Clinical Stages in Patients with Primary and Subsequent Cancers Based on the Czech Cancer Registry 1976–2005

Of 1,486,984 new cancers registered in the Czech Cancer Registry in 1976-2005, 290,312 (19.5%) were multiple malignant neoplasms (MMNs), of which there were 65,292 primary and 89,796 subsequent cases in men and 59,970 primary and 75,254 subsequent cases in women. The duplicities were higher in women, and the triplicities and others (3–6 MMNs) were higher in men. The most frequent diagnoses were the primary cancers of skin, gastrointestinal and urinary tract, male genital organs, respiratory tract in men, and cancers of skin, breast, female genital organs, and gastrointestinal tract in women. The analysis of the early and advanced clinical stages shows that the number of subsequent advanced stages increased after primary advanced stages. Their time-age-space distributions visualized maps of MMNs in 14 Czech regions. These results support the improvement of algorithms of dispensary care for the early detection of the subsequent neoplasms.


Introduction
The health status of the Czech population can be seen as very vulnerable, mainly because of the high risk of cancer especially in younger age. This fact is confirmed by data in Globocan 2008 [1]. Cancer diagnoses are registered since 1959. The IARC criteria are used were for their notificationed since May 1976 by criteria of the IARC. The annual surveys of Health Information and Statistics of the Czech Republic [2] confirmed the continued trend of cancer occurrence, observed in the Czech areas from 1905 [3] and continuously described from 1933 [4]. The cancer incidence increased from 24,471 (254.4/100,000) in 1959 over 35,407 (347.5/100,000) in 1977 to 78,846 (751.5/100,000) in 2009 [2]. In view of new diagnostic and treatment modalities, the prevalence of cancers (ICD-10: C00-97, D00-09) increased from 174,311 (1,682.2/100,000) in 1989 to 461,545 (4,510/100,000) in 2005. Under the conditions of continuous diagnostics, treatment, medical surveillance, and cancer evidence, the survivors can reach in 2015 nearly 317,000 cases in men (of which 33.2% in age 35-64 years) and 434,000 in women (of which 42.6% in age 35-64 years) [5]. The differences between the numbers of cases and numbers of persons indicated the multiple malignant neoplasms (MMNs). After the preliminary report of their trend [6], this paper is another contribution to this issue.

Methods
The data of MMNs were based on the number of cancers reported to the Czech Cancer Registry between May 1976 and December 2005 and were verified and anonymised up to October 17, 2007. The percentage of multiple cancers of all diagnoses (ICD-10: C00-97, D00-09, D37-48, i.e. including the skin cancer) in males and females was compared with the number of newly diagnosed cases in the same codes. The primary and subsequent cancers were prepared in contingency tables and analysed by age, time and space distribution,          (Figures 3, 4, 5, 6, 7, 8, 9, 10, and 11). The most frequent values of primarysubsequent cancers of 14 regions reached the population of Northern Moravia-primary 12.7% and subsequent 13.7%, Prague-primary 11.8% and subsequent 11.8%, and Southern Moravia-primary 11.8% and subsequent 11.7%. The distribution of advanced stages presents two percentage values.

Results
The comparison with total advanced stages in subsequent cancers was higher in regions nos. 11 (12.   4 (9.7%), and 1 (9.5%), while the comparison with all subsequent cancers in the relevant region was higher in regions nos. 6 (15.4%), 7 (14.7%), 4 (13.6%), 5 (13.6%) and 13 (12.4%) as an indicator of late diagnosis of subsequent cancer during medical surveillance (Table 3)  stages featured 40.3% in men and 36.9% in women. Of total deceased cases were 30% early stages in men and 39.8% in women, 11% advanced stages in men and 12.1% in women; the unknown stages featured 11% in men and 12.1% in women.

Discussion
From ongoing analysis of Cancer Registry database were published the results of the MMNs of breast [7], skin [8], prostate [9], gastrointestinal tract [10], brain [11], lung [12], head and neck [13], testis [14], and penis cancer [15]. We pointed to the current and future relationships of MMNs with ethical and economic burden of the Czech population [16]. We used experiences of more than 50 references, concerning the MMNs. Unfortunately the excellent source which analysed the MMNs of SEER database [17] did not contain data about clinical stages as well as the most of another recent reference [18]. Registered new cases of malignant neoplasms contain also other primary subsequent cancer diagnoses, first described by Billroth and von Winiwarer in 1889 [19]. As their possible causes were assessed the previous radiotherapy [20][21][22][23] and chemotherapy [24][25][26][27][28], dialysis [29], transplantation [30][31][32], and genetic predisposition [33,34]. Their relationship for the risk of the MMNs was not statistically significant. Nevertheless, there is an agreement that the mutual coincidence of these causes can promote the occurrence of subsequent cancers with high burden on patients, their families, and oncologists, including the extraordinary difficulty of palliative care in the terminal period.

ISRN Oncology
It can be assumed that the dispensary care can bring except the metastasis also other topographically and histologically different cancers. Their treatment has similar conditions by clinical stages even when the subsequent cancer can change the treatment scheme of the primary disease. 22,607 advanced stages, that is, 13.7% of all 165,050 subsequent cases during 29 years-is it high or low number? It is important to note that the number of subsequent advanced stages increased with advanced stage of primary disease. These results can contribute to the algorithms of dispensary care The presented maps of MMNs by clinical stages are an example of using spatial analysis in our epidemiological research. Spatial epidemiology is the study of the geographical variation in disease risk, incidence, or prevalence [35]. As a growing field of research, spatial epidemiology provides new insights into multiple cancers as it pertains also to the management of permanent medical surveillance in cancer patients [36] and prevention in the health population by modern visualization [37].

Conclusion
Over 29 years, nearly one in five cancers registered in the Czech population was associated with additional cancer. A total of 165,050 subsequent neoplasms 13.7% were diagnosed in the advanced stage. The results suggest that information about multiple neoplasms and their clinical stages is necessary as a part of annual statistical cancer report. The most of subsequent advanced stages can be prevented by the therapeutic guidelines.