Lung cancer guidelines in Sweden, Denmark, Norway and Finland: a comparison

Abstract

Background: The Nordic countries are similar in terms of demographics and health care organization. Yet there are marked differences in lung cancer mortality, for which Denmark historically has had the poorest outcome. One of several possible reasons for these differences could have to do with how lung cancer is diagnosed and treated in the different Nordic countries. However, among the four most populous Nordic countries: Sweden, Denmark, Norway and Finland, there is a paucity of knowledge about differences and similarities in recommendations in the national guidelines for non-small cell lung cancer (NSCLC) and the methodology by which the guidelines are developed.

Methods: We identified and evaluated the development and content of the available clinical care guidelines for NSCLC in the four countries. Moreover, we compared the integrated cancer pathways in these countries. We have used case examples to illustrate areas with clear differences in clinical care recommendations.

Results: There are notable differences in the methodology by which the guidelines are developed, published and updated to comply with international recommendations. The Norwegian guidelines are developed and updated according to the most rigorous methodology and have so far been updated most frequently. We found that on the basis of recommendations patients with NSCLC are treated differently with regard to bevacizumab therapy and radiation dosing regimens. Cerebral imaging practices in patients with locally advanced NSCLC also differ. There is, moreover, a marked difference with regard to efforts to help patients to quit smoking. All except Finland have integrated cancer pathways for fast track diagnosis and treatment. Guidelines for follow-up of lung cancer patients also differ, with the Danish follow-up regimen as the most comprehensive. To obtain consensus on optimal clinical care, areas with differences in recommendations or where recommendations are based on a low level of evidence should be subjected to further studies.

Introduction

Sweden, Denmark, Norway and Finland are the four most populous Nordic countries. Geographically and culturally, they are part of Northern Europe with generally high standards of living and well-functioning governments and state administrations. In many ways, the societies of these Nordic countries are similar in terms of population demographics and social structure. Health care is organized similarly with free access to a tax-financed, income-independent, health care system provided to all citizens. Cancer statistics are also similar in the sense that lung cancer is the leading cause of cancer-related death in all countries [1–4]. However, Denmark has the highest lung cancer incidence and in spite of recent improvements also still has the highest mortality [5,6].

Well-known prognostic risk factors in lung cancer include: stage, age, comorbidity, performance status and smoking [7,8]. There are, however, other non-patient-related factors that may also affect the prognosis such as a timely and correct diagnosis [9], the optimal treatment [10], and possibly an effective follow up regimen to identify disease relapse [11]. Differences in these factors between countries may have led to corresponding differences in prognosis.

One way to achieve improvements in diagnostic accuracy, treatment selection and clinical processes is to standardize procedures and treatments by providing nationwide treatment guidelines. Clinical guidelines are usually regarded as reflecting optimal care, or as level of care that must be provided to everybody. Accordingly, national guidelines should be based on the most recent evidence-based research and should be regularly updated. They should also take into account the target population and available health care resources.

To our knowledge, no recent comparison of lung cancer guidelines in the four largest Nordic countries has been published. Given marked differences in lung cancer mortality despite the similarities between the four countries, such a comparison will be relevant in order to identify possible significant differences in guideline development methodology and clinical care recommendations and thus areas that could be improved or subjected to further research.

The mere size and extent of the clinical guidelines for lung cancer render comparing and presenting all clinical care recommendations systematically beyond the scope of this article. The main focus here is to highlight clear differences between some or all the countries in the clinical recommendations regarding non-small cell lung cancer (NSCLC) and in the methods by which guidelines are developed and updated. Although our focus is on differences, we shall also present designated key areas of clinical care, where the recommendations are in accordance with one another.

To demonstrate differences in the guidelines between countries we present a series of cases, from the clearly curable patient over the borderline curable to the incurable patient.

Methods

The guideline documents were obtained through the websites of the following institutions: Sweden: The Swedish National Board of Health and Welfare and the Regional Cancer Centers (RCC), Denmark: The Danish Health Authority and Danish Lung Cancer Group (DLCG), Norway: The Norwegian Directorate of Health and Finland: The Finnish Medical Society. We last visited the websites containing the guidelines on 12 July 2016 when copies of available guideline documents were retrieved. The documents had to be openly accessible via the websites. Password-protected documents were not included. If one guideline document linked to another national guideline document, this was also included. N.L.C. assessed the Danish, Swedish and Norwegian guidelines in their original language. The Finnish guidelines and Finnish Medical Society’s webpages were assessed by S.H. and A.J.

Results

In the sections below, we briefly present the guidelines of the individual countries. Key methodological characteristics are presented in Table 1.

Table 1. An Overview of key methodological characteristics and year of update of national clinical guidelines for lung cancer care in Denmark, Sweden, Norway and Finland.

Country	Publishedby	Last updated	Diseases	Systematicliterature review	No. ofReferences	Grading ofevidence	No. ofauthors
Denmark visitation, diagnosis and staging	CS	2014	NSCLC; SCLC	Not stated	172	No	N/A
Denmark pathology	CS	2015	–	Not stated	10	No	2
Denmark surgery	–	2001	–	–	–	–	–
Denmark oncology	CS	2016	NSCLC; SCLC	Not stated	73^a	No	N/A
Norway	AUT	2016	SCLC; NSCLC; Carci; Mes; Thy; TC	Yes	506	Yes	19
Sweden	AUT	2015	SCLC; NSCLC; Carci; Mes; Thy; TC	Not stated	350^a	Yes^b	28
Finnish	CS	2015	SCLC; NSCLC	Yes	232	Yes	16

CS: clinical society; AUT: authorities; SCLC: small cell lung cancer; Thy: thymoma; TC: thymic carcinoma; Carci: carcinoid tumor; Mes: malignant mesothelioma.

^a References provided after each section, thus reference duplicates are possible.

^b Indirectly (see text).

Swedish guidelines

The Swedish National Board of Health and Welfare published the ‘National’ guidelines for lung cancer [2] in 2011. The document focuses on areas where there has been controversy or that need to be clarified and provides an evidence-based framework for the development of the clinical guidelines as presented below.

The RCC first published the Swedish lung cancer ‘clinical’ guidelines in 1991. They were updated in 2001, partly amended in 2008 and the latest version, written by practicing clinicians, was published in 2015 [1]. This is a cancer care program, which covers all aspects of lung cancer care and provides evidence-based clinical practice algorithms.

Danish guidelines

The Danish Health Authority last published the Integrated Cancer Pathway Guidelines for lung cancer [12] in 2013. The document consists of a general introduction, which applies to all cancer pathways, followed by a disease-specific section outlining the guidelines for diagnostic work-up, treatment and follow-up. There are links to the DLCG’s webpage, which contains three separate supplemental guideline documents formulated by the clinical communities: visitation, diagnosis and staging [13]; oncology [14], and pathology [15]. These documents provide a more detailed set of recommendations and algorithms. The surgical guidelines have not been updated since 2001 and these guidelines were no longer available online in July 2016.

Norwegian guidelines

The Norwegian lung cancer guidelines [16] cover all aspects of lung cancer care in one document.

The Norwegian Directorate of Health publishes the guidelines and is the only institution mandated to formulate national guidelines in Norway. The authors are representatives from the clinical community. The guidelines have been amended five times since the first edition in 2013 and the sixth edition was published in June 2016. The guidelines are assessed on a yearly basis and updated if this is deemed necessary.

The Norwegian guidelines are based on available scientific literature and guidelines from other countries. Links to the Danish, European, British and American guidelines are provided.

The Finnish guidelines

Representatives from the Medical Society of Finland have formulated the guidelines [4] together with the Finnish Respiratory Society and the Finish Society of Oncology. The guidelines were published in 2001, partly amended in 2008 and updated in 2016. Flowcharts are available on the website [17] illustrating the algorithm by which the guidelines are developed, published and implemented. This algorithm is designed to assure updates at specific time intervals, though these are not stated. The aim of the guidelines is to present information on the epidemiological development of lung cancer in Finland and to provide an update on diagnostic procedures and treatment in order to harmonize lung cancer care in Finland.

Integrated cancer pathways

The overall objective of a cancer pathway is to assure a ‘fast-track’ diagnosis and well-coordinated course of treatment, with minimal delay for patients suspected of having a malignant disease. Thus, aside from clinical guidelines, standard time frames between different steps in clinical care are provided (Table 2) along with algorithms for correct registration.

Table 2. Standard time frames in cancer packages for Denmark, Sweden and Norway.

Course element	Denmark	Sweden	Norway
From referral to onset of diagnostic work-up	6 calendar days	5 calendar days	7 calendar days
Onset until completion of diagnostic work-up	24 calendar days	21 calendar days	21 calendar days
Completion of diagnostic work-up until onset of treatment
Sur	14 calendar days	14 calendar days	14 calendar days
RT	15 calendar days	14 calendar days	14 calendar days
Che	11 calendar days	10 calendar days	7 calendar days

Sur: surgery; RT: radiotherapy; Che: chemotherapy.

Denmark was the first Nordic country to implement a lung cancer pathway in 2009. Norway [18] and Sweden [19] followed suit in 2015 and 2016, respectively.

Presently there are no integrated cancer pathways in Finland. However, the Ministry of Social Affairs and Health has established a working group for the improvement of cancer care in Finland. According to their report, it is expected that similar pathways with standard timeframes will be implemented by the year 2020 [20].

Clinical practice

In the following sections, we have highlighted key elements in clinical care.

Screening

The guidelines from all four countries state that more knowledge about selection criteria, negative consequences and cost-effectiveness is needed, and that results of ongoing studies must be awaited before specific recommendations can be provided.

Smoking cessation

The Norwegian and Swedish guidelines contain elaborate and explicit recommendations on smoking cessation. The online edition of the Finnish lung cancer guidelines provides a link to a clinical guideline on smoking cessation. The Norwegian, Swedish and Finnish guidelines cover in detail both pharmacological and non-pharmacological steps to achieve smoking cessation.

The Danish guidelines include a statement that all smokers who have been evaluated on suspicion of lung cancer should receive a brochure on smoking cessation, but include no specific recommendations to the health care provider on this issue.

PET scans

Fluorine-18 (F-18) fluorodeoxyglucose (FDG) positron emission tomography (PET) scans have become an integral staging modality in all four countries. In Denmark and Sweden, all potentially curable patients (Stages I, II and IIIa) should be offered a PET scan before treatment.

In Finland, a PET scan is recommended above Stage Ia. In patients with Stage Ia, a PET scan may be undertaken but should not delay surgical treatment.

In Norway, Stage Ia patients may also be offered surgery without a preceding PET scan if so decided at a multi-disciplinary team (MDT) conference. Otherwise, all potentially curable patients should be offered a PET scan.

Otherwise, the diagnostic work-up and staging of lung cancer patients are similar in the four countries. Thus, all (treatable) patients are required to have a histologically or cytologically verified diagnosis and are staged according to the TNM seventh edition. Endobronchial and endoscopic ultrasound are generally preferred over mediastinoscopy

Illustrative cases

The following examples do not cover all differences between the recommendations; rather, we use the examples to highlight elements of clinical care in specific patient categories with dissimilarity in the clinical care recommendations.

The clearly curable patient

A 61-year-old woman, physically active, Eastern Cooperative Oncology Group (ECOG) performance status (PS) = 0, current smoker, 30 pack-years and a near normal lung function, is discussed at the MDT and found to have peripherally located Stage Ia T1bN0M0 squamous cell carcinoma and is referred to surgery.

According to the Danish, Swedish and Norwegian integrated cancer pathways, the patient is required to receive surgery within 14 calendar days. In Finland, no time frame is provided.

Video-assisted thorascopic surgery (VATS) is recommended in Finland while VATS is regarded as a suitable alternative to thoracotomy in the Swedish and Norwegian guidelines. There are no available Danish guidelines regarding surgical technique.

After successful surgery, she should according to the Danish regimen be followed-up with a contrast-enhanced chest computed tomography (CT) scan every 3 months for the first 2 years and then for every 6 months until 5 years, provided that the patient can undergo further treatment should a recurrence of cancer be detected. In Norway, a similar follow-up is conducted, but per every 6 months for 5 years.

In Sweden, chest CT scan is not recommended over X-ray. Patients are usually followed-up every 3 months the first year and then every 6 months for 3–5 years, although no specific algorithm is spelled out. In Finland, provided that the patient is candidate for further treatment in case of relapse or a new primary cancer, the patient would be followed-up with chest X-ray every 6 months and depending on clinical evaluation, possibly an annual chest CT scan for the first 2 years. Then, an annual follow-up for a minimum of 5 years.

If relapse is suspected, the Norwegian and Danish guidelines recommend a new standard diagnostic work-up and staging. How to handle suspected relapse is not described in the Finnish and Swedish guidelines.

A patient with loco-advanced disease treated with curative intent

A 71-year-old man, former smoker, PS = 1 is diagnosed with Stage IIIa (T2N2M0) squamous cell carcinoma. Aside from a minor cough and dyspnea, the patient has no other symptoms (including neurologic symptoms). The patient is discussed at the MDT and offered concomitant chemo-radio therapy with curative intent. In Norway, Denmark and Sweden cerebral imaging, preferably with an MRI, should be offered to all Stage IIIa patients before undertaking curative therapy—regardless of symptoms. In Finland, a cerebral MRI is not performed in this case although an MRI of neurologically asymptomatic patients is recommended when extensive surgery is being considered.

In terms of chemotherapy, platinum-based combination therapy is universally recommended but for radiotherapy there appear to be different dosing regimens: Denmark and Finland recommend 60–66 gray (Gy) in 30–33 fractions while Norway recommends 66–70 Gy, and in Sweden even higher dosing regimens are recommended: up-scaling to 74 Gy is mentioned as an option and 60 Gy is regarded as an insufficient dose. The follow-up regimen in Denmark, Norway and Finland is the same as mentioned in the former case. The Swedish guidelines provide recommendations only on postoperative follow-up, and this group of patients is not mentioned.

The incurable patient with Stage IV disease

A 68-year-old woman, PS =1, diagnosed with a T3N2M1b adenocarcinoma. An epidermal growth factor receptor (EGFR) mutation analysis and test for anaplastic lymphoma kinase (ALK) rearrangement is recommended in all four countries in patients with an inoperable adenocarcinoma.

The patient will be offered palliative chemotherapy. In terms of treatment strategy there is little difference between the four countries, thus all recommend treatment according to histology and activating mutations. Without activating mutations, the patient would receive combination platinum-based chemotherapy in all four countries. In Denmark, Sweden and Finland, the neo-angiogenesis inhibitor bevacizumab can be added to mutation negative adenocarcinoma patients; whereas, this is not recommended in Norway.

Regarding the follow-up regimen for incurable patients no specific Swedish or Finnish algorithm is provided. In Norway, based on tumor location(s) and growth pattern, an individualized approach is recommended, although a 6-week interval between evaluations is recommended. A chest and upper abdomen CT is recommended for treatment evaluation and prior to new treatment initiatives as long as the patient is a candidate for further treatment. In Denmark, a chest and upper abdomen CT is performed every 3 months, as long as the patient’s performance status allows further oncological treatment. The Danish and Norwegian guidelines state that either the lung or oncology department should do the follow-up; this aspect is not mentioned in the other guidelines.

Discussion

We have seen that there are differences in guideline recommendations and the question is whether these differences might relate to corresponding differences in lung cancer mortality? Take, for example, the stronger focus on smoking cessation for patients diagnosed with lung cancer in Finland, Norway and Sweden as compared to Denmark: Continued smoking after diagnosis results in a markedly increased all-cause mortality and it has been estimated that a 65-year-old patient with a low-stage NSCLC may have a 70% 5-year survival chance if the patient quits smoking as compared to 33% with continued smoking [21]. A difference in prognosis of this magnitude may in fact explain a good part of the observed difference in mortality between Denmark versus Norway, Finland and Sweden. It should be noted, however, that differences in the clinical guidelines may not necessarily reflect actual differences in the clinical care that the patients receive and we do not know how systematic and effective the smoking cessation efforts in Finland, Norway and Sweden are in reality.

Clinical guidelines are widely used to guide treatment decisions and they support implementation of evidence-based medicine by making direct recommendations for treatment [22]. In cancer care, clinical guidelines have had a measurable positive effect on clinical practice and treatment outcomes [23]. In lung cancer treatment, remarkable savings have also been achieved in contexts where clinicians have followed restrictive guidelines rather than being without predetermined rules for what treatment should be used [24].

In Norway, where the guidelines have been updated most frequently, the responsibility for updates lies solely with the authorities. In Sweden, RCC is responsible for updating the guidelines, and it is stated that this should be done on a yearly basis, but we identified no amendments since the latest version from 2015. In Finland and Denmark, the clinical communities are primarily responsible for updating the guidelines. In Finland, where there is an algorithm that should assure regular updates, there is a time span of 8 years between the two most recent versions.

By collecting the clinical guidelines in one document as a comprehensive cancer care program, which is the case in all countries except Denmark, the multidisciplinary nature of lung cancer care is reflected in the guidelines document itself. An equal and updated contribution from the different sub-specialties within lung cancer care is probably also assured. This is stressed by the fact that the outdated Danish guidelines on lung cancer surgery are no longer available.

It is, however, not just a matter of formulating guidelines. They need to be implemented too; yet implementation strategies are not mentioned in any of the guideline documents. Implementing new guidelines is complex and differences in local capacity and resources could also be expressed in varying clinical practice. Recommendations are not laws and are generally phrased in terms such as ‘should’ and ‘can’, but never as ‘must’, thus allowing for differences in interpretation and hence clinical practice.

Do regular updates and collected documents then facilitate implementation of new measures and harmonize clinical care? The uniformity, or lack hereof, within clinical lung cancer care has been studied by Wouters et al. [25]. They revealed a variation in treatment patterns in the Dutch health care system, which could not be explained solely by annual case volume and hospital teaching status. Moreover, Hudson et al. [26] conducted a survey among British lung cancer clinicians regarding cerebral imaging in newly diagnosed NSCLC patients with no neurologic symptoms. The questionnaire included changes in clinical practice after the publication of the 2011 National Institute for Health and Care Excellence (NICE) guidelines. They found that the new guidelines had influenced clinical practice, but had not resulted in national uniformity. Ongoing studies [27] will hopefully add more knowledge about how to implement clinical guidelines.

Common to the described case examples regarding, for instance, recommendations for cerebral imaging and follow-up regimens is the fact that they are based on low-grade evidence. On the other hand, there has been, particularly in Denmark, which historically has had the highest lung cancer mortality, a political motivation to implement and fund measures that have not necessarily been tested or proved in a scientific setting. Such measures aimed at improving outcomes for cancer patients include integrated cancer pathways and aggressive follow-up regimens [28]. Areas where the supporting evidence is low should undergo further research and the corresponding guidelines regularly updated in order to achieve consensus on optimal clinical practice, harmonize recommendations, and ultimately assure optimal clinical care.

Limitations

There are several limitations to the present comparison. Firstly, it is not a comprehensive systematic comparison and we address only a few key elements of clinical care. Secondly, differences in the structure, level of detail, and included elements of care make a direct comparison difficult. Furthermore, we did not assess differences in included references. Additional or revised versions of the guidelines may also have been published since the completion of the present comparison, which could affect the relevance of the cases presented above.

Conclusion

All four Nordic countries have clinical guidelines for lung cancer. However, the methodology, by which the guidelines are formulated, developed and maintained, differs considerably between the countries

There are many similarities in the clinical care recommendations for lung cancer in the four Nordic countries. Of particular interest are areas with clear differences between recommendations. These include bevacizumab therapy, radiotherapy, cerebral imaging, smoking cessation efforts, and follow-up. Identified differences in recommendations may serve as a basis for potential improvements. In the meantime, such differences for clinical practice may be used strategically to compare and learn from the outcome for otherwise comparable patients subjected to different treatments in the four Nordic countries.

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.