In this manuscript we provide the first comprehensive population-based analysis of survival of patients with endometrial cancer from Germany available to date. Overall, age-adjusted 5-year relative survival in 2002-2006 was 81.0%. A moderate age gradient was observed, with 5-year RS decreasing from 90.0% in age group 15-49 years to 74.8% in age group 70+ years. Prognosis furthermore strongly varied by histologic subtypes and stage, with age-adjusted 5-year RS ranging from 43.1% (for sarcoma) to 94.3% (for squamous metaplasia), and reaching 91.2% for localized, 50.5% for regional, and 19.8% for distant stage. For the recent 5-year period under investigation, a trend towards improvement in survival was seen for most subgroups assessed, which was though rather modest and, except for age group 65-74 years, not statistically significant.
We found similar results when data were restricted to Saarland only. Therefore, the previous estimates of cancer survival from Germany, which were often based on Saarland alone, most likely had been representative. However, the extended database allowed much more detailed and precise estimates: For example, due to inclusion of 30,906 cases from multiple registries rather than 1,577 cases from Saarland alone, the standard error for 5-year relative survival of endometrial cancer overall decreased from 1.9% to 0.4%. Furthermore, our estimates of overall 5-year RS of 81.0% for Germany in 2002-2006 are very close to the corresponding estimate of 80.4% for the USA in 2002-2006 , and only slightly higher than the estimated EUROCARE-4 mean of 78.0% in 2000-2002 .
Our finding of no major improvement in survival for most subgroups within the 5-year period is consistent with three large population-based studies [7, 15, 26] which likewise showed that survival of endometrial cancer has been stagnating. For the calendar period 2000-2004, a trend towards improvement in survival was seen in 12 European countries, but reached statistical significance only for Estonia . Furthermore, the EUROCARE-4 study using data from 47 European cancer registries  showed that survival figures remained rather stable over the calendar period 1997-2002, though improvements in survival were seen over the period 1991-1996. A study based on the SEER data from the USA also found no improvement in 5-year relative survival for the period 1998-2003 . These trends are in contrast to observations for earlier periods. A steady increase in 5-year RS estimates for earlier periods had been reported, for example, for the Nordic  and other European countries [28–30], which could be mainly attributed to early diagnosis due to introductions of ultrasonography in the 1980s  and to advances in techniques of endometrial biopsy .
Given that survival of endometrial cancer is already rather good overall, with 5-year RS estimates exceeding 80% in 2002-2006 for Germany and the USA , and approaching 80% in 2000-2002 for most European countries , further improvement may be difficult to achieve and stagnation of survival rates may not be too surprising. So far, screening (e.g., by transvaginal ultrasound) for endometrial cancer in asymptomatic women at average risk is not recommended due to lack of sufficient evidence [32–35]. Increased rates in high-risk histologic subtypes with poor survival such as uterine sarcomas [36–38], as suggested by other studies , also contribute to stagnation of further improvement in overall survival rates. Poor survival of uterine sarcomas is likely due to lack of reliable diagnostic test [36, 37], and to limited beneficial effect of adjuvant therapies .
Our finding of a statistically significant improvement in survival only for age group 65-74 years, but not for other age groups, may reflect enhanced dissemination of effective therapy to older age groups, but not to the "oldest old". A previous analysis of EUROCARE data  also reported that survival in age group 55-69 years improved more than that in age group 70-84 years. Our observations of a less favorable prognosis in elderly women and of a moderate age gradient are consistent with other studies [8, 41, 42]. The less favorable prognosis of endometrial cancer in the oldest age group might be in part attributable to comorbidities and less access to therapeutic innovations [6, 43], as old patients are generally under-represented in cancer clinical trials . Nevertheless, the age gradient in relative survival for patients with endometrial cancer is less pronounced than the age gradient observed for other types of cancer, and 5-year relative survival exceeded 70% even in the oldest age group.
We observed a strong variation in survival by histologic subtypes, consistent with other studies [8, 42, 44]. The predominant theory for the etiology of endometrial cancer is that development and progression of this cancer is strongly related to high bioavailable estrogens and/or low progesterone (unopposed estrogen hypothesis) [5, 45, 46]. The physiological effects of these hormones on the endometrium are transmitted by estrogen receptors (ER) and progesterone receptors (PR) [47, 48]. Given that the expressions and distributions of ER (ER-a and ER-b) and PR (PR-A and PR-B) have been associated with different survival of endometrial cancer in several studies [49, 52], it is plausible to assume that different profiles of ER/PR expressions and distributions in histologic subtypes of endometrial cancer may contribute to the strong variation in survival by histologic subtypes.
In agreement with previous studies (7-9, 42], we found a strong gradient in survival by stage. Early detection is the key for overall good prognosis of endometrial cancer as most women diagnosed at localized stage can be cured by surgery alone . Endometrial cancer is usually diagnosed at an early stage (86% in our data) due to abnormal vaginal bleeding. Women (especially after menopause) experiencing abnormal vaginal bleeding should undergo diagnostic tests, e.g., endometrial sampling with cytological examination and measuring endometrial thickness with transvaginal ultrasound (TVU) [34, 54]. Although there is insufficient evidence to recommend screening for endometrial cancer in asymptomatic women at average risk, women at very high risk of endometrial cancer should consider beginning annual testing for early detection at age 35 years [32, 33].
Although information on treatment was too incomplete to be used in our data, surgery is the cornerstone of therapy for endometrial cancer regardless of stages of the disease . For patients with advanced stage or with aggressive histologic subtypes, adjuvant therapy is desirable. In addition, centralized care provided by gynecologic oncologists is also an important prognostic factor for endometrial cancer, particularly for patients diagnosed at distant stage as they are more likely to undergo staging surgery and to receive adjuvant chemotherapy [56, 57].
Our study has several strengths and limitations. This is the first population-based study from Germany providing survival estimates of endometrial cancer, using a pooled German national dataset with a large sample size (30,906 cases) and covering a population of 33 million people (40% of the German population). Furthermore, this study provided most up-to-date and comprehensive survival estimates of endometrial cancer in the early 21st century, using the techniques of standard and model-based period analysis. Limitations are mainly related to limited staging information. Stage information was available for 44% of cases only, precluding joint stratification by stage and histology in time trend analyses. Patients with stage information were on average 2.6 years younger and had more often adenocarcinoma than carcinoma NOS, sarcoma or other (mixture) histologies, and had a slightly higher age-adjusted survival than those without stage information (81.1 (0.4)) versus 79.5 (0.6). Another limitation concerns lack of treatment information.