Breast cancer survival and stage at diagnosis in Australia, Canada, Denmark, Norway, Sweden and the UK, 2000-2007:A population-based study

Background: We investigate whether differences in breast cancer survival in six high-income countries can be explained by differences in stage at diagnosis using routine data from population-based cancer registries. Methods: We analysed the data on 257 362 women diagnosed with breast cancer during 2000-7 and registered in 13 population-based cancer registries in Australia, Canada, Denmark, Norway, Sweden and the UK. Flexible parametric hazard models were used to estimate net survival and the excess hazard of dying from breast cancer up to 3 years after diagnosis.Results:Age-standardised 3-year net survival was 87-89% in the UK and Denmark, and 91-94% in the other four countries. Stage at diagnosis was relatively advanced in Denmark: only 30% of women had Tumour, Nodes, Metastasis (TNM) stage I disease, compared with 42-45% elsewhere. Women in the UK had low survival for TNM stage III-IV disease compared with other countries. Conclusion: International differences in breast cancer survival are partly explained by differences in stage at diagnosis, and partly by differences in stage-specific survival. Low overall survival arises if the stage distribution is adverse (e.g. Denmark) but stage-specific survival is normal; or if the stage distribution is typical but stage-specific survival is low (e.g. UK). International differences in staging diagnostics and stage-specific cancer therapies should be investigated. © 2013 Cancer Research UK. All rights reserved.

Lung cancer survival and stage at diagnosis in Australia, Canada, Denmark, Norway, Sweden and the UK:A population-based study, 2004-2007

Background: The authors consider whether differences in stage at diagnosis could explain the variation in lung cancer survival between six developed countries in 2004-2007. Methods: Routinely collected population-based data were obtained on all adults (15-99 years) diagnosed with lung cancer in 2004-2007 and registered in regional and national cancer registries in Australia, Canada, Denmark, Norway, Sweden and the UK. Stage data for 57 352 patients were consolidated from various classification systems. Flexible parametric hazard models on the log cumulative scale were used to estimate net survival at 1 year and the excess hazard up to 18 months after diagnosis. Results: Age-standardised 1-year net survival from non-small cell lung cancer ranged from 30% (UK) to 46% (Sweden). Patients in the UK and Denmark had lower survival than elsewhere, partly because of a more adverse stage distribution. However, there were also wide international differences in stage-specific survival. Net survival from TNM stage I non-small cell lung cancer was 16% lower in the UK than in Sweden, and for TNM stage IV disease survival was 10% lower. Similar patterns were found for small cell lung cancer. Conclusions: There are comparability issues when using population-based data but, even given these constraints, this study shows that, while differences in stage at diagnosis explain some of the international variation in overall lung cancer survival, wide disparities in stage-specific survival exist, suggesting that other factors are also important such as differences in treatment. Stage should be included in international cancer survival studies and the comparability of population-based data should be improved.

Stage at diagnosis and colorectal cancer survival in six high-income countries:A population-based study of patients diagnosed during 2000-2007

Background. Large international differences in colorectal cancer survival exist, even between countries with similar healthcare. We investigate the extent to which stage at diagnosis explains these differences. Methods. Data from population-based cancer registries in Australia, Canada, Denmark, Norway, Sweden and the UK were analysed for 313 852 patients diagnosed with colon or rectal cancer during 2000-2007. We compared the distributions of stage at diagnosis. We estimated both stage-specific net survival and the excess hazard of death up to three years after diagnosis, using flexible parametric models on the log-cumulative excess hazard scale. Results. International differences in colon and rectal cancer stage distributions were wide: Denmark showed a distribution skewed towards later-stage disease, while Australia, Norway and the UK showed high proportions of 'regional' disease. One-year colon cancer survival was 67% in the UK and ranged between 71% (Denmark) and 80% (Australia and Sweden) elsewhere. For rectal cancer, one-year survival was also low in the UK (75%), compared to 79% in Denmark and 82-84% elsewhere. International survival differences were also evident for each stage of disease, with the UK showing consistently lowest survival at one and three years. Conclusion. Differences in stage at diagnosis partly explain international differences in colorectal cancer survival, with a more adverse stage distribution contributing to comparatively low survival in Denmark. Differences in stage distribution could arise because of differences in diagnostic delay and awareness of symptoms, or in the thoroughness of staging procedures. Nevertheless, survival differences also exist for each stage of disease, suggesting unequal access to optimal treatment, particularly in the UK. © 2013 Informa Healthcare.

Prescribing for weight loss in primary care: evidence from a population based study

Background Taking antiobesity medication can be a cost effective way to lose weight. Uptake is determined in part by a General Practitioner's decision to prescribe weight loss medication and, in part, by patient preference. It is probable that the latter may indicate a patient's readiness to lose weight.


Methods Analysis of cross-sectional data (from February 2003 to March 2011) from a population based prescribing database (~1.75 million people) using an adjusted Poisson regression.


Results The number of antiobesity medications increased from 23.4 per 1000 population in 2004 to 30.7 per 1000 population in 2010 and was three times higher in female than in male subjects. Against this background, a marked seasonal variation in the number of antiobesity medications dispensed was evident (p<0.001), peaking in June/July with a trough in December/January (±8.0% peak to trough). The seasonal component was stronger in female subjects, ±11.2% peak to trough, compared with ±3.5% for male subjects.


Conclusions Obese patients, particularly women, increase their uptake of weight loss medication in the months leading up to the summer holiday period. The period prior to the summer may represent a time that health professionals could promote increased participation of obese patients in weight loss programmes.

Risk of Several Cancers is Higher in Urban Areas after Adjusting for Socioeconomic Status. Results from a Two-Country Population-Based Study of 18 Common Cancers

Some studies suggest that there are urban-rural variations in cancer incidence but whether these simply reflect urban-rural socioeconomic variation is unclear. We investigated whether there were urban-rural variations in the incidence of 18 cancers, after adjusting for socioeconomic status. Cancers diagnosed between 1995 and 2007 were extracted from the population-based National Cancer Registry Ireland and Northern Ireland Cancer Registry and categorised by urban-rural status, based on population density of area of residence at diagnosis (rural 15 people per hectare). Relative risks (RR) were calculated by negative binomial regression, adjusting for age, country and three area-based markers of socioeconomic status. Risks were significantly higher in both sexes in urban than rural residents with head and neck (males RR urban vs. rural = 1.53, 95 % CI 1.42-1.64; females RR = 1.29, 95 % CI 1.15-1.45), esophageal (males 1.21, 1.11-1.31; females 1.21, 1.08-1.35), stomach (males 1.36, 1.27-1.46; females 1.19, 1.08-1.30), colorectal (males 1.14, 1.09-1.18; females 1.04, 1.00-1.09), lung (males 1.54, 1.47-1.61; females 1.74, 1.65-1.84), non-melanoma skin (males 1.13, 1.10-1.17; females 1.23, 1.19-1.27) and bladder (males 1.30, 1.21-1.39; females 1.31, 1.17-1.46) cancers. Risks of breast, cervical, kidney and brain cancer were significantly higher in females in urban areas. Prostate cancer risk was higher in rural areas (0.94, 0.90-0.97). Other cancers showed no significant urban-rural differences. After adjusting for socioeconomic variation, urban-rural differences were evident for 12 of 18 cancers. Variations in healthcare utilization and known risk factors likely explain some of the observed associations. Explanations for others are unclear and, in the interests of equity, warrant further investigation. © 2014 The New York Academy of Medicine.

Drugs affecting the renin-angiotensin system and survival from cancer: a population based study of breast, colorectal and prostate cancer patient cohorts

Background: Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) are commonly prescribed to the growing number of cancer patients (more than two million in the UK alone) often to treat hypertension. However, increased fatal cancer in ARB users in a randomized trial and increased breast cancer recurrence rates in ACEI users in a recent observational study have raised concerns about their safety in cancer patients. We investigated whether ACEI or ARB use after breast, colorectal or prostate cancer diagnosis was associated with increased risk of cancer-specific mortality.

Methods: Population-based cohorts of 9,814 breast, 4,762 colorectal and 6,339 prostate cancer patients newly diagnosed from 1998 to 2006 were identified in the UK Clinical Practice Research Datalink and confirmed by cancer registry linkage. Cancer-specific and all-cause mortality were identified from Office of National Statistics mortality data in 2011 (allowing up to 13 years of follow-up). A nested case–control analysis was conducted to compare ACEI/ARB use (from general practitioner prescription records) in cancer patients dying from cancer with up to five controls (not dying from cancer). Conditional logistic regression estimated the risk of cancer-specific, and all-cause, death in ACEI/ARB users compared with non-users.

Results: The main analysis included 1,435 breast, 1,511 colorectal and 1,184 prostate cancer-specific deaths (and 7,106 breast, 7,291 colorectal and 5,849 prostate cancer controls). There was no increase in cancer-specific mortality in patients using ARBs after diagnosis of breast (adjusted odds ratio (OR) = 1.06 95% confidence interval (CI) 0.84, 1.35), colorectal (adjusted OR = 0.82 95% CI 0.64, 1.07) or prostate cancer (adjusted OR = 0.79 95% CI 0.61, 1.03). There was also no evidence of increases in cancer-specific mortality with ACEI use for breast (adjusted OR = 1.06 95% CI 0.89, 1.27), colorectal (adjusted OR = 0.78 95% CI 0.66, 0.92) or prostate cancer (adjusted OR = 0.78 95% CI 0.66, 0.92).

Conclusions: Overall, we found no evidence of increased risks of cancer-specific mortality in breast, colorectal or prostate cancer patients who used ACEI or ARBs after diagnosis. These results provide some reassurance that these medications are safe in patients diagnosed with these cancers.

Keywords: Colorectal cancer; Breast cancer; Prostate cancer; Mortality; Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers

Oesophageal adenocarcinoma and prior diagnosis of Barrett's oesophagus: a population-based study

Objective: Endoscopic surveillance of Barrett's oesophagus (BO) provides an opportunity to detect early stage oesophageal adenocarcinoma (OAC). We sought to determine the proportion of OAC patients with a prior diagnosis of BO on a population basis and to evaluate the influence of a prior diagnosis of BO on survival, taking into account lead and length time biases.

Design: A retrospective population-based study of all OAC patients in Northern Ireland between 2003 and 2008. A prior BO diagnosis was determined by linkage to the Northern Ireland BO register. Stage distribution at diagnosis and histological grade were compared between patients with and without a prior BO diagnosis. Overall survival, using Cox models, was compared between patients with and without a prior BO diagnosis. The effect of adjusting the survival differences for histological grade and estimates of lead and length time bias was assessed.

Results: There were 716 OAC cases, 52 (7.3%) of whom had a prior BO diagnosis. Patients with a prior BO diagnosis had significantly lower tumour stage (44.2% vs 11.1% had stage 1 or 2 disease; p<0.001), a higher rate of surgical resection (50.0% vs 25.5%; p<0.001) and had a higher proportion of low/intermediate grade tumours (46.2% vs 26.5%; p=0.011). A prior BO diagnosis was associated with significantly better survival (HR for death 0.39; 95% CI 0.27 to 0.58), which was minimally influenced by adjustment for age, sex and tumour grade (adjusted HR 0.44; 95% CI 0.30 to 0.64). Correction for lead time bias attenuated but did not abolish the survival benefit (HR 0.65; 95% CI 0.45 to 0.95) and further adjustment for length time bias had little effect.

Conclusions: The proportion of OAC patients with a prior diagnosis of BO is low; however, prior identification of BO is associated with an improvement in survival in OAC patients.

Survival for haematological malignancies in Europe between 1997 and 2008 by region and age: results of EUROCARE-5, a population-based study

Background: More effective treatments have become available for haematological malignancies from the early 2000s, but few large-scale population-based studies have investigated their effect on survival. Using EUROCARE data, and HAEMACARE morphological groupings, we aimed to estimate time trends in population-based survival for 11 lymphoid and myeloid malignancies in 20 European countries, by region and age. Methods: In this retrospective observational study, we included patients (aged 15 years and older) diagnosed with haematological malignancies, diagnosed up to Dec 31, 2007, and followed up to Dec 31, 2008. We used data from the 30 cancer registries (across 20 countries) that provided continuous incidence and good quality data from 1992 to 2007. We used a hybrid approach to estimate age-standardised and age-specific 5-year relative survival, for each malignancy, overall and for five regions (UK, and northern, central, southern, and eastern Europe), and four 3-year periods (1997–99, 2000–02, 2003–05, 2006–08). For each malignancy, we also estimated the relative excess risk of death during the 5 years after diagnosis, by period, age, and region. Findings: We analysed 560 444 cases. From 1997–99 to 2006–08 survival increased for most malignancies: the largest increases were for diffuse large B-cell lymphoma (42·0% [95% CI 40·7–43·4] to 55·4% [54·6–56·2], p<0·0001), follicular lymphoma (58·9% [57·3–60·6] to 74·3% [72·9–75·5], p<0·0001), chronic myeloid leukaemia (32·3% [30·6–33·9] to 54·4% [52·5–56·2], p<0·0001), and acute promyelocytic leukaemia (50·1% [43·7–56·2] to 61·9% [57·0–66·4], p=0·0038, estimate not age-standardised). Other survival increases were seen for Hodgkin's lymphoma (75·1% [74·1–76·0] to 79·3% [78·4–80·1], p<0·0001), chronic lymphocytic leukaemia/small lymphocytic lymphoma (66·1% [65·1–67·1] to 69·0% [68·1–69·8], p<0·0001), multiple myeloma/plasmacytoma (29·8% [29·0–30·6] to 39·6% [38·8–40·3], p<0·0001), precursor lymphoblastic leukaemia/lymphoma (29·8% [27·7–32·0] to 41·1% [39·0–43·1], p<0·0001), acute myeloid leukaemia (excluding acute promyelocytic leukaemia, 12·6% [11·9–13·3] to 14·8% [14·2–15·4], p<0·0001), and other myeloproliferative neoplasms (excluding chronic myeloid leukaemia, 70·3% [68·7–71·8] to 74·9% [73·8–75·9], p<0·0001). Survival increased slightly in southern Europe, more in the UK, and conspicuously in northern, central, and eastern Europe. However, eastern European survival was lower than that for other regions. Survival decreased with advancing age, and increased with time only slightly in patients aged 75 years or older, although a 10% increase in survival occurred in elderly patients with follicular lymphoma, diffuse large B-cell lymphoma, and chronic myeloid leukaemia. Interpretation: These trends are encouraging. Widespread use of new and more effective treatment probably explains much of the increased survival. However, the persistent differences in survival across Europe suggest variations in the quality of care and availability of the new treatments. High-resolution studies that collect data about stage at diagnosis and treatments for representative samples of cases could provide further evidence of treatment effectiveness and explain geographic variations in survival.

Common community-acquired infections and subsequent risk of multiple myeloma: a population-based study

The role of bacteria and viruses as aetiological agents in the pathogenesis of cancer has been well established for several sites, including a number of haematological malignancies. Less clear is the impact of such exposures on the subsequent development of multiple myeloma (MM). Using the population-based U.S. Surveillance Epidemiology and End Results-Medicare dataset, 15,318 elderly MM and 200,000 controls were identified to investigate the impact of 14 common community-acquired infections and risk of MM. Odds ratios (ORs) and associated 95% confidence intervals (CIs) were adjusted for sex, age and calendar year of selection. The 13-month period prior to diagnosis/selection was excluded. Risk of MM was increased by 5-39% following Medicare claims for eight of the investigated infections. Positive associations were observed for several infections including bronchitis (adjusted OR 1.14, 95% CI 1.09-1.18), sinusitis (OR 1.15, 95% CI 1.10-1.20) pneumonia (OR 1.27, 95% CI 1.21-1.33), herpes zoster (OR 1.39, 95% CI 1.29-1.49) and cystitis (OR 1.09, 95% CI 1.05-1.14). Each of these infections remained significantly elevated following the exclusion of more than 6 years of claims data. Exposure to infectious antigens may therefore play a role in the development of MM. Alternatively, the observed associations may be a manifestation of an underlying immune disturbance present several years prior to MM diagnosis and thereby part of the natural history of disease progression.