European Journal of Cancer (2014) 50, 831– 839

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Testicular cancer incidence to rise by 25% by 2025 inEurope? Model-based predictions in 40 countries usingpopulation-based registry data

0959-8049/$ - see front matter � 2013 Elsevier Ltd. All rights reserved.

http://dx.doi.org/10.1016/j.ejca.2013.11.035

⇑ Corresponding author at: Section of Environment and radiation, International Agency for Research on Cancer, 150 Cours Albert T69372 Lyon CEDEX 08, France. Tel.: +33 (0)4 72 73 83 12.

E-mail address: Lecornetc@students.iarc.fr (C. Le Cornet).

Charlotte Le Cornet a,b,⇑, Joannie Lortet-Tieulent c, David Forman c, Remi Beranger a,b,d,Aude Flechon e, Beatrice Fervers b,d,e, Joachim Schuz a, Freddie Bray c

a Section of Environment and Radiation, International Agency for Research on Cancer, 150 Cours Albert Thomas, 69372 Lyon CEDEX 08, Franceb Unite Cancer et Environnement, Centre Leon Berard, 28 rue Laennec, 69373 Lyon CEDEX 08, Francec Section of Cancer Information, International Agency for Research on Cancer, 150 Cours Albert Thomas, 69372 Lyon CEDEX 08, Franced Universite Claude Bernard – Lyon1, 43 Boulevard du 11 Novembre 1918, 69622 Villeurbanne CEDEX, Francee Centre de Lutte Contre le Cancer, Centre Leon Berard, 28 rue Laennec, 69373 Lyon CEDEX 08, France

Available online 23 December 2013

KEYWORDS

Testicular neoplasmsEuropePredictionIncidenceTime trend

Abstract Background: Testicular cancer mainly affects White Caucasian populations,accounts for 1% of all male cancers, and is frequently the most common malignancy amongyoung adult men. In light of the escalating rates of testicular cancer incidence in Europe, andin support of future planning to ensure optimal care of patients with what can be a curabledisease, we predict the future burden in 40 European countries around 2025.Methods: Current observed trends were extrapolated with the NORDPRED model to esti-mate the future burden of testicular cancer in the context of changes in risk versus changesin demographics.Findings: Despite substantial heterogeneity in the rates, the vast majority of European coun-tries will see an increasing burden over the next two decades. We estimate there will be 23,000new cases of testicular cancer annually in Europe by 2025, a rise of 24% from 2005. Some ofthe most rapid increases in testicular cancer are observed in Croatia, Slovenia, Italy and Spain,and a transition is underway, whereby recent attenuations and declines in rates in certain

homas,

832 C. Le Cornet et al. / European Journal of Cancer 50 (2014) 831–839

high-risk countries in Northern Europe contrast with the increasing trends and escalatingburden in Southern Europe. According to our estimates for 2025, around one in 100 men willbe diagnosed with the disease annually in the highest risk countries of Europe (Croatia,Slovenia and Norway).Interpretation: Elucidating the key determinants of testicular cancer and the equitableprovision of optimal care for patients across Europe are priorities given the steady rise inthe number of patients by 2025, and an absence of primary prevention opportunities.Funding: None.

� 2013 Elsevier Ltd. All rights reserved.

1. Introduction

Over 52,000 new cases of testicular cancer were esti-mated worldwide in 2008 [1]. The disease affects mainlyWhite Caucasian populations, with rates in several ofthe highest-risk populations in Europe (Switzerland,Norway and Denmark) ten times those observed in mostpopulations residing in Asia and Africa [2]. WithinEuropean countries, testicular cancer incidence ratesvary sevenfold [3], and account for 1% of all male can-cers. It is frequently the most common malignancyamong young adult men (aged 15–34).

Attention was first drawn to rises in testicular cancerin England and Wales [4], and Denmark [5] half a cen-tury ago; numerous reports subsequently emergeddetailing the rapid and general increases in incidencerates in adolescent men and young adults in manyEuropean countries over the last few decades [6–10] withtesticular cancer trends mainly driven by birth cohorteffects [8,11–13]. Reasons for the distinct geographicaland temporal variations in testicular cancer incidenceare still however not well understood.

In light of the escalation in testicular cancer incidencein many populations and the high curability of the dis-ease if adequate treatment regimens are adopted, wepredict the future burden in 40 European countries forthe year 2025 to support decision makers in resourceallocation and planning for the optimal care of patients.Based on age-period-cohort models, we extrapolate theobserved trends or make regional assumptions to quan-tify the future burden using, where possible, the high-quality data from population-based cancer registriesacross Europe. We highlight the increase in incidencerates and the number of future patients requiring carein terms of changes in risk versus changes in populationageing and growth. The results are discussed in the con-text of disease aetiology and the prospects for preven-tion and treatment of testicular cancer.

2. Data sources and methods

2.1. Data sources

We extracted the number of testicular cancer inci-dence (ICD10 C62) by year of diagnosis and 5-yearage group from several sources. Firstly, data series from

regional or national population-based cancer registriesin Europe were extracted from Cancer Incidence in Five

Continents (CI5) Volumes I to IX [2]. The specificrequirement for the inclusion of a registry was at leastfifteen consecutive years of data available alongsidecompilation in the latest Volume (IX) of the CI5 series.This criterion is indicative of each registry’s data qualityover time given that the editorial process involves adetailed assessment of the comparability, completenessand validity of the incidence data. Twenty-six of the40 countries in Europe satisfied these criteria; three pop-ulations were further excluded (Estonia, Iceland andMalta) as the small size of the underlying populationslimited the potential for robust model-based predictions.

To improve on the timeliness of the information (thelast year of diagnosis available in Volume (IX) of CI5 is2002), the incidence database was supplemented withmore timely data series available from publications bythe corresponding cancer registries, the European Can-cer Observatory website, the cancer statistics of Nordiccountries NORDCAN [14], or directly obtained fromthe Registries in the cases of Ireland, France, Denmark,Finland, Norway and Sweden. Of the 23 countriesselected, we obtained national data for 17 countries(Table 1). For the six remaining countries, regional reg-istries were aggregated to obtain a proxy of the(unknown) national incidence; in each country the pop-ulation coverage of the registries was <15%. Russiandata were derived from CI5 with more than 15 yearsof follow-up based on St. Petersburg records but thequality has never been assessed adequately which awareon the interpretation of estimations and predictions forthis country. The varying start-up and final years avail-able for each registry within a given country led to apragmatic selection of registries that sought to maximiseboth the number of included registries and the length ofperiod of study. Corresponding population data wereobtained from the same sources as the incidence data.We selected the maximum number of most recent 5-yearperiods for each population. For the remaining 17 Euro-pean countries which did not satisfy the inclusion crite-ria or were excluded due to the small population size(shown in Table 2), we extracted incidence estimatesfrom global estimates of cancer in GLOBOCAN [1]except for Estonia, Malta and Iceland which haddata available in CI5 for 2005. The male population

Table 1Testicular cancer incidence in 2005 and in 2025 in 23 European countries with corresponding percentage changes in incidence.

Region Population* Populationcoverageofthenationalpopulationin 2005

Periodused forpredictions

Nationalmalepopulation2005(millions)**

Nationalnewcases2005**

Cumulativerisk 2005(ages 0–74)**

Cumulativeriskcountryrank 2005

Nationalforecastedmalepopulation2025(millions)

National predictednew cases 2025

Cumulativerisk 2025(ages 0–74)**

Cumulativeriskcountryrank 2025

Changeinincidencebetween2005and 2025(%)

Changedue tochangeinrisk(%)

Changedueto changeinpopulation(%)

Central andEasternEurope

Belarus 100 1983–2002 4.7 88 0.13 22 4.2 141 0.23 21 60.9 73.8 �12.9Bulgaria 100 1994–2008 3.8 187 0.34 16 3.2 207 0.50 16 10.8 34.1 �23.3CzechRepublic

100 1989–2008 5.0 435 0.57 8 5.3 518 0.72 9 19.0 25.9 �6.9

Poland* 9.4 1988–2002 18.5 796 0.29 18 18.4 909 0.36 20 14.2 22.4 �8.2RussianFederation

100 1994–2008 66.0 1259 0.13 23 64.3 1435 0.16 22 13.9 18.5 �4.6

Slovakia 100 1988–2007 2.6 239 0.58 6 2.7 303 0.80 4 26.6 35.4 �8.8

NorthernEurope

Denmark 100 1991–2010 2.7 289 0.79 2 2.9 291 0.79 5 0.8 0.9 �0.1Finland 100 1991–2010 2.6 114 0.33 17 2.8 196 0.57 15 71.6 72.2 �0.6Ireland 100 1995–2009 2.1 149 0.48 14 2.6 242 0.71 10 62.1 55.2 6.9Latvia 100 1988–2007 1.1 37 0.24 20 1.0 53 0.43 19 46.0 57.0 �10.9Lithuania 100 1987–2006 1.6 32 0.14 21 1.5 24 0.12 23 �26.2 �14.0 �12.2Norway 100 1991–2010 2.3 251 0.80 1 2.7 331 0.95 2 31.7 21.7 10.0Sweden 100 1991–2010 4.5 293 0.49 11 5.1 412 0.65 11 40.6 34.2 6.4England 100 1988–2007 29.5 1986 0.49 12 33.6 2145 0.48 17 8.0 �0.5 8.5

SouthernEurope

Croatia 100 1988–2007 2.1 151 0.48 13 2.1 262 0.95 3 73.6 82.9 �9.3Italy* 5.8 1988–2007 28.5 1898 0.45 15 30.2 2879 0.77 8 51.7 65.1 �13.5Slovenia 100 1988–2007 1.0 96 0.64 5 1.0 145 1.10 1 50.3 67.8 �17.5Spain* 8.1 1986–2005 21.0 838 0.25 19 24.7 1393 0.45 18 66.2 79.5 �13.3

WesternEurope

Austria 100 1990–2009 4.0 343 0.58 7 4.2 356 0.63 12 3.7 10.0 �6.2France* 7.1 1988–2007 29.6 2041 0.50 10 32.9 2612 0.62 13 28.0 25.3 2.7Germany* 1.3 1988–2007 40.4 3852 0.65 4 39.5 3956 0.78 7 2.7 20.5 �17.8Switzerland* 12.8 1988–2007 3.6 370 0.70 3 4.0 302 0.62 14 �18.2 �13.3 �5.0TheNetherlands

100 1989–2008 8.1 599 0.53 9 8.6 826 0.78 6 37.9 42.7 �4.8

Total 285.3 16,343 297.5 19,938 22.0

Other countries(see Table 2)

65.8 2047 63.1 2860 39.7

Europe 351.1 18,390 360.6 22,798 24.0

* Regional registries: Poland: Kielce, Warsaw and Cracow; Italy: Modena, Parma, Ragusa, Romagna and Varese; Spain: Granada, Murcia, Navarra and Tarragona; France: Bas-Rhin, Calvados,Doubs, Isere, Somme and Tarn; Germany: Saarland; Switzerland: Geneva and St. Gall-Appenzell.** Average of 2004–2006, except for Spain (2003–2005), Poland and Belarus (2000–2002).

C.

Le

Co

rnet

eta

l./Eu

rop

ean

Jo

urn

al

of

Ca

ncer

50

(2

01

4)

83

1–

83

9833

Table 2Testicular cancer incidence in 2005 and in 2025, estimated in 17 European countries based on the stated referent country.

Region Population Referentcountry

Nationalmalepopulation2005(millions)

Estimatednationalnew cases2005

Nationalforecastedmalepopulation2025(millions)

Nationalpredictednew cases2025

Changeinincidencebetween2005and 2025(%)

Changedue tochangeinrisk (%)

Changedueto changeinpopulation(%)

Central andEastern Europe

Hungary Austria 4.8 402 4.6 403 0.1 10.0 �9.9Republic ofMoldova

Belarus 1.8 20 1.5 34 65.1 73.8 �8.7

Romania Belarus 10.6 224 10.0 361 61.0 73.8 �12.8Ukraine Belarus 21.7 508 19.3 807 58.9 73.8 �14.9

Northern Europe Estonia Latvia 0.6 11 0.6 17 54.5 57.0 �2.5Iceland Sweden 0.1 7 0.2 10 44.3 34.2 10.1

Southern Europe Albania Bulgaria 1.6 38 1.6 55 46.5 34.1 12.4Bosnia andHerzegovina

Bulgaria 1.8 79 1.7 95 21.4 34.1 �12.7

Cyprus Bulgaria 0.5 41 0.6 61 49.0 34.1 14.9Greece Bulgaria 5.5 78 5.8 105 34.5 34.1 0.4Malta Italy 0.2 8 0.2 12 53.8 65.1 �11.3Montenegro Bulgaria 0.3 6 0.3 8 31.5 34.1 �2.6Portugal Spain 5.1 127 5.1 217 71.0 79.5 �8.5Serbia Bulgaria 4.9 149 4.8 193 29.0 34.1 �5.1TFYRMacedonia*

Bulgaria 1 59 1.0 78 32.4 34.1 �1.7

Western Europe Belgium TheNetherlands

5.1 269 5.5 373 38.6 42.7 �4.1

Luxembourg France 0.2 21 0.3 31 50.7 25.3 25.4

Total 65.8 2047 63.1 2860 39.7

* The former Yugoslav Republic of Macedonia.

834 C. Le Cornet et al. / European Journal of Cancer 50 (2014) 831–839

predictions (medium-fertility variant) were obtainedfrom the United Nations (UN) World Population Pros-

pects 2010 Revision up to 2030, by country, year andage [15].

2.2. Statistical methods

Incidence rates were calculated by 5-year period ofdiagnosis and 5-year age group. Age-standardised inci-dence rates (ASR) per 100,000 were estimated usingthe European standard population [16]. Cumulativerisks were computed for ages 0–74 and expressed as per-centages, and assume no competing causes of death. Topredict the numbers of new cases and rates of testicularcancer in 2025 by country and age, we fitted theNORDPRED model [17] to recent trends, assumingthey served as proxies for the changing prevalence anddistribution of risk factors with time. This model hasbeen shown to perform well empirically in projectingcurrent trends into the future [18]. The three or fourmost recent five-year observed periods (depending onseries availability) were extrapolated using a powerfunction to level off the growth, with a projection ofthe recent linear trend for the last ten years that wasattenuated by 25%, 50% and 75% in the second, thirdand fourth prediction periods, respectively. The numbers

of new cases were predicted in 2025 by taking a weightedaverage of the projected incidence rates for the last twoprediction periods, centering on 2025 and then applyingthe UN population forecasts available for each countryfor that year. Mean annual differences in the numbers ofpredicted cases of testicular cancer in 2025 were comparedwith 2005 and are presented in terms of changes in risk(rates), and changes in demographics (population growthand ageing) [19].

For the remaining 17 of 40 European countries, com-prising 19% (less than 67 million) of the total 351 millionmen in Europe in 2005, either long-term observed inci-dence data were not available, or the population sizewas too small for the model to perform adequately(Estonia, Iceland and Malta).To predict the future bur-den in 2025 in these countries we first estimated thenumber of cases in 2005 by applying the age-specificrates estimated from GLOBOCAN 2008 [1] to the corre-sponding 2005 population data [15]. We then selected a‘referent country’ for each of the 17 countries on thebasis of geographical proximity and comparable testicu-lar cancer incidence rates in 2008 (see Table 2). In pre-dicting the incidence in these 17 countries, wecombined the forecasted change in demographics inthe country of interest with the predicted change in riskin the referent country.

C. Le Cornet et al. / European Journal of Cancer 50 (2014) 831–839 835

Stata 11.2 was used for data management and plot-ting the observed, and modelled trends. The modellinganalyses were performed using R 2.15 and the functionsavailable in Epi package version 1.1.36 [20], R Studioand the NORDPRED package (http://www.kreftregist-eret.no/en/Research/Projects/Nordpred/Nordpred-soft-ware/).

3. Results

The observed and predicted trends in the age-stand-ardised incidence rates (ASR) of testicular cancer arepresented in Fig. 1, for 23 European countries, and therates circa 2005 and 2025 are compared in Fig. 2. Whilethere is remarkable heterogeneity in the observed inci-dence rates between countries and regions, a generalincrease in rates in the range of 20–70% is predictedfor most countries. The exceptions are predominantlyin some Northern and Western European countries likein Denmark, England, Germany and Austria, whererates are predicted to stabilise in the next decades.

Several of the largest increases in incidence are pre-dicted to occur in Southern Europe, where rates have

SlovakiaCzech Rep.

Poland

Russia

Belarus

Bulgaria

Denmark

Finland

Latvia

Lithuania

Sweden

Norway

Ireland

England

CroatiaSlovenia

Italy

Spain

SwitzerlandFrance

Germany

Austria

Netherlds

15

1015

15

1015

1955

1965

1975

1985

1995

2005

2015

2025

1955

1965

1975

1985

1995

2005

2015

2025

Central & Eastern Europe Northern Europe

Southern Europe Western Europe

Observed Predicted

Age−

stan

dard

ized

(Eur

ope)

inci

denc

e pe

r 100

000

per

yea

r

Year

Fig. 1. Trends in testicular cancer incidence rates in 23 Europeancountries 1960–2025: observed rates (solid lines) versus predicted rates(dashed lines), by region. Age-standardised (Europe) rates per 100,000men.

increased rapidly over the last decades, notably in Croa-tia, Slovenia, Italy and Spain (Fig. 1). In 2005, Norwayhas the highest incidence rates of testicular cancer inEurope (10.9 cases per 100,000 men) and while rates inthe country are predicted to increase to 12.9 by 2025.They are predicted to be surpassed by rates in twoSouthern European countries, Slovenia (15.2) and Croa-tia (13.2). The cumulative risk (ages 0–74) of testicularcancer incidence among Slovenian men is predicted torank higher than Norway and Croatia in 2025, withthe cumulative risk in all three countries around 1%(Table 1). Western European countries have a ratherhomogenous incidence in the observed period (Fig. 2),although incidence in the Netherlands is predicted toincrease rapidly by 2025, surpassing the high rates ofGermany by 2025.

An overall incidence increase is expected by 2025 ofgreater than 20% in 13 countries, with the largestincreases in Finland and Croatia (72%). Table 1 breaksdown the predicted changes in incidence between 2005and 2025 into changes due to demographic and riskcomponents. The change due to risk has a greater influ-ence on the overall predicted increase, with incrementsin risk seen in 21 of the 23 countries (except Lithuaniaand Switzerland). Changes in population (size and agestructure) are predicted to impact only modestly onthe testicular cancer incidence burden in future years.In 18 of the 23 countries, the demographic effect is fore-casted to reduce the number of males at risk, notably inBulgaria, Germany and Slovenia. In combination, anoverall incidence increase is expected by 2025 of greaterthan 20% in 13 countries, with the largest increases inFinland and Croatia (72%).

France, Italy and Germany are predicted to have thehighest testicular cancer cases diagnosed annually inEurope in 2025 with over 2500 new cases in Franceand Italy and around 4000 in Germany.

Table 2 shows the estimated future testicular cancerincidence between 2005 and 2025 in the 17 Europeancountries where model-based predictions were not possi-ble. Incidence is projected to rise in each country, withthe increase by 2025 varying from 21% in Bosnia andHerzegovina to 71% in Portugal. Based on the modestincreases in risk in Austria (3.7%), only in Hungaryare incidence rates estimated to remain stable between2005 and 2025.

4. Discussion

We predict that by 2025, there will be almost 23,000new cases of testicular cancer in Europe per year, a riseof almost 24% from the estimated 18,400 cases in 2005.Despite substantial heterogeneity in the rates of thedisease in the recorded past and the predicted future,the vast majority of European countries will see anincreasing burden over the next two decades. The

8.59.6

8.58.0

8.56.8

10.68.9

10.87.4

6.13.4

10.66.3

13.27.0

15.28.9

1.61.9

5.63.2

6.66.7 7.9

4.68.9

6.79.7

6.610.610.8 12.910.9

2.11.8 3.21.8

4.84.0 6.8

4.79.7

7.910.9

8.1

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16Age−standardised incidence rate (E) per 100 000

Western Europe

Southern Europe

Northern Europe

Central & Eastern Europe

Switzerland*Austria

France*Germany*

The Netherlands

Spain*Italy*

CroatiaSlovenia

LithuaniaLatvia

EnglandFinland

SwedenIreland

DenmarkNorway

Russian FederationBelarusPoland*Bulgaria

Czech RepublicSlovakia

ASR in 2005 ASR in 2025

Fig. 2. Testicular cancer incidence rates 2004–2006 and predicted rates circa 2025 in European countries, by region. Age-standardised (Europe)rates per 100,000 men.

836 C. Le Cornet et al. / European Journal of Cancer 50 (2014) 831–839

predicted increase is seen in 20 of the 23 populationswith recorded incidence data, estimated at over 20%over the two decades in 13 countries, with the mostrapid increases predicted in Southern Europe, in Croa-tia, Slovenia, Italy and Spain.

The cumulative risk of testicular cancer is predictedto reach around 1% in Croatia and Slovenia and thusone in 100 men will be diagnosed with the disease beforethe age of 75 in these countries by 2025, similar to thepredicted risk in Norway. The rapid increases in Spainand Slovenia have been previously reported, with the6% mean annual increases contrasted with the 1–2%rises in Norway, Switzerland, Italy, France and Den-mark [11]. Likewise, a recent study of trends in Croatiaestimated a mean growth in incidence of 7% per annumover a quarter century [21]. There thus appears to be agradual transition from Northern and Western countriestowards Southern European countries in the magnitudeof the trends and the consequent scale of the burden oftesticular cancer in Europe.

The uniformly increasing incidence burden from tes-ticular cancer in Europe is being driven by increasingrisk in men in most populations rather than the ongoingchanges in the national demographic profiles in eachcountry. Unlike predictions for most epithelial cancers– where population ageing and growth are often themajor contributors to the projected increasing cancerburden [22] – testicular cancer largely affects young to

middle-aged adults (aged 15–44). The number of newcases would be projected to then steadily decline overthe next 20 years in the absence of the observed increasesin risk (e.g. rates instead remaining constant), given thediminishing size of the underlying populations withinthese age groups in the majority (18 of 23) of the Euro-pean countries studied.

The country-specific geographical and temporal vari-ations outlined here suggest multifactorial origin and arole for highly prevalent environmental determinantsof the disease. Evolving incidence of testicular cancerin migrant populations supports the role of environmen-tal factors in the aetiology. Even if the risk factorsinvolved in the development of testicular cancer remainunclear, consistent associations were found with ethnic-ity [11,23], some genetic polymorphisms [24] and crypt-orchidism [23,25]. Testicular cancer, hypospadias andcryptorchidism have been postulated as being part ofthe testicular dysgenesis syndrome (TDS), presumablyoriginating from dysfunction in genital developmentduring intra-uterine life [26]. While cryptorchidism andhypospadias events are not routinely recorded, the fewstudies published to date have revealed interesting tem-poral relations between birth defects and testicular can-cer occurrence [27]; further aetiological clues may begained by further Europe-wide comparative analyses.The lack of consistency in particular associations fromnumerous epidemiological studies over the last decades

C. Le Cornet et al. / European Journal of Cancer 50 (2014) 831–839 837

equally lends support to a complex aetiology involvinginteractions and multiple risk determinants. The lackof association with adulthood exposure is in line withcurrent hypotheses supporting the prenatal origin ofTesticular cancer [28]. Further plausible factors havebeen suggested to associate with the disease such asendocrine disruptors [26], family history [23] and mater-nal factors [23,25].

An intriguing observation is the prospect of a declinein testicular cancer incidence among those male popula-tions who have experienced the greatest risk in Europe.Rates in Denmark, Germany, Austria, Switzerland andEngland – all countries with very high levels of humandevelopment as well as elevated incidence rates of thedisease – appear to be leveling off in recent years andthus a decreasing number of new cases is predicted inthese countries. Denmark was the first country toobserve an attenuation in the increasing trends [8], fol-lowed by Sweden, United Kingdom and Switzerland[6]. Our results confirm the recent plateauing of ratesin those countries (alongside Germany and Austria),except in Sweden where rates appear to be on theincrease. In North America, a plateau has been reportedamong men in Ontario, Canada and in the United States(U.S.) [10,29]. A recent attenuation was also observed inAustralia [10]. Increasing migration in high-risk coun-tries, with first generation migrants commonly at lowerrisk than the host population, has been postulated as apotential contributory factor, and one that should beroutinely considered in the analysis and interpretationof time trend studies [30]. However, when investigatedin Denmark for instance, the proportion of migrantswas too small to substantially affect the overall rates.

This is to our knowledge the first attempt to predictthe cancer burden in Europe based on the long-termrecorded incidence data from high-quality population-based cancer registries and an extrapolation of ratesbased on the fitting of age-period-cohort models. Thepredicted increases in testicular cancer incidence inmany European countries are unlikely the result ofimproving ascertainment or better diagnostic proce-dures. Firstly, the course of the disease is rapidly fatalif left untreated. Also, cancer into this age group is veryunlikely to be missed clinically or to be unreported, andin addition, much of the estimation involves use of datafrom well-established population-based cancer registrieswith standardised procedures [7]. At older ages, there issome prospect of misclassification of lymphomas arisingin the testis to testicular cancer rather than lymphoma[31], although the impact on the predicted figures pre-sented here is likely to be minor.

The inherent weaknesses in this study centres on therequirement to directly or indirectly extrapolate recenttrends, or the best current estimates in a given countryin predicting the future burden. The exercise is hazard-ous and we can be reasonably confident that trends

observed in the past will not necessarily hold in future.In the best case scenario, reliable and quantifiable infor-mation on specific risk factors would be available fortesticular cancer and the prediction model modified toaccommodate such data [32]. The future burden in Eur-ope in our study was, by necessity, largely derived usingthe NORDPRED age-period-cohort model to therecorded incidence trends in a given country. Such meth-ods have been shown empirically to provide among thebest estimates of future cancer burden in comparisonwith 15 different prediction methods for 20 cancers infour Nordic countries [17] and in terms of short-termmortality predictions of 12 cancers nationally andregionally in Canada [33]. In addition, another recentCanadian study comparing predictive models hasreported NORDPRED as the best performing modelfor cancer predictions where cohort effects are signifi-cant [18]; the importance of early life and birth cohorteffects on testicular cancer risk has been demonstratedpreviously in numerous studies [8,34–36].

It is important to emphasise the large uncertaintiesassociated with trends-based long-term predictions.The rates in several Nordic countries are leveling off(in Norway and Denmark) and are predicted to be sur-passed by several countries showing rapidly rising trends(Slovenia and Croatia). It is however conceivable thatthese latter countries will experience a similar diminu-tion of the rates during the period of prediction, and itwould be useful to know the extent to which the levelingof the rates is purely cohort-driven, given this is inherentassumption of the NORDPRED models in predictingthe future burden. As an example, any attenuation intesticular cancer incidence arising from a period-inducedplateau may not be fully accounted for in the future bur-den estimates.

In six of the 40 countries, predictions were based onregional registries, and for some highly populated coun-tries with relatively low registration coverage (Germany,France, Italy, Spain and Poland) there is an inherentconcern that the sentinel registries can provide a reason-able proxy of the national profile and burden; it has tobe assumed that rates derived from 13 million maleswere representative of the 138 million males in the fivecountries combined. However the difference betweenthe French national estimation [37] in 2005 and ournational estimation based on six registries is relativelyminor (2002 cases versus 2041 cases). In Germany, thepredictions were only based on Saarland and the repre-sentativeness is questionable, given the testicular cancerincidence rates are among the lowest observed amongthe established network of registries now functioningin the country. In 14 of the 40 countries (covering almost20% of the European population), predictions couldonly be obtained on the basis of projections of recentnational estimates for 2008 obtained from GLOBO-CAN [1]. Estonia, Malta and Iceland had predictions

838 C. Le Cornet et al. / European Journal of Cancer 50 (2014) 831–839

based on their observed data available in CI5 for 2005.We assumed that the unknown temporal developmentswere akin to those observed in a selected neighbouringcountry with similar levels of risk, and thus the predic-tions in these countries must be viewed with particularcaution. If we had taken another neighbouring countrywe would have variations in the predictions estimationfor those 17 countries. Finally attention should bedrawn to the fact that the UN forecasted populationdata are, by their nature, themselves predictions, basedon forecasts of birth and death rates and levels of immi-gration, and emigration.

In summary, 23,000 new cases of testicular cancer inEurope are predicted in the year 2025, a 24% increasefrom 2005.The disease is projected to lead to aroundone in 100 men being diagnosed per year in severalcountries within two decades. Some of the most rapidincreases in testicular cancer are observed in SouthernEuropean countries, and there appears to be a transitionunderway, whereby the historically high-risk countriesof Northern and Western Europe are beginning to seeattenuations, plateaus, or declines in rates. Furtherafield, a recent study has shown that testicular canceris emerging as an important cause of morbidity andmortality in young men in the relatively low incidenceareas of Latin America and some parts of Asia [10]. Epi-demiological studies of testicular cancer will continue tobe fundamental in gaining insight into such a disease,given there are so few known causal determinants, andthus, at present, little scope for primary prevention.

Advances in treatment have led to major declines intesticular cancer mortality in many European countriesfrom the mid-1970s, which has translated into cohortsof men at successively lower risk of death from the dis-ease [11,13]. Almost four decades after the introductionof cisplatin-based therapy however, disparities in testic-ular cancer mortality persist across Europe and there isslower progress in care delivery in several lower-resourcecountries in Southern and Eastern Europe [9]. The plan-ning of services is an integral component of cancer con-trol programmes. In predicting the future disease burdenour study aims to support prioritisation of the necessaryresources in European countries, ensuring the equitableand effective management and provision of optimal careof testicular cancer patients in the future.

Conflict of interest statement

None declared.

Acknowledgements

This work was developed at the International Agencyfor Research on Cancer (IARC, http://www.iarc.fr). Nospecific funding was received for this study. Ms Le Cor-net is partially supported by a collaborative research

agreement between IARC and Centre Leon Berard(NORDTEST project). The authors gratefully acknowl-edged the following cancer registries who have contrib-uted in sharing their data needed as baseline forincidence prediction: Austria – Austrian Cancer Regis-try(Mrs Zielonke); Landes Salzburg Tumour Registry,Tyrol Cancer Registry; Belarus -Belarusian Cancer Regis-try (Prof. Okeanov); Bulgaria – Bulgarian NationalCancer Registry (Dr. Dimitrova); Croatia – CroatianNational Cancer Registry (Prof. Znaor); Czech Republic– Czech National Cancer Registry (Dr. Holub, Dr. Toman);Denmark – Danish Cancer Registry(Dr. Larsen, Mrs.Gjerstorff); Finland – Finnish Cancer Registry; France– Doubs Cancer Registry (Dr. Woronoff), Isere CancerRegistry (Dr. Colonna), Somme Cancer Registry (Dr.Lapotre-Ledoux, Prof. Ganry), Tarn Cancer Registry(Dr. Grosclaude); Germany – Saarland Cancer Registry(Dr. Kaatsch, Mr. Holleczek); Ireland – National CancerRegistry Ireland (Dr. Comber); Italy – Tumour Registryof Modena (Prof. Federico), Parma Cancer Registry(Dr. Michiara), Ragusa Cancer Registry (Dr. Tumino),Romagna Tumour Registry (Dr. Falcini), VareseTumour Registry(Dr. Crosignani); Latvia – LatvianCancer Registry (Dr. Maurina); Lithuania – LithuanianCancer Registry (Dr. Smailyte); Norway – Cancer Regis-try of Norway (Prof. Ursin);Poland – Cracow City andDistrict Cancer Registry (Dr. Rachtan), Kielce RegionalCancer Registry (Dr. Gozdz), Warsaw Cancer Registry(Dr. Zwierko, Prof. Zatonski); Slovakia – SlovakiaNational Cancer Registry (Dr. Safaei Diba, Dr. Kaiserova);Slovenia – Cancer Registry of Republic of Slovenia (Prof.Primic Zakelj); Spain –Granada Cancer Registry (Dr.Sanchez-Perez), Murcia Cancer Registry (Dr. Sanchez),Navarra Cancer Registry (Dr. Ardanaz Aicua), Tarrag-ona Cancer Registry; Sweden – Swedish Cancer Regis-try(Ms. Klint, Dr. Heyman); Switzerland – GenevaCancer Registry (Prof. Bouchardy), St. Gallen-AppenzellCancer Registry (Dr. Ess);The Netherlands – The Nether-lands Cancer Registry, Comprehensive Cancer CentreSouth (Dr. Janny van den Eijnden-van Raaij); England– Eastern England, Northern and Yorkshire Cancer Reg-istry, North West Cancer Intelligence Service, OxfordCancer Intelligence Unit, South West Cancer Registry(Mr. David Meecham,Dr. Gill Lawrence, Dr. Stiller);Russian Federation (Dr. Somarsundaram Subramanian,Sabrina Maraf).

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