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Corresponding author. Address for correspondence: Simona Borilova, MD, Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, Zluty kopec 7, Brno 656 53, Czech Republic.
Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, Brno, Czech RepublicDepartment of Comprehensive Cancer Care, Faculty of Medicine, Masaryk University, Brno, Czech Republic
Institute of Biostatistics and Analyses, Faculty of Medicine, Masaryk University, Brno, Czech RepublicInstitute of Health Information and Statistics of the Czech Republic, Prague, Czech Republic
Department of Cardiac Surgery, University Hospital Hradec Kralove, Hradec Kralove, Czech RepublicDepartment of Cardiac Surgery, Faculty of Medicine in Hradec Kralove, Charles University, Hradec Kralove, Czech Republic
Department of Radiation Oncology, Masaryk Memorial Cancer Institute, Brno, Czech RepublicDepartment of Radiation Oncology, Faculty of Medicine, Masaryk University, Brno, Czech Republic
Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, Brno, Czech RepublicDepartment of Comprehensive Cancer Care, Faculty of Medicine, Masaryk University, Brno, Czech Republic
The Czech Republic (CR) is situated in the “heart of Europe” and borders Slovakia, Austria, Poland, and Germany (Fig. 1). The CR was part of Czechoslovakia until 1992. Currently, the CR ranks eighth in terms of population (10.7 million) and 15th in the area (77,247 km2) among the 27 European Union (EU) member states, and the standard of living reaches 92.9% of the EU average measured by gross domestic product (GDP) per inhabitant according to purchasing power parity.
During the communist era (1948–1989), the uncontrolled development of heavy industry and the construction of lignite power plants led to significant environmental pollution, negatively affecting the population’s health. After the fall of the communist regimen in 1989, the industry was restructured, the composition of the vehicle fleet and the fuels used changed, environmental protection became a priority, and living conditions improved. These changes resulted in a significant decrease in pollutant emissions; for example, by 2000, the total annual emissions of solid pollutants, SO2, CO, and NOx decreased by 92%, 87%, 57%, and 38%, respectively.
Czech Hydrometeorological Institute Emissions of air pollutants in the Czech Republic: air pollution in the territory of the Czech Republic in the year 2000.
The improvement of living conditions after 1989 was reflected in an increase in life expectancy (for men from 68.12 to 76.4 y; for women from 75.59 to 82.2 y; 1989–2019).
Universal accessibility to health care is guaranteed by the legislation in the CR. The system is financed primarily through mandatory health insurance. In 2020, the ratio of general government expenditure devoted to health to GDP was 9.2%, the highest in the EU.
In the long term, the age-standardized world incidence rate of tumors in the CR is steadily increasing (292.6 per 100,000), and the cancer mortality reveals stabilization or a slight decline (106.2 per 100,000). In an international comparison, the CR ranks 16th to 17th in the incidence of malignant neoplasms and 22nd in cancer mortality in Europe in 2020.
The most complex treatment of adult patients with cancer is provided in a network of 15 comprehensive cancer centers, 10 of which are certified lung cancer centers and seven are highly specialized thoracic surgery cancer centers (TSCCs). Modern systemic treatments such as immunotherapy or targeted therapy can only be administered in comprehensive cancer centers, where most patients with lung cancer in the CR are being treated (73%).
According to the Czech National Cancer Registry (CNCR), in 2020, the crude rate of new lung cancer (LC) cases (International Classification of Diseases, Tenth Revision, codes C33 and C34) was 58 per 100,000 persons (world age-standardized rate, W-ASR: 24.3 per 100,000), which accounts for 8.0% of all newly diagnosed cancers, with 6162 diagnosed LCs in total (4259 in men and 2372 in women). In the same year, 5304 people died of LC in the CR. The crude rate of deaths was 49.6 per 100,000 (W-ASR: 20.0 per 100,000), which accounts for 18.9% of all cancer deaths. These numbers make LC the third most common cancer (excluding nonmelanoma skin cancers) and the leading cause of cancer mortality in the CR.
Throughout the past decade, LC incidence and mortality have decreased in men but increased in women, with the prevalence of LC rising in both sexes (Fig. 2). In the past 20 years, we have found a doubling of the 5-year survival rate in patients with LC from 9.6% to 19.3% (Fig. 3). Even with the improved survival rate, most LCs (>40%) are still diagnosed in the metastatic stage without any significant shift in the past 10 years (Fig. 3).
Figure 3(A) Trends of LC age-standardized 5-year relative survival rate in treated patients. (B) The trend in the proportion of diagnosed clinical stages. The 5-year relative survival rates have increased over time, reflecting the improving quality of cancer care in the Czech Republic. Source: Czech National Cancer Registry. LC, lung cancer.
Despite the well-known fact that smoking is the main cause of LC, a quarter of the Czech population smokes tobacco, as reported by the State Institute of Health in 2020. During the past decade, the number of smokers in the population has been slowly declined. Since 2012, the prevalence of smoking among men and women decreased from 36.5% to 28.3% and from 26.3% to 18.2%, respectively. In most cases, Czechs smoke classic cigarettes, approximately 10 cigarettes per day. In contrast, only approximately 5% of the Czech population smoke electronic cigarettes, and this number has been steady since 2017.
Csémy L., Dvořáková Z., Fialová A., Kodl M., Malý M., Skývová M. Národní výzkum užívaní tabáku a alkoholu v České republice 2020, SZÚ Praha. Státní Zdravotní Ústav [National survey of tobacco and alcohol use in the Czech Republic 2020, SZÚ Prague. State Health Institute]. http://www.szu.cz/uploads/documents/szu/aktual/nauta_2020.pdf, 2021. [Accessed 21 September 2022].
After lengthy discussions, an antismoking law banning smoking in public places became effective on May 31, 2017—symbolically coinciding with World No Tobacco Day. Smoking cessation assistance in 2020 was provided in 43 Centers for Tobacco Addiction within hospitals, in approximately 200 outpatient facilities and 300 specialized pharmacies. Moreover, in 2016, the National Smoking Cessation Hotline was established.
Thanks to these implementations, the CR improved its ranking from 31st to 23rd according to the 2019 European Tobacco Control Scale, obtaining 49 per 100 points.
Less than one-fifth of LC cases are diagnosed in the early stage (clinical stage I or II) in the CR, which was one of the reasons why a pilot screening program was launched in January 2022.
This “Lung Tumor Early Detection Program” is designed for current or former smokers aged 55 to 74 years who have smoked 20 or more pack-years. The primary contact for patients is their primary care provider or pulmonologist. In the case of current smokers, a short intervention is carried out, and those determined to quit smoking are referred to a Center for Tobacco Addiction, a trained doctor, or a counseling center in a pharmacy. Subsequent imaging with low-dose computed tomography (CT) is carried out at an accredited radiology department (14 centers) following the National Radiological Standard intended for the pilot screening program. Patients with positive CT findings will be referred to one of the seven TSCCs.
As the LC screening program is at its beginning, most lung tumors are diagnosed owing to symptoms or as incidental findings. Most patients are referred to pulmonologists for diagnostics and staging by their primary care provider. The histologic diagnosis is predominantly obtained by bronchoscopy (BRS) (85%).
The essential procedure in diagnosing LC—BRS is performed by a specialized pulmonologist. A 2020 survey revealed that 254 bronchoscopies per 100,000 inhabitants were conducted (27,600 in total), which is more than double since 1975 (112 per 100,000).
In the past two decades, we have found a positive trend in the number of endobronchial ultrasound BRS (EBUS), which increased from 544 to 2351 procedures per year. Currently, EBUS and radial EBUS are available at 17 and 10 hospitals in the CR, respectively.
CT for primary assessment is widely available throughout the country. If further investigation is needed, mainly for patients with curative intent, a full-body fluorodeoxyglucose-positron emission tomography (FDG-PET) examination should be performed. In the CR, PET-CT is currently available at 18 hospitals. If the FDG-PET examination is not available or its result is inconclusive, a biopsy of mediastinal nodes greater than or equal to 1 cm in the short axis is recommended. Most cases of LC are presented and discussed on a multidisciplinary tumor board (MTB) in specialized oncologic centers.
LC is diagnosed morphologically by histologic or cytologic examinations in most departments of pathology or pulmonary cytology following standardized recommendations. Since 2010, NSCLC samples have been tested in specialized centers for “predictive diagnostics.” A total of 12 laboratories cooperating with specialized oncologic centers dealing with LC diagnostics and treatment are providing testing of predictive markers. Testing standards have changed in the past 12 years following international guidelines. Currently, EGFR, ALK-1, and ROS-1 are tested in all adenocarcinoma or NSCLC—not otherwise specified in a reflex manner at the time of diagnosis. Most EGFR is tested routinely by polymerase chain reaction–based method, ALK-1 and ROS-1 are immunohistochemically screened, and positivity is verified by molecular-genetic investigations. Following the demands of (pulmo)oncologists after the MTB discussion, there is a possibility to test samples of LCs by next-generation sequencing using a standardized gene panel. A liquid biopsy is used routinely to search for EGFR mutations and, at the time of progression, to detect T790M and other resistance mutations at the request of a (pulmo)oncologist. Moreover, all representative tissue fragments of NSCLC are tested for programmed death-ligand 1 (PD-L1) expression by standardized immunohistochemistry at the time of diagnosis.
SCLC is diagnosed in 15% to 18% yearly. In the category of NSCLC, adenocarcinoma is the most frequent type, accounting for more than 40% of cases, and more than one-third represent squamous cell carcinoma. In tested NSCLC, approximately 13% have been found to have EGFR mutation. In contrast, ALK translocations and ROS-1 aberrations have been detected only in 3% and less than 1% of cases, respectively.
The decision for surgery on a patient with LC is based on a recommendation by an MTB, and this practice is established in all specialized hospitals across the CR. Surgery for LC is performed by board-certified thoracic surgeons. Thoracic surgery certification is a subspecialization; therefore, training for board certification can be commenced only after completing the general surgery or cardiac surgery training.
General thoracic surgery for LC is performed by seven TSCCs associated with university hospitals and 13 smaller volume care hospitals. Although there is a tendency to centralize LC treatment to the TSCCs to provide the best care, all these hospitals provide standard procedures such as diagnostic biopsies or anatomical lung resections performed by either video-assisted thoracoscopic surgery (VATS) or open thoracotomy. In some centers, VATS operations are even conducted as nonintubated. Robotic surgery is now only used in one center but will be implemented in all TSCCs in the near future. Following guidelines, anatomical lung resection with mediastinal lymph node sampling performed by VATS is the treatment of choice. Nevertheless, there is a growing number of sublobar anatomical resections for T1a tumors and in patients with limited lung function.
Unfortunately, there is no nationwide database for thoracic surgery. Hence, no accurate national figures on specific procedures performed for LC are currently available. Data from CNCR reveal that between the years 2019 and 2022, 72%, 60%, and 38% of patients underwent surgery for LC stages I, II, and III, respectively.
Radiotherapy (RT) in the CR is provided by 28 centers. Most of them are equipped with linear accelerators. One workplace is equipped with a proton beam irradiator, one with a cobalt irradiator, and one with a Leksell Gama Knife for cranial stereotactic RT. Some departments use modern TrueBeam from Varian, some Elekta Synergy or Versa, two use TomoTherapy, and two CyberKnife. Patients with LC can be treated in all these facilities.
In some hospitals in the CR, stereotactic RT is used for selected early stages of LC, solitary lung, or other metastases. Fractionation and radiation dose are used according to the current European guidelines.
The techniques used in LC irradiation in our country are mainly intensity-modulated RT and volumetric-modulated RT. The use of planning CT is standard in the CR. In most departments, four-dimensional CT or deep inspiration breath hold can also be used. Which technique is preferred depends on the tumor localization and the influence of breathing movements on the tumor. CNCR reported that between the years 2019 and 2022, of all patients with newly diagnosed LC, 25.2% were treated by RT. As expected, RT was most often used in stage III (45.6%).
The national recommendations for the systemic treatment of LC in the CR follow the European Society for Medical Oncology guidelines and are developed and updated annually by the Czech Society for Oncology. Oncologic systemic therapy can be prescribed only by board-certified medical oncologists.
The CR regulates the prices and sets reimbursement levels through the State Institute for Drug Control, a drug regulatory agency responsible for marketing authorization, pharmacovigilance, clinical trial regulation, and pharmacy and wholesaler supervision. The State Institute for Drug Control coordinates and leads the pricing and reimbursement process in the participation of marketing authorization holders and health insurance companies. Drug availability for patients is mainly limited by drug reimbursement. According to the 2021 Waiting to Access Innovative Therapies Indicator Survey, the availability rate for oncology drugs in the CR was 66%, slightly above the EU average (59%). Yet, the time between marketing authorization and availability is 657 days, 100 days longer than the EU average (545 d).
For medications with an excellent benefit without reimbursement, an application for approval of exceptional reimbursement can be submitted according to Section 16 of the amendment to the Act on Public Health. The application process takes a minimum of 28 days, which is challenging, for example, in a neoadjuvant setting, and approval is not guaranteed.
For resected NSCLC, from stage Ib with risk factors and higher, four cycles of platinum-based chemotherapy are the only treatment option because there is no reimbursement for immunotherapy in the adjuvant or neoadjuvant setting. Regarding EGFR-sensitizing mutations, neither osimertinib is covered in the adjuvant setting. The standard treatment for nonresectable stage III is chemoradiation, either concurrent or sequential, according to the patient's performance status. Durvalumab as a consolidation therapy is reimbursed for 12 months for patients with PD-L1 expression greater than or equal to 1 and only after the completion of concurrent chemoradiation.
The treatment choice for advanced NSCLC depends on histologic type, molecular analysis, and reimbursement, especially in nonsquamous NSCLC with targetable mutations. As found in Table 1, drugs for common mutations such as EGFR or ALK are generally available. Nevertheless, the therapy for rare mutations is not reimbursed, and the application for exceptional reimbursement is usually submitted. In the absence of targetable mutations, the treatment decision in the first line is subject to PD-L1 expression, as summarized in Table 2.
Table 1Availability of Targeted Therapy in the CR in November 2022
Targeted Therapy/Mutation
First Line
Second Line
Third and Subsequent Line
Gefitinib/sensitizing EGFR mutation
Erlotinib/sensitizing EGFR mutation
PD after chemotherapy
Afatinib/sensitizing EGFR mutation
PD after chemotherapy
Osimertinib/sensitizing EGFR mutation
T790M present
Alectinib/ALK translocation
PD after crizotinib
Brigatinib/ALK translocation
PD after crizotinib
Ceritinib/ALK translocation
PD after crizotinib
Crizotinib/ALK translocation
Lorlatinib/ALK translocation
PD after alectinib/ceritinib
PD after crizotinib or another ALK inhibitor
Crizotinib/ROS-1 translocation
Entrectinib/ROS-1 translocation
Dabrafenib + trametinib/BRAF mutation
Amivantamab/E20i EGFR mutation
Larotrectinib/NTRK fusion
Entrectinib/NTRK fusion
Selpercatinib/RET fusion
Pralsetinib/RET fusion
Sotorasib/KRAS G12C mutation
Tepotinib/METex14 mutation
Capmatinib/METex14 mutation
Widely available
Available with conditions (mentioned in table)
Not available (not reimbursed)
Source: State Institute for Drug Control.
Note: Therapies in green color are widely reimbursed; in contrast, yellow-marked therapies are coved by insurance only under specific conditions. For example, lorlatinib can be used in the second line only if the patient is pretreated only with alectinib or ceritinib. Treatment with red-marked drugs is not reimbursed. Therefore, the application for exceptional reimbursement is usually submitted.
Treatment of limited-stage SCLC is mainly multimodal and always discussed during MTB. For patients with extensive-stage SCLC, the reimbursement of durvalumab in combination with chemotherapy (platinum + etoposide) has recently been approved (November 2022).
Challenges
During the past decade, the CR has taken important steps in tobacco control and LC prevention and treatment. Nevertheless, there is still plenty of room for improvement. With a quarter of the Czech population still smoking, more antismoking campaigns and education are needed. It is hoped that the newly launched pilot screening program in 2022 will lead to more early stage LC detections, challenging Czech thoracic surgeons, who will likely have to address an initially increased number of lung resections.
In June 2018, the LUCAS registry mapping the path from diagnosis to treatment was founded. Although the registry provides valuable information, it is currently limited to nine centers; there is still a demand for a national LC-specific registry to provide needed information on the national level. Establishing this kind of registry would be financially demanding, but it could surely provide valuable information about the Czech health care system and subsequently increase its efficiency.
With more next-generation sequencing testing and the fast development of new targeted therapies, the biggest challenge for the CR is to accelerate the pricing and reimbursement process. The CR is slightly above the EU average in availability rate for oncology drugs, but compared with our western neighbor Germany, the time to drug availability is six times longer. Better access to novel drugs will definitely improve the quality of life and survival rate of patients with LC in the CR.
Ladislav Dusek: Conceptualization, Resources, Visualization, Writing—original draft, Writing—review and editing.
Lenka Jakubikova: Writing—original draft, Writing—review and editing.
Pavel Turcani: Writing—original draft, Writing—review and editing.
Radoslav Matej: Resources, Writing—original draft, Writing—review and editing.
Ivo Hanke: Writing—original draft, Writing—review and editing.
Radana Dymackova: Writing—original draft, Writing—review and editing.
Ondrej Bilek: Writing—original draft, Writing—review and editing.
Norbert Pauk: Writing—review and editing.
Marek Svoboda: Conceptualization, Resources, Writing—original draft, Writing—review and editing, Visualization, Supervision.
Acknowledgments
This work was supported by The Ministry of Health, Czech Republic—Conceptual Development of Research Organization (MMCI 00209805); The Ministry of Health, Czech Republic (MH CZ DRO-VFN 64165 and AZV NU22-03-00130) and by Charles University (project Cooperatio Laboratory medicine); and The Charles University research program Cooperatio 34—Internal disciplines.
References
Czech Statistical Office
Czech Republic in international comparison (selected indicators).
Csémy L., Dvořáková Z., Fialová A., Kodl M., Malý M., Skývová M. Národní výzkum užívaní tabáku a alkoholu v České republice 2020, SZÚ Praha. Státní Zdravotní Ústav [National survey of tobacco and alcohol use in the Czech Republic 2020, SZÚ Prague. State Health Institute]. http://www.szu.cz/uploads/documents/szu/aktual/nauta_2020.pdf, 2021. [Accessed 21 September 2022].
Disclosure: Dr. Borilova reports receiving support for attending meetings and/or travel from Bristol-Myers Squibb, Merck Sharp & Dohme, AstraZeneca, Roche, and Servier; honoraria for lectures and presentations from Bristol-Myers Squibb. Dr. Bilek reports receiving support for attending meetings and/or travel from Bristol-Myers Squibb, Merck Sharp & Dohme, AstraZeneca, and Roche; honoraria for lectures, presentations, speakers’ bureaus, manuscript writing, or educational events from Bristol-Myers Squibb, Merck Sharp & Dohme, AstraZeneca, and Roche. The remaining authors declare no conflict of interest.
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