Cancer Control in Central and Eastern Europe: Current Situation and Recommendations for Improvement EDUARD VRDOLJAK,a GYORGY BODOKY,b JACEK JASSEM,c RAZVAN A. POPESCU,d JOZEF MARDIAK,e,f ROBERT PIRKER,g TANJA Cˇ UFER,h l m ˇ ˇ ˇ C´ ,n AGIM SALLAKU,o SEMIR BESLIJA ,i ALEXANDRU ENIU,j VLADIMIR TODOROVIC´ ,k KATERˇ INA KUBA´ CKOV A´ , GALIA KURTEVA, ZORICA TOMASEVI pˇ q r ˇ ´ ´ SNEZHANA SMICHKOSKA, ZARKO BAJIC, BRANIMIR I. SIKIC a
Department of Oncology, Clinical Hospital Center Split, School of Medicine, University of Split, Split, Croatia; b Department of ´ ´ Oncology, St. L a´ szl o´ Teaching Hospital, Budapest, Hungary; c Medical University of Gda nsk, Gda nsk, Poland; d Department of Medical Oncology, Tumor Center Aarau, Aarau, Switzerland; e 2nd Department of Oncology, Faculty of Medicine, Comenius University, Bratislava, Slovak Republic; f National Cancer Institute, Bratislava, Slovak Republic; g Division of Oncology and Hematology, Department of Medicine I, Medical University of Vienna, Vienna, Austria; h University Clinic Golnik, Golnik, Slovenia; i Institute of Oncology, Clinical Center, University of Sarajevo, Sarajevo, Bosnia and Herzegovina; j Department of Breast Tumors, Cancer Institute “Prof. Dr. I. Chiricuta,” Cluj-Napoca, Romania; k Oncology and Radiotherapy Clinic, Clinical Centre of Montenegro, Podgorica, Montenegro; l Department of Oncology, University Hospital Motol, Charles University, Prague, Czech Republic; m National Hospital of Oncology, Sofia, Bulgaria; n Daily Chemotherapy Hospital, Institute for Oncology and Radiology of Serbia, Belgrade, Serbia; o Oncology Institute, University Hospital Center Mother Teresa, Tirana, Albania; p Institute of Radiotherapy and Oncology, Skopje, Macedonia; q Biometrika Healthcare Research, Zagreb, Croatia; r Oncology Division, Department of Medicine, Stanford University School of Medicine, Stanford, California, USA Disclosures of potential conflicts of interest may be found at the end of this article.
Key Words. Cancer x Incidence x Mortality x Oncology x South-East Europe x Health care budget
ABSTRACT The incidence of many cancers is higher in Western European (WE) countries, but mortality is frequently higher in Central and Eastern European (CEE) countries. A panel of oncology leaders from CEE countries participating in the South Eastern European Research Oncology Group (SEEROG) was formed in 2015, aiming to analyze the current status and trends of oncology care in CEE and to propose recommendations leading to improved care and outcomes. The SEEROG panel, meeting during the 11th Central European Oncology Congress, proposed the following: (a) national cancer control plans (NCCPs) required in all CEE countries, defining priorities in cancer care, including finance allocation considering limited health care budgets; (b) national cancer registries, describing in detail epidemiological trends; (c) efforts to strengthen comprehensive cancer centers; (d) that multidisciplinary care should be mandated by the NCCPs; (e) that smaller hospitals should be connected to multidisciplinary
tumor boards via the Internet, providing access to specialized expertise; (f) nationwide primary prevention programs targeting smoking, obesity, and alcohol consumption and centrally evaluated secondary prevention programs for cervical, colorectal, and breast cancers; (g) prioritize education for all involved in cancer care, including oncology nurses, general practitioners, and palliative care providers; (h) establish outpatient care in day hospitals to reduce costs associated with the current inpatient model of care in CEE countries and to improve patients’ quality of life; (i) long-term pharmacoeconomic evaluations of new therapies in CEE countries; (j) increase national oncology budgets in view of the higher mortality rates in CEE compared with WE countries; and (k) CEE countries urgently need help from the European Union to increase and monitor overall investment in cancer care. The Oncologist 2016;21:1183–1190
Implications for Practice: Significant differences in cancer incidence and mortality have been observed between European countries. While the incidence of many cancer types is higher in Western European (WE) countries, the mortality is generally higher in Central and Eastern Europe (CEE). The primary purpose of this review was to describe the current status and trends of oncology care in the CEE region, to raise awareness among physicians, regulators, and payers, and to propose the most needed changes in order to make the oncology care in CEE closer to the WE standards.
Correspondence: Eduard Vrdoljak, M.D., Ph.D., Department of Oncology, Clinical Hospital Center Split, School of Medicine, University of Split, Spinˇci´ceva 1, HR-21.000 Split, Croatia. Telephone: 38598448431; E-Mail: [email protected] Received April 6, 2016; accepted for publication May 17, 2016; published Online First on July 8, 2016. ©AlphaMed Press 1083-7159/2016/$20.00/0 http://dx.doi.org/ 10.1634/theoncologist.2016-0137
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INTRODUCTION Cancer is a leading global health problem. On the basis of estimates made by the International Agency for Research on Cancer (IARC), the incidence and mortality rates of many types of cancer and all cancers combined vary widely by geographic localization [1]. Importantly, the IARC estimated that more than half of newly diagnosed cases and two thirds of cancer deaths occur in low- and medium-income countries [1]. There are significant differences in cancer incidence and mortality across Europe; the overall incidence is higher in Western European (WE) countries, whereas the mortality rate is higher in the Central and Eastern European (CEE) countries [2]. Furthermore, while cancer mortality has generally been decreasing in WE countries lately, this trend has not been observed in CEE countries [3–6]. Moreover, the incidence rates of several cancers in CEE countries have already reached the rates in WE or Nordic countries [2]. Possible explanations for such differences could be different prevalence of underlying risk factors and host susceptibility, variations in cancer detection, the distribution of cancer types (more deadly cancer types in CEE), more advanced stages, higher mortality from noncancer causes, and differences in cancer registration, as well as different treatment and follow-up care. Unfortunately, most probably because of a combination of the above-mentioned reasons, cancer survival in CEE countries is, in general, significantly lower than it is in the WE countries [7–11]. Generally speaking, higher national income and health care budgets are associated with the higher cancer incidences and lower mortality in WE [12]. There are wide variations in the per capita health care expenditure and in quality of cancer care in Europe, especially when comparisons are made between “old” and “new” European Union (EU) members or between developed and developing countries [12]. Unfortunately, oncology care is not independent of the other segments of the health care system, so the allocation of resources and efforts for effective management of cancer detection and care is inevitably in balance with other health care needs, like a system of connected vessels. The objectives of the present study were to describe the current status and trends of oncology care in the CEE region, to raise awareness among physicians and payers, and to propose the most important changes needed to improve oncology care in CEE countries.
MATERIALS AND METHODS A panel of oncology leaders from CEE countries was established in 2015 within the South Eastern European Research Oncology Group (SEEROG). Our vision was to define the current status of oncology care in the CEE region and to propose solutions to the issue. The expanded SEEROG panel of oncology leaders from 13 CEE countries met during the 11th Central European Oncology Congress (CEOC) held in 2015 in Croatia, and the project “IMPACT” (Improving Patient’s Cancer Outcomes in Central Europe) was launched. To define the problem and propose solutions, we created a questionnaire, which was distributed during March and April 2015 to selected oncology leaders—members of the SEEROG and CEOC scientific bodies from Albania, Bosnia and Herzegovina, Bulgaria, Croatia, Czech Republic, Hungary, Macedonia,
Montenegro, Poland, Romania, Serbia, Slovakia, and Slovenia. The questionnaire dealt with incidence, mortality, sociodemographic and economic background, risk factors, prevention, diagnosis, treatment, and resources available for oncology care. We collected additional socioeconomic and cancer registry data from publicly available sources, such as GLOBOCAN 2012 [2], World Health Organization Global Health Observatory Data Repository [13], the World Bank [14], and Eurostat [15]. Analysis was done for all cancers combined and then, separately, for prostate, breast, lung, colorectal, endometrial, bladder, ovary, and renal cancers, and melanoma. Parameters of cancer prevention, oncology care, incidences, and mortality from CEE countries were compared with three neighboring WE countries (Austria, Germany, and Italy), with a sample of the rest of WE (Luxembourg, The Netherlands, Switzerland, France, and Belgium), and with Nordic countries (Finland, Sweden, Denmark, and Norway). A panel discussion of the results, including suggestions for improvement of the state of CEE oncology care, was held at the CEOC in June 2015.
RESULTS Risk Factors, Primary Prevention, and Early Detection Obesity is a risk factor for colon, rectal, breast (in postmenopausal women), endometrial, kidney, adenocarcinoma of the esophagus, and pancreatic cancer, and it is associated with a worse prognosis [16–19]. Five (38%) CEE countries have nationwide primary prevention programs targeting obesity and insufficient physical activity [20]. In CEE countries, the median proportion of the population with insufficient physical activity is lower than in neighboring WE, other WE, and Nordic countries [13]; however, the prevalence of obesity is higher. The latter is more prevalent in higherincome countries, such as Czech Republic, Hungary, Croatia, Slovenia, and Poland, than in the lower-income countries, such as Albania, Former Yugoslav Republic (FYR) Macedonia, or Bosnia and Herzegovina. The higher-income CEE countries are also characterized by higher alcohol consumption. This may be associated with higher incidences of cancers of the oral cavity, pharynx, esophagus, bowel, liver, larynx, and female breast [21, 22]. However, this higher alcohol intake is not accompanied by nationwide primary prevention programs targeting alcohol consumption; only a quarter of CEE countries have implemented such programs [20]. Thus, resources for prevention of alcohol consumption do not match the severity of the problem. Taxation of alcoholic beveragesadjustedforpurchasingpowerislowerinCEEcountries than in Nordic countries. The higher prevalence of tobacco smoking in CEE countries (40% in men and 27% in women) than in neighboring WE countries (34% in men and 29% in women), other WE countries (28% in men and 22% in women), or Nordic countries (24% in men and 21% in women) [13] is the major cause for higher incidence of lung cancer and other smoking-related cancers and, consequently, the higher overall cancer mortality.Tobacco smoking is the cancer risk factor most often targeted by primary prevention programs in the region [20]. Restrictions of direct and indirect forms of advertising, promotion, and
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Vrdoljak, Bodoky, Jassem et al. sponsorship of tobacco products are similar in different CEE countries, and tobacco advertising legal limitations are comparable to those in WE or Nordic countries. Despite this, the prevalence of smoking is still higher, likely because the most effective antitobacco measure, that is, adjusting the cost of cigarettes for purchasing power, is missing [13]. Consequently, cigarettes are more affordable in CEE countries than in WE or Nordic countries. Moreover, smoking cessation programs are lacking throughout the CEE region [20]. Screening programs and early diagnosis are known to reduce mortality rates of colorectal, breast, and cervical cancers [5]; however, only 6 of 13 (46%) CEE countries have implemented screening programs for cervical, breast, and colorectal cancers [20].
Recommendations x We advocate increasing resources for primary prevention programs targeted toward common cancer risk factors. In particular, nationwide primary prevention programs targeting diet, physical activity, obesity, and alcohol consumption should be more widely implemented. x Cost-effectiveness analysis of cancer primary prevention programs should also consider their cardiovascular benefits in medical and economic terms. This recommendation is in line with the European Guide for Quality National Cancer Control Programs recommendation to avoid duplication and seek synergies. x It is important to increase awareness and knowledge, among the general public and primary health care providers, of the association between obesity and cancer. x Taxation and pricing of tobacco products should be significantly increased throughout the CEE region. A substantial part of the collected income should be directed toward improvement of oncology care. x Comprehensive, population-based, valid, and reliable cancer registries should be created in all countries. x Further research in effective primary prevention programs on CEE populations is needed. Because primary prevention programs sometimes need decades to demonstrate their effects, cancer registries’ data should be used for long-term assessment of cancer prevention effects. x Screening programs for colorectal, breast, and cervical cancer should be implemented in all CEE countries, with continued effort on early detection of all cancers.
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weaknesses in the organization of oncology care and health care systems in general. A common, underlying, root cause is also the lower financial and human resources investment in all aspects of oncology care [20]. Health care budgets per capita and the expenditures on innovative cancer therapies in absolute terms are at least 5 times lower in CEE countries than in neighboring WE countries [20]. Even considering different purchasing power in both regions, with such differences it is simply not realistic to expect comparable outcomes. In the whole CEE region, higher shares of total health care budgets are spent on drugs than in WE or Nordic countries [20]. This is partially because of the fact that innovative therapies and equipment costs are similar around Europe, whereas the cost of labor and other costs, such as hospitalization, are on average lower in CEE countries. CEE, and particularly non-EU, countries, have considerably less radiotherapy equipment—in particular, equipment allowing for the high- precision conformal techniques, such as intensity-modulated radiotherapy, imageguided radiotherapy, or stereotactic radiotherapy [13, 23]. CEE oncologists with 3–5 years of experience, working in public hospitals, earn approximately 3 times less than their Austrian colleagues [20].This difference is smaller than the difference in gross national income, which is on average almost 7 times higher in Austria than in CEE countries [14]. Hence, it would be very demanding for CEE countries to significantly increase the level of salaries of oncology professionals given the current economic situation. Such discrepancies in income stimulate the “brain drain,” which compromises the strongest point of quality of cancer care in the region: well-trained, welleducated, and motivated medical professionals. Pharmacoeconomic analyses based on the modeling of data from various international, multicenter, randomized controlled but short-term, focused trials [9] and highly homogenous trials that enroll fewer than 1% of cancer patients from CEE countries [10] may be less applicable to specific local CEE populations. Additionally, such analyses may carry the risk of simplification and the lower predictive validity for particular CEE country circumstances [24]. Therefore, with no long-term, real-world, postmarketing studies specific for CEE countries, they may lack a sound informational basis for health care investment decision making.
Increased Investment Effects Incidence, Mortality, and Investment in Oncology Care A complex mixture of factors is responsible for the differences in incidence and mortality between CEE countries and the rest of the continent. Besides epidemiologic differences in genetic, environmental, and lifestyle factors, different incidences of particular cancer types are also important. CEE countries have a higher incidence of the more lethal lung cancer [2, 5], while neighboring WE, other WE, and Nordic countries have higher incidences of prostate and breast cancer, which generally have better survival rates [2, 5]. Probably equally important for the current status ofcancer mortality rates are less effective cancer control strategies in CEE countries: lower coverage, quality, and frequency of primary prevention, scarcity of screening programs (leading to late tumor stage at diagnosis), lower availability of treatment options, lack of real multidisciplinary teams, lower quality and availability of infrastructure, and
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Mortality-to-incidence ratio is calculated by dividing the mortality rate by the incidence rate. It presents a populationbased indicator of survival and is a good approximation of the 5-year relative survival rate for most but not all tumor sites [25]. Correlation of health expenditures per capita with the mortality-to-incidence ratio is high in the CEE region (Spearman’s r 5 –0.91 for male patients and r 5 –0.76 for female patients) but low in Western Europe (Spearman’s r 5 –0.17 for male patients and r 5 –0.20 for female patients) (Figs. 1, 2). In other words, every unit increase of health care expenditure per capita may be associated with a significant decrease in mortality-to-incidence ratio in CEE countries but would not have a comparable effect in Western Europe and Nordic countries. This may not be equally true for all cancer types. Direct medical and indirect morbidity costs of different cancer types are different [26] and rapidly changing because of the ©AlphaMed Press 2016
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Figure 1. Correlation of health expenditures per capita and mortality-to-incidence ratio: all cancers/male (n 5 25); a red square represents a Central and Eastern European country; a yellow rhombus represents a neighboring Western European (WE) country; a blue circle represents other WE countries; and a green triangle represents Nordic countries [2, 14].
continuous advances in diagnostic therapy and all fields of therapy, especially the implementation of innovative anticancer drugs. It is obvious that we urgently need more investment in oncology in general, but an equally important issue is the question of the efficient allocation of the available resources. Austria has somewhat higher overall health expenditures per capita than does Sweden, but Sweden has a significantly better (lower) mortality-to-incidence ratio for all cancer types [2, 27]. Overall expenditures are 72% higher in Switzerland, but Finland has an equally good mortality-to-incidence ratio. Similar examples concern the CEE region. Czech Republic has expenditures on oncology drugs per capita comparable to those of Hungary, Croatia, and Poland, and notably lower than those of Slovenia, but has a significantly better mortality-to-incidence ratio in breast, lung, colorectal, and renal cancers [2, 27]. Hence, the important question is where exactly the investments should be made. Although the incidence and mortality rates for lung cancer are highest in CEE countries, the difference in mortality-to-incidence ratio between CEE and neighboring WE countries is only 9% in males and 5% in females (Table 1) [2]; therefore, investment in the prevention and early detection of lung cancer is justified. But after diagnosis, lung cancer therapies are equally ineffective, so consequently, the mortality rates in CEE are quite similar to those in neighboring WE countries. Therefore, improvement in lung cancer prevention and early detection strategies may affect overall mortality, whereas major investments in the treatment of advanced lung cancers will have less impact. In contrast, there
are large differences in survival rates of patients with screenable and treatable cancers—such as prostate, breast, and colorectal cancers—between CEE and WE countries. Major investments in the improvement of screening and treatment of these cancers are more likely to effectively reduce the differences between CEE and WE countries. Here, the point should be raised that improved screening programs for some cancers, especially prostate cancer, could result in higher incidence on the basis of detection of clinically unimportant cases, decreased mortality, and consequently, a lower mortality-to-incidence ratio.
Recommendations x Evidence-based primary and secondary cancer prevention programs are of paramount importance and should be implemented in all CEE countries to diminish the proportion of advanced cancers at diagnosis and to decrease cancer mortality. x There is a need for routine monitoring and analysis of the relationship between investments in different aspects of oncology care and mortality rates. x Properly designed, country- or region-specific studies should be done routinely to assess the real effect of new therapies. These include postmarketing open or dynamic cohort studies accompanied with the continuous monitoring of the association of mortality-to-incidence ratios with the variation in usage of innovative cancer treatments. x The CEE region urgently needs assistance from EU funds to increase the level of overall investment in cancer care to reduce the unacceptable disparities in mortality-to-incidence ratios across Europe.
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Figure 2. Correlation of health expenditures per capita and mortality-to-incidence ratio: all cancers/female (n 5 25); a red square represents a Central and Eastern European country; a yellow rhombus represents a neighboring Western European (WE) country; a blue circle represents other WE countries; and a green triangle represents Nordic countries [2, 14]. Abbreviation: FYR, Former Yugoslav Republic.
Population-Based Cancer Registries Comprehensive population-based cancer registries are not available in all CEE countries, and even if they exist,their validity, reliability, and usage vary [1, 20, 28, 29]. Although Slovenia established one of the first nationwide cancer registries in the world in 1950, some CEE countries still do not have obligatory cancer registration. In addition, the CEE registries are usually limited to incidence and mortality data stratified by cancer site, sex, and age, but with no further details on risk factors, tumor stage at diagnosis, treatment, and outcomes [30]. Several studies have documented higher cancer mortality rates in CEE countries than in WE or Nordic countries despite comparable or lower incidences [1, 5, 6, 12, 31].Within the CEE region,there are also large differences in age-adjusted incidence rates, whereas mortality rates are generally similar [1, 2]. This inconsistency may be attributed to lack of national registries in some CEE countries or the less-then-perfect validity and reliability of collected data. In some instances, it is difficult to understand large differences between neighboring countries that share a similar distribution of known risk factors, similar populations, genetic backgrounds, health care systems, and education and investments in prevention and oncology care. It is possible that mortality records are more reliable and more valid than incidence records, but in some cases, mortality data are also of low validity [1]. As cancer patients are treated in different types of independent facilities and as autopsy rates are declining, it is more difficult to ensure the completeness and validity of mortality data [20].
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Recommendations x An absolute necessity is the implementation of high-quality cancer registries. x All national registries should comply with the IARC and European Network of Cancer Registries guidelines to secure a standardized/comparable, valid, and reliable analysis. x In addition to national cancer registries, the development of hospital or multi-institutional cancer databases with more detailed data from particular centers should be encouraged. These databases should collaborate closely with national registries, while ensuring high standards for personal data protection and data quality. x Analysis and dissemination of updated data should be faster to allow for real-time analyses. The IMPACT CEOC panel members share a common vision of a jointly managed, virtual CEE data center, adequately equipped and funded by all CEE countries and the EU. This would allow more powerful and faster collection, analysis, and dissemination of data from national or multi-institutional registries. Such an endeavor would promote the standardization and sharing of best practices between countries. The ultimate goal is the development of a unique, real-time CEE/EU cancer database in addition to national, regional, and hospital registries. Selected data from primary electronic hospital discharge charts and pathology and primary care records could be anonymized and uploaded to the global CEE/ EU cancer database on a daily basis. In return, the system would ©AlphaMed Press 2016
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Table 1. Incidence, mortality, and mortality-to-incidence ratio differences between CEE and neighboring WE countries CEE Cancer Male All tumors Prostate Bladder Colorectal Melanoma Renal Lung Female All tumors Breast Corpus uteri Colorectal Bladder Melanoma Renal Lung Ovary
Neighboring WE
Relative difference (%)
Incidence
Mortality
M/I
Incidence
Mortality
M/I
Incidence
Mortality
M/I
271 36 18.7 40 5.7 10.3 58
175 12 6.1 21 2.4 5.1 50
0.65 0.37 0.34 0.53 0.41 0.41 0.89
313 75 21.2 40 11.1 13.1 39
129 10 3.3 13 1.8 3.8 31
0.41 0.14 0.17 0.33 0.32 0.35 0.81
215 2108 213 0 295 227 33
26 17 46 38 25 25 38
37 62 50 38 22 15 9
220 59 15 23 4.6 4.4 4.7 17 11.1
96 16 2.9 11 1.3 1.4 1.7 13 5.8
0.44 0.30 0.30 0.49 0.30 0.35 0.32 0.83 0.49
253 91 12 23 5.1 11.7 5.4 18 7.4
83 16 1.9 8 1 1.1 1.7 14 4.7
0.33 0.17 0.17 0.35 0.22 0.27 0.27 0.79 0.63
215 254 20 0 211 2166 215 26 33
14 0 34 27 23 21 0 28 19
25 43 43 29 27 23 16 5 229
Incidence and mortality are presented as age-standardized (European standard population) rates per 100,000 inhabitants. CEE countries are Albania, Bosnia and Herzegovina, Bulgaria, Croatia, Czech Republic, Hungary, Macedonia, Montenegro, Poland, Romania, Serbia, Slovakia, and Slovenia. Neighboring WE countries are Austria, Germany, and Italy. Abbreviations: CEE, Central and Eastern Europe; M/I, mortality-to-incidence ratio; WE, Western Europe. Source: [2].
promote the standardization and dissemination of bestregister practices and strongly promote the scientific research in cancer prevention and care.
National Cancer Control Plans One of the prerequisites of successful cancer control is the development of comprehensive national or regional cancer control plans. Unfortunately, 7 of 13 (54%) of the CEE countries do not have national cancer control plans (NCCPs). Moreover, the countries of the CEE region with NCCPs in place face significant problems with their implementation. In most cases, the major issues are the lack of financial support and the lack of an organizational structure and network that would enable them to implement the NCCP strategy. Most NCCPs that currently exist do not include detailed planning of finances [32].
Recommendations x All CEE countries should develop and implement an NCCP, with appropriate financial and political support. x These plans should include detailed strategies on primary prevention, screening, diagnostics, treatment, and rehabilitation of cancer, research, and educational activities, as well as an implementation plan and outcome measures. x The financial and organizational structure to support implementation of the national cancer control plan should be a mandatory part of the NCCP. x The NCCP should be used to rationally improve nonmedical aspects of cancer care, such as reduction of social
exclusions and facilitation of patients’ return to social, occupational, and family functioning, as well as psychological support.
SUMMARY OF RECOMMENDATIONS Large differences in cancer epidemiology, in the majority of oncology care parameters and in treatment outcomes, exist between CEE countries and neighboring WE countries. Mortality-to-incidence ratios are much less favorable in CEE countries, and CEE cancer mortality age-standardized rates are among the worst in the world [2]. To accelerate the development of oncology care in CEE countries and to reduce the apparent disparities across Europe, CEE countries should undertake several measures.
Recommendations x All CEE countries should develop and implement national cancer strategic plans that will help to define the priorities in cancer control and the action priorities within their limited national health care budgets. x National cancer registries should be established in all countries. x Instead of a large number of independent facilities, consolidation into comprehensive oncology centers with multidisciplinary teams should be implemented. x Multidisciplinary approaches should be foreseen by national strategic cancer plans and made obligatory. A stopgap measure may be virtual Internet-based multidisciplinary tumor boards, allowing smaller hospitals that do not have
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x x
x
x x x
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comprehensive oncology care to make better-informed decisions about cancer treatments. Nationwide primary prevention programs targeting smoking, obesity, and alcohol consumption should be widely implemented. Screening programs for cervical, colorectal, and breast cancer should be implemented, and the reach and efficacy of the screening programs should be centrally evaluated. Improved education for all involved in oncology care is needed. Special attention should be on training specialists in cancer management (radiation oncology, medical oncology, and surgery). Also, very important and needed throughout the region is education for oncology nurses and general practitioners. Development of clinical guidelines and training for general practitioners for management and follow-up of cancer patients and survivors is needed. The current prevalence of inpatient/hospital-based care in the CEE should be changed to modern forms of ambulatory, day hospital, and clinic treatments. Day and ambulatory treatments may be superior in both direct and indirect costs, as well as quality of life for patients and families. Access to early diagnostic and novel, clinically meaningful treatment modalities is essential to close the gap between CEE and WE cancer control indicators. Less effective and old diagnostic and treatment strategies should be abandoned. Long-term routine pharmacoeconomic evaluations of new therapies in achieving outcomes in postmarketing, real-life settings should be encouraged. National independent systems of oncology care quality and outcomes’ evaluations may reduce the intracountry variability. Allocation of health care budgets for oncology should consider the high mortality rates, in comparison with those of the neighboring WE countries, and increase investments to diminish those gaps. Countries in the CEE region urgently need additional EU funds to decrease inequalities in cancer control in Europe.
ACKNOWLEDGMENTS The work was partially funded by a grant from Roche.
AUTHOR CONTRIBUTIONS Conception/Design: Eduard Vrdoljak, Gyorgy Bodoky, Jacek Jassem, Razvan A. ˇ Popescu, Jozef Mardiak, Robert Pirker, Tanja Cufer, Semir Beˇslija, Alexandru Eniu, Vladimir Todorovi´c, Kateˇrina Kub´acˇkov´a, Galia Kurteva, Agim Sallaku, ˇ ˇ Snezhana Smichkoska, Zarko Baji´c, Branimir I. Siki´c Provision of study material or patients: Eduard Vrdoljak, Gyorgy Bodoky, Jacek ˇ Jassem, Razvan A. Popescu, Jozef Mardiak, Robert Pirker, Tanja Cufer, Semir Beˇslija, Alexandru Eniu, Vladimir Todorovi´c, Kateˇrina Kub´acˇkov´a, Galia Kurteva, Zorica Tomaˇsevi´c, Agim Sallaku, Snezhana Smichkoska, Zˇ arko Baji´c, Branimir I. Sˇ iki´c Collection and/or assembly of data: Eduard Vrdoljak, Gyorgy Bodoky, Jacek ˇ Jassem, Razvan A. Popescu, Jozef Mardiak, Robert Pirker, Tanja Cufer, Semir Beˇslija, Alexandru Eniu, Vladimir Todorovi´c, Kateˇrina Kub´acˇkov´a, Galia ˇ Kurteva, Zorica Tomaˇsevi´c, Agim Sallaku, Snezhana Smichkoska, Zarko Baji´c, ˇ c Branimir I. Siki´ Data analysis and interpretation: Eduard Vrdoljak, Gyorgy Bodoky, Jacek ˇ Jassem, Tanja Cufer, Semir Beˇslija, Alexandru Eniu,Vladimir Todorovi´c, Zorica Tomaˇsevi´c, Zˇ arko Baji´c, Branimir I. Sˇ iki´c Manuscript writing: Eduard Vrdoljak, Gyorgy Bodoky, Jacek Jassem, Razvan A. ˇ Popescu, Jozef Mardiak, Robert Pirker, Tanja Cufer, Semir Beˇslija, Alexandru Eniu,Vladimir Todorovi´c, Kateˇrina Kub´acˇkov´a, Galia Kurteva, Zorica Tomaˇsevi´c, ˇ c ˇ Agim Sallaku, Snezhana Smichkoska, Zarko Baji´c, Branimir I. Siki´ Final approval of manuscript: Eduard Vrdoljak, Gyorgy Bodoky, Jacek Jassem, ˇ Razvan A. Popescu, Jozef Mardiak, Robert Pirker, Tanja Cufer, Semir Beˇslija, Alexandru Eniu, Vladimir Todorovi´c, Kateˇrina Kub´acˇkov´a, Zorica Tomaˇsevi´c, Agim Sallaku, Snezhana Smichkoska, Zˇ arko Baji´c, Branimir I. Sˇ iki´c
DISCLOSURES Eduard Vrdoljak: Bayer, AstraZeneca, Amgen, Merck, Merck Sharp & Dohme, GlaxoSmithKline, Novartis, Pfizer, Roche (C/A); Gyorgy Bodoky: Amgen, Astellas, Bayer, Janssen, Eli Lilly, Merck, Nordic Pharma, Novartis, Pfizer, Roche (C/A); Jacek Jassem: Roche, AstraZeneca, Amgen, Boehringer Ingelheim, Merck (C/A); Razvan A. Popescu: Amgen, Bayer, Bristol-Myers Squibb, Eli Lilly, Merck, Novartis, Roche, Sanofi (C/A), AbbVie, Johnson & Johnson, Novartis, Pfizer, Roche (RF); Robert Pirker: AstraZeneca, Boehringer Ingelheim, Eli Lilly, Merck Sharp & Dohme, Synta (C/A), Boehringer Ingelheim, Eli Lilly, Pierre Fabre (H); Alexandru Eniu: Roche, AstraZeneca (RF); Vladimir Todorovi´c: Roche, Sanofi, Pfizer, Inmed (H); Zˇ arko Baji´c: Roche, Pfizer, ˇ c: Threshold (C/A), Genentech/ AstraZeneca, Takeda (H); Branimir I. Siki´ Roche, Novartis, Sanofi, CellDex, Gilead (RF). The other authors indicated no financial relationships. (C/A) Consulting/advisory relationship; (RF) Research funding; (E) Employment; (ET) Expert testimony; (H) Honoraria received; (OI) Ownership interests; (IP) Intellectual property rights/ inventor/patent holder; (SAB) Scientific advisory board
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2. Ferlay J, Soerjomataram I, Ervik M et al. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer; 2013. Available from: http:// globocan.iarc.fr. Accessed June 19, 2015.
7. Chino F, Peppercorn J, Taylor DH Jr. et al. Selfreported financial burden and satisfaction with care among patients with cancer. The Oncologist 2014; 19:414–420.
3. Znaor A, van den Hurk C, Primic-Zakelj M et al. Cancer incidence and mortality patterns in South Eastern Europe in the last decade: Gaps persist compared with the rest of Europe. Eur J Cancer 2013;49:1683–1691. 4. Karim-Kos HE, de Vries E, Soerjomataram I et al. Recent trends of cancer in Europe: A combined approach of incidence, survival and mortality for 17 cancer sites since the 1990s. Eur J Cancer 2008;44: 1345–1389. 5. Bosetti C, Bertuccio P, Malvezzi M et al. Cancer mortality in Europe, 2005-2009, and an overview of trends since 1980. Ann Oncol 2013;24:2657–2671.
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8. Jemal A, Center MM, DeSantis C et al. Global patterns of cancer incidence and mortality rates and trends. Cancer Epidemiol Biomarkers Prev 2010;19: 1893–1907.
12. Ades F, Senterre C, de Azambuja E et al. Discrepancies in cancer incidence and mortality and its relationship to health expenditure in the 27 European Union member states. Ann Oncol 2013; 24:2897–2902. 13. World Health Organization. Global Health Observatory Data Repository. Available at http:// apps.who.int/gho/data/node.main.510?lang5en. Accessed August 23, 2015. 14. The World Bank. World Bank Open Data. Available at http://data.worldbank.org/indicator. Accessed August 23, 2014.
9. Colditz GA, Wolin KY, Gehlert S. Applying what we know to accelerate cancer prevention. Sci Transl Med 2012;4:127rv4.
15. Eurostat—DataExplorer. Availableathttp://appsso. eurostat.ec.europa.eu/nui/submitViewTableAction. do. Accessed August 30, 2015.
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16. Goday A, Barneto I, Garc´ıa-Almeida JM et al. Obesity as a risk factor in cancer: A national consensus of the Spanish Society for the Study of Obesity and the Spanish Society of Medical Oncology. Clin Transl Oncol 2015;17:763–771.
11. De Angelis R, Sant M, Coleman MP et al. Cancer survival in Europe 1999-2007 by country and age: Results of EUROCARE–5—A population-based study. Lancet Oncol 2014;15:23–34.
17. Ligibel JA, Alfano CM, Courneya KS et al. American Society of Clinical Oncology position
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countries: Final results from the ESTRO-HERO survey. Radiother Oncol 2014;112:155–164.
18. Giacosa A, Barale R, Bavaresco L et al. Cancer prevention in Europe: The Mediterranean diet as a protective choice. Eur J Cancer Prev 2013;22:90–95.
24. Purmonen T. Pharmacoeconomic Methods for Estimating Cost-Effectiveness and Budget Impact of Cancer Treatments in Finland [dissertation]. Kuopio, Finland: University of Eastern Finland, 2012.
19. Wolin KY, Carson K, Colditz GA. Obesity and cancer. The Oncologist 2010;15:556–565. 20. Impact CEOC study groupSurvey of CE Europe countries oncology opinion leaders. Results presented at: 11th Central European Oncology Congress; June 17–20, 2015; Opatija, Croatia. 21. Bray F, Jemal A, Torre LA et al. Long-term realism and cost-effectiveness: Primary prevention in combatting cancer and associated inequalities worldwide. J Natl Cancer Inst 2015;107:djv273. 22. Bagnardi V, Rota M, Botteri E et al. Alcohol consumption and site-specific cancer risk: A comprehensive dose-response meta-analysis. Br J Cancer 2015;112:580–593. 23. Grau C, Defourny N, Malicki J et al. Radiotherapy equipment and departments in the European
25. Asadzadeh Vostakolaei F, Karim-Kos HE, Janssen-Heijnen MLG et al. The validity of the mortality to incidence ratio as a proxy for sitespecific cancer survival. Eur J Public Health 2011; 21:573–577. 26. Chang S, Long SR, Kutikova L et al. Estimating the cost of cancer: Results on the basis of claims data analyses for cancer patients diagnosed with seven types of cancer during 1999 to 2000. J Clin Oncol 2004;22:3524–3530. 27. United Nations. Department of Economic and Social Affairs PD (2015). World Population Prospects: The 2015 Revision. Available at http:// esa.un.org/unpd/wpp/DVD/. Accessed August 23, 2015.
28. The ESMO MOSES Task Force. Medical Oncology Status in Europe Survey (MOSES) Phase II. Lugano, Switzerland: European Society for Medical Oncology, 2006. 29. Vrdoljak E, Torday L, Sella A et al. Insights into cancer surveillance in Central and Eastern Europe, Israel and Turkey. Eur J Cancer Care (Engl) 2015;24: 99–110. 30. Coebergh JW, van den Hurk C, Louwman M et al. EUROCOURSE recipe for cancer surveillance by visible population-based cancer RegisTrees in Europe: From roots to fruits. Eur J Cancer 2015;51: 1050–1063. 31. Bray F, Ren J-S, Masuyer E et al. Global estimates of cancer prevalence for 27 sites in the adult population in 2008. Int J Cancer 2013;132: 1133–1145. 32. Atun R, Ogawa TM-MJ. Analysis of National Cancer Control Programmes in Europe; 2009. Available at http://hdl.handle.net/10044/1/4204.
EDITOR’S NOTE: See the related commentary, “Cancer Control in Central and Eastern Europe,” by Carlo La Vecchia and Pierfranco Conte, on page 1161 of this issue. For Further Reading: Mark Lawler, Thierry Le Chevalier, Martin J. Murphy, Jr. et al. A Catalyst for Change: The European Cancer Patient’s Bill of Rights. The Oncologist 2014;19:217–224. Article Excerpt: Strengthening and upholding the rights of individual cancer patients and their families are the guiding principles of this initiative. In order to provide tangible benefits for European cancer patients, the ECC proposes the creation of a “European Cancer Patient’s Bill of Rights,” a patient charter that will underpin equitable access to an optimal standard of care for Europe’s citizens. Three patient-centered principles (termed “Articles”) underpin the European Cancer Patient’s Bill of Rights: Article 1: The right of every European citizen to receive the most accurate information and to be proactively involved in his/ her care. Article 2: The right of every European citizen to optimal and timely access to appropriate specialized care, underpinned by research and innovation. Article 3: The right of every European citizen to receive care in health systems that ensure improved outcomes, patient rehabilitation, best quality of life and affordable health care.
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Department of Oncology, Clinical Hospital Center Split, School of Medicine, University of Split, Split, Croatia; b Department of ´ ´ Oncology, St. L a´ szl o´ Teaching Hospital, Budapest, Hungary; c Medical University of Gda nsk, Gda nsk, Poland; d Department of Medical Oncology, Tumor Center Aarau, Aarau, Switzerland; e 2nd Department of Oncology, Faculty of Medicine, Comenius University, Bratislava, Slovak Republic; f National Cancer Institute, Bratislava, Slovak Republic; g Division of Oncology and Hematology, Department of Medicine I, Medical University of Vienna, Vienna, Austria; h University Clinic Golnik, Golnik, Slovenia; i Institute of Oncology, Clinical Center, University of Sarajevo, Sarajevo, Bosnia and Herzegovina; j Department of Breast Tumors, Cancer Institute “Prof. Dr. I. Chiricuta,” Cluj-Napoca, Romania; k Oncology and Radiotherapy Clinic, Clinical Centre of Montenegro, Podgorica, Montenegro; l Department of Oncology, University Hospital Motol, Charles University, Prague, Czech Republic; m National Hospital of Oncology, Sofia, Bulgaria; n Daily Chemotherapy Hospital, Institute for Oncology and Radiology of Serbia, Belgrade, Serbia; o Oncology Institute, University Hospital Center Mother Teresa, Tirana, Albania; p Institute of Radiotherapy and Oncology, Skopje, Macedonia; q Biometrika Healthcare Research, Zagreb, Croatia; r Oncology Division, Department of Medicine, Stanford University School of Medicine, Stanford, California, USA Disclosures of potential conflicts of interest may be found at the end of this article.
Key Words. Cancer x Incidence x Mortality x Oncology x South-East Europe x Health care budget
ABSTRACT The incidence of many cancers is higher in Western European (WE) countries, but mortality is frequently higher in Central and Eastern European (CEE) countries. A panel of oncology leaders from CEE countries participating in the South Eastern European Research Oncology Group (SEEROG) was formed in 2015, aiming to analyze the current status and trends of oncology care in CEE and to propose recommendations leading to improved care and outcomes. The SEEROG panel, meeting during the 11th Central European Oncology Congress, proposed the following: (a) national cancer control plans (NCCPs) required in all CEE countries, defining priorities in cancer care, including finance allocation considering limited health care budgets; (b) national cancer registries, describing in detail epidemiological trends; (c) efforts to strengthen comprehensive cancer centers; (d) that multidisciplinary care should be mandated by the NCCPs; (e) that smaller hospitals should be connected to multidisciplinary
tumor boards via the Internet, providing access to specialized expertise; (f) nationwide primary prevention programs targeting smoking, obesity, and alcohol consumption and centrally evaluated secondary prevention programs for cervical, colorectal, and breast cancers; (g) prioritize education for all involved in cancer care, including oncology nurses, general practitioners, and palliative care providers; (h) establish outpatient care in day hospitals to reduce costs associated with the current inpatient model of care in CEE countries and to improve patients’ quality of life; (i) long-term pharmacoeconomic evaluations of new therapies in CEE countries; (j) increase national oncology budgets in view of the higher mortality rates in CEE compared with WE countries; and (k) CEE countries urgently need help from the European Union to increase and monitor overall investment in cancer care. The Oncologist 2016;21:1183–1190
Implications for Practice: Significant differences in cancer incidence and mortality have been observed between European countries. While the incidence of many cancer types is higher in Western European (WE) countries, the mortality is generally higher in Central and Eastern Europe (CEE). The primary purpose of this review was to describe the current status and trends of oncology care in the CEE region, to raise awareness among physicians, regulators, and payers, and to propose the most needed changes in order to make the oncology care in CEE closer to the WE standards.
Correspondence: Eduard Vrdoljak, M.D., Ph.D., Department of Oncology, Clinical Hospital Center Split, School of Medicine, University of Split, Spinˇci´ceva 1, HR-21.000 Split, Croatia. Telephone: 38598448431; E-Mail: [email protected] Received April 6, 2016; accepted for publication May 17, 2016; published Online First on July 8, 2016. ©AlphaMed Press 1083-7159/2016/$20.00/0 http://dx.doi.org/ 10.1634/theoncologist.2016-0137
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INTRODUCTION Cancer is a leading global health problem. On the basis of estimates made by the International Agency for Research on Cancer (IARC), the incidence and mortality rates of many types of cancer and all cancers combined vary widely by geographic localization [1]. Importantly, the IARC estimated that more than half of newly diagnosed cases and two thirds of cancer deaths occur in low- and medium-income countries [1]. There are significant differences in cancer incidence and mortality across Europe; the overall incidence is higher in Western European (WE) countries, whereas the mortality rate is higher in the Central and Eastern European (CEE) countries [2]. Furthermore, while cancer mortality has generally been decreasing in WE countries lately, this trend has not been observed in CEE countries [3–6]. Moreover, the incidence rates of several cancers in CEE countries have already reached the rates in WE or Nordic countries [2]. Possible explanations for such differences could be different prevalence of underlying risk factors and host susceptibility, variations in cancer detection, the distribution of cancer types (more deadly cancer types in CEE), more advanced stages, higher mortality from noncancer causes, and differences in cancer registration, as well as different treatment and follow-up care. Unfortunately, most probably because of a combination of the above-mentioned reasons, cancer survival in CEE countries is, in general, significantly lower than it is in the WE countries [7–11]. Generally speaking, higher national income and health care budgets are associated with the higher cancer incidences and lower mortality in WE [12]. There are wide variations in the per capita health care expenditure and in quality of cancer care in Europe, especially when comparisons are made between “old” and “new” European Union (EU) members or between developed and developing countries [12]. Unfortunately, oncology care is not independent of the other segments of the health care system, so the allocation of resources and efforts for effective management of cancer detection and care is inevitably in balance with other health care needs, like a system of connected vessels. The objectives of the present study were to describe the current status and trends of oncology care in the CEE region, to raise awareness among physicians and payers, and to propose the most important changes needed to improve oncology care in CEE countries.
MATERIALS AND METHODS A panel of oncology leaders from CEE countries was established in 2015 within the South Eastern European Research Oncology Group (SEEROG). Our vision was to define the current status of oncology care in the CEE region and to propose solutions to the issue. The expanded SEEROG panel of oncology leaders from 13 CEE countries met during the 11th Central European Oncology Congress (CEOC) held in 2015 in Croatia, and the project “IMPACT” (Improving Patient’s Cancer Outcomes in Central Europe) was launched. To define the problem and propose solutions, we created a questionnaire, which was distributed during March and April 2015 to selected oncology leaders—members of the SEEROG and CEOC scientific bodies from Albania, Bosnia and Herzegovina, Bulgaria, Croatia, Czech Republic, Hungary, Macedonia,
Montenegro, Poland, Romania, Serbia, Slovakia, and Slovenia. The questionnaire dealt with incidence, mortality, sociodemographic and economic background, risk factors, prevention, diagnosis, treatment, and resources available for oncology care. We collected additional socioeconomic and cancer registry data from publicly available sources, such as GLOBOCAN 2012 [2], World Health Organization Global Health Observatory Data Repository [13], the World Bank [14], and Eurostat [15]. Analysis was done for all cancers combined and then, separately, for prostate, breast, lung, colorectal, endometrial, bladder, ovary, and renal cancers, and melanoma. Parameters of cancer prevention, oncology care, incidences, and mortality from CEE countries were compared with three neighboring WE countries (Austria, Germany, and Italy), with a sample of the rest of WE (Luxembourg, The Netherlands, Switzerland, France, and Belgium), and with Nordic countries (Finland, Sweden, Denmark, and Norway). A panel discussion of the results, including suggestions for improvement of the state of CEE oncology care, was held at the CEOC in June 2015.
RESULTS Risk Factors, Primary Prevention, and Early Detection Obesity is a risk factor for colon, rectal, breast (in postmenopausal women), endometrial, kidney, adenocarcinoma of the esophagus, and pancreatic cancer, and it is associated with a worse prognosis [16–19]. Five (38%) CEE countries have nationwide primary prevention programs targeting obesity and insufficient physical activity [20]. In CEE countries, the median proportion of the population with insufficient physical activity is lower than in neighboring WE, other WE, and Nordic countries [13]; however, the prevalence of obesity is higher. The latter is more prevalent in higherincome countries, such as Czech Republic, Hungary, Croatia, Slovenia, and Poland, than in the lower-income countries, such as Albania, Former Yugoslav Republic (FYR) Macedonia, or Bosnia and Herzegovina. The higher-income CEE countries are also characterized by higher alcohol consumption. This may be associated with higher incidences of cancers of the oral cavity, pharynx, esophagus, bowel, liver, larynx, and female breast [21, 22]. However, this higher alcohol intake is not accompanied by nationwide primary prevention programs targeting alcohol consumption; only a quarter of CEE countries have implemented such programs [20]. Thus, resources for prevention of alcohol consumption do not match the severity of the problem. Taxation of alcoholic beveragesadjustedforpurchasingpowerislowerinCEEcountries than in Nordic countries. The higher prevalence of tobacco smoking in CEE countries (40% in men and 27% in women) than in neighboring WE countries (34% in men and 29% in women), other WE countries (28% in men and 22% in women), or Nordic countries (24% in men and 21% in women) [13] is the major cause for higher incidence of lung cancer and other smoking-related cancers and, consequently, the higher overall cancer mortality.Tobacco smoking is the cancer risk factor most often targeted by primary prevention programs in the region [20]. Restrictions of direct and indirect forms of advertising, promotion, and
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Vrdoljak, Bodoky, Jassem et al. sponsorship of tobacco products are similar in different CEE countries, and tobacco advertising legal limitations are comparable to those in WE or Nordic countries. Despite this, the prevalence of smoking is still higher, likely because the most effective antitobacco measure, that is, adjusting the cost of cigarettes for purchasing power, is missing [13]. Consequently, cigarettes are more affordable in CEE countries than in WE or Nordic countries. Moreover, smoking cessation programs are lacking throughout the CEE region [20]. Screening programs and early diagnosis are known to reduce mortality rates of colorectal, breast, and cervical cancers [5]; however, only 6 of 13 (46%) CEE countries have implemented screening programs for cervical, breast, and colorectal cancers [20].
Recommendations x We advocate increasing resources for primary prevention programs targeted toward common cancer risk factors. In particular, nationwide primary prevention programs targeting diet, physical activity, obesity, and alcohol consumption should be more widely implemented. x Cost-effectiveness analysis of cancer primary prevention programs should also consider their cardiovascular benefits in medical and economic terms. This recommendation is in line with the European Guide for Quality National Cancer Control Programs recommendation to avoid duplication and seek synergies. x It is important to increase awareness and knowledge, among the general public and primary health care providers, of the association between obesity and cancer. x Taxation and pricing of tobacco products should be significantly increased throughout the CEE region. A substantial part of the collected income should be directed toward improvement of oncology care. x Comprehensive, population-based, valid, and reliable cancer registries should be created in all countries. x Further research in effective primary prevention programs on CEE populations is needed. Because primary prevention programs sometimes need decades to demonstrate their effects, cancer registries’ data should be used for long-term assessment of cancer prevention effects. x Screening programs for colorectal, breast, and cervical cancer should be implemented in all CEE countries, with continued effort on early detection of all cancers.
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weaknesses in the organization of oncology care and health care systems in general. A common, underlying, root cause is also the lower financial and human resources investment in all aspects of oncology care [20]. Health care budgets per capita and the expenditures on innovative cancer therapies in absolute terms are at least 5 times lower in CEE countries than in neighboring WE countries [20]. Even considering different purchasing power in both regions, with such differences it is simply not realistic to expect comparable outcomes. In the whole CEE region, higher shares of total health care budgets are spent on drugs than in WE or Nordic countries [20]. This is partially because of the fact that innovative therapies and equipment costs are similar around Europe, whereas the cost of labor and other costs, such as hospitalization, are on average lower in CEE countries. CEE, and particularly non-EU, countries, have considerably less radiotherapy equipment—in particular, equipment allowing for the high- precision conformal techniques, such as intensity-modulated radiotherapy, imageguided radiotherapy, or stereotactic radiotherapy [13, 23]. CEE oncologists with 3–5 years of experience, working in public hospitals, earn approximately 3 times less than their Austrian colleagues [20].This difference is smaller than the difference in gross national income, which is on average almost 7 times higher in Austria than in CEE countries [14]. Hence, it would be very demanding for CEE countries to significantly increase the level of salaries of oncology professionals given the current economic situation. Such discrepancies in income stimulate the “brain drain,” which compromises the strongest point of quality of cancer care in the region: well-trained, welleducated, and motivated medical professionals. Pharmacoeconomic analyses based on the modeling of data from various international, multicenter, randomized controlled but short-term, focused trials [9] and highly homogenous trials that enroll fewer than 1% of cancer patients from CEE countries [10] may be less applicable to specific local CEE populations. Additionally, such analyses may carry the risk of simplification and the lower predictive validity for particular CEE country circumstances [24]. Therefore, with no long-term, real-world, postmarketing studies specific for CEE countries, they may lack a sound informational basis for health care investment decision making.
Increased Investment Effects Incidence, Mortality, and Investment in Oncology Care A complex mixture of factors is responsible for the differences in incidence and mortality between CEE countries and the rest of the continent. Besides epidemiologic differences in genetic, environmental, and lifestyle factors, different incidences of particular cancer types are also important. CEE countries have a higher incidence of the more lethal lung cancer [2, 5], while neighboring WE, other WE, and Nordic countries have higher incidences of prostate and breast cancer, which generally have better survival rates [2, 5]. Probably equally important for the current status ofcancer mortality rates are less effective cancer control strategies in CEE countries: lower coverage, quality, and frequency of primary prevention, scarcity of screening programs (leading to late tumor stage at diagnosis), lower availability of treatment options, lack of real multidisciplinary teams, lower quality and availability of infrastructure, and
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Mortality-to-incidence ratio is calculated by dividing the mortality rate by the incidence rate. It presents a populationbased indicator of survival and is a good approximation of the 5-year relative survival rate for most but not all tumor sites [25]. Correlation of health expenditures per capita with the mortality-to-incidence ratio is high in the CEE region (Spearman’s r 5 –0.91 for male patients and r 5 –0.76 for female patients) but low in Western Europe (Spearman’s r 5 –0.17 for male patients and r 5 –0.20 for female patients) (Figs. 1, 2). In other words, every unit increase of health care expenditure per capita may be associated with a significant decrease in mortality-to-incidence ratio in CEE countries but would not have a comparable effect in Western Europe and Nordic countries. This may not be equally true for all cancer types. Direct medical and indirect morbidity costs of different cancer types are different [26] and rapidly changing because of the ©AlphaMed Press 2016
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Figure 1. Correlation of health expenditures per capita and mortality-to-incidence ratio: all cancers/male (n 5 25); a red square represents a Central and Eastern European country; a yellow rhombus represents a neighboring Western European (WE) country; a blue circle represents other WE countries; and a green triangle represents Nordic countries [2, 14].
continuous advances in diagnostic therapy and all fields of therapy, especially the implementation of innovative anticancer drugs. It is obvious that we urgently need more investment in oncology in general, but an equally important issue is the question of the efficient allocation of the available resources. Austria has somewhat higher overall health expenditures per capita than does Sweden, but Sweden has a significantly better (lower) mortality-to-incidence ratio for all cancer types [2, 27]. Overall expenditures are 72% higher in Switzerland, but Finland has an equally good mortality-to-incidence ratio. Similar examples concern the CEE region. Czech Republic has expenditures on oncology drugs per capita comparable to those of Hungary, Croatia, and Poland, and notably lower than those of Slovenia, but has a significantly better mortality-to-incidence ratio in breast, lung, colorectal, and renal cancers [2, 27]. Hence, the important question is where exactly the investments should be made. Although the incidence and mortality rates for lung cancer are highest in CEE countries, the difference in mortality-to-incidence ratio between CEE and neighboring WE countries is only 9% in males and 5% in females (Table 1) [2]; therefore, investment in the prevention and early detection of lung cancer is justified. But after diagnosis, lung cancer therapies are equally ineffective, so consequently, the mortality rates in CEE are quite similar to those in neighboring WE countries. Therefore, improvement in lung cancer prevention and early detection strategies may affect overall mortality, whereas major investments in the treatment of advanced lung cancers will have less impact. In contrast, there
are large differences in survival rates of patients with screenable and treatable cancers—such as prostate, breast, and colorectal cancers—between CEE and WE countries. Major investments in the improvement of screening and treatment of these cancers are more likely to effectively reduce the differences between CEE and WE countries. Here, the point should be raised that improved screening programs for some cancers, especially prostate cancer, could result in higher incidence on the basis of detection of clinically unimportant cases, decreased mortality, and consequently, a lower mortality-to-incidence ratio.
Recommendations x Evidence-based primary and secondary cancer prevention programs are of paramount importance and should be implemented in all CEE countries to diminish the proportion of advanced cancers at diagnosis and to decrease cancer mortality. x There is a need for routine monitoring and analysis of the relationship between investments in different aspects of oncology care and mortality rates. x Properly designed, country- or region-specific studies should be done routinely to assess the real effect of new therapies. These include postmarketing open or dynamic cohort studies accompanied with the continuous monitoring of the association of mortality-to-incidence ratios with the variation in usage of innovative cancer treatments. x The CEE region urgently needs assistance from EU funds to increase the level of overall investment in cancer care to reduce the unacceptable disparities in mortality-to-incidence ratios across Europe.
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Figure 2. Correlation of health expenditures per capita and mortality-to-incidence ratio: all cancers/female (n 5 25); a red square represents a Central and Eastern European country; a yellow rhombus represents a neighboring Western European (WE) country; a blue circle represents other WE countries; and a green triangle represents Nordic countries [2, 14]. Abbreviation: FYR, Former Yugoslav Republic.
Population-Based Cancer Registries Comprehensive population-based cancer registries are not available in all CEE countries, and even if they exist,their validity, reliability, and usage vary [1, 20, 28, 29]. Although Slovenia established one of the first nationwide cancer registries in the world in 1950, some CEE countries still do not have obligatory cancer registration. In addition, the CEE registries are usually limited to incidence and mortality data stratified by cancer site, sex, and age, but with no further details on risk factors, tumor stage at diagnosis, treatment, and outcomes [30]. Several studies have documented higher cancer mortality rates in CEE countries than in WE or Nordic countries despite comparable or lower incidences [1, 5, 6, 12, 31].Within the CEE region,there are also large differences in age-adjusted incidence rates, whereas mortality rates are generally similar [1, 2]. This inconsistency may be attributed to lack of national registries in some CEE countries or the less-then-perfect validity and reliability of collected data. In some instances, it is difficult to understand large differences between neighboring countries that share a similar distribution of known risk factors, similar populations, genetic backgrounds, health care systems, and education and investments in prevention and oncology care. It is possible that mortality records are more reliable and more valid than incidence records, but in some cases, mortality data are also of low validity [1]. As cancer patients are treated in different types of independent facilities and as autopsy rates are declining, it is more difficult to ensure the completeness and validity of mortality data [20].
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Recommendations x An absolute necessity is the implementation of high-quality cancer registries. x All national registries should comply with the IARC and European Network of Cancer Registries guidelines to secure a standardized/comparable, valid, and reliable analysis. x In addition to national cancer registries, the development of hospital or multi-institutional cancer databases with more detailed data from particular centers should be encouraged. These databases should collaborate closely with national registries, while ensuring high standards for personal data protection and data quality. x Analysis and dissemination of updated data should be faster to allow for real-time analyses. The IMPACT CEOC panel members share a common vision of a jointly managed, virtual CEE data center, adequately equipped and funded by all CEE countries and the EU. This would allow more powerful and faster collection, analysis, and dissemination of data from national or multi-institutional registries. Such an endeavor would promote the standardization and sharing of best practices between countries. The ultimate goal is the development of a unique, real-time CEE/EU cancer database in addition to national, regional, and hospital registries. Selected data from primary electronic hospital discharge charts and pathology and primary care records could be anonymized and uploaded to the global CEE/ EU cancer database on a daily basis. In return, the system would ©AlphaMed Press 2016
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Table 1. Incidence, mortality, and mortality-to-incidence ratio differences between CEE and neighboring WE countries CEE Cancer Male All tumors Prostate Bladder Colorectal Melanoma Renal Lung Female All tumors Breast Corpus uteri Colorectal Bladder Melanoma Renal Lung Ovary
Neighboring WE
Relative difference (%)
Incidence
Mortality
M/I
Incidence
Mortality
M/I
Incidence
Mortality
M/I
271 36 18.7 40 5.7 10.3 58
175 12 6.1 21 2.4 5.1 50
0.65 0.37 0.34 0.53 0.41 0.41 0.89
313 75 21.2 40 11.1 13.1 39
129 10 3.3 13 1.8 3.8 31
0.41 0.14 0.17 0.33 0.32 0.35 0.81
215 2108 213 0 295 227 33
26 17 46 38 25 25 38
37 62 50 38 22 15 9
220 59 15 23 4.6 4.4 4.7 17 11.1
96 16 2.9 11 1.3 1.4 1.7 13 5.8
0.44 0.30 0.30 0.49 0.30 0.35 0.32 0.83 0.49
253 91 12 23 5.1 11.7 5.4 18 7.4
83 16 1.9 8 1 1.1 1.7 14 4.7
0.33 0.17 0.17 0.35 0.22 0.27 0.27 0.79 0.63
215 254 20 0 211 2166 215 26 33
14 0 34 27 23 21 0 28 19
25 43 43 29 27 23 16 5 229
Incidence and mortality are presented as age-standardized (European standard population) rates per 100,000 inhabitants. CEE countries are Albania, Bosnia and Herzegovina, Bulgaria, Croatia, Czech Republic, Hungary, Macedonia, Montenegro, Poland, Romania, Serbia, Slovakia, and Slovenia. Neighboring WE countries are Austria, Germany, and Italy. Abbreviations: CEE, Central and Eastern Europe; M/I, mortality-to-incidence ratio; WE, Western Europe. Source: [2].
promote the standardization and dissemination of bestregister practices and strongly promote the scientific research in cancer prevention and care.
National Cancer Control Plans One of the prerequisites of successful cancer control is the development of comprehensive national or regional cancer control plans. Unfortunately, 7 of 13 (54%) of the CEE countries do not have national cancer control plans (NCCPs). Moreover, the countries of the CEE region with NCCPs in place face significant problems with their implementation. In most cases, the major issues are the lack of financial support and the lack of an organizational structure and network that would enable them to implement the NCCP strategy. Most NCCPs that currently exist do not include detailed planning of finances [32].
Recommendations x All CEE countries should develop and implement an NCCP, with appropriate financial and political support. x These plans should include detailed strategies on primary prevention, screening, diagnostics, treatment, and rehabilitation of cancer, research, and educational activities, as well as an implementation plan and outcome measures. x The financial and organizational structure to support implementation of the national cancer control plan should be a mandatory part of the NCCP. x The NCCP should be used to rationally improve nonmedical aspects of cancer care, such as reduction of social
exclusions and facilitation of patients’ return to social, occupational, and family functioning, as well as psychological support.
SUMMARY OF RECOMMENDATIONS Large differences in cancer epidemiology, in the majority of oncology care parameters and in treatment outcomes, exist between CEE countries and neighboring WE countries. Mortality-to-incidence ratios are much less favorable in CEE countries, and CEE cancer mortality age-standardized rates are among the worst in the world [2]. To accelerate the development of oncology care in CEE countries and to reduce the apparent disparities across Europe, CEE countries should undertake several measures.
Recommendations x All CEE countries should develop and implement national cancer strategic plans that will help to define the priorities in cancer control and the action priorities within their limited national health care budgets. x National cancer registries should be established in all countries. x Instead of a large number of independent facilities, consolidation into comprehensive oncology centers with multidisciplinary teams should be implemented. x Multidisciplinary approaches should be foreseen by national strategic cancer plans and made obligatory. A stopgap measure may be virtual Internet-based multidisciplinary tumor boards, allowing smaller hospitals that do not have
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comprehensive oncology care to make better-informed decisions about cancer treatments. Nationwide primary prevention programs targeting smoking, obesity, and alcohol consumption should be widely implemented. Screening programs for cervical, colorectal, and breast cancer should be implemented, and the reach and efficacy of the screening programs should be centrally evaluated. Improved education for all involved in oncology care is needed. Special attention should be on training specialists in cancer management (radiation oncology, medical oncology, and surgery). Also, very important and needed throughout the region is education for oncology nurses and general practitioners. Development of clinical guidelines and training for general practitioners for management and follow-up of cancer patients and survivors is needed. The current prevalence of inpatient/hospital-based care in the CEE should be changed to modern forms of ambulatory, day hospital, and clinic treatments. Day and ambulatory treatments may be superior in both direct and indirect costs, as well as quality of life for patients and families. Access to early diagnostic and novel, clinically meaningful treatment modalities is essential to close the gap between CEE and WE cancer control indicators. Less effective and old diagnostic and treatment strategies should be abandoned. Long-term routine pharmacoeconomic evaluations of new therapies in achieving outcomes in postmarketing, real-life settings should be encouraged. National independent systems of oncology care quality and outcomes’ evaluations may reduce the intracountry variability. Allocation of health care budgets for oncology should consider the high mortality rates, in comparison with those of the neighboring WE countries, and increase investments to diminish those gaps. Countries in the CEE region urgently need additional EU funds to decrease inequalities in cancer control in Europe.
ACKNOWLEDGMENTS The work was partially funded by a grant from Roche.
AUTHOR CONTRIBUTIONS Conception/Design: Eduard Vrdoljak, Gyorgy Bodoky, Jacek Jassem, Razvan A. ˇ Popescu, Jozef Mardiak, Robert Pirker, Tanja Cufer, Semir Beˇslija, Alexandru Eniu, Vladimir Todorovi´c, Kateˇrina Kub´acˇkov´a, Galia Kurteva, Agim Sallaku, ˇ ˇ Snezhana Smichkoska, Zarko Baji´c, Branimir I. Siki´c Provision of study material or patients: Eduard Vrdoljak, Gyorgy Bodoky, Jacek ˇ Jassem, Razvan A. Popescu, Jozef Mardiak, Robert Pirker, Tanja Cufer, Semir Beˇslija, Alexandru Eniu, Vladimir Todorovi´c, Kateˇrina Kub´acˇkov´a, Galia Kurteva, Zorica Tomaˇsevi´c, Agim Sallaku, Snezhana Smichkoska, Zˇ arko Baji´c, Branimir I. Sˇ iki´c Collection and/or assembly of data: Eduard Vrdoljak, Gyorgy Bodoky, Jacek ˇ Jassem, Razvan A. Popescu, Jozef Mardiak, Robert Pirker, Tanja Cufer, Semir Beˇslija, Alexandru Eniu, Vladimir Todorovi´c, Kateˇrina Kub´acˇkov´a, Galia ˇ Kurteva, Zorica Tomaˇsevi´c, Agim Sallaku, Snezhana Smichkoska, Zarko Baji´c, ˇ c Branimir I. Siki´ Data analysis and interpretation: Eduard Vrdoljak, Gyorgy Bodoky, Jacek ˇ Jassem, Tanja Cufer, Semir Beˇslija, Alexandru Eniu,Vladimir Todorovi´c, Zorica Tomaˇsevi´c, Zˇ arko Baji´c, Branimir I. Sˇ iki´c Manuscript writing: Eduard Vrdoljak, Gyorgy Bodoky, Jacek Jassem, Razvan A. ˇ Popescu, Jozef Mardiak, Robert Pirker, Tanja Cufer, Semir Beˇslija, Alexandru Eniu,Vladimir Todorovi´c, Kateˇrina Kub´acˇkov´a, Galia Kurteva, Zorica Tomaˇsevi´c, ˇ c ˇ Agim Sallaku, Snezhana Smichkoska, Zarko Baji´c, Branimir I. Siki´ Final approval of manuscript: Eduard Vrdoljak, Gyorgy Bodoky, Jacek Jassem, ˇ Razvan A. Popescu, Jozef Mardiak, Robert Pirker, Tanja Cufer, Semir Beˇslija, Alexandru Eniu, Vladimir Todorovi´c, Kateˇrina Kub´acˇkov´a, Zorica Tomaˇsevi´c, Agim Sallaku, Snezhana Smichkoska, Zˇ arko Baji´c, Branimir I. Sˇ iki´c
DISCLOSURES Eduard Vrdoljak: Bayer, AstraZeneca, Amgen, Merck, Merck Sharp & Dohme, GlaxoSmithKline, Novartis, Pfizer, Roche (C/A); Gyorgy Bodoky: Amgen, Astellas, Bayer, Janssen, Eli Lilly, Merck, Nordic Pharma, Novartis, Pfizer, Roche (C/A); Jacek Jassem: Roche, AstraZeneca, Amgen, Boehringer Ingelheim, Merck (C/A); Razvan A. Popescu: Amgen, Bayer, Bristol-Myers Squibb, Eli Lilly, Merck, Novartis, Roche, Sanofi (C/A), AbbVie, Johnson & Johnson, Novartis, Pfizer, Roche (RF); Robert Pirker: AstraZeneca, Boehringer Ingelheim, Eli Lilly, Merck Sharp & Dohme, Synta (C/A), Boehringer Ingelheim, Eli Lilly, Pierre Fabre (H); Alexandru Eniu: Roche, AstraZeneca (RF); Vladimir Todorovi´c: Roche, Sanofi, Pfizer, Inmed (H); Zˇ arko Baji´c: Roche, Pfizer, ˇ c: Threshold (C/A), Genentech/ AstraZeneca, Takeda (H); Branimir I. Siki´ Roche, Novartis, Sanofi, CellDex, Gilead (RF). The other authors indicated no financial relationships. (C/A) Consulting/advisory relationship; (RF) Research funding; (E) Employment; (ET) Expert testimony; (H) Honoraria received; (OI) Ownership interests; (IP) Intellectual property rights/ inventor/patent holder; (SAB) Scientific advisory board
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EDITOR’S NOTE: See the related commentary, “Cancer Control in Central and Eastern Europe,” by Carlo La Vecchia and Pierfranco Conte, on page 1161 of this issue. For Further Reading: Mark Lawler, Thierry Le Chevalier, Martin J. Murphy, Jr. et al. A Catalyst for Change: The European Cancer Patient’s Bill of Rights. The Oncologist 2014;19:217–224. Article Excerpt: Strengthening and upholding the rights of individual cancer patients and their families are the guiding principles of this initiative. In order to provide tangible benefits for European cancer patients, the ECC proposes the creation of a “European Cancer Patient’s Bill of Rights,” a patient charter that will underpin equitable access to an optimal standard of care for Europe’s citizens. Three patient-centered principles (termed “Articles”) underpin the European Cancer Patient’s Bill of Rights: Article 1: The right of every European citizen to receive the most accurate information and to be proactively involved in his/ her care. Article 2: The right of every European citizen to optimal and timely access to appropriate specialized care, underpinned by research and innovation. Article 3: The right of every European citizen to receive care in health systems that ensure improved outcomes, patient rehabilitation, best quality of life and affordable health care.
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