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Volume 2013 (2013), Article ID 829486, 10 pages
Clinical Stages in Patients with Primary and Subsequent Cancers Based on the Czech Cancer Registry 1976–2005
1Department of Science and Research, University Hospital Brno, Jihlavska 20, 625 00 Brno, Czech Republic
2Laboratory on Geoinformatics and Cartography, Department of Geography, Faculty of Science, Masaryk University, Kotlarska 2, 611 37 Brno, Czech Republic
3Department of Internal Medicine, University Hospital Brno, Pekarska 53, 602 00 Brno, Czech Republic
4Department of Surgery, University Hospital Brno, Jihlavska 20, 625 00 Brno, Czech Republic
Received 13 April 2013; Accepted 9 June 2013
Academic Editors: N. Fujimoto, O. Hansen, R. Nahta, K. Sonoda, M. Stracke, and K. van Golen
Copyright © 2013 Edvard Geryk et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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.
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 . 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  confirmed the continued trend of cancer occurrence, observed in the Czech areas from 1905  and continuously described from 1933 . 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 . 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) . The differences between the numbers of cases and numbers of persons indicated the multiple malignant neoplasms (MMNs). After the preliminary report of their trend , this paper is another contribution to this issue.
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, and clinical stages of early (ST I, II), advanced (ST III, IV), and unknown cases. Their input data correspond with the classification of diseases at the time of diagnosis and with the level of cancer evidence in 14 Czech regions.
A total of 1,486,984 new malignant neoplasms (50.9% men, 49.1% women) were registered in the Czech Cancer Registry between 1976 and 2005. This number includes 1,430,458 (96.2%) cancers (C00-97), 42,630 (2.9%) neoplasms in situ (D00-09), and 13,896 (0.9%) neoplasms of uncertain behaviour (D37-48). Of all newly registered cancers, there were notified 290,312 (19.5%) MMNs. In men were diagnosed 65,292 primary and 89,796 subsequent cancers and in women 59,970 primary and 75,254 subsequent cancers. A total of 84% duplicities were higher in women than 79.6% in men, while triplicities and others (3–6 MMNs) were in 19.1% cases of men and 15.4% of women. In men, there were the most frequent primary cancers of skin 46%, gastrointestinal 13.5% and urinary tract 9.6%, male genital organs 8.1% and respiratory tract 7.7%; in women, there were cancers of skin 39.4%, breast 17.3%, female genital organs 14.7%, and gastrointestinal tract 9.8%. The most frequent MMNs were 53,616 primary and 70,119 subsequent cancers of skin as a warning sign for the risk of following neoplasms. The most frequent subsequent diagnoses following primary cases were 26,790 cancers of gastrointestinal tract (54.6% men, 45.4%), 12,801 of respiratory tract (76.9% men, 23.1% women), 10,704 of urinary tract (66.6% men, 33.4% women), 9,394 of breast (0.9% men, 99.1% women), 5,284 of lymphoid and haematopoietic tissue (54.3% men, 45.7% women), and 6,804 of male and 9,309 of female genital organs (Table 1).
The yearly number of MMNs increased from 2,543 cases in 1976 to 17,091 in 2005, of which the primary cancers increased from 2,365 in 1976 to 5,411 in 1995 and then decreased to 1,983 in 2005, while the subsequent cancers increased from 178 in 1976 to 15,108 in 2005 (Figure 1). The predominance of unknown stages in both sexes over other stages lasted until 1994; from the next years their number decreased especially in the early stages of primary cancers. The percentage occurrence of stage IV was permanently higher in men than in women.
Let us see the situation in age groups. The values of the primary cancers in age group up to 49 years are 8.3% cases in men and 15.7% in women, in group 50–69 years 52.4% in men and 47.8% in women, in group 70–79 years 31.3% in men and 26.7% in women, and in group over 80 years 8% in men and 9.8% in women. After the exclusion of unknown stages, the numbers of early stages were higher in men in group of 70–79 years, in women in group up to 49 years, and in group over 80 years. The numbers of advanced stages were higher in men in group of 50–79 years.
Of the total 65,292 primary cancers in men, were diagnosed 24,263 (37.1%) cases of early stages (of which 28.2% ST I) and 6,051 (9.3%) cases of advanced stages (of which 4.2% ST IV); the unknown stages featured 34,978 (53.6%) cases. Of the total 59,970 primary cancers in women were diagnosed 27,922 (46.6%) cases of early stages (of which 32.6% ST I), 5,707 (9.5%) cases of advanced stages (of which 3.2% ST IV); the unknown stages featured 26,341 (43.9%) cases. The specific position presents 22,607 subsequent cancers of advanced stages (ST III, IV), of which 6,172 cases (i.e. 12.4% of 49,717) followed primary ST I, 2,865 cases (i.e. 17.3% of 16,533) followed primary ST II, 1,905 cases (i.e. 24.1% of 7,890) followed primary ST III, 1,355 cases (i.e. 27.2% of 4,976) followed primary ST IV, and 10,310 cases (i.e. 12% of 85,934) followed primary unknown stages (Table 2). The number of subsequent advanced stages increased with the advanced stage of primary disease.
The geographical distribution of MMNs by stages during 1976–2005 shows relevant maps (Figures 3, 4, 5, 6, 7, 8, 9, 10, and 11). The most frequent values of primary-subsequent 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.
The comparison with total advanced stages in subsequent cancers was higher in regions nos. 11 (12.7%), 14 (12.1%), 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). Of the various comparisons are presented 9,037 advanced stages of subsequent cancers following primary neoplasms with higher value of 1603 (35.7%) gastrointestinal tract in men and 1718 (37.8%) in women, 1489 (33.2%) respiratory tract in men and 636 (14%) in women, 843 (18.5%) breast, 742 (16.3%), female genital organs, 498 (11.1%) male female genital organs, and 376 (8.4%) urinary tract in men and 218 (4.8%) in women (Figure 2).
Up to October 17, 2007, there were registered of 65,292 primary cancers of men 18,887 (28.9%) surviving and 46,405 (71.1%) deaths, of 59,970 primary cancers of women 22,274 (37.1%) surviving and 37,696 (62.9%) deaths. Of total surviving cases were 54.7% early stages in men and 58% in women, 5% advanced stages in men and 5.2% in women; the unknown 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.
From ongoing analysis of Cancer Registry database were published the results of the MMNs of breast , skin , prostate , gastrointestinal tract , brain , lung , head and neck , testis , and penis cancer . We pointed to the current and future relationships of MMNs with ethical and economic burden of the Czech population . We used experiences of more than 50 references, concerning the MMNs. Unfortunately the excellent source which analysed the MMNs of SEER database  did not contain data about clinical stages as well as the most of another recent reference .
Registered new cases of malignant neoplasms contain also other primary subsequent cancer diagnoses, first described by Billroth and von Winiwarer in 1889 . As their possible causes were assessed the previous radiotherapy [20–23] and chemotherapy [24–28], dialysis , transplantation [30–32], 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.
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 and early detection of the subsequent neoplasms. During 1977–2005, nearly every fifth cancer disease of the Czech population was associated with the occurrence of histologically different neoplasms.
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 . 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  and prevention in the health population by modern visualization .
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.
Edvard Geryk contributed in the analysis of input data and drafting of the paper, Radim Štampach was involved in the preparation of maps, Petr Dítě supervised the research design and execution of analysis, Jiří Kozel contributed in preparation of input anonymous data from source database, Teodor Horváth checked the codes of clinical stages, and Petr Kubíček supervised the maps and contributed in final draft. All authors read and approved the final version of the paper and declare that it is not under simultaneous consideration by any other publication.
Conflict of Interests
The authors declare that they have no conflict interests.
The source of cancer numbers was the database of Czech Cancer Registry which presented comprehensive information from May 1976 to October 2007 by notification of the Institute of Health Information and Statistics of the Czech Republic in Prague, and the authors wish to thank Mrs. Eliška Vanková for her specifying information of cancer codes.
- IARC, “Globocan,” Lyon, France, IARC, 2008, http://globocan.iarc.fr/.
- IHIS, Cancer incidence in the Czech Republic. Health statistics, editorial series, http://www.uzis.com/.
- “Twenty-five years of the Czech Association for combat and exploration of malignant tumors in Prague,” Prague, Czech Republic, 1930.
- J. Weiss, “Contribution to the statistics of the cancer increasing,” Practical Medicine, vol. 22, article 617, 1933.
- M. Konečný, E. Geryk, P. Kubíček, et al., Cancer Prevalence in the Czech Republic, 1989-2005-2015, vol. 69, Masaryk University, Brno, Czech Republic, 2008.
- E. Geryk, P. Dítě, J. Kozel, et al., “Cancer multiplicites in the Czech population,” Casopís Lékařů Českých, vol. 149, no. 4, pp. 178–183, 2010 (Czech).
- E. Geryk, M. Bendová, and J. Kozel, “Breast cancer and subsequent primary malignant neoplasms in the Czech Republic 1976–2005,” Oncology, vol. 3, no. 1, pp. 54–61, 2009 (Czech).
- E. Geryk, P. Dítě, L. Sedláková, et al., “Trends of multiple non-melanoma skin cancers in a view of their epidemiology,” Practice Dermatology, vol. 4, no. 1, pp. 5–9, 2010 (Czech).
- E. Geryk, P. Dítě, J. Kozel, et al., “Other primary neoplasms in patients with prostate cancer in comparison of its incidence, mortality and prevalence,” Oncology, vol. 4, no. 2, pp. 89–93, 2010 (Czech).
- P. Dítě and E. Geryk, “Trends of primary and subsequent cancers of the gastrointestinal tract in the czech population, 1976–2005,” Digestive Diseases, vol. 28, no. 4-5, pp. 657–669, 2010.
- E. Geryk, J. Kozel, R. Štampach et al., “Multiple cancers of nervous system and other primary neoplasms,” Oncology, vol. 5, no. 3, pp. 175–180, 2011 (Czech).
- T. Horvath, E. Geryk, J. Kozel, et al., “Lung cancer in multiple malignant neoplasms,” in Proceedings of the 3rd Lung Cancer Conference, Geneva, Switzerland, 2012.
- E. Geryk, J. Kozel, T. Horváth, et al., “Patients with multiple cancers of head and neck,” Oncology, vol. 6, no. 5, pp. 260–265, 2012 (Czech).
- E. Geryk, J. Kozel, D. Pacík, R. Štampach, and T. Horváth, “Multiple cancers of testis,” Practice Urology, vol. 14, no. 1, pp. 34–38, 2013 (Czech).
- E. Geryk, D. Pacik, J. Kozel, et al., “Penile cancers associated with occurrence of other neoplasms,” Urology Letters, vol. 10, no. 4, pp. 1–6, 2012 (Czech).
- E. Geryk, P. Koška, P. Dítě, et al., “Cancers, health and economy: parts of Pandoras box?” Oncology, vol. 7, no. 1, pp. 314–320, 2013 (Czech).
- R. E. Curtis, D. M. Freedman, E. Ron, et al., New Malignancies Among Cancer Survivors: SEER Cancer Registries 1973–2000, National Cancer Institute, Bethesda, Md, USA, 2006.
- ACS, “Multiple primary cancers,” in Cancer Facts and Figures 2009, pp. 24–41, American Cancer Society, Atlanta, Ga, USA, 2009.
- T. Billroth and A. von Winiwarer, Die Allgemeine Chirurgische Patologie Und Therapie, G. Reimer, Berlin, Germany, 1889.
- J. M. Holland, A. Arsanjani, B. J. Liem, S. Christopher Hoffelt, J. I. Cohen, and K. R. Stevens, “Second malignancies in early stage laryngeal carcinoma patients treated with radiotherapy,” Journal of Laryngology and Otology, vol. 116, no. 3, pp. 190–193, 2002.
- N. N. Baxter, J. E. Tepper, S. B. Durham, D. A. Rothenberger, and B. A. Virnig, “Increased risk of rectal cancer after prostate radiation: a population-based study,” Gastroenterology, vol. 128, no. 4, pp. 819–824, 2005.
- M. Clarke, R. Collins, S. Darby, et al., “Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials,” The Lancet, vol. 366, no. 9503, pp. 2087–2106, 2005.
- C. Rubino, A. Shamsaldin, M. G. Lê et al., “Radiation dose and risk of soft tissue and bone sarcoma after breast cancer treatment,” Breast Cancer Research and Treatment, vol. 89, no. 3, pp. 277–288, 2005.
- P. Valagussa, A. Moliterni, M. Terenziani, M. Zambetti, and G. Bonadonna, “Second malignancies following CMF-based adjuvant chemotherapy in resectable breast cancer,” Annals of Oncology, vol. 5, no. 9, pp. 803–808, 1994.
- J. M. Kaldor, N. E. Day, B. Kittelmann et al., “Bladder tumours following chemotherapy and radiotherapy for ovarian cancer: a case-control study,” International Journal of Cancer, vol. 63, no. 1, pp. 1–6, 1995.
- L. B. Travis, M. Gospodarowicz, R. E. Curtis, et al., “Lung cancer following chemotherapy and radiotherapy for Hodgkin's disease,” Journal of the National Cancer Institute, vol. 94, no. 3, pp. 182–192, 2002.
- R. E. Curtis, D. M. Freedman, M. E. Sherman, and J. F. Fraumeni Jr., “Risk of malignant mixed mullerian tumors after tamoxifen therapy for breast cancer,” Journal of the National Cancer Institute, vol. 96, no. 1, pp. 70–74, 2004.
- A. J. Swerdlow, M. E. Jones, D. H. Brewster et al., “Tamoxifen treatment for breast cancer and risk of endometrial cancer: a case-control study,” Journal of the National Cancer Institute, vol. 97, no. 5, pp. 375–384, 2005.
- C. K. Fairley, A. G. R. Sheil, J. J. McNeil et al., “The risk of ano-genital malignancies in dialysis and transplant patients,” Clinical Nephrology, vol. 41, no. 2, pp. 101–105, 1994.
- S. A. Birkeland, H. H. Storm, L. U. Lamm et al., “Cancer risk after renal transplantation in the nordic countries, 1964–1986,” International Journal of Cancer, vol. 60, no. 2, pp. 183–189, 1995.
- R. E. Curtis, P. A. Rowlings, H. J. Deeg et al., “Solid cancers after bone marrow transplantation,” The New England Journal of Medicine, vol. 336, no. 13, pp. 897–904, 1997.
- S. Euvrard, J. Kanitakis, and A. Claudy, “Skin cancers after organ transplantation,” The New England Journal of Medicine, vol. 348, no. 17, pp. 1681–1691, 2003.
- T. Kirchhoff, N. D. Kauff, N. Mitra et al., “BRCA mutations and risk of prostate cancer in Ashkenazi jews,” Clinical Cancer Research, vol. 10, no. 9, pp. 2918–2921, 2004.
- H. D. Nelson, L. H. Huffman, R. Fu, and E. L. Harris, “Genetic risk assessment and BRCA mutation testing for breast and ovarian cancer susceptibility: systematic evidence review for the U.S. Preventive Services Task Force,” Annals of Internal Medicine, vol. 143, no. 5, pp. 326–379, 2005.
- R. S. Ostfeld, G. E. Glass, and F. Keesing, “Spatial epidemiology: an emerging (or re-emerging) discipline,” Trends in Ecology and Evolution, vol. 20, no. 6, pp. 328–336, 2005.
- M. Konečný and W. Reinhardt, “Early warning and disaster management: the importance of geographic information,” International Journal of Digital Earth, vol. 3, no. 3, pp. 217–220, 2010.
- R. Štampach, K. Konečný, et al., “Dynamic cartographic methods for visualization of health statistics,” in Cartography in Central and Eastern Europe, pp. 431–442, Springer, Berlin, Germany, 2010.