Abstract
In the present study, we report the first analysis of the clinical managment of patients with primary ovarian cancer following the summarized data of the Joint Clinical Registries of the Coordinating Tumor Center of Berlin (Dachverband Tumorzentrum Berlin e.V.). All data were summarized for the period of 2005 to 2008 regarding age, histopathology, time of surgical intervention, follow-up and survival, based on 1124 provided data sets of patients with suspected ovarian tumours. We identified 946 patients with a diagnosis of primary ovarian cancer, mostly of advanced T3 tumour stage (63.7%), FIGO III and IV stage (40.6%) or grade II and III (91%) histology. The median age at time of diagnosis was 61 years (range 15 to 94 years). Most patients (n=414, 69.8%) underwent cytoreductive surgery within one month of diagnosis. The median follow-up period was 26 months; 241 patients died in the analyzed period. The calculated 3-year survival rate was 63.3%, although the median overall survival has not yet been reached. We detected positive correlation of tumour stage (p<0.001) and of FIGO stage (p<0.001) with survival, and these were evaluated as being prognostically significant. The implementation of institutional based clinical registries as part of the modern clinical managment of patients with ovarian cancer is feasible and well accepted inside the gynaecological departments of Berlin.
Annually 9670 women are diagnosed with primary malignant ovarian tumours according to the recent epidemiological data for Germany (1), where epithelial ovarian cancer representing with 90% the largest group (2). Ovarian cancer occurs with an incidence of 15.8 per 100.000 and is the fifth most common cancer in German women, but with respect to mortality (5636 death events, 2006) it is the deadliest of all gynecological malignancies (1).
Although more recent data clearly shows an improvement in treatment and survival during the last decades, the prognosis of patients with ovarian cancer remains poor (1, 3). Due to the lack of specific symptoms, most patients are diagnosed with advanced stage disease when it has spread throughout the peritoneal cavity (FIGO III and IV) (4). Recent advances in the histopathology of epithelial ovarian tumours recognized different subtypes and supports the evidence that ovarian cancer represents a groups of distinct entities with different types of carcinogenesis, which requires an individual approach to each (2). Surgical staging, based on a midline incision laparotomy with careful examination of the abdominal cavity, is essential for individual prognosis (2). The state of the art therapy of advanced stage disease includes a primary cytoreductive surgery followed by combined chemotherapy of platinum and paclitaxel. Recent improvements in debulking surgery demonstrate a significant survival benefit for patients, in particular those with complete tumour resection (5, 6). Current studies clearly indicate that in addition to time, extent and quality of ovarian cancer surgery, surgical outcome is more related to surgeon- and hospital-related factors than to intrinsic or tumour biological characteristics (7, 8). Data for quality of care for ovarian cancer demonstrated a remarkable variety of the adherence to treatment guidelines among German hospitals. A special German-wide program started in 1999 aimed at the improvement of outcome in ovarian cancer, including regularly updates of the guidelines and educational programs (8).
Improvement of clinical data assessment and regular surveys of the pattern of care may help to optimize the management of oncological patients (8-10). Clinical cancer registries play an essential role, collecting data about diagnosis, treatment and follow-up of cancer patients. Although gynaecological cancer has one of the highest mortality rates german-wide, there is no sufficient data about treatment and survival of patients with gynaecological cancer. A special program supported by the German Ministry of Health started in 2004 aiming to improve further development of regional tumor centers and clinical registries. In Germany, these are organised on a regional principle, although no general standards for data collection and evaluation were established. Commonly in most former eastern German states, the structures of the previously established regional registries (before 1990) still exist and were optimized recently (11). For the federal state of Berlin, the Coordinating Tumor Center (Dachverband Tumorzentrum Berlin e.V.) saw in the implementation of clinical registries a main objective and actively supported all Oncological Departments in participating. Here, clinical registries are primarily based at the reporting institutions (primary, secondary or tertiary level hospitals). In this survey, we present the first prospective analysis for Berlin of the Joint Clinical Data within the partnership of the regional Gynaecological Departments with the Coordinating Tumor Center of Berlin.
Patients and Methods
Based on the reports to the Coordinating Tumor Center of Berlin (Dachverband Tumorzentrum Berlin e.V.) we summarized and analyzed for the first time data of patients with primary ovarian cancer treated in Berlin. The established clinical registries at 13 participating Gynaecological Departments provided data regarding 1124 patients registered for the period of four years between 2005 to 2008.
Most participating clinical registries encode the patients' data using the Giessener Tumordokumentationssytem (GTDS) software (12). The provided clinical data were analyzed with respect to diagnosis, age and time of the surgical therapy, FIGO, TNM and grading. The current WHO and FIGO classifications were used for the clinical staging, and the Gynecologic Oncology Group criteria were used for the histologic grading (3, 13). Regular follow-up was performed by the participating Gynaecological Departments and defined as the interval from the histological confirmation of diagnosis until dead or last contact with the patients following the current guidlines (2,14), so that we were also able to analyze the survival time.
All statistical evaluations were performed using SPSS for Windows statistical software, version 18.0 (SPSS Inc., Chicago, IL, USA). All performed evaluations were carried out for the generation of a hypothesis only. Therefore, all analyses were carried out in a primarily descriptive manner. For continuous variables, median and range were need, otherwise frequency and percentages were calculated. For the survival analysis the Kaplan Meier method with the Log rank test and the Cox regression model were performed. A p-value of less than 0.05 was considered to have statistical significance.
Results
During the period from January 2005 to December 2008, 13 out of the 19 Gynaecological Departments of Berlin (68.4%) provided regular clinical data to the Coordinating Tumor Center group. Thus 1124 patients with suspected ovarian tumours were identified after exclusion of benign tumours and recurrences. A total of 178 of the diagnosed cases represented borderline ovarian tumours, so that for the final analysis data for 946 primary ovarian cancer cases were utilized.
On the basis of this data, the cumulated incidence of primary diagnosed ovarian cancer for the Federal State of Berlin was 283 cases in 2005, 276 in 2006, 195 in 2007 and 192 cases in 2008. The median incidence for the analyzed period of four years was 236 cases of primary ovarian cancer. According to the place of residence, 663 women (70.3%) were registered in Berlin, 143 patients (15.2%) came from other German federal states and 137 (14.5%) from the adjacent state of Brandenburg. For 3 patients (0.3%) there were no residence data in the registries.
Patients and tumour characteristic. Patients with primary ovarian cancer diagnosed in Berlin between 2005 and 2008 had median age at time of diagnosis of 61 years, with a range from 15 to 94 years. Following the current WHO classification, 158 (23.9%) of the patients presented with T1 tumour stage and 68 (10.2%) with T2 stage ovarian cancer. Most patients (n=424, 63.7%) were diagnosed with T3 stage ovarian cancer, whereas for 12 patients (1.8%) only Tx-registration and for 4 women (0.6%) incomplete data were available. For 280 of all recruited patients (29.6%) the tumor stage data were not provided to the clinical registries.
According to the FIGO classification, 59 of the patients (12.9%) showed FIGO stage I tumours, 15 (3.3%) FIGO stage II, 153 (33.4%) FIGO III and 231 (50.4%) FIGO stage IV tumours. Thus, following the current clinical registry for Berlin, 384 of the patients with primary ovarian cancer (40.6%) presented advanced stage disease at time of diagnosis (see Table I). Remarkably for 488 (51.6%) of all primary registered ovarian cancer patients, the FIGO data were not provided. Clinical data for grade II and III tumours were recorded for 630 patients (91.0%), compared to 50 cases with well differentiated ovarian cancer grade I (7.2%). For one patient (0.1%), an undifferentiated tumour grade 4 was diagnosed, whereas 11 cases (1.6%) presented a Gx status. The group with incomplete grading comprised 26.8% of all patients (n=254).
Time of primary surgical intervention. The interval between diagnosis and primary surgical intervention was also part of the clinical registry and data were provided to the Coordinating Tumor Center group. The largest group of patients (n=414, 69.8%) underwent cytoreductive surgery within one month of diagnosis. For 58 women (9.8%), the surgery was performed between 1 and 3 months, and for other 29 women (4.9%) between 3 and 6 months after diagnosis. Primary surgical intervention atfer more than 6 months was documented for 91 patients (15.4%). For 354 of all cases (37.4%) the time point of the surgery was not specified.
Follow-up and survival analysis. The median follow-up period was 26 months with a range of 0 to 52 months. During the observation period, 241 (25.5%) patients died from their disease. We identified 71 (29.5%) death events in the first six months, and 39 (16.2%) between 6 to 12 months after primary diagnosis. A total of 64 (26.6%) of all death events were registered in the second year after diagnosis (≥12months) and 34 (14.1%) in the third year (≥24 months of diagnosis). Eight women (3.3%) died 3 years or more after diagnosis. For 25 death events, the interval to primary diagnosis was not provided (Table I). The calculated 3-year survival rate was 63.3%, but the median overall survival has not yet been reached.
Analysis of prognostic factors for primary ovarian cancer. After the evaluation of all registered clinical variables we identified a survival benefit for patients with small tumours (T1 and T2 stage) and also with early stage disease (FIGO I and II). The calculated survival rate showed positive correlation to the tumour stage (p<0.001) and the FIGO stage (p<0.001).
Discussion
This is the first systematic and prospective analysis of the Joint Clinical Registries data of Berlin's Gynaecological Departments under the guidance of the Coordinating Tumor Center group (Dachverband Tumorzentrum Berlin e.V.). The successfull implementation of regional clinical registries in Germany is not common following a current goverment survey (11). A regional-wide assessment of clinical data according to the requirements of clinical registry have been established in only 6 out of 16 German federal states, most of them representing advanced form of the previously established cancer registries of the East German Health System. For Berlin, 13 hospitals of different health care levels are joined in 8 subregistries, although no regulatory requirements have been established. In our analysis, we summarised these results for the first four years of registration. Thus our report represent nearby 70% of all gynaecological patients treated due to ovarian tumours in Berlin. The Coordinating Tumor Center group initiated a program for advanced implementation of the Berlin-wide activities of the clinic based registries. A minimal data set was consistently defined: age, place of recidence, TNM stage, FIGO stage, grading, time of surgery and the follow-up period.
Ovarian cancer is predominantly a disease of elderly women (1,3). For the 946 patients analyzed, the median age at time of diagnosis was 61 years, and thus represents exactly the age-adjusted distribution of primary ovarian cancer in Germany (1). The median incidence of 236 cases/year which we evaluated is certainly low in comparison to the estimated 360 cases/year (10.5 per 100.000) (1), but correlates at 65.6% to a good representability of our survey.
The summarized clinical data showed that the most of the 946 patients presented advanced T3 tumours (63.7%) with FIGO III and IV stage (40.6%) and grade III (91%) histology. Although a remarkable proportion of the registry data were not available for statistical analysis, the fundamental characteristics of epithelial ovarian cancer as an advanced stage disease at time of primary diagnosis, also characterize also most patients of the Berlin, confirming with other population based surveys (15-17). Despite to a short follow-up period, the evaluated 3-year survival of 63.3% represents a good level of implementation of the therapy guidlines for the treatment of patients with ovarian cancer and corresponds to that of other European and German surveys (8, 16). Especially with respect to the low survival rate for ovarian cancer clinical registries may provide extensive influence for the successful implementation of new treatment options and therapy guidelines in clinical practice (9, 10).
Current surveys about the treatment of ovarian cancer patients, additional scientific activities of the treating physicians and their organization in Europe highlighted substantially deficits and great national and regional differences (8, 16, 18). The implementation of nation wide and regional clinical registries may substantially support the pattern of care for ovarian cancer and is strongly supported by the regional and federal authorities (11). Similar criteria for the required data set and data recruiting mode have to be determined. The development and implementation of applied software solutions is essential for optimization with respect to the time and manpower intense procedures (9, 12, 15). The pool of the provided data of the Coordinating Tumor Center of Berlin can be used for internal quality of care studies, educational, scientific programs and for further analysis of distinct financial aspects of the clinical management, and may help to initiate further surveys.
Summarizing, these first results of the Joint Clinical Registries of Berlin about the management of ovarian cancer patients are encouraging. Gynaecological Departments at different health care levels and with different clinical orientation were able to implement sufficiently the clinical registry and to comply with most requirements for the diagnosis, treatment and follow-up of patients with ovarian malignancies.
- Received March 24, 2011.
- Revision received June 9, 2011.
- Accepted June 10, 2011.
- Copyright© 2011 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved