Japanese Journal of Clinical Oncology 31:438-443 (2001)
© 2001 Foundation for Promotion of Cancer Research
Survival of Testicular Cancer Patients in Osaka, Japan
1Department of Cancer Control and Statistics, Osaka Medical Center for Cancer and Cardiovascular Diseases and 2Osaka University School of Medicine, Osaka, Japan
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONAcknowlegmentREFERENCES |
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Background: Testicular cancer is one of those cancers for which the prognosis has improved remarkably since the introduction of effective chemotherapy.
Methods: Study subjects were 709 testicular cancer patients who were registered to the population-based Osaka Cancer Registry (OCR) as diagnosed between 1975 and 1992. The testicular cancer patients diagnosed/treated in the Osaka Medical Center for Cancer and Cardiovascular Diseases (OMCC) were also analyzed for comparison.
Results: The 5-year relative survival was 75.2% for the total of 709 patients and 77.9% for those diagnosed during 1990–92. These figures were much lower than those for patients in the USA and in Europe. In contrast, the 5-year survival of the 113 patients diagnosed in the OMCC during 1975–93 was 91.5% and similar to those in the USA and in Europe.
Conclusions: The present study suggests that there are problems in the speed and extent of diffusion of effective chemotherapy for testicular cancer in Osaka.
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONAcknowlegmentREFERENCES |
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Testicular cancer is one of those cancers for which the prognosis has improved remarkably during recent years. Since the introduction of effective chemotherapy, especially with cis-diamminedichloroplatinum, testicular cancer has become curable (1). According to data from population-based cancer registries in the USA and in Europe, the 5-year survival of testicular cancer patients in recent years is ~95% (2,3). In Japan, it is also reported that the results of the treatment of testicular cancer have improved since the early 1980s in university hospitals and cancer hospitals (4,5), but the survival based on a population-based cancer registry has not yet been reported, because testicular cancer is relatively rare (6). Therefore, in the present study, we calculated the survival of testicular cancer patients using data from the population-based Osaka Cancer Registry (OCR) and compared them with data from the USA and Europe. We also calculated the survival based on data from the hospital-based cancer registry of the Osaka Medical Center for Cancer and Cardiovascular Diseases (OMCC) in order to make clear where the problem lies.
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SUBJECTS AND METHODS |
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TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONAcknowlegmentREFERENCES |
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The study subjects were 709 testicular cancer patients who were registered to the OCR as diagnosed during 1975–92 and who resided in Osaka Prefecture except Osaka City. In the OCR, active follow-ups were conducted for those cancer patients who were diagnosed since 1975 and who resided in Osaka Prefecture except Osaka City, by checking the residential registers regularly. Carcinoma in situ cases (no cases), second primary cancer cases (six cases) and death certificate only (DCO) cases (40 cases) were excluded from study subjects for survival analysis, following the methods of the EUROCARE study (7).
Data for comparison were taken from the EUROCARE study (2), the SEER program (3,8), the National Cancer Data Base in the USA (9) and the report from England and Wales (10). In order to make clear where the problem lies, we calculated the survival for the 113 testicular cancer patients diagnosed/treated during 1975–93 in the OMCC.
Life-table methods were used for calculating survivals in most cases, but in the case of <40 patients Kaplan–Meier methods were used. The starting point of survival time was defined as the date of the first diagnosis and the end-point was defined as death from any cause. Closing date was defined as the date 5 years after the starting point. Cases lost to follow-up were treated as censored cases at the latest date when they were confirmed as alive. Expected survival was estimated using the survival probability in the general population similar to the subjects with respect to sex, age and calendar period of observation. Sex, age and calendar year specific survival probabilities were calculated based on the cohort survival tables prepared by the National Cancer Center using life tables of the Japanese population (11) and Ederer II methods (12) were adopted. The relative survival was calculated as the ratio of the observed to the expected survival. The standard error and 95% confidence interval of the relative survival were then calculated. However, as standard errors of the survivals were not presented in the report from the SEER program, significance tests of the difference could not be conducted in the comparison between Osaka and the USA.
The relative survival was analyzed by clinical stage, year of diagnosis, histology type and size of hospitals where the patients were treated. A similar classification of clinical stage of cancer as in the SEER program was adopted in the OCR and the hospital-based cancer registry of the OMCC, where the stage at diagnosis was classified into the following three groups:
1. localized: cancer is confined to the original organ;
2. regional: cancer spreads to regional lymph nodes and/or spreads to immediately adjacent tissues;
3. distant: cancer metastasis to distant organs.
The prognostic factors were analyzed by the Cox proportional hazards model. In this analysis, the dependent variable was vital status in 5 years from diagnosis and independent variables were age, year of diagnosis (1975–83/1984–92), clinical stage (localized/regional/distant), histology type (seminoma/non-seminoma germ cell tumor) and size of hospital where the patients were treated (university hospitals and cancer hospital (OMCC)/large-sized hospitals/medium- and small-sized hospitals and clinics). Cancer report cards in the OCR contain the items of treatment, i.e. admission, surgical operation, chemotherapy and so on. When there were two or more report cards per patient, the hospital of treatment was decided based on the contents described in all cards. In this statistical analysis, STATA software was used (13).
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RESULTS |
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TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONAcknowlegmentREFERENCES |
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Table 1 shows the 5-year relative survival of the OCR testicular cancer patients. The number of cases lost to follow-up at the time of 5 years after diagnosis was 38 (5.4%). The survival was 75.2% [95% confidence interval (CI): 71.9–78.5%] for the total of 709 patients.
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By year of diagnosis, the 5-year relative survival was 59.5% for the patients diagnosed in 1975–77 and increased to 73.9, 72.3 and 80.9% for those diagnosed in 1978–80, 1981–83 and 1984–86, respectively, but it did not improve thereafter and remained at 78.9 and 77.9% for those diagnosed in 1987–89 and 1990–92. By clinical stage, the relative survival was 95.1% for localized stage, 69.4% for regional stage and 33.1% for distant stage. By histology type, the survival was 87.0% for seminoma and 60.8% for non-seminoma germ cell tumors. By size of hospitals where patients were treated, the survival was 83.9% for university and cancer hospital (OMCC), 76.6% for large-sized hospitals with >400 general beds, 69.7% for medium-sized hospitals with 150–399 general beds and 53.5% for small-sized hospitals with <150 general beds and clinics.
According to the EUROCARE study, the 5-year relative survival of testicular cancer patients diagnosed in 1985–89 was 90% (95% CI: 88–92%). It was 79% for those diagnosed in 1978–80 and 92% for those diagnosed in 1987–89 (2). The SEER program shows that the survival was 78.5% for those diagnosed in 1974–76, 91.7% for those diagnosed in 1980–92 and 95.4% for those diagnosed in 1989–96 (3). Therefore, the survival had been over 10% lower in Osaka than in the USA and Europe throughout the period. The distribution of clinical stage in Osaka (localized 61.2%, regional 13.8% and distant 25.0%, calculated from Table 1) was slightly unfavorable than that in the USA for those diagnosed in 1986–91, i.e. localized 66%, regional 20% and distant 12% (8). Distribution by histology type in Osaka (seminoma 59.4%, non-seminoma germ cell tumor 37.4%, others 3.2%, calculated from Table 1) was similar to that in the USA, i.e. seminoma 54.1%, non-seminoma germ cell tumor 40.5%, others 5.2% (9).
Fig. 1 shows the relative survivals of the testicular cancer patients by clinical stage in the earlier period (1975–83) and the later period (1984–92). For comparison, the survival of those patients in the USA diagnosed in 1986–91 reported from the SEER program (8) is also shown in Fig. 1. For the localized stage patients, the survival was 93.3% in the former period and there was no difference between Osaka and the USA. However, for regional and distant stage patients, there were marked differences between Osaka and the USA, although the survival tended to have improved between the two periods in Osaka.
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Fig. 2 shows the relative survivals for the OCR cancer patients by size of hospitals where the patients were treated in the two periods. The survival was highest in university hospitals and cancer hospital (OMCC) and higher in large-sized than in medium-sized hospitals, although it tended to have improved for all three categories of hospitals between the two periods.
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Table 2 shows the results of multivariate analysis of prognostic factors for the OCR testicular cancer patients. Here the analysis was conducted for 582 patients, excluding from the original 709 patients those of no or unknown treatment and of unknown histology type and of other than germ cell tumors. Table 2 indicates that hospital size where patients were treated is a significant or marginally significant prognostic factor for testicular cancer after adjustment for age, year of diagnosis, clinical stage and histology type.
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Table 3 shows the relative survival of 113 testicular cancer patients diagnosed in the OMCC during 1975–93. Almost all of them (112) were treated in the OMCC. The number of cases lost to follow-up after 5 years from diagnosis was only one. The survival was 91.5% (95% CI: 86.0–97.0%) for the total of 113 patients. This figure was significantly higher than that based on the OCR, i.e. 75.2% (95%CI: 71.9–78.5%) in Table 1. The distribution of clinical stage and histology type was slightly more favorable for the OMCC patients than the OCR patients and the number of patients diagnosed before 1980 was relatively small compared with those diagnosed thereafter (Tables 1 and 2).
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In Fig. 3, the relative survival is shown by clinical stage for the OMCC patients diagnosed in 1981–93. For comparison, the survival of those in the USA diagnosed in 1986–91 is also shown. The survival of the OMCC was 99.7% for localized stage, 93.6% for regional stage and 73.5% for distant stage. These figures were similar to those in the USA.
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONAcknowlegmentREFERENCES |
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In the present study, the 5-year relative survival of 709 testicular cancer patients in Osaka, Japan was calculated for the first time based on the population-based Osaka Cancer Registry and it was shown that the survival had remained at the level of >10% lower than that in the USA or in Europe. According to the EUROCARE II study (2), the survival in Europe could be divided into three groups, i.e. high rates (89–93%), intermediate rates (79–84%) and low rates (<50%). The intermediate group included post-socialist countries of Eastern Europe (Slovenia, Slovakia, Poland). The survival in Osaka corresponds to the intermediate rates. It was also shown from the present study that the survival in Osaka was lower for regional and distant stages than in the USA.
In the comparison of the survivals among Osaka, the USA and Europe, however, it should be taken into account that the completeness of the OCR is not so good. As described in Methods, there were 40 DCO cases of testicular cancer in addition to the 709 study subjects diagnosed in 1975–92 in the Osaka Cancer Registry. These DCO cases were excluded from the study subjects, following the methods of the EUROCARE study. In the case of the high proportion of DCO cases there may be unpredictable biases and the survival may be overestimated or underestimated (7). When the 27 cases who were first notified by death certificates and were registered by tracing back to hospitals/clinics were excluded and the study subjects were limited to the 682 cases registered actively by hospitals/clinics, the 5-year relative survival was calculated as 78.2%, only slightly higher than the original 75.2%.
The completeness of registration of testicular cancer in the OCR during 1975–92 was estimated to be 80.5% based on Ajiki et al.’s equation (14), i.e. completeness (%) = [100 – DCN (%) x I/D]/[100 – DCN (%)], where DCN = cases notified first from death certificates, I = incidence cases, D = death cases, as DCN = 40 + 27 = 67, I = 709 + 40 = 749 and DCN (%) = 8.9% from the data shown above and D = 250 from mortality statistics in Osaka. Assuming that all non-registered cases were alive at the time of 5 years after the first diagnosis, the 5-year relative survival was calculated as 80% for the total patients and 82.2% for those diagnosed in 1990–92. Although these figures are overestimated, they remain at a low level of ~10% lower than in the USA and Europe.
According to the SEER program (8), the 5-year survival of testicular cancer patients diagnosed in1986–91 was 95.3% for whites and 86.1% for blacks. The report from England and Wales showed that the survival of the patients diagnosed in 1986–90 was 93% for the most affluent class and 91% for the most deprived class (12). As the survival in Osaka was about 80% for those diagnosed in 1984–92 (Table 1), the survival in Osaka was lower than that for those patients in the socio-economically lowest class in the USA and England and Wales.
By size of hospitals where the patients were treated, the survival was highest for those treated in university hospitals and the cancer hospital and higher for those treated in large-sized hospitals. It was also shown that the survival of those patients diagnosed/treated in the cancer hospital, OMCC was not different from that in the USA or in Europe. Here it should be taken into account that the completeness of the OCR was not so good and that the completeness might differ by hospital size. If, in the extreme case, testicular cancer patients with good prognoses had been under-reported especially in medium- and small-sized hospitals and clinics, then the calculated survival might have been artificially low in those patients treated in these hospitals and clinics. However, there are no means of estimating the completeness of registration by hospital from the data at hand as DCN (%) and the I/D ratio are indices of completeness not for each hospital but for the population as a whole. Hence it is impossible to recalculate survivals by hospitals assuming that all non-registered cases were alive as we did for the total OCR series.
By the Cox proportional hazards model, it was shown that the size of hospitals where the patients were treated was a significant or marginally significant prognostic factor after adjustment for year of diagnosis, clinical stage and histology type. Here, those patients of no or unknown treatment and of unknown histology and of other than germ cell tumors were excluded from the analysis. Excluded patients are those with poor prognoses. When the hazard ratios were recalculated for 575 cases instead of the original 582 cases, limited to those cases registered actively by hospitals and clinics, the hazard ratios were about the same as those in Table 2. Therefore, it can be said that the size of hospitals was a prognostic factor when those with poor prognoses were excluded from the analysis.
Putting together the findings of the present study, it is strongly suggested that there are severe problems in the speed and extension of diffusion of effective chemotherapy for testicular cancer in Osaka. Since the publication of a clinical trial of a three-drug combination chemotherapy (cis-diamminedichloroplatinum, vinblastine and bleomycin) for advanced testicular cancer patients in 1977 (1), the prognosis was reported to have improved remarkably not only in the USA and Europe. In Japan, it was also reported that the results for testicular cancer patients have improved in university hospitals and cancer hospitals. For the diffusion of effective chemotherapy, however, there should be important prerequisites, i.e. the arrangement of infrastructure of hospitals and oncologists. It is suggested from the present study that there are problems in the infrastructure for effective chemotherapy for testicular cancer in Osaka. It is urgently necessary to confirm from the population-based cancer registry data whether or not similar problems exist in other locations in Japan.
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Acknowlegment |
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TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONAcknowlegmentREFERENCES |
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This study was supported in part by a Grant-in-Aid for cancer research from the Japanese Ministry of Health and Welfare (8-2).
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FOOTNOTES |
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+ For reprints and all correspondence: Akira Oshima, Department of Cancer Control and Statistics, Osaka Medical Center for Cancer and Cardiovascular Diseases, 1–3–3 Nakamichi, Higashinari-ku, Osaka 537-8511, Japan
Abbreviations: OCR, Osaka Cancer Registry; OMCC, Osaka Medical Center for Cancer and Cardiovascular Diseases; DCO, death certificate only; EUROCARE study, European Cancer Registry-based Study of Survival and Care of Cancer Patients; SEER program, Surveillance, Epidemiology and End Results program
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REFERENCES |
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Received March 16, 2001; accepted May 14, 2001.
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