Cancer incidence and mortality trends in France over 1990-2018 for solid tumors: the sex gap is narrowing.

OBJECTIVE: To analyze trends in cancer incidence and mortality (France, 1990-2018), with a focus on men-women disparities. METHODS: Incidence data stemmed from cancer registries (FRANCIM) and mortality data from national statistics (CépiDc). Incidence and mortality rates were modelled using bidimensional penalized splines of age and year (at diagnosis and at death, respectively). Trends in age-standardized rates were summarized by the average annual percent changes (AAPC) for all-cancers combined, 19 solid tumors, and 8 subsites. Sex gaps were indicated using male-to-female rate ratios (relative difference) and male-to-female rate differences (absolute difference) in 1990 and 2018, for incidence and mortality, respectively. RESULTS: For all-cancers, the sex gap narrowed over 1990-2018 in incidence (1.6 to 1.2) and mortality (2.3 to 1.7). The largest decreases of the male-to-female incidence rate ratio were for cancers of the lung (9.5 to 2.2), lip - oral cavity - pharynx (10.9 to 3.1), esophagus (12.6 to 4.5) and larynx (17.1 to 7.1). Mixed trends emerged in lung and oesophageal cancers, probably explained by differing risk factors for the two main histological subtypes. Sex incidence gaps narrowed due to increasing trends in men and women for skin melanoma (0.7 to 1, due to initially higher rates in women), cancers of the liver (7.4 to 4.4) and pancreas (2.0 to 1.4). Sex incidence gaps narrowed for colon-rectum (1.7 to 1.4), urinary bladder (6.9 to 6.1) and stomach (2.7 to 2.4) driven by decreasing trends among men. Other cancers showed similar increasing incidence trends in both sexes leading to stable sex gaps: thyroid gland (0.3 to 0.3), kidney (2.2 to 2.4) and central nervous system (1.4 to 1.5). CONCLUSION: In France in 2018, while men still had higher risks of developing or dying from most cancers, the sex gap was narrowing. Efforts should focus on avoiding risk factors (e.g., smoking) and developing etiological studies to understand currently unexplained increasing trends.

Merkel cell carcinoma in France: a registries-based, comprehensive epidemiological survey.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare primary cutaneous neuroendocrine carcinoma. Owing to its low incidence, epidemiological data are scarce and have never been analysed in France to identify the main epidemiological trends. METHODS: Data from MCC patients diagnosed between 1998 and 2010 were obtained from 11 French cancer registries in the FRANCIM network. The main epidemiological characteristics of MCC were investigated between 2006 and 2010 because comprehensive data were only available for this period. The main focus was tumour incidence and mortality over time. RESULTS: Between 1998 and 2010, 562 cases of MCC were reported in the registries. From 2006 to 2010 (290 cases), European- and world-standardized incidence rates were 0.26 and 0.43 per 100,000 person-years in men and 0.24 and 0.38 per 100,000 person-years in women. MCC is more frequent in females in France (56.9%) with male/female ratio 1.1. Relative survival rates were 84%, 56% and 42% at one, three and 5 years, respectively. CONCLUSIONS: The incidence of MCC clearly increased over time in all areas under focus. The standardized incidence in France was comparable to the incidence observed in other countries for the same period, but French data are too recent to conclude on an increase in MCC incidence. Prognosis remains poor in all countries in which data are available.

[Estimating the incidence of colorectal cancer in France from a hospital discharge database, 1999-2003]. / Estimations départementales de l'incidence du cancer colorectal en France à partir des données hospitalières, 1999-2003.

BACKGROUND: Cancer incidence in France is monitored by district-level cancer registries, which cover only 15% of the population. Incidence at the national and regional level are estimated from mortality data by extrapolating the ratio between incidence and mortality observed in the districts covered by a cancer registry. Using the incidence/mortality ratio might not be relevant at the district-level (département). This study aims to produce district-level estimations of colorectal cancer incidence, using the ratio between incident cases from cancer registries and surgery admissions for colorectal cancer identified in the national hospital discharge database. METHODS: This ratio was studied for the period 1999-2003 in the 13 districts covered by a cancer registry. For each sex separately, the number of incident cases was analyzed according to the number of surgery admissions for resection of colorectal cancer using a Poisson model. Age was introduced in the model as a fixed effect and district as a random effect. The model's ability to predict incidence was tested through cross-validation. The model was then extrapolated in order to estimate incidence of colorectal cancer in all French districts. RESULTS: In the districts covered by a cancer registry, cross-validation showed the model had a good predictive ability, except in men for one district where the difference between predicted and observed incidence reached 10%. Estimated incidence rates, age-standardized on the world population, ranged broadly from 29 to 44 per 100,000 in men and from 17 to 27 per 100,000 in women. Incidence did not show any clear geographical pattern. CONCLUSION: Among districts covered by a cancer registry, cross-validation showed overall good accuracy of predicted incidence. Inclusion of several admissions per patient was certainly a minor source of error in these estimations. Indeed, our selection only included 2% of multiple admissions, without geographical variations, in 2002 and 2003, years for which patient identifiers were available in the hospital discharge database. Estimated incidence rates presented moderate geographical variations and their prediction intervals should be taken into account.

[Time trends in the geographic variation of thyroid cancer incidence by tumor size from 1983 to 2000 in France]. / Disparités géographiques d'évolution d'incidence des cancers de la thyroïde par taille entre 1983 et 2000 en France.

BACKGROUND: The aim of this investigation was to study geographic time trends of thyroid cancer incidence according to tumor size in France, 1983 to 2000. METHODS: Incidence data were provided from six French registries over the period 1983-2000 covering seven administrative districts. Five tumor size groups were distinguished: < 10mm, 10-20mm, 20-40mm, > 40mm and unknown size. Papillary cancers diagnosed in women were analyzed according to tumor size in each geographic area. World age standardized rates were calculated and annual percent change rates were estimated for each tumor size group in each geographic area. Loglinear Poisson regression models were used to study geographic discrepancies in time trends incidences. RESULTS: The six French registries included 2222 papillary thyroid cancers in women between 1983 et 2000. Thyroid cancer incidence was increasing in the six geographic areas. Geographical variations in time trends incidence between registries reflected geographical variations in time trends incidence of small sized tumors (less than 10mm). CONCLUSION: Wide geographic variations in thyroid cancer incidence were noticed for small size tumors, which may be correlated with geographic variations in medical practices.

[Predictive value and sensibility of hospital discharge system (PMSI) compared to cancer registries for thyroïd cancer (1999-2000)]. / Valeur prédictive et sensibilité du programme de médicalisation des systèmes d'information (PMSI) par rapport aux registres des cancers: application au cancer de la thyroïde (1999-2000).

BACKGROUND: Cancer registries have a complete recording of new cancer cases occurring among residents of a specific geographic area. In France, they cover only 13% of the population. For thyroid cancer, where incidence rate is highly variable according to the district conversely to mortality, national incidence estimates are not accurate. A nationwide database, such as hospital discharge system, could improve this estimate but its positive predictive value and sensibility should be evaluated. METHODS: The positive predictive value and the sensitivity for thyroid cancer case ascertainment (ICD-10) of the national hospital discharge system in 1999 and 2000 were estimated using the cancer registries database of 10 French districts as gold standard. The linkage of the two databases required transmission of nominative information from the health facilities of the study. From the registries database, a logistic regression analysis was carried out to identify factors related to being missed by the hospital discharge system. RESULTS: Among the 973 standardized discharge charts selected from the hospital discharge system, 866 were considered as true positive cases, and 107 as false positive. Forty five of the latter group were prevalent cases. The predictive positive value was 89% (95% confidence interval (CI): 87-91%) and did not differ according to the district (p=0,80). According to the cancer registries, 322 thyroid cancer cases diagnosed in 1999 or 2000 were missed by the hospital discharge system. Thus, the sensitivity of this latter system was 73% (70-76%) and varied significantly from 62% to 85% across districts (p<0.001) and according to the type of health facility (p<0.01). CONCLUSION: Predictive positive value of the French hospital discharge system for ascertainment of thyroid cancer cases is high and stable across districts. Sensitivity is lower and varies significantly according to the type of health facility and across districts, which limits the interest of this database for a national estimate of thyroid cancer incidence rate.

[Lung cancer mortality among women in France. Trend analysis and projection between 1975 and 2014, with a bayesian age-cohort model]. / Mortalité par cancer du poumon chez les femmes françaises. Analyse de tendance et projection à l'aide d'un modèle âge-cohorte bayésien, de 1975 à 2014.

BACKGROUND: With 4,500 deaths in year 2000, female lung cancer mortality rates increased by 3% every year over the last two decades in France. This trend, not observed among males, is attributed to the regular increase of female smoking. In order to answer French Health decider's concerns, we estimated the future female lung cancer mortality rates and numbers of deaths for the next fifteen years, in France and its regions. METHODS: Analyses were based on numbers of female deaths from lung cancer observed between 1975 and 1999, and on past and future population estimates for 1975-2014, at national and regional levels. Mortality rates and numbers of deaths in France and its regions by 5-year periods and 5-year age groups were given in the 1975-1999 death certificate data base, and were projected for 2000-2014. The analysis used a bayesian approach of the age-cohort model with auto-regressive constraints on parameters. Estimated mortality rates were standardized on truncated 20-85 + world population. RESULTS: French female lung cancer mortality increased by 3% every year between 1975 and 1999. In period 1995-1999, truncated 20-85 + mortality rates, and number of deaths per year were respectively 11.4 per 100,000 and 4,000. Mortality rates increased in all regions but variations were maximum in Corsica (+ 314%) and minimum in Auvergne (+ 37%). For the whole of France, the estimated truncated 20-85 + standardized rate, was respectively, 14.1 and 22.5 per 100,000 in period 2000-04 and period 2010-14, which represents a 60% increase between these two time periods. At the regional level, the maximum variation was found in Languedoc-Roussillon (107%), the minimum in Nord-Pas-de-Calais (40%). CONCLUSIONS: The bayesian approach of the age-cohort model is increasingly used because it produces stable projections, without having to include other cancer parameters. Nevertheless, it would be interesting to extend this model by incorporating a tobacco consumption component, in order to assess scenarios based on consumption decreases.

Recent trends in incidence, geographical distribution, and survival of papillary thyroid cancer in France.

BACKGROUND: Over the past few decades, the incidence of thyroid cancer has dramatically increased in many countries. This increase was mainly seen in papillary cancer. The role of diagnostic practices and the effects of other risk factors were suggested to explain this increase. We provide a descriptive analysis in terms of changes in incidence, geographical distribution, and survival to check the relevance of assumptions about the increase. METHODS: A detailed analysis of changes in incidence recorded in French cancer registries between 1982 and 2010 was performed taking into account age, period, and birth cohort. The geographical distribution of the incidence in the 2006-2010 period was estimated from the standardized incidence ratios. The net survival was estimated to evaluate the effects of sex, age, and period of diagnosis in patients diagnosed between 1989 and 2004 and followed-up until 2013. RESULTS: The incidence of papillary cancer has increased sharply over the 1982-2010 period; the average annual rate of increase was 7.8% in men and 7.2% in women. The increase has slowed in the recent period in people aged less than 50 at the time of diagnosis. It has also slowed in the cohorts born 1945 and after. There was a strong geographic disparity in incidence between areas covered by cancer registries. Finally, the net survival was very high; the 10-year net survival was 96% and improved progressively from 82% in patients diagnosed between 1989 and 1993 to 95% in those diagnosed between 1999 and 2004. CONCLUSION: The increased incidence results most probably from the effect of medical practice, although other risk factors seem also involved, but to a lesser extent. The increase seems to have slowed down in the recent years, especially in the youngest age groups. This observation suggests a recent trend towards saturation of the effects of medical practices in post-1945 cohorts associated with an effect of the gradual dissemination of the recommendations relative to the management of thyroid nodules.

National cancer incidence is estimated using the incidence/mortality ratio in countries with local incidence data: is this estimation correct?

BACKGROUND: In countries with local cancer registration, the national cancer incidence is usually estimated by multiplying the national mortality by the incidence/mortality (I/M) ratio from pooled registries. This study aims at validating this I/M estimation in France, by a comparison with estimation obtained using the ratio of incidence over hospital discharge (I/HD) or the ratio of incidence over health insurance data (long-duration diseases, I/LDD). METHODS: This comparison was performed for 22 cancer sites over the period 2004-2006. In France, a longitudinal I/M approach was developed relying on incidence and mortality trend analyses; here, the corresponding estimations of national incidence were extracted for 2004-2006. The I/HD and I/LDD estimations were performed using a common cross-sectional methodology. RESULTS: The three estimations were found similar for most cancers. The relative differences in incidence rates (vs. I/M) were below 5% for numerous cancers and below 10% for all cancers but three. The highest differences were observed for thyroid cancer (up to +21% in women and +8% in men), skin melanoma (up to +13% in women and +8% in men), and Hodgkin disease in men (up to +15%). Differences were also observed in women aged over 60 for cervical cancer. Except for thyroid cancer, differences were mainly due to the smoothing performed in the I/M approach. CONCLUSION: Our results support the validity of I/M approaches for national estimations, except for thyroid cancer. The longitudinal version of this approach has, furthermore, the advantage of providing smoothed estimations and trend analyses, including useful birth-cohort indicators, and should thus be preferred.

Modelling the effect of breast cancer screening on related mortality using French data.

INTRODUCTION: This study aimed at modelling the effect of organized breast cancer screening on mortality in France. It combined results from a Markov model for breast cancer progression, to predict number of cases by node status, and from relative survival analyses, to predict deaths. The method estimated the relative risk of mortality at 8 years, in women aged 50-69, between a population screened every two years and a reference population. METHODS: Analyses concerned cases diagnosed between 1990 and 1996, with a follow-up up to 2004 for the vital status. Markov models analysed data from 3 screening programs (300,000 mammographies) and took into account opportunistic screening among participants to avoid bias in parameter's estimates. We used survival data from cancers in the general population (n=918, 7 cancer registries) and from screened cancers (n=565, 3 cancer registries), after excluding a subgroup of screened cases with a particularly high survival. Sensitivity analyses were performed. RESULTS: Markov model main analysis lacked of fit in two out of three districts. Fit was improved in stratified analyses by age or district, though some lack of fit persisted in two districts. Assuming 10% or 20% overdiagnosed screened cancers, mortality reduction was estimated as 23% (95% CI: 4, 38%) and 19% (CI: -3, 35%) respectively. Results were highly sensitive to the exclusion in the screened cancers survival analysis. Conversely, RR estimates varied moderately according to the Markov model parameters used (stratified by age or district). CONCLUSION: The study aimed at estimating the effect of screening in a screened population compared to an unscreened control group. Such a control group does not exist in France, and we used a general population contaminated by opportunistic screening to provide a conservative estimate. Conservative choices were systematically adopted to avoid favourable estimates. A selection bias might however affect the estimates, though it should be moderate because extreme social classes are under-represented among participants. This modelling provided broad estimates for the effect of organized biennial screening in France in the early nineteen-nineties. Results will be strengthened with longer follow-up.

Multi-state Markov models in cancer screening evaluation: a brief review and case study.

This work presents a brief overview of Markov models in cancer screening evaluation and focuses on two specific models. A three-state model was first proposed to estimate jointly the sensitivity of the screening procedure and the average duration in the preclinical phase, i.e. the period when the cancer is asymptomatic but detectable by screening. A five-state model, incorporating lymph node involvement as a prognostic factor, was later proposed combined with a survival analysis to predict the mortality reduction associated with screening. The strengths and limitations of these two models are illustrated using data from French breast cancer service screening programmes. The three-state model is a useful frame but parameter estimates should be interpreted with caution. They are highly correlated and depend heavily on the parametric assumptions of the model. Our results pointed out a serious limitation to the five-state model, due to implicit assumptions which are not always verified. Although it may still be useful, there is a need for more flexible models. Over-diagnosis is an important issue for both models and induces bias in parameter estimates. It can be addressed by adding a non-progressive state, but this may provide an uncertain estimation of over-diagnosis. When the primary goal is to avoid bias, rather than to estimate over-diagnosis, it may be more appropriate to correct for over-diagnosis assuming different levels in a sensitivity analysis. This would be particularly relevant in a perspective of mortality reduction estimation.

Sib-pair linkage analysis of alcohol dependence taking into account covariates and age-of-onset variability: evaluation of the residual approach.

The construction of residuals allowed us to consider a phenotype related to alcohol dependence (ALDX1) adjusted for age, gender and current smoking status. Using the Haseman and Elston regression test, we compared genome scan results for detection of loci for the unadjusted and adjusted ALDX1 phenotypes in the Collaborative Study on the Genetics of Alcoholism (COGA) data. More markers were significant at the 1% level for the binary than for the residual analyses. Overall, our residual analyses do not show substantial improvement in their ability to detect linkage for alcohol dependence in the COGA data. This may be due to the relatively small sample size of discordant sib pairs.