Annals of Oncology Advance Access originally published online on April 29, 2007
Annals of Oncology 2007 18(7):1253-1259; doi:10.1093/annonc/mdm126
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© 2007 European Society for Medical Oncology
supportive care |
Trends in population-based cancer survival in Germany: to what extent does progress reach older patients?
1 Division for Clinical Epidemiology and Ageing Research, German Cancer Research Center, Heidelberg
2 Saarland Cancer Registry, Saarbrücken, Germany
* Correspondence to: Prof. H. Brenner, Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Bergheimer Strasse 20, 69115 Heidelberg, Germany. Tel: +49-6221-548140; Fax: +49-6221-548142; E-mail: h.brenner{at}dkfz.de
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Abstract |
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Background: The ageing of populations makes outcome monitoring among elderly cancer patients particularly important.
Patients and methods: Using data from the population-based Cancer Registry of Saarland, we examined age-specific trends in 5-year relative survival from 1979 to 2003 for patients with 15 common cancers in Germany. Model-based period analysis was applied to estimate 5-year relative survival for four age groups (15–54, 55–64, 65–74, 75+) in the periods 1979–1983, 1984–1988, 1989–1993, 1994–1998, and 1999–2003.
Results: Overall, 5-year relative survival improved steadily from 42.2% in 1979–1983 to 56.7% in 1999–2003. From the youngest to the oldest age group, 5-year relative survival increased by 14.5, 12.1, 12.5, and 8.4 percent units, respectively, after adjusting for changes in the spectrum of cancer sites, and survival significantly improved for 10, 12, 11, and 5 cancer sites, respectively. The age gradient particularly increased for cancer sites with major progress in chemotherapeutic treatment regimens, such as ovarian cancer, non-Hodgkin’s lymphoma and leukemia.
Conclusions: Relative survival of cancer patients increased considerably for many forms of cancer in Germany from 1979 to 2003. Increases were much less pronounced among elderly patients, leading to an increasing age gradient in prognosis.
Key words: age-specific survival trends, cancer survival trends, elderly, Germany, modeling
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introduction |
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In most developed countries, both the absolute number and the proportion of elderly (65+ years) people are rising rapidly, and so do the number and proportion of elderly cancer patients, given the strong increase of cancer incidence with age [1]. These demographic trends present a double challenge, on the one hand from the public health point of view, as the social cost of cancer treatment will be rising strongly, and on the other hand from the clinical side, as the clinical management of cancer in elderly patients is characterized by increased complexity, due to potentially impaired treatment tolerance, increased prevalence of serious comorbidity, and poor social support in the elderly [2, 3]. Little is known about the exact extent these factors have on survival outcomes in the elderly [4].
During the past two decades, the survival of cancer patients has improved considerably for many forms of cancer in European countries [5], and period survival estimates, recently reported from several countries including Germany [6–8], indicate that the improvement in survival has been ongoing during the most recent years for which data are available. At the same time, cancer survival in elderly patients has often been found to be lower than among younger patients for many cancer sites, even if relative survival was considered, which corrects for differences in background mortality at different ages [5, 9, 10]. According to the results of a recent study, for many forms of cancer, elderly patients have profited less from survival increases during the last decade in the United States than younger patients [11]. With the ongoing shift towards more elderly cancer patients in the future, monitoring of survival outcomes in these patients is of high priority. In this paper, we describe and examine cancer survival trends among different age groups in Germany from 1979 to 2003.
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database
Data from the Saarland Cancer Registry were used. The registry covers the entire population (
1.06 million people) of the federal state of Saarland in the South West of Germany since 1967. The completeness of incidence data for the registry, which has been a regular contributor to international studies [12, 13], has been estimated to be >95% [14]. Patients’ vital status is regularly assessed via record linkage with statewide mortality data. Patients were included if they were at least 15 years of age at the time of the diagnosis, had a first diagnosis of cancer, and were not notified by death certificate only or diagnosed by an autopsy only. Site-specific analyses, for which cancer sites were classified according to International Classification of Diseases-9, were restricted to the 15 most commonly diagnosed cancers during 1999–2003 (these cancers accounted for 83.9% of all cancers diagnosed in 1999–2003).
survival calculations
All estimates presented in this paper are relative survival estimates [15], which were calculated by the period analysis methodology [16], using calendar period-, age-, and sex-specific life tables for Germany. Period estimates of survival, which are based on the survival experience of patients only during the calendar years for which the estimates are derived [17], have been shown to closely predict survival later observed for patients diagnosed in that period [18–20]. Patients were categorized into four age groups as follows: 15–54, 55–64, 65–74, and 75+, and period survival estimates for the following 5-year periods were calculated: 1979–1983, 1984–1988, 1989–1993, 1994–1998, and 1999–2003.
Overall and age group-specific survival estimates were calculated for all cancer sites together, and for each of the 15 common cancer sites separately. In the analyses of all sites together, in addition to the crude analysis, the survival estimates were adjusted for the change in the spectrum of cancer sites over the examined 25-year period, using the 1999–2003 period as standard. Adjustment was done by assigning cancer site-specific weights to patients with various types of cancers before survival analysis, so that the overall weight for each cancer site was equal in all periods, according to the method developed by Brenner et al. [21]. This adjustment method was also used to adjust for age in the comparison of overall 5-year relative survival estimates for individual cancer sites separately (Table 3). Calculations for all sites together, and of the cancer spectrum adjusted survival estimates were done on the SAS 9.1 platform [22], by the publicly available SAS macro adperiodh [21]. For individual cancer sites, estimates for all ages together and age group-specific survival, as well as tests for differences in the overall 5-year survival estimates and for trend were obtained according to a model-based approach, as described in detail by Brenner and Hakulinen [23]. Briefly, Poisson regression models for relative survival [24] were used, in which excess mortality was modeled as a function of year of follow-up (categorical variable) and time period (numerical variable, 1 = 1979–1983, 2 = 1984–1988, 3 = 1989–1993, 4 = 1994–1998, 5 = 1999–2003), using the logarithm of the person-time at risk as the offset.
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patient characteristics
Table 1 describes the numbers and age distributions of cancer of patients included in this analysis. The total number of patients registered with cancer has increased by >40% from the first (1979–1983) to the last (1999–2003) 5-year period. The largest rise, >200%, was seen in the occurrence of prostate cancer; rises in the occurrence of skin melanoma, non-Hodgkin’s lymphoma, and oral cavity, colon, kidney, pancreatic, and breast cancer were also above average. A steady decline was seen in the number of stomach cancer cases (overall –31%), while the decrease in urinary bladder cancer cases is most likely due to the removal of superficial papillary urothelial neoplasms from malignant tumors in the early 1990s [25]. As the total population of Saarland was very stable throughout the study period (with fluctuations between 1.042 million and 1.084 million over the entire period), the described changes in case numbers closely correspond to changes in crude cancer incidence rates.
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The median age of patients at diagnosis has remained rather stable for most sites during the study period. Changes of >2 years between the first and the last period were seen for patients with prostate cancer (a decrease from 73 to 69 years), and for patients with cancers of the oral cavity, kidney, and skin melanomas (rises of 3, 4, and 6 years, respectively). Overall, 57.5 percentage of patients were aged 65 or older at diagnosis in 1999–2003. The proportion of younger patients was much higher than average among patients with oral cavity cancers, skin melanomas, and breast cancer, and lower than average among patients with prostate, colon, bladder, pancreas, and stomach cancer.
overall survival
Table 2 provides estimates of crude and cancer spectrum adjusted 5-year relative survival for all cancer sites overall and for each age group during the study period. Crude 5-year relative survival increased from 42.2% in 1979–1983 to 56.7% in 1999–2003, with steadily rising increases in each consecutive period (2.8, 2.9, 3.4, and 5.4 percent units, respectively). Five-year relative survival was highest in the youngest age group and lowest in the oldest age group throughout the study period. A similar increase in 5-year survival over time was seen in all age groups. After accounting for changes in the spectrum of cancer sites, the increases in the 5-year overall relative survival from period to period were reduced to 2.2, 2.7, 3.0, and 3.8 percent units, respectively. In the age groups 55–64, 65–74, and 75+, changes in the spectrum of cancer sites were responsible for 2.2, 3.8, and 5.8 percent units of the observed total rise in overall 5-year relative survival, respectively. Improvements in the survival of patients in the oldest age group during the 1980s was mostly due to changes in the spectrum of cancer sites, and major improvements in adjusted survival occurred only after 1993. Overall, 5-year relative survival increased by 14.5, 12.1, 12.5, and 8.4 percent units from the youngest to the oldest age group after adjustment for changes in the spectrum of cancer sites, and the adjusted age gradient increased substantially during the study period.
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site-specific trends
Table 3 shows site and age group-specific changes in the 5-year relative survival of cancer patients from 1979–1983 to 1999–2003. The largest improvements were seen for patients with colon, rectum, and prostate cancer, as well as for patients with non-Hodgkin’s lymphomas and leukemia. For all of these cancer sites, 5-year relative survival improved by
16–20 percent units. Improvements of 10–15 percent units were seen for patients with stomach, breast, ovarian, and kidney cancer and for patients with skin melanomas. For patients with lung and corpus cancer, a moderate improvement was seen (7.0 and 4.5 percent units, respectively), while no major improvement, or even some decline, was observed in the prognosis of patients with oral cavity, pancreas, and urinary bladder cancer.
age-specific trends
Overall, significant improvements were seen for 10, 12, 11, and 5 cancers in the age groups 15–54, 55–64, 65–74, and 75+, respectively. A more detailed presentation of age-specific trends is given for selected forms of cancer in Figure 1.
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gastrointestinal cancers
For patients with stomach cancer (Figure 1, upper left graph), 5-year relative survival increased in all age groups, even though the increase was not statistically significant in the youngest age group (Table 3). Survival nearly doubled among patients aged 55–64 and 75+, but improvements were only moderate among the other age groups. Overall, the age gradient was slightly reduced, and survival converged for the two youngest and the two oldest age groups by the latest period. For patients with colon cancer (Figure 1, upper right graph), improvements increased with age, and the age gradient of 21.7 percent units between the youngest and the oldest age group for the period 1979–1983 was reduced to 8.2 percent units by the latest period. Among patients with rectum cancer, all age groups experienced a significant improvement. A quite stable age gradient of 10–15 percent units between the oldest and all other age groups was seen throughout the five examined periods (trends not shown).
gynecological cancers
Among patients with breast cancer (Figure 1, left side, second from top), a steady improvement in survival over time was seen in the three younger age groups, while patients >75 years of age only started to experience moderate improvement in survival in the latest period. As a result, the age gradient increased from 1.7 percent units in 1979–1983 to 9.9 percent units in 1999–2003. Among patients with ovarian cancer (Figure 1, right side, second from top), a strong continuous trend of improving survival was seen for patients aged 15–54, while the survival of patients aged 55–74 started improving only from 1994 on. Finally, among patients aged 75+, there was no improvement in survival during the study period. The age gradient therefore substantially increased over time, and reached 50 percent units, the strongest age gradient among the examined cancer sites in 1999–2003. Among patients with endometrial cancer, survival improved moderately for patient's aged 55–74, but not for the youngest and the oldest age groups (trends not shown).
urological cancers
For prostate cancer patients (Figure 1, left side, third graph from top), survival improved steadily from 1989 on in the age groups 15–74, while improvements were seen from 1993 on only in the age group 75+. In the latter group, relative survival lagged behind the survival of younger patients by 10 percent units since then. Among patients with bladder cancer, a strong age gradient, with survival differences of 20–30 percent units between the youngest and the oldest age group was seen throughout the study period (trends not shown). The prognosis of patients with kidney cancer improved considerably during the study period, and the age gradient, which was most pronounced between age groups 55–64 and 65–74, widened to >20 percent units (trends not shown).
other common cancers
Among patients with lung cancer (Figure 1, third graph from the top, right side), some modest improvement was seen for all age groups, but survival remained generally very poor. The age gradient was rather small throughout the study period. In the most recent period (1999–2003), 5-year relative survival was 23% in the youngest age group, compared with 17% in all other age groups. Among patients with non-Hodgkin’s lymphomas (Figure 1, left side, bottom graph), strong improvement in 5-year relative survival by 30 percent units occurred among patients aged 15–64, while improvement was smaller for those aged 65–74, and only weak, nonsignificant improvement was seen in the survival of the oldest patients. As a result, the age gradient increased to 40 percent units by 1999–2003. For patients with leukemia (Figure 1, right side, bottom graph), 5-year relative survival of patients in the age groups 15–64 and 65–74 doubled between 1979–1983 and 1999–2003, with a persisting gradient of 10 percent units between these age groups. No improvement was achieved among patients aged 75+. This way, the overall age gradient rose to >30 percent units.
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discussion |
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From 1979 to 2003, 5-year relative survival of cancer patients improved substantially, and nominally approximately equally in all age groups among patients diagnosed with cancer in Saarland. However, after adjustment for the change in the spectrum of cancer sites (which effectively adjusted for the overall effect of decreasing stomach cancer incidence and increasing prostate cancer incidence), this improvement was less pronounced among older patients than among younger patients, resulting in an increasing total age gradient over time. In the site-specific analyses, significant increases in 5-year relative survival were more often seen among age groups <75 years than among patients >75 years of age.
Generally, better treatment or a more favorable stage distribution by wider use of screening measures, increased health awareness, or prompter diagnostic work-up may explain improvements in survival. In the study period, systematic screening was only available for breast (clinical breast examination), colorectal (fecal occult blood testing), and prostate cancer (digital rectal examination) in Germany. As the utilization of these measures has been generally low [26], and nationwide colonoscopy (since 2002) and mammography (since 2004) screening programs were only started recently, systematic screening is unlikely to have contributed strongly to the survival improvements during the study period. Prostate-specific antigen (PSA) testing is currently not included in the German cancer screening program, although a clinical guideline exists [27]. As the Saarland Ministry of Health was strongly [28], although ultimately unsuccessfully, promoting for a nationwide PSA testing recommendation, it is possible that opportunistic PSA screening contributed to the survival improvement seen for patients from the 1990s on.
Significant advances were made in the treatment of many different cancers during the study period. For colon cancer, advances in adjuvant chemotherapy, which is well tolerated by the elderly [29, 30], and generally high operation and resection rates even among elderly patients in Germany [31], may explain the rise in survival and the decrease in the age gradient during the study period.
For breast cancer, advances in adjuvant chemotherapy and hormonal therapy contributed to improvements in survival [32]. The widening of the age gradient may be explained by the less strictly applied treatment guidelines among postmenopausal women and the elderly than among younger women in Germany [33]. Furthermore, delayed presentation [34, 35] and later stage, both associated with lower survival, were also found to be associated with older age in Germany [36]. For skin melanomas, earlier diagnosis as well as better disease management was indicated as contributing factors to improving survival [37].
The strongest rises in the age gradient occurred for cancer sites with chemotherapeutic treatment regimens, such as ovarian cancer, non-Hodgkin’s lymphoma, and leukemia. For ovarian cancer, in Germany, widespread deficits in compliance with existing treatment guidelines were found even in hospitals participating in cooperative studies [38]. Furthermore, older age was associated with lower survival, even after controlling for stage and comorbidity [38]. International studies identified undertreatment among elderly patients, irrespective of their comorbidity status [39, 40], and the lack of well-designed clinical trials as potential reasons for suboptimal care among ovarian cancer patients [41, 42].
Among patients with non-Hodgkin’s lymphoma, advanced age was found to be associated with decreased use of chemotherapy, irrespective of the presence of comorbidity [43]. For patients with leukemia, long-term clinical experience indicates that while treatment outcomes improved considerably for younger adults in the recent decades [44], only little improvement could be achieved among elderly patients, mainly due to frequent treatment resistance, toxicity, treatment-related death, and cytogenetic abnormalities [45, 46].
Widening age gradients in population-based cancer survival were reported from the United States before [11]. As elderly patients are frequently underrepresented in cancer clinical trials [47], the generalizability of trial results for elderly patients is questionable [48]. While existing data indicates that for the fit elderly, most of the available treatment regimens can be safely administered and are as effective as among young patients [30, 49], there is a lack of knowledge about optimal treatment of elderly cancer patients with serious comorbidities. Comprehensive geriatric assessment of elderly patients may help to optimize treatment among this large group of cancer patients [50].
Among the strengths of this study, it is noteworthy that the use of period analysis allowed us to provide more up-to-date age-specific survival estimates than were available before. Furthermore, application of a novel modeling approach [23] enabled enhanced precision of survival estimates and enhanced the power of trend tests compared with application of ‘conventional’ period analysis. On the other hand, several limitations have to be kept in mind. Estimates for the youngest and the oldest age groups for some cancer sites could not be separately evaluated due to small sample sizes. Survival trends for bladder cancer have to be interpreted with caution due to the change in malignancy criteria over time. Furthermore, detailed data on stage at diagnosis for all examined 5-year periods could have improved the possibility for interpreting the results.
In conclusion, long-term survival has improved substantially for the majority of the 15 examined cancer sites in the last two decades in Germany. However, the improvement among older patients was distinctly smaller for many forms of cancer than improvement among younger patients, and for several cancer sites, no improvement at all in the relative survival of the elderly was seen. As the number of elderly patients will be on the rise in the future, it remains highly important to optimize cancer care among this growing segment of the cancer patient population.
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This study was carried out in the framework of the IMPROVE Study, with the support of the Deutsche Krebshilfe (German Cancer Aid), grant no. 70-3166-Br5. There is no conflict of interest.
Received for publication October 30, 2006. Revision received March 14, 2007. Accepted for publication March 14, 2007.
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