Sabine Siesling

Cancer survival in Europe 1999–2007 by country and age: results of EUROCARE-5—a population-based study

BACKGROUND Cancer survival is a key measure of the effectiveness of health-care systems. EUROCARE-the largest cooperative study of population-based cancer survival in Europe-has shown persistent differences between countries for cancer survival, although in general, cancer survival is improving. Major changes in cancer diagnosis, treatment, and rehabilitation occurred in the early 2000s. EUROCARE-5 assesses their effect on cancer survival in 29 European countries. METHODS In this retrospective observational study, we analysed data from 107 cancer registries for more than 10 million patients with cancer diagnosed up to 2007 and followed up to 2008. Uniform quality control procedures were applied to all datasets. For patients diagnosed 2000-07, we calculated 5-year relative survival for 46 cancers weighted by age and country. We also calculated country-specific and age-specific survival for ten common cancers, together with survival differences between time periods (for 1999-2001, 2002-04, and 2005-07). FINDINGS 5-year relative survival generally increased steadily over time for all European regions. The largest increases from 1999-2001 to 2005-07 were for prostate cancer (73.4% [95% CI 72.9-73.9] vs 81.7% [81.3-82.1]), non-Hodgkin lymphoma (53.8% [53.3-54.4] vs 60.4% [60.0-60.9]), and rectal cancer (52.1% [51.6-52.6] vs 57.6% [57.1-58.1]). Survival in eastern Europe was generally low and below the European mean, particularly for cancers with good or intermediate prognosis. Survival was highest for northern, central, and southern Europe. Survival in the UK and Ireland was intermediate for rectal cancer, breast cancer, prostate cancer, skin melanoma, and non-Hodgkin lymphoma, but low for kidney, stomach, ovarian, colon, and lung cancers. Survival for lung cancer in the UK and Ireland was much lower than for other regions for all periods, although results for lung cancer in some regions (central and eastern Europe) might be affected by overestimation. Survival usually decreased with age, although to different degrees depending on region and cancer type. INTERPRETATION The major advances in cancer management that occurred up to 2007 seem to have resulted in improved survival in Europe. Likely explanations of differences in survival between countries include: differences in stage at diagnosis and accessibility to good care, different diagnostic intensity and screening approaches, and differences in cancer biology. Variations in socioeconomic, lifestyle, and general health between populations might also have a role. Further studies are needed to fully interpret these findings and how to remedy disparities. FUNDING Italian Ministry of Health, European Commission, Compagnia di San Paolo Foundation, Cariplo Foundation.

Recent trends of cancer in Europe: A combined approach of incidence, survival and mortality for 17 cancer sites since the 1990s

INTRODUCTION We present a comprehensive overview of most recent European trends in population-based incidence of, mortality from and relative survival for patients with cancer since the mid 1990s. METHODS Data on incidence, mortality and 5-year relative survival from the mid 1990s to early 2000 for the cancers of the oral cavity and pharynx, oesophagus, stomach, colorectum, pancreas, larynx, lung, skin melanoma, breast, cervix, corpus uteri, ovary, prostate, testis, kidney, bladder, and Hodgkins disease were obtained from cancer registries from 21 European countries. Estimated annual percentages change in incidence and mortality were calculated. Survival trends were analyzed by calculating the relative difference in 5-year relative survival between 1990-1994 and 2000-2002 using data from EUROCARE-3 and -4. RESULTS Trends in incidence were generally favorable in the more prosperous countries from Northern and Western Europe, except for obesity related cancers. Whereas incidence of and mortality from tobacco-related cancers decreased for males in Northern, Western and Southern Europe, they increased for both sexes in Central Europe and for females nearly everywhere in Europe. Survival rates generally improved, mostly due to better access to specialized diagnostics, staging and treatment. Marked effects of organised or opportunistic screening became visible for breast, prostate and melanoma in the wealthier countries. Mortality trends were generally favourable, except for smoking related cancers. CONCLUSION Cancer prevention and management in Europe is moving in the right direction. Survival increased and mortality decreased through the combination of earlier detection, better access to care and improved treatment. Still, cancer prevention efforts have much to attain, especially in the domain of female smoking prevalence and the emerging obesity epidemic.

Rare cancers are not so rare: the rare cancer burden in Europe

PURPOSE Epidemiologic information on rare cancers is scarce. The project Surveillance of Rare Cancers in Europe (RARECARE) provides estimates of the incidence, prevalence and survival of rare cancers in Europe based on a new and comprehensive list of these diseases. MATERIALS AND METHODS RARECARE analysed population-based cancer registry (CR) data on European patients diagnosed from 1988 to 2002, with vital status information available up to 31st December 2003 (latest date for which most CRs had verified data). The mean population covered was about 162,000,000. Cancer incidence and survival rates for 1995-2002 and prevalence at 1st January 2003 were estimated. RESULTS Based on the RARECARE definition (incidence <6/100,000/year), the estimated annual incidence rate of all rare cancers in Europe was about 108 per 100,000, corresponding to 541,000 new diagnoses annually or 22% of all cancer diagnoses. Five-year relative survival was on average worse for rare cancers (47%) than common cancers (65%). About 4,300,000 patients are living today in the European Union with a diagnosis of a rare cancer, 24% of the total cancer prevalence. CONCLUSION Our estimates of the rare cancer burden in Europe provide the first indication of the size of the public health problem due to these diseases and constitute a useful base for further research. Centres of excellence for rare cancers or groups of rare cancers could provide the necessary organisational structure and critical mass for carrying out clinical trials and developing alternative approaches to clinical experimentation for these cancers.

Influence of tumour stage at breast cancer detection on survival in modern times: Population based study in 173 797 patients

Objectives To assess the influence of stage at breast cancer diagnosis, tumour biology, and treatment on survival in contemporary times of better (neo-)adjuvant systemic therapy. Design Prospective nationwide population based study. Setting Nationwide Netherlands Cancer Registry. Participants Female patients with primary breast cancer diagnosed between 1999 and 2012 (n=173 797), subdivided into two time cohorts on the basis of breast cancer diagnosis: 1999-2005 (n=80 228) and 2006-12 (n=93 569). Main outcome measures Relative survival was compared between the two cohorts. Influence of traditional prognostic factors on overall mortality was analysed with Cox regression for each cohort separately. Results Compared with 1999-2005, patients from 2006-12 had smaller (≤T1 65% (n=60 570) v 60% (n=48 031); P<0.001), more often lymph node negative (N0 68% (n=63 544) v 65% (n=52 238); P<0.001) tumours, but they received more chemotherapy, hormonal therapy, and targeted therapy (neo-adjuvant/adjuvant systemic therapy 60% (n=56 402) v 53% (n=42 185); P<0.001). Median follow-up was 9.8 years for 1999-2005 and 3.9 years for 2006-12. The relative five year survival rate in 2006-12 was 96%, improved in all tumour and nodal stages compared with 1999-2005, and 100% in tumours ≤1 cm. In multivariable analyses adjusted for age and tumour type, overall mortality was decreased by surgery (especially breast conserving), radiotherapy, and systemic therapies. Mortality increased with progressing tumour size in both cohorts (2006-12 T1c v T1a: hazard ratio 1.54, 95% confidence interval 1.33 to 1.78), but without a significant difference in invasive breast cancers until 1 cm (2006-12 T1b v T1a: hazard ratio 1.04, 0.88 to 1.22), and independently with progressing number of positive lymph nodes (2006-12 N1 v N0: 1.25, 1.17 to 1.32). Conclusions Tumour stage at diagnosis of breast cancer still influences overall survival significantly in the current era of effective systemic therapy. Diagnosis of breast cancer at an early tumour stage remains vital.OBJECTIVES To assess the influence of stage at breast cancer diagnosis, tumour biology, and treatment on survival in contemporary times of better (neo-)adjuvant systemic therapy. DESIGN Prospective nationwide population based study. SETTING Nationwide Netherlands Cancer Registry. PARTICIPANTS Female patients with primary breast cancer diagnosed between 1999 and 2012 (n=173,797), subdivided into two time cohorts on the basis of breast cancer diagnosis: 1999-2005 (n=80,228) and 2006-12 (n=93,569). MAIN OUTCOME MEASURES Relative survival was compared between the two cohorts. Influence of traditional prognostic factors on overall mortality was analysed with Cox regression for each cohort separately. RESULTS Compared with 1999-2005, patients from 2006-12 had smaller (≤ T1 65% (n=60,570) v 60% (n=48,031); P<0.001), more often lymph node negative (N0 68% (n=63,544) v 65% (n=52,238); P<0.001) tumours, but they received more chemotherapy, hormonal therapy, and targeted therapy (neo-adjuvant/adjuvant systemic therapy 60% (n=56,402) v 53% (n=42,185); P<0.001). Median follow-up was 9.8 years for 1999-2005 and 3.9 years for 2006-12. The relative five year survival rate in 2006-12 was 96%, improved in all tumour and nodal stages compared with 1999-2005, and 100% in tumours ≤ 1 cm. In multivariable analyses adjusted for age and tumour type, overall mortality was decreased by surgery (especially breast conserving), radiotherapy, and systemic therapies. Mortality increased with progressing tumour size in both cohorts (2006-12 T1c v T1a: hazard ratio 1.54, 95% confidence interval 1.33 to 1.78), but without a significant difference in invasive breast cancers until 1 cm (2006-12 T1b v T1a: hazard ratio 1.04, 0.88 to 1.22), and independently with progressing number of positive lymph nodes (2006-12 N1 v N0: 1.25, 1.17 to 1.32). CONCLUSIONS Tumour stage at diagnosis of breast cancer still influences overall survival significantly in the current era of effective systemic therapy. Diagnosis of breast cancer at an early tumour stage remains vital.

Improved survival of colon cancer due to improved treatment and detection: a nationwide population-based study in The Netherlands 1989–2006

BACKGROUND We described changes in treatment of colon cancer over time and the impact on survival in The Netherlands in the period 1989-2006. PATIENTS AND METHODS All 103,744 patients with invasive colon cancer during 1989-2006 in The Netherlands were included. Data were extracted from The Netherlands Cancer Registry. Trends in treatment over time were analysed and multivariable relative survival analysis was carried out. RESULTS The administration of adjuvant chemotherapy in stage III patients <75 years increased from 19% in 1989-1993 to 79% in 2004-2006 and from 1% to 19% in stage III patients ≥75 years. Among stage IV patients, resection rates of the primary tumour decreased from 72% to 63%, while chemotherapy administration increased from 23% to 64% in those <75 years. Survival increased from 52% to 58% in males and from 55% to 58% among females. Stage III patients with adjuvant chemotherapy exhibited a relative excess risk of 0.4 (95% confidence interval 0.4-0.4) compared with those without. Among stage IV patients, resection of primary tumour, palliative chemotherapy, and metastasectomy were important prognostic factors. CONCLUSIONS There were substantial improvements in management and survival of colon cancer from 1989 to 2006. Stage III disease patients with colon cancer experienced the largest improvement in survival, most likely related to the increased administration of adjuvant chemotherapy.

Trends in incidence of and mortality from cancer in The Netherlands in the period 1989–1998

This paper summarises the population-based major trends in cancer incidence and mortality in the period 1989-1998 in The Netherlands. Trends of the European age-adjusted incidence and mortality rates were estimated by the Estimated Annual Percentage Change (EAPC) method. Increases in incidence were found for cancer of the breast and lung for females. For males, an increase was observed for cancer of the prostate, colon, rectum and testis. In both groups, oesophageal and pharyngeal cancer increased, but that of stomach and gallbladder cancer decreased. The main increases in mortality were found for pharyngeal cancer in males, lung in females and oesophageal cancer in both sexes. Decreases were shown for stomach cancer for both sexes and lung cancer for males. Trends in incidence may be a result of changes in behaviour, smoking habits in preceding decades are related to the increase in lung cancer for females, and early detection, screening programmes increased the incidence for breast and prostate cancers. Decreases in mortality may be related to more successful treatment of leukaemia, Hodgkins lymphoma, colorectal and testicular cancers. Primary prevention of cancer remains important.

Survival of women with cancers of breast and genital organs in Europe 1999–2007: Results of the EUROCARE-5 study

BACKGROUND Survival differences across Europe for patients with cancers of breast, uterus, cervix, ovary, vagina and vulva have been documented by previous EUROCARE studies. In the present EUROCARE-5 study we update survival estimates and investigate changes in country-specific and over time survival, discussing their relationship with incidence and mortality dynamics for cancers for which organised screening programs are ongoing. METHODS We analysed cases archived in over 80 population-based cancer registries in 29 countries grouped into five European regions. We used the cohort approach to estimate 5-year relative survival (RS) for adult (⩾15years) women diagnosed 2000-2007, by age, country and region; and the period approach to estimate time trends (1999-2007) in RS for breast and cervical cancers. RESULTS In 2000-2007, 5-year RS was 57% overall, 82% for women diagnosed with breast, 76% with corpus uteri, 62% with cervical, 38% with ovarian, 40% with vaginal and 62% with vulvar cancer. Survival was low for patients resident in Eastern Europe (34% ovary-74% breast) and Ireland and the United Kingdom [Ireland/UK] (31-79%) and high for those resident in Northern Europe (41-85%) except Denmark. Survival decreased with advancing age: markedly for women with ovarian (71% 15-44years; 20% ⩾75years) and breast (86%; 72%) cancers. Survival for patients with breast and cervical cancers increased from 1999-2001 to 2005-2007, remarkably for those resident in countries with initially low survival. CONCLUSIONS Despite increases over time, survival for womens cancers remained poor in Eastern Europe, likely due to advanced stage at diagnosis and/or suboptimum access to adequate care. Low survival for women living in Ireland/UK and Denmark could indicate late detection, possibly related also to referral delay. Poor survival for ovarian cancer across the continent and over time suggests the need for a major research effort to improve prognosis for this common cancer.

Mass screening programmes and trends in cervical cancer in Finland and the Netherlands

With respect to cervical cancer management, Finland and the Netherlands are comparable in relevant characteristics, e.g., fertility rate, age‐of‐mother at first birth and a national screening programme for several years. The aim of this study is to compare trends in incidence of and mortality from cervical cancer in Finland and the Netherlands in relation to the introduction and intensity of the screening programmes. Therefore, incidence and mortality rates were calculated using the Cancer Registries of Finland and the Netherlands. Data on screening intensity were obtained from the Finnish Cancer Registry and the Dutch evaluation centre at ErasmusMC‐Rotterdam. Women aged 30–60 have been screened every 5 years, in Finland since 1992 and in the Netherlands since 1996. Screening protocols for smear taking and referral to the gynaecologist are comparable. Incidence and mortality rates have declined more in Finland. In 2003, age‐adjusted incidence and mortality in Finland were 4.0 and 0.9 and in the Netherlands 4.9 and 1.4 per 100,000 woman‐years, respectively. Excess smear use in the Netherlands was estimated to be 24 per 1,000 women during a 5‐year interval compared to 121 in Finland. The decline in mortality in Finland seems to be almost completely related to the screening programme whereas in the Netherlands it was initially considered to be a natural decline. Differences in risk factors might also play a role: the Netherlands has higher population density and higher percentages of immigrants and (female) smokers. The greater excess smear use in Finland might also have affected incidence.

Breast cancer survival in the US and Europe: A CONCORD high-resolution study.

Breast cancer survival is reportedly higher in the US than in Europe. The first worldwide study (CONCORD) found wide international differences in age‐standardized survival. The aim of this study is to explain these survival differences. Population‐based data on stage at diagnosis, diagnostic procedures, treatment and follow‐up were collected for about 20,000 women diagnosed with breast cancer aged 15–99 years during 1996–98 in 7 US states and 12 European countries. Age‐standardized net survival and the excess hazard of death up to 5 years after diagnosis were estimated by jurisdiction (registry, country, European region), age and stage with flexible parametric models. Breast cancers were generally less advanced in the US than in Europe. Stage also varied less between US states than between European jurisdictions. Early, node‐negative tumors were more frequent in the US (39%) than in Europe (32%), while locally advanced tumors were twice as frequent in Europe (8%), and metastatic tumors of similar frequency (5–6%). Net survival in Northern, Western and Southern Europe (81–84%) was similar to that in the US (84%), but lower in Eastern Europe (69%). For the first 3 years after diagnosis the mean excess hazard was higher in Eastern Europe than elsewhere: the difference was most marked for women aged 70–99 years, and mainly confined to women with locally advanced or metastatic tumors. Differences in breast cancer survival between Europe and the US in the late 1990s were mainly explained by lower survival in Eastern Europe, where low healthcare expenditure may have constrained the quality of treatment.

Improved survival among younger but not among older patients with Multiple Myeloma in the Netherlands, a population-based study since 1989

UNLABELLED This study assesses whether new treatment strategies developed in clinical trials translate into improved survival for multiple myeloma (MM) patients in the Netherlands. All patients diagnosed with MM in the Northern part of the Netherlands between 1989 and 2005 were retrieved from two regional population-based cancer registries. Information on study participation was derived from linkage with trial information systems. The effect of period of diagnosis (1989-1992, 1993-1996, 1997-2000, 2001-2005), age (<50, 50-65, 66-74, 75), gender, Salmon-Durie (SD) stage, trial participation and treatment on relative survival were studied. In total 4985 patients were included. When trial participation was analysed for exact periods in which trials were open, 16% of patients aged 65 years with SD-stage I and 38% with SD-stage II or III were enrolled compared to 2% of patients aged >65 years with SD-stage I and 5% with SD-stage II or III. Relative survival decreased with age (p<.001), with advanced stage (p<.001) and was better for patients enrolled in trials (p<.001). Five-year relative survival increased from 34% (95% confidence interval (95% CI) 28-39%) in 1989-1992 to 56% (95% CI 50-61%) in 2001-2005 for patients 65 years. The excess mortality was 37% lower in 2001-2005 than in 1989-1992 for these patients, adjusted for age, stage, trial participation and gender (p<.001). Survival did not improve for older patients. IN CONCLUSION MM survival improved among younger but not among older patients since the mid-1990s. The improved survival of younger patients coincided with increasing trial participation and increasing use of high-dose chemotherapy and autologous stem-cell transplantation.