Henrike E. Karim-Kos

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.

Trends of cutaneous melanoma in The Netherlands: increasing incidence rates among all Breslow thickness categories and rising mortality rates since 1989

BACKGROUND It has been debated that the epidemic of melanoma is largely due to overdiagnosis, since increases in incidence were mainly among thin melanomas and mortality rates remained stable. Our objective was to examine this controversy in The Netherlands. PATIENTS AND METHODS Information on newly diagnosed melanoma patients was obtained from The Netherlands Cancer Registry. European Standardized Rates and estimated annual percentage change were calculated for the period 1989-2008. Cohort-based, period-based and multivariate survival analyses were carried out. RESULTS The incidence rate of melanoma increased with 4.1% (95% confidence interval 3.6-4.5) annually. Incidence rates of both thin melanomas (≤ 1 mm) and thick melanomas (> 4 mm) increased since 1989. Mortality rates increased mainly in older patients (> 65 years). Ten-year relative survival of males improved significantly from 70% in 1989-1993 to 77% in 2004-2008 (P < 0.001) and for females the 10-year relative survival increased from 85% to 88% (P < 0.01). Recently diagnosed patients had a better prognosis even after adjusting for all known prognostic factors. CONCLUSION Since incidence of melanomas among all Breslow thickness categories increased as well as the mortality rates, the melanoma epidemic in The Netherlands seems to be real and not only due to overdiagnosis.

The validity of the mortality to incidence ratio as a proxy for site-specific cancer survival

BACKGROUND The complement of the cancer mortality to incidence ratio [1-(M/I)] has been suggested as a valid proxy for 5-year relative survival. Whether this suggestion holds true for all types of cancer has not yet been adequately evaluated. METHODS We used publicly available databases of cancer incidence, cancer mortality and relative survival to correlate relative survival estimates and 1-(M/I) estimates from Denmark, Finland, Iceland, Norway, Sweden, the USA and the Netherlands. We visually examined for which tumour sites 5-year relative survival cannot simply be predicted by the 1-(M/I) and evaluated similarities between countries. RESULTS Country-specific linear regression analyses show that there is no systematic bias in predicting 5-year relative survival by 1-(M/I) in five countries. There is a small but significant systematic underestimation of survival from prognostically poor tumour sites in two countries. Furthermore, the 1-(M/I) overestimates survival from oral cavity and liver cancer with >10% in at least two of the seven countries. By contrast, the proxy underestimates survival from soft tissue, bone, breast, prostate and oesophageal cancer, multiple myeloma and leukaemia with >10% in at least two of the seven countries. CONCLUSION The 1-(M/I) is a good approximation of the 5-year relative survival for most but not all tumour sites.

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.

Prostate cancer: Trends in incidence, survival and mortality in the Netherlands, 1989–2006

BACKGROUND Prostate cancer occurrence and stage distribution changed dramatically during the end of the 20th century. This study aimed to quantify and explain trends in incidence, stage distribution, survival and mortality in the Netherlands between 1989 and 2006. METHODS Population-based data from the nationwide Netherlands Cancer Registry and Causes of Death Registry were used. Annual incidence and mortality rates were calculated and age-adjusted to the European Standard Population. Trends in rates were evaluated by age, clinical stage and differentiation grade. RESULTS 120,965 men were newly diagnosed with prostate cancer between 1989 and 2006. Age-adjusted incidence rates increased from 63 to 104 per 100,000 person-years in this period. Two periods of increasing incidence rates could be distinguished with increases predominantly in cT2-tumours between 1989 and 1995 and predominantly in cT1c-tumours since 2001. cT4/N+/M+-tumour incidence rates decreased from 23 in 1993 to 18 in 2006. The trend towards earlier detection was accompanied by a lower mean age at diagnosis (from 74 in 1989 to 70 in 2006), increased frequency of treatment with curative intent and improved 5-year relative survival. Mortality rates decreased from 34 in 1996 to 26 in 2007. CONCLUSIONS The increase of prostate cancer incidence in the early 1990s was probably caused by increased prostate cancer awareness combined with diagnostic improvements (transrectal ultrasound, (thin) needle biopsies), but not PSA testing. The subsequent peak since 2001 is probably attributable to PSA testing. The decline in prostate cancer mortality from 1996 onwards may be the consequence of increased detection of cT2-tumours between 1989 and 1995. Unfortunately, data on the use of PSA tests and other prostate cancer diagnostics to support these conclusions are lacking.

Progress in Standard of Care Therapy and Modest Survival Benefits in the Treatment of Non-small Cell Lung Cancer Patients in the Netherlands in the Last 20 Years

Introduction: Lung cancer is the leading cause of cancer mortality worldwide. We analyzed changes in treatment and their potential effect on survival of non-small cell lung cancer (NSCLC) patients in the Netherlands. Methods: All NSCLC patients diagnosed during 1989–2009 (n=147,760) were selected from the population-based Netherlands Cancer Registry. Differences in treatment over time were tested by the Cochran-Armitage trend test. The effects of sex, age, histology, and treatment on relative survival were estimated in multivariable models. Follow-up was completed until January 1, 2010. Results: Between 1989 and 2009, the proportion of younger patients (younger than 75 years) with stage I undergoing surgery increased from 84 to 89% and among elderly (75 years or elder) from 35 to 49%; for stage II, this proportion decreased from 80 to 70% and remained about 25% in respectively younger and older patients. Adjuvant chemotherapy for stage II increased to from 0 to 24% in younger patients but remained less than 5% among the elderly. Chemoradiation increased from 8 to 43% among younger patients with stage III and from 1 to 13% among elderly. In stage IV, chemotherapy in younger patients increased from 10 to 54% and in elderly from 5 to 21%. Five-year relative survival of the total group increased from 14.8 to 17% (especially among females, younger patients, and within each stage), which could be partly explained by changes in treatment and better staging. Conclusions: Over a 20-year period, application of therapy, which is currently considered as standard, has improved. This resulted in small improvements in survival within all stages.

Progress against cancer in the Netherlands since the late 1980s: an epidemiological evaluation.

Progress against cancer through prevention and treatment is often measured by survival statistics only instead of analyzing trends in incidence, survival and mortality simultaneously because of interactive influences. This study combines these parameters of major cancers to provide an overview of the progress achieved in the Netherlands since 1989 and to establish in which areas action is needed. The population‐based Netherlands Cancer Registry and Statistics Netherlands provided incidence, 5‐year relative survival and mortality of 23 major cancer types. Incidence, survival and mortality changes were calculated as the estimated annual percentage change. Optimal progress was defined as decreasing incidence and/or improving survival accompanied by declining mortality, and deterioration as increasing incidence and/or deteriorating survival accompanied by increasing mortality rates. Optimal progress was observed in 12 of 19 cancer types among males: laryngeal, lung, stomach, gallbladder, colon, rectal, bladder, prostate and thyroid cancer, leukemia, Hodgkin and non‐Hodgkin lymphoma. Among females, optimal progress was observed in 12 of 21 cancers: stomach, gallbladder, colon, rectal, breast, cervical, uterus, ovarian and thyroid cancer, leukemia, Hodgkin and non‐Hodgkin lymphoma. Deterioration occurred in three cancer types among males: skin melanoma, esophageal and kidney cancer, and among females six cancer types: skin melanoma, oral cavity, pharyngeal, esophageal, pancreatic and lung cancer. Our conceptual framework limits misinterpretations from separate trends and generates a more balanced discussion on progress.

Trends in cervical cancer in the Netherlands until 2007: Has the bottom been reached?

We explored trends in incidence and mortality of cervical cancer by age, stage and morphology, and linked the observed trends to screening activities. Data was retrieved from the Netherlands Cancer Registry during 1989–2007 (incidence) and Statistics Netherlands during 1970–2007 (mortality). Trends were evaluated by calculating the estimated annual percentage change (EAPC). Joinpoint regression analysis was used to detect changes in trends. Cervical intraepithelial neoplasia (CIN) detection rates were calculated by data from “the nationwide network and registry of histo‐ and cytopathology” during 1990–2006. Total age‐adjusted incidence rate (European standardized rate (ESR)) was 7.9 per 100,000 woman years in 2007. During 1989–1998, incidence rates decreased with an EAPC of −1.3% (95% confidence interval (CI) −2.2 to −0.3), during 1998–2001 with −6.7% (95% CI: −16.4 to 4.1), and increased during 2001–2007 with 2.3% (95% CI: 0.4 to 4.2). Total mortality ESR was 1.9 per 100,000 woman years in 2007. Mortality rates decreased during 1970–1994 annually with −4.1% (95% CI: −4.6% to −3.7%), and with −2.6% (95% CI: −3.8% to −1.5%) during 1994–2007. The observed trend in total incidence is similar to the trend in squamous cell carcinomas in age group 35–54 years, suggesting that the observed trends are likely to be associated to changes in the screening program. This is supported by the trend in CINIII detection rates. In conclusion, incidence and mortality overall decreased and leveled off. On top of that there was an extra decrease that was compensated by a following recent increase in incidence, probably resulting from reorganization of the Dutch screening program.

Explanations for worsening cancer survival.

If cancer survival is reported to be worsening over time or inferior compared to other countries, politicians and health-care workers may get blamed because suboptimal care is presumed to be the cause. Yet, a variety of reasons exist for cancer survival statistics to change for the worse, of which deterioration of care is only one. Another explanation is that the improved diagnosis of premalignant lesions causes survival statistics to reflect only the most aggressive cancers—those with the poorest prognosis. In addition, deleterious changes in the distribution of prognostic factors and in the distribution of sociodemographic characteristics may negatively affect survival proportions. In this article, we identify the pitfalls that might be encountered in comparisons of published, population-based survival data from different time periods or populations.

Socioeconomic Inequalities in Neglected Tropical Diseases: A Systematic Review

Background Neglected tropical diseases (NTDs) are generally assumed to be concentrated in poor populations, but evidence on this remains scattered. We describe within-country socioeconomic inequalities in nine NTDs listed in the London Declaration for intensified control and/or elimination: lymphatic filariasis (LF), onchocerciasis, schistosomiasis, soil-transmitted helminthiasis (STH), trachoma, Chagas’ disease, human African trypanosomiasis (HAT), leprosy, and visceral leishmaniasis (VL). Methodology We conducted a systematic literature review, including publications between 2004–2013 found in Embase, Medline (OvidSP), Cochrane Central, Web of Science, Popline, Lilacs, and Scielo. We included publications in international peer-reviewed journals on studies concerning the top 20 countries in terms of the burden of the NTD under study. Principal findings We identified 5,516 publications, of which 93 met the inclusion criteria. Of these, 59 papers reported substantial and statistically significant socioeconomic inequalities in NTD distribution, with higher odds of infection or disease among poor and less-educated people compared with better-off groups. The findings were mixed in 23 studies, and 11 studies showed no substantial or statistically significant inequality. Most information was available for STH, VL, schistosomiasis, and, to a lesser extent, for trachoma. For the other NTDs, evidence on their socioeconomic distribution was scarce. The magnitude of inequality varied, but often, the odds of infection or disease were twice as high among socioeconomically disadvantaged groups compared with better-off strata. Inequalities often took the form of a gradient, with higher odds of infection or disease each step down the socioeconomic hierarchy. Notwithstanding these inequalities, the prevalence of some NTDs was sometimes also high among better-off groups in some highly endemic areas. Conclusions While recent evidence on socioeconomic inequalities is scarce for most individual NTDs, for some, there is considerable evidence of substantially higher odds of infection or disease among socioeconomically disadvantaged groups. NTD control activities as proposed in the London Declaration, when set up in a way that they reach the most in need, will benefit the poorest populations in poor countries.