Improved survival for patients with de novo metastatic prostate cancer in the last 20 years.

INTRODUCTION: During recent years, several new life-prolonging therapeutic options have been introduced for patients with metastatic prostate cancer (mPCa). The aim of the present study was to evaluate the changes in the survival of patients diagnosed with mPCa prior to and in the early period of the implementation of these new agents. PATIENTS AND METHODS: The study population consisted of 207 men diagnosed in 1997 and 316 men diagnosed in the period 2007-2013 with de novo mPCa and managed with initial endocrine therapy. Men were followed for overall survival and PCa-specific survival. RESULTS: At the time of diagnosis, men diagnosed in the period 2007-2013 had less co-morbidity, lower prostrate-specific antigen levels and lower clinical tumour categories than men diagnosed in 1997. A significantly higher proportion of men diagnosed in 1997 were managed with surgical castration (57% versus 9%). Only one patient diagnosed in 1997 received second-line therapy compared with 81 men (26%) diagnosed in the period 2007-2013. The median overall survival was significantly longer for men diagnosed between 2007 and 2013 compared with men diagnosed in 1997 (39.4 months versus 24.2 months, p < 0.0001). Likewise, the cumulative incidence of PCa-specific death was higher among men diagnosed in 1997 compared with men diagnosed between 2007 and 2013, with 5-year cumulative incidences of 72% and 47%, respectively (p < 0.0001). CONCLUSION: Survival in men diagnosed with metastatic PCa has improved significantly over time. The improved survival can in part be explained by lead-time bias, but also by the introduction of new life-prolonging treatments.

Trends in cancer in the elderly population in Denmark, 1980-2012.

BACKGROUND: Age is the strongest risk factor for developing cancer. The aim of the present analysis is to give an overview of the trends in cancer incidence, mortality, prevalence, and relative survival in Denmark from 1980 to 2012 focusing on age, comparing persons aged 70 years or more with those aged less than 70 years. MATERIAL AND METHODS: Data derived from the NORDCAN database with comparable data on cancer incidence, mortality, prevalence and relative survival in the Nordic countries. The Danish data originate from the Danish Cancer Registry and the Danish Cause of Death Registry with follow-up for death or emigration until the end of 2013. RESULTS: Incidence and mortality rates of all sites, but non-melanoma skin cancer, were higher and relative survival was lower among persons aged 70 years or more than those aged less than 70 years. The age distribution (age group-specific percentages of total number of incident cases) remained constant over time while the percentage of persons dying from cancer decreased with time up to the age of 79 years but increased for those aged 80 years or more, in whom about a third of all cancer deaths occurred in 2012. In 2003-2007, the five-year relative survival was 48% for men aged 70-79 years, 38% for men aged 80-89 years, and 29% for men aged 90 years or more and the corresponding figures for women were 46%, 39%, and 36%, respectively. There was a substantial increase in the number of prevalent cancer cases aged 70 years or older, especially among those aged 90 years or more. CONCLUSION: An increase in elderly cancer patients is expected over the coming 20 years due to an increasing elderly population. Healthcare providers need to focus on developing specific strategies for treatment of elderly cancer patients in the future.

Less pitfalls and variation in population based cancer survival comparisons within the European Union: Lessons from colorectal cancer patients in neighbouring regions in Denmark and Germany - The Fehmarn Belt project.

BACKGROUND: International comparisons of cancer registry based survival are often used as a marker of the performance of health care services on cancer. These are debated for comparability, validity and lack of detail with respect to prognostic factors. With a view to cross border collaborative cancer research and care in the European Union (EU), we used the established routine registration systems for cancer in the neighbouring regions Zealand, Denmark, and Schleswig-Holstein, Germany, to study if available routine registration suffices for the study of diagnosis, treatment and follow-up for colorectal cancer patients. The aim was to assess to which extent differences in survival between the regions could be explained. METHODS: Colorectal cancer patients recorded 2004-2010 in Schleswig-Holstein (colon: 10,631; rectum 5683) and region Zealand (colon: 3205; rectum 1747) were studied. Excluding cases aged 90+ or only known from death certificates, one- and four-year relative survival by stage for the periods 2004-2006 and 2007-2009 (one-year) were calculated. FINDINGS: A high proportion of patients in Schleswig-Holstein were known only from death certificates (colon 11%; rectum 6.9%) compared to <0.3% in region Zealand. Colon cancer incidence (asr-e) (men 36; women 28) and mortality (men 12; women 8.7) in Schleswig-Holstein were 10 per 100,000 lower than in Zealand; minor differences were seen for rectum cancer. One and four-year overall survival increased in both regions but was superior in Schleswig-Holstein. For patients with reported stage I-III, negligible differences in survival were seen; with further restriction to patients with treatment reported, even so in stage IV patients 2007-2009. INTERPRETATION: Improved data quality and comparability than presently used in the large international survival studies is needed. If stage and treatment is taken into account, more valid international comparisons of cancer survival are possible. Reporting and follow-up must be improved and cases only known from death certificates (DCO) minimised. A high proportion DCO (excluded from analyses) may produce higher survival, whereas a low the opposite. Co-morbidity and socio-economic status should be included alongside other prognostic variables in survival studies. Barriers towards proper follow-up and monitoring of outcome e.g. privacy legislation must be considered with a view to future patient mobility.

Survival of patients diagnosed with cancer in the Nordic countries up to 1999-2003 followed to the end of 2006. A critical overview of the results.

UNLABELLED: Differences in Nordic cancer patient survival observed today originate from the 1970s, but were first identified in a mortality prediction from 1995. This paper provides timely comparisons of survival using NORDCAN, a database with comparable information from the Nordic cancer registries. Elucidation of the differences is important when monitoring cancer care generally and evaluating the impact of cancer plans. MATERIAL AND METHODS: The NORDCAN database 1964-2003 with follow-up for death through 2006, was used to analyse incidence, mortality, and survival for all NORDCAN cancer sites. We analysed 5-year relative survival and excess mortality rates in the first three months and 2-5 years after diagnosis. RESULTS: The time trends in survival 1989-2003 were largely similar between the Nordic countries with increases in 14 sites among men and 16 among women. In all countries the excess mortality rates were highest in the first three months after diagnosis, but decreased to similar levels across all countries 2-5 years after diagnosis. Comparing countries excess mortality was highest in Denmark irrespective of follow-up period. Lower survival was observed for Danish cancer patients in 23 of the 33 cancer sites in men and 26 of 35 sites in women. Low and similar levels of survival were observed for cancers of the oesophagus, lung, liver and pancreas, while an 8-10 percentage point difference in survival was found between countries for colorectal cancer. CONCLUSION: The notable differences in Nordic cancer patient survival can be linked to national variations in risk factors, co-morbidity, and the implementation of screening. Improved treatment and primary prevention, in particular the targeting of tobacco and alcohol use, is required to improve cancer control. The recently-initiated cancer plans in Denmark and Norway are yet to show an observable effect on the corresponding cancer survival.

Trends in the overall survival of cancer patients diagnosed 1964-2003 in the Nordic countries followed up to the end of 2006: the importance of case-mix.

AIM: Overall survival after cancer is frequently used when assessing the health care service performance as a whole. While used by the public, politicians, and the media, it is often discarded by clinicians and epidemiologists due to the heterogeneous mix of different cancers, risk factors and treatment modalities. We studied the trend in the Nordic 5-year relative survival and excess mortality for all cancers combined to see if the impact of case-mix and variations between countries in diagnostic methods such as breast screening and PSA testing could explain the lower survival in Denmark. MATERIAL AND METHODS: From the NORDCAN database 1964-2003, we defined two cohorts of cancer patients, one excluding non-melanoma skin cancer and another also excluding breast and prostate cancer. We estimated age-standardised incidence and mortality rates, 5-year relative survival, and excess mortality rates for varying follow-up periods, and age-specific 5-year relative survival by country, sex and 5-year diagnostic period. RESULTS: Prostate cancer is the main driver of the incidence increase in men, as do breast cancer in women, whereas cancer mortality in all Nordic countries is declining. The 5-year relative survival ratios are increasing in each Nordic population, but less so in Denmark. Country differences in survival stem mainly from follow-up periods immediately after diagnosis. Adjusting for the case-mix of diagnoses diminished differences a little while exclusion of breast and prostate cancer reduced the gap between countries in survival and excess mortality more considerably, yet post-adjustment, Danish patients still fare worse during the first three months after diagnosis. CONCLUSION: Adjustment for case-mix and exclusion of sites where diagnostic procedures change the pattern of incidence is important when comparing overall cancer survival across countries, but the correction only explains part of the observed differences in survival. Other factors such as stage at presentation, co-morbidity, tobacco and alcohol consumption are likely contributors.

Colorectal cancer survival in the Nordic countries and the United Kingdom: excess mortality risk analysis of 5 year relative period survival in the period 1999 to 2000.

A deficit in colorectal cancer survival in Denmark and in the UK compared to Sweden, Norway and Finland was found in the EUROCARE studies. We set out to explore if these differences still exist. Patients diagnosed with colorectal cancer as their first invasive cancer at age 15-89 in the period 1994-2000 were identified using data from 11 cancer registries in the UK and from four Nordic countries. Five-year relative period survival using deaths in 1999-2000 following cancers diagnosed in 1994-2000 was analysed with excess mortality risk modelling. Follow-up time since diagnosis with age as an effect-modifier in the first half year was the most important factor with the highest excess risk of death immediately after diagnosis and with higher age and decreasing with length of follow-up. Variations between countries were bigger in the first half year following diagnosis than in the interval 0.5-5 years with about 30% higher risk in UK and Denmark. The differences between countries are still substantial and the order has not changed, even if the five year relative survival has improved since the EUROCARE studies. Patient management, diagnostics, and comorbidity likely explain the excess deaths in UK and Denmark during the first 6 months. The effect of stage and quality of management and treatment should be examined in population based studies with detailed patient information. Use of more detailed age-intervals than conventionally applied in survival studies proved to be important in statistical modelling and is recommended for future studies.

Depleted uranium and cancer in Danish Balkan veterans deployed 1992-2001.

In a population based retrospective cohort study we studied cancer risk in Danish soldiers deployed to the war in the Balkans. In particular, leukaemia, earlier linked to ammunition enforced with depleted uranium (DU) in other deployed soldiers, was a concern. Military personnel, 13,552 men and 460 women, without known cancer at first deployment to the Balkans, January 1, 1992 to December 31, 2001 were followed through December 2002. We found 96cases of cancer, 84 among men (standardised incidence ratio (SIR) 0.9) and 12 among women (SIR 1.7). Only four male bone cancers (SIR 6.0), with three during the first year of follow-up, exceeded expectations. Earlier reports on increased risk of leukaemia and testis cancer among deployed military personnel to the Balkans are not corroborated by our study. Quick and open communication about potential risks, a health check, a telephone counselling line and careful monitoring, and diminished anxiety all helped contain the 'Balkan syndrome' in Denmark.

Education and employment prospects in cerebral palsy.

Parents and paediatric neurologists need information on the long-term social prognosis of children with cerebral palsy (CP). No large population-based study has been performed on this topic. On 31 December 1999, to find predictors in childhood of subsequent education and employment, 819 participants with CP born between 1965 and 1978 (471 males; mean age 28y 10 mo, SD 4y, range 21 to 35y) in the Danish Cerebral Palsy Registry were compared with 4406 controls without CP born between 1965 and 1978 (2546 males; mean age 28y 10 mo, SD 4y, range 21 to 35y). Diagnostic subtypes of the 819 participants with CP were: 31% hemiplegia, 43% diplegia, 18% tetraplegia, and 8% other types. Level of motor impairment with respect to walking ability was: 62% able to walk without assistance, 21% with assistance, and 16% not able to walk (for 1% of study children walking ability was not known). Relevant information was obtained from Denmark's unique registries. Of the participants with CP, 33% vs 77% of controls, had education beyond lower secondary school (i.e. after age 15-16y), 29% were competitively employed (vs 82% of controls), 5% were studying, and 5% had specially created jobs. Excluding participants with CP with an estimated developmental quotient (DQ) of less than 50 or inability to walk at age 5 to 6 years, the odds ratios (multivariate analysis) for not being competitively employed were 1.9 for diplegia versus hemiplegia, 22.5 for DQ 50 to 85 versus DQ greater than 85, and 3.7 for those with epilepsy versus those without epilepsy. The severity of motor impairment among participants with CP able to walk had just a minor influence. Only half the participants with CP who had attended mainstream schooling were employed. In conclusion several childhood characteristics seemed to predict long-term social prognosis.