Impact of neuroendocrine morphology on cancer outcomes and stage at diagnosis: a UK nationwide cohort study 2013-2015.

BACKGROUND: The diagnosis of neuroendocrine neoplasms (NENs) is often delayed. This first UK population-based epidemiological study of NENs compares outcomes with non-NENs to identify any inequalities. METHODS: Age-standardised incidence rate (ASR), 1-year overall survival, hazard ratios and standardised mortality rates (SMRs) were calculated for all malignant NENs diagnosed 2013-2015 from UK national Public Health records. Comparison with non-NENs assessed 1-year overall survival (1YS) and association between diagnosis at stage IV and morphology. RESULTS: A total of 15,222 NENs were identified, with an ASR (2013-2015 combined) of 8.6 per 100,000 (95% CI 8.5-8.7); 4.6 per 100 000 (95% CI, 4.5-4.7) for gastro-entero-pancreatic (GEP) NENs. The 1YS was 75% (95% CI, 73.9-75.4) varying significantly by sex. Site and morphology were prognostic. NENs (predominantly small cell carcinomas) in the oesophagus, bladder, prostate, and female reproductive organs had a poorer outcome and were three times more likely to be diagnosed at stage IV than non-NENs. CONCLUSION: Advanced stage at diagnosis with significantly poorer outcomes of some NENs compared with non-NENs at the same anatomical site, highlight the need for improved access to specialist services and targeted service improvement.

The fraction of cancer attributable to modifiable risk factors in England, Wales, Scotland, Northern Ireland, and the United Kingdom in 2015.

BACKGROUND: Changing population-level exposure to modifiable risk factors is a key driver of changing cancer incidence. Understanding these changes is therefore vital when prioritising risk-reduction policies, in order to have the biggest impact on reducing cancer incidence. UK figures on the number of risk factor-attributable cancers are updated here to reflect changing behaviour as assessed in representative national surveys, and new epidemiological evidence. Figures are also presented by UK constituent country because prevalence of risk factor exposure varies between them. METHODS: Population attributable fractions (PAFs) were calculated for combinations of risk factor and cancer type with sufficient/convincing evidence of a causal association. Relative risks (RRs) were drawn from meta-analyses of cohort studies where possible. Prevalence of exposure to risk factors was obtained from nationally representative population surveys. Cancer incidence data for 2015 were sourced from national data releases and, where needed, personal communications. PAF calculations were stratified by age, sex and risk factor exposure level and then combined to create summary PAFs by cancer type, sex and country. RESULTS: Nearly four in ten (37.7%) cancer cases in 2015 in the UK were attributable to known risk factors. The proportion was around two percentage points higher in UK males (38.6%) than in UK females (36.8%). Comparing UK countries, the attributable proportion was highest in Scotland (41.5% for persons) and lowest in England (37.3% for persons). Tobacco smoking contributed by far the largest proportion of attributable cancer cases, followed by overweight/obesity, accounting for 15.1% and 6.3%, respectively, of all cases in the UK in 2015. For 10 cancer types, including two of the five most common cancer types in the UK (lung cancer and melanoma skin cancer), more than 70% of UK cancer cases were attributable to known risk factors. CONCLUSION: Tobacco and overweight/obesity remain the top contributors of attributable cancer cases. Tobacco smoking has the highest PAF because it greatly increases cancer risk and has a large number of cancer types associated with it. Overweight/obesity has the second-highest PAF because it affects a high proportion of the UK population and is also linked with many cancer types. Public health policy may seek to mitigate the level of harm associated with exposure or reduce exposure levels-both approaches may effectively impact cancer incidence. Differences in PAFs between countries and sexes are primarily due to varying prevalence of exposure to risk factors and varying proportions of specific cancer types. This variation in turn is affected by socio-demographic differences which drive differences in exposure to theoretically avoidable 'lifestyle' factors. PAFs at UK country level have not been available previously and they should be used by policymakers in devolved nations. PAFs are estimates based on the best available data, limitations in those data would generally bias toward underestimation of PAFs. Regular collection of risk factor exposure prevalence data which corresponds with epidemiological evidence is vital for analyses like this and should remain a priority for the UK Government and devolved Administrations.

Investigation of the international comparability of population-based routine hospital data set derived comorbidity scores for patients with lung cancer.

INTRODUCTION: The International Cancer Benchmarking Partnership (ICBP) identified significant international differences in lung cancer survival. Differing levels of comorbid disease across ICBP countries has been suggested as a potential explanation of this variation but, to date, no studies have quantified its impact. This study investigated whether comparable, robust comorbidity scores can be derived from the different routine population-based cancer data sets available in the ICBP jurisdictions and, if so, use them to quantify international variation in comorbidity and determine its influence on outcome. METHODS: Linked population-based lung cancer registry and hospital discharge data sets were acquired from nine ICBP jurisdictions in Australia, Canada, Norway and the UK providing a study population of 233 981 individuals. For each person in this cohort Charlson, Elixhauser and inpatient bed day Comorbidity Scores were derived relating to the 4-36 months prior to their lung cancer diagnosis. The scores were then compared to assess their validity and feasibility of use in international survival comparisons. RESULTS: It was feasible to generate the three comorbidity scores for each jurisdiction, which were found to have good content, face and concurrent validity. Predictive validity was limited and there was evidence that the reliability was questionable. CONCLUSION: The results presented here indicate that interjurisdictional comparability of recorded comorbidity was limited due to probable differences in coding and hospital admission practices in each area. Before the contribution of comorbidity on international differences in cancer survival can be investigated an internationally harmonised comorbidity index is required.

Ovarian cancer symptom awareness and anticipated delayed presentation in a population sample.

BACKGROUND: While ovarian cancer is recognised as having identifiable early symptoms, understanding of the key determinants of symptom awareness and early presentation is limited. A population-based survey of ovarian cancer awareness and anticipated delayed presentation with symptoms was conducted as part of the International Cancer Benchmarking Partnership (ICBP). METHODS: Women aged over 50 years were recruited using random probability sampling (n = 1043). Computer-assisted telephone interviews were used to administer measures including ovarian cancer symptom recognition, anticipated time to presentation with ovarian symptoms, health beliefs (perceived risk, perceived benefits/barriers to early presentation, confidence in symptom detection, ovarian cancer worry), and demographic variables. Logistic regression analysis was used to identify the contribution of independent variables to anticipated presentation (categorised as < 3 weeks or ≥ 3 weeks). RESULTS: The most well-recognised symptoms of ovarian cancer were post-menopausal bleeding (87.4%), and persistent pelvic (79.0%) and abdominal (85.0%) pain. Symptoms associated with eating difficulties and changes in bladder/bowel habits were recognised by less than half the sample. Lower symptom awareness was significantly associated with older age (p ≤ 0.001), being single (p ≤ 0.001), lower education (p ≤ 0.01), and lack of personal experience of ovarian cancer (p ≤ 0.01). The odds of anticipating a delay in time to presentation of ≥ 3 weeks were significantly increased in women educated to degree level (OR = 2.64, 95% CI 1.61 - 4.33, p ≤ 0.001), women who reported more practical barriers (OR = 1.60, 95% CI 1.34 - 1.91, p ≤ 0.001) and more emotional barriers (OR = 1.21, 95% CI 1.06 - 1.40, p ≤ 0.01), and those less confident in symptom detection (OR = 0.56, 95% CI 0.42 - 0.73, p ≤ 0.001), but not in those who reported lower symptom awareness (OR = 0.99, 95% CI 0.91 - 1.07, p = 0.74). CONCLUSIONS: Many symptoms of ovarian cancer are not well-recognised by women in the general population. Evidence-based interventions are needed not only to improve public awareness but also to overcome the barriers to recognising and acting on ovarian symptoms, if delays in presentation are to be minimised.

Survival from twenty adult cancers in the UK and Republic of Ireland in the late twentieth century.

BACKGROUND: International studies have shown that cancer survival was generally low in the UK and the Republic of Ireland compared to western and northern European countries, but no systematic comparative analysis has been performed between the UK countries and the Republic of Ireland. METHODS: Population-based survival for 20 adult malignancies was estimated for the UK and the Republic of Ireland. Data on adults (15-99 years) diagnosed between 1991 and 1999 in England, Scotland, Wales, Northern Ireland (1993-99) and the Republic of Ireland (1994-99) were analysed. All cases were followed up until the end of 2001. Relative survival was estimated by sex, period of diagnosis and country, and for the nine regions of England. Predicted survival was estimated using the hybrid approach. RESULTS: Overall, cancer survival in UK and Republic of Ireland improved during the 1990s, but there was geographic variation in survival across the UK and Republic of Ireland. Survival was generally highest in Ireland and Northern Ireland and lowest in England and Wales. Survival tended to be higher in Scotland for cancers for which early detection methods were in place. In England, survival tended to be lower in the north and higher in the south. CONCLUSIONS: The geographic variations in survival seen across the UK and Republic of Ireland are narrower than between these countries and comparable European countries. Artefact is likely to explain some, but not all of the differences across the UK and Republic of Ireland. Geographic differences in stage at diagnosis, co-morbidity and other clinical factors may also be relevant.

Recent trends in the incidence, geographical distribution, and survival from thyroid cancer in Wales, 1985-2010.

BACKGROUND: Previous studies of thyroid cancer incidence in Wales have given varying results with suggestions of an excess of cases in geographic areas that were previously exposed to the radioactive fallout from the 1986 Chernobyl nuclear reactor incident. Our objective in this study was to provide an up-to-date comprehensive analysis of time trends in the incidence, geographical distribution, and survival from thyroid cancer in Wales. METHODS: We identified thyroid cancer cases, registered from 1985 through 2010 in the Welsh Cancer Intelligence and Surveillance Unit (WCISU). Age standardized rates were determined from the European standard population. A Poisson regression model was fitted to assess temporal trends and rate ratios (RRs) and confidence intervals (CIs) were determined and compared across consecutive time periods: 1985-1997 and 1998-2010. Standardized incidence ratios were calculated for each of the 22 local authority areas. Relative survival and Kaplan-Meier curves were computed to analyze all cause and thyroid cancer-specific survival. RESULTS: A total of 1747 thyroid cancer cases were registered from 1985 to 2010. Age standardized incidence rates were 2.8 and 1.2 per 100,000 population per year for females and males respectively. Incidence rates increased with time (RR 1.3 [CI 1.2-1.5], p < 0.001; 1998-2010 vs. 1985-1997). The incidence of papillary cancer increased progressively over the study period (RR 2.22 [CI 1.91-2.57], p < 0.001; 1998-2010 vs. 1985-1997), while rates for other (nonpapillary) histological subtypes remained static (RR 0.95 [CI 0.84-1.08], p = 0.45; 1998-2010 vs. 1985-1997). We identified two geographical areas of increased incidence, but the spatial distribution of cases was inconsistent with exposure to radioactive fallout. Five-year relative survival from all-cause mortality improved from 74.2 [CI 66.8-80.1] in 1985-1989 to 82.6 [CI 77.1-86.9] in 2000-2004, but remained poor for patients over the age of 65 years (p < 0.001, > 65 years vs. 15-64 years) and patients with anaplastic thyroid cancer (p < 0.001; anaplastic vs. other histological varieties). CONCLUSIONS: The incidence of thyroid cancer has increased in Wales, predominantly due to an increase in papillary cancers. The current geographical distribution of cases does not support a radiation effect in the region. Survival has remained poor for patients over the age of 65 years and those with anaplastic carcinoma.

Leukaemia incidence in Welsh children linked with low level radiation--making sense of some erroneous results published in the media.

A series of self-published epidemiological reports purporting to show a major excess risk of leukaemia in pre-school children living near the Irish Sea coast of Wales have been presented in the media as evidence of the harmful effects of low level radiation arising from Sellafield. The Welsh Cancer Intelligence and Surveillance Unit (WCISU), the body responsible for population-based cancer information in Wales, can provide insights into the validity of these reports, which appear to be a consequence of various mistakes. This raises important questions about the research governance of such reports and the communication of scientific findings via the mass media. Without suitable safeguards the media are in danger of promulgating misinformation.