring alarm symptoms or anaemia were identified, who were further characterised as having co-occurrence of 19 other 'vague' potential cancer symptoms. Sex- and age-specific 9-month cancer risk for each fatigue-vague symptom cohort were calculated. RESULTS: Of 285 382 patients presenting with new-onset fatigue, 84% (n = 239 846) did not have co-occurring alarm symptoms or anaemia. Of these, 38% (n = 90 828) presented with ≥1 of 19 vague symptoms for cancer. Cancer risk exceeded 3% in older males with fatigue combined with any of the vague symptoms studied. The age at which risk exceeded 3% was 59 years for fatigue-weight loss, 65 years for fatigue-abdominal pain, 67 years for fatigue-constipation, and 67 years for fatigue-other upper gastrointestinal symptoms. For females, risk exceeded 3% only in older patients with fatigue-weight loss (from 65 years), fatigue-abdominal pain (from 79 years), or fatigue-abdominal bloating (from 80 years). CONCLUSION: In the absence of alarm symptoms or anaemia, fatigue combined with specific vague presenting symptoms, alongside patient age and sex, can guide clinical decisions about referral for suspected cancer.

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.