Acute/subacute side effects were evaluated in 39 testicular cancer patients before infra-diaphragmatic radiotherapy, twice during therapy and 3, 6, and 12 months after treatment discontinuation. The evaluation was primarily based on questionnaires filled in by the patients. At the end of radiotherapy nausea was reported by all responding patients, and 29 patients complained of diarrhea. Two-thirds of the patients reported abdominal pain and/or meteorism, and one-half complained of retching and/or vomiting. During therapy the median weight was significantly reduced by three kilos and the median value of the performance status decreased by 20%. The hematological and biochemical toxicity was low. At the 3-month evaluation more patients complained of nausea, abdominal pain, and meteorism than before irradiation. Compared to the pretreatment situation the patients evaluated their physical condition to be reduced during treatment and at the first follow-up visit. One year posttreatment the patients had regained their physical fitness. All patients in income-producing activity were on sick leave during the period of radiotherapy and for 5 weeks (median) thereafter. In conclusion, infra-diaphragmatic radiotherapy leads to significant but reversible acute/subacute side effects lasting for a median of 9 weeks. It is hoped that better symptomatic therapy and modifications of the radiotherapy technique will reduce the side effects.
Although the incidence of testicular cancer is increasing, substantial differences in incidence between countries and populations exist. These differences cannot be explained solely by genetic differences, but environmental exposures, particularly early exposures, have been implicated in the etiology of testicular cancer. To assess whether early exposures contribute to the incidence of testicular cancer, we identified 93 172 Finnish men who immigrated to Sweden between 1969 and 1996 and followed them for the occurrence of testicular cancer. The risk of testicular cancer was lower for Finnish immigrants to Sweden than for the Swedish general population (standardized incidence ratio [SIR] = 0.34, 95% confidence interval [CI] = 0.21 to 0.53). The reduced risk was associated with both seminomas and non-seminomas. Neither age at immigration nor duration of stay in Sweden had any impact on the reduced risk. Although the type of environmental exposures remains unknown, the results strongly indicate that early exposures are major determinants for testicular cancer.
Incidence rates of testicular cancer are increasing among postpubescent men. This suggests that putative exposures may operate early in life and have changed over time. The age at which endocrine activity accelerates (age at puberty) may be such an exposure. This study was undertaken to investigate the relationship between age at puberty and testicular cancer risk.
A population-based case-control study was conducted in the province of Ontario, Canada which included males, aged 16 to 59 years, diagnosed with testicular germ cell cancer between 1987 and 1989, and age-matched controls. Data were collected on 502 cases, 346 case mothers, 975 controls, and 522 control mothers. Surrogate measures for age at puberty included age at starting to shave, appearance of hair, growth spurt, and voice change.
A protective effect of later puberty was evident for all four measures of puberty as reported by both subjects and mothers, and greater protection was conferred when the greatest number of later puberty events were reported. Risk associated with earlier puberty was inconclusive.
As age at puberty is decreasing in the population, the proportion of boys experiencing the protective effect of later puberty may be diminishing. This may help explain the increasing incidence of testicular cancer.
BACKGROUND: Undescended testis, which is a risk factor for testicular cancer, is usually treated surgically, but whether the age at treatment has any effect on the risk is unclear. We studied the relation between the age at treatment for undescended testis and the risk of testicular cancer. METHODS: We identified men who underwent orchiopexy for undescended testis in Sweden between 1964 and 1999. Cohort subjects were identified in the Swedish Hospital Discharge Register and followed for the occurrence of testicular cancer through the Swedish Cancer Registry. Vital statistics and data on migration status were taken from the Register of Population and Population Changes for the years 1965 through 2000. We estimated the relative risk of testicular cancer using Poisson regression of standardized incidence ratios, comparing the risk in the cohort with that in the general population. We also analyzed the data by means of Cox regression, using internal comparison groups. RESULTS: The cohort consisted of 16,983 men who were surgically treated for undescended testis and followed for a total of 209,984 person-years. We identified 56 cases of testicular cancer during follow-up. The relative risk of testicular cancer among those who underwent orchiopexy before reaching 13 years of age was 2.23 (95% confidence interval [CI], 1.58 to 3.06), as compared with the Swedish general population; for those treated at 13 years of age or older, the relative risk was 5.40 (95% CI, 3.20 to 8.53). The effect of age at orchiopexy on the risk of testicular cancer was similar in comparisons within the cohort. CONCLUSIONS: Treatment for undescended testis before puberty decreases the risk of testicular cancer.
Analysis of rates from disease registers are often reported inadequately because of too coarse tabulation of data and because of confusion about the mechanics of the age-period-cohort model used for analysis. Rates should be considered as observations in a Lexis diagram, and tabulation a necessary reduction of data, which should be as small as possible, and age, period and cohort should be treated as continuous variables. Reporting should include the absolute level of the rates as part of the age-effects. This paper gives a guide to analysis of rates from a Lexis diagram by the age-period-cohort model. Three aspects are considered separately: (1) tabulation of cases and person-years; (2) modelling of age, period and cohort effects; and (3) parametrization and reporting of the estimated effects. It is argued that most of the confusion in the literature comes from failure to make a clear distinction between these three aspects. A set of recommendations for the practitioner is given and a package for R that implements the recommendations is introduced.
Comment In: Stat Med. 2008 Apr 30;27(9):1557-61; author reply 1561-417847157
Previously published papers have indicated a fairly strong familial dependence intesticular cancer patients. This is particularly evident in brothers. We have applied a frailty model with familial dependence to family data on brothers of testicular cancer patients from the Norwegian Radium Hospital. The model is a two-level frailty, with variation in susceptibility at both the family and the individual level. Specifically, the frailty variable is assumed to be compound Poisson distributed to allow individuals to be non-susceptible. The underlying Poisson parameter is gamma distributed to model how testicular cancer is distributed among families. This is an extension of a previous compound Poisson frailty model developed for individual testicular cancer data, and an alternative to traditional modelling of survival time family data. The likelihood construction and ascertainment problems are looked at in detail. To avoid ascertainment bias, the likelihood is based on the probability of observing the disease status for each brother in a family, given that at least one brother is ascertained. The estimated relative risk for brothers is 7.4. This paper expands on a previous analysis of the data by using a frailty model, which makes it possible to examine how the cancer is distributed among families. The estimated gamma-shaped parameter is 0.151 (95 per cent confidence interval 0.078-0.294), and this indicates that in order to obtain the high relative risks observed for brothers of testicular cancer patients, the distribution of susceptibility has to be strongly skewed among the families. The vast majority of families have a very low risk and a small proportion have a high risk. In addition, a quantity similar to the relative risk is derived to show that the susceptibility is skewly distributed also if the Poisson parameter is Bernoulli or stable distributed. This indicates that the results are valid also if other distributions are used to model familial dependence in the compound Poisson frailty model.
There are two striking epidemiological features of testicular cancer. First, the incidence has increased strongly over the past few decades. Secondly, the incidence is greatest among younger men, and then declines from a certain age. We have constructed a statistical model to fit these observations. The idea of the model is that a subgroup of men is particularly susceptible to testicular cancer. In statistical terminology this is called a frailty model, since it focuses on varying frailty of the individuals. The frailty, or susceptibility, is considered as being established by birth, and due to a mixture of genetic and environmental effects. The strong increase in incidence over calendar time points to strong environmental effects, which are thought to operate in fetal life, causing damage to the fetus. Based on data from the Norwegian Cancer Registry we fit a frailty model to incidence data collected during 1953-93. The model gives a good fit and we discuss the interpretations of our findings.
A few twin studies on cancer have addressed questions on the possible carcinogenic or protective effects of twining by comparing the occurrence of cancer in twins and singletons. The nationwide Swedish Family-Cancer Database of 10.2 million individuals and 69,654 0- to 70-year-old twin pairs were used to calculate standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) for all main cancers compared to singletons. The overall risk of cancer in same- or different-sex twins was at the same level as the risk for singletons. Testicular cancer, particularly seminoma, was increased among same-sex twins (1.54) and all twins to an SIR of 1.38. Among other tumors, neurinomas and non-thyroid endocrine gland tumors were increased. Colorectal cancers and leukemia were decreased among all twins. Melanoma and squamous cell skin cancer were decreased in male same-sex twins. The data on this unselected population of twins suggest that twinning per se is not a risk factor of cancer. In utero hormonal exposures or postnatal growth stimulation may be related to the risk of testicular cancer and pituitary tumors. Protective effects against colorectal cancer may be related to a beneficial diet, and in melanoma and skin cancer, to socioeconomic factors. The study involved multiple comparisons, and internal consistency between the results was one of the main factors considered for their plausibility. The results should encourage others working on twin and singleton populations to examine the specific associations and emerging hypotheses.
To examine the pattern of testicular cancer incidence by age, time period and birth cohort since 1969 in Canada.
In addition to analyses of the secular trends by age group and birth cohort separately, an age-period-cohort model and the submodels with standard Poisson assumptions were fitted to the data.
The overall age-adjusted incidence of testicular cancer increased in Canada, from 2.8 per 100,000 males in 1969-71 to 4.2 in 1991-93. The younger age groups showed much higher absolute incidence rates in the recent period compared with those in the early period. Age-period-cohort modelling of data restricted to males aged 20-84 years suggested that the observed increase in testicular cancer could be largely attributed to a birth cohort effect. A steady increase in risk was observed among men born since 1945; those born between 1959 and 1968 were 2.0 (95% CI, 1.5-2.6) times as likely to develop testicular cancer as those born between 1904 and 1913.
The risk of testicular cancer has increased over time and changing exposure to environmental factors early in life may be responsible for this.