A marked increase in incidence of TC has occurred since 1989 in the southern part of the Netherlands, which correlates with increasing risks for birth cohorts since 1945. There has been a marked decrease in mortality since 1979.
TNM testicular cancer stage classification changed several times between 1970 and 2004. To prevent misclassification of the tumours we have made our own stage classification, in which all tumours are classified in the same way. But through this stage classification it becomes more difficult to compare the study results to other studies.
The changes in histological classification over the years have no meaningful influences on our histological classification into seminoma and non-seminoma TC.
Unfortunately, the ECR does not have access to death certificates. The registry partly solve the problem of potential incompleteness by active registration based on a national computerised archive of pathological diagnosis (PALGA) and on clinical diagnosis derived from a computerised national hospital discharges system (LMR).
Incidence and APC models
The incidence of TC increased by 110% in the period 1970–2004: seminoma TC started to increase in 1990 and non-seminoma TC some years earlier. This increase can be attributed almost entirely to the increase in localised TC tumours. As a result of the increasing incidence and the decreasing mortality, the prevalence of TC in the Netherlands increased from 37 per 100,000 person-years in 1990 to 64 per 100,000 in 2002 and the prognosis is that the prevalence in 2010 will be 132 per 100,000.19 As a consequence the claim for medical care in the Netherlands will rise markedly, since active follow-up for localised TC seems to be efficacious (unlike the situation in many other tumour sites20, 21).
The fact that the rate of the incidence increase in the eastern part of the ECR region was comparable to the incidence increase of the whole ECR region indicates that the expansion of the ECR region in 1988 did not introduce a bias in the TC incidence.
The incidence of nongerm cell TC was low and relatively constant during the whole study period and did not influence the overall TC incidence.
The fact that the incidence of both seminoma and non-seminoma TC is increasing suggests that one or more mutual risk factors, probably introduced by changes in environment and lifestyle, might be responsible for the increase in incidence. Because the AC model gave the most efficient fit of all APC models, and the increased risks of incidence for birth cohorts since 1950 also suggest that the risk factor exerts its effect in utero and/or early in life. When the risk factor would exert its effect later in life, it would probably affect boys and men of different ages. An increased incidence would then be more attributable to period effects then to birth cohort effects as is found in our study.
The result of our AC model is comparable to that of 2 other studies, which analysed multiple European populations and found the best fit to be an AC model for most populations.7, 11 A study in the United States found the best fit with an APC model, but the birth cohort effect was dominant.12 All 3 studies found an increase in risk with successive birth cohorts, which is comparable to the results of our study.
There are several hypotheses explaining the increase of TC incidence. One of them suggests that there is an increase in incidence of several testicular diseases (for example cryptorchidism and TC) through changes in genetic and/or environmental factors, including endocrine disrupters.22 Another hypothesis suggests that lifestyle changes such as an increase in maternal age and an increase in the number of first-born children causes the increase of TC incidence.23 In the Netherlands, the average age of the mother at birth of her first-born child increased from 24.9 years in the 1960s to 26.4 years in the 1980s and the average number of children per mother decreased from 3.0 to 1.5. This resulted in an increase in the percentage of first-born children from 35% in the 1960s to 45% in the 1980s. Although these changes are in the same period as the increase in relative risk of birth cohorts on TC, we cannot verify this hypothesis in our data because these possible risk factors of TC were not registered in the ECR.
The risk factors that are responsible for the increase in incidence may initiate or promote the development of both histologies, in utero and/or early in life, but apparently have a shorter latency time for nonseminomas than for seminomas, explaining the difference in the age-peaks of seminoma and non-seminoma TC.
The incidence of TC has been increasing for many decades in most European countries, but with a varying start.3, 7 A study of TC in Scotland found that the increase in incidence was more pronounced in the age-group <40 than in the age-group ≥40.24 The rise in incidence seems to have started later in the ECR-region, compared to most other European countries, but the absolute incidence and the age-distribution of the incidence have become similar to those of other European countries.
We also found a small nonsignificant decrease in the relative risk for birth cohorts 1935 and 1940, as was found in Denmark, France, Norway, Italy, Slovenia, Spain and Sweden.7, 10, 11
Through the relative small population in our study, it was not possible to perform a more detailed APC-analysis for example smaller period and cohort groups or separate analysis for seminoma and non-seminoma groups.
The mortality rate dropped from around 1 per 100,000 person-years in the mid 1970s to 0.4 in 1986 and fluctuated thereafter between 0.2 and 0.5. However, in this last period the numbers became very small. This pattern of decrease is comparable to the mortality rates found in the populations of the United States and the European Union. The steep decrease is probably related to improved TC survival in that time.24, 25, 26, 27 There was a small and nonsignificant annual decrease of −1.2% (p = 0.61) in mortality in the area of the ECR in the period 1987–2005. And in almost the same period (1987–2004) the incidence increased by 4.2% (p = <0.001). Thus although the incidence was rising, mortality did not rise. This can be attributed to the higher percentage of less-aggressive tumours, which have higher survival rate than more aggressive tumours, and increased survival rates for TC in the ECR region.27 These increased survival rates can be attributed to the introduction of cisplatin-containing chemotherapy in the 1970s.6
A marked increase in incidence of TC was observed in the south of the Netherlands, predominantly for tumours with lower aggressiveness and for both the seminoma and non-seminoma TCs. This occurred predominantly in birth cohorts since 1945; in utero and/or early life influences seem likely. The marked decrease in mortality since the 1970s was most likely caused by improved treatment.
Future investigations should focus on factors that influence the development of testicular tumours.