Cost of lung cancer diagnosis: cost differences between national health system and private sector.

1.
Background
In the last 5 years a screening program is proposed to all smokers, ex-smokers and patients with chronic obstructive pulmonary disease (COPD) [1]. We are expecting new proposals on lung cancer screening based on newly published studies [2] and artificial intelligence software [3–5]. Moreover, the next and most important step to achieve a complete methodology for lung cancer screening has been recently elucidated by combining serum biomarkers to radiological findings [6,7]. The screening program assisted in the diagnosis of pulmonary nodules, based on a radiological finding. Novel diagnostic techniques such as radial-ebus, convex probe ebus have proved their efficiency over the past 10 years [8,9]. However, in order to further improve the diagnostic yield, we had to improve also the navigation yield. In order to achieve this aspect of the biopsy procedures we had to use radiological equipment. Indeed we used the above endoscopic tools with C-Arm fluoroscopy, Cios-Spin, Dyna-CT and O-Arm [10–14]. This combination of radiological techniques has been proven to be safe for the patients with minimal radiation exposure [14]. Again technological advancements led to creating diagnostic suites with electromagnetic platforms incorporating and combining radiological examinations (recent CT scans) with navigation catheters through the bronchoscopes [15]. Robotic assisted bronchoscopy with Monarch and Ion systems was the next step in the development of diagnostic techniques in order to minimize operators' error during navigation. The time of navigation was reduced significantly [16,17]. In order to further enhance the diagnostic yield, we used the methodology of rapid on site evaluation (ROSE) and confocal laser scanning microscopy. The ROSE technique requires education in order to prepare biopsy samples in such an order that the operator can identify malignant cells and if the biopsy sample is sufficient for diagnosis [18,19]. On the other hand for confocal laser endomicroscopy scanning, new equipment was developed [20,21]. The operator, however, again has to be educated in identifying malignant cells and perform a targeted biopsy. All new technologies and combination of diagnostic methodologies increase the diagnostic yield of pulmonary nodules. However, at the same time the cost increases, not only for acquiring expensive diagnostic equipment, but also biopsy tools. Moreover, the combination of other medical specialties in the diagnostic suite such as radiologists and cytologists also increases the cost of diagnosis. In this manuscript we will refer to the cost–effectiveness of the diagnostic methodologies and try to identify similarities and differences between the national health system and private institutions. Also, we will comment on the very important issue of certification for all endoscopic diagnostic procedures by national health boards. All the information provided is for Greece. The same price for the same tools is available for the past 10 years and can be accessed by all doctors in Greece in the national health system called EOPPY.
1.1.
Diagnostic techniques: equipment & tools
A CT scan of the thorax without the addition of intravenous contrast fluid costs 80 euros and it is free of charge in national health system hospitals (NHS) while in the private sector patients have to pay 10.67 euros. The private clinic is reimbursed from the state with 50% of 80 euros due to clawback and rebate. Radial-endobronchial ultrasound equipment costs between 50–80 euros for the basic equipment. The ultrasound probe catheters cost between 12,000 and 18,000 euros depending on the different company (Fuji or Olympus) and different diameter. Olympus has three different probes. These catheters are meant for 10–15 uses since they are very sensitive. The tools for biopsy and the sheath catheter with guiding catheter (cost 1030 euros single use), biopsy forceps (10 euro single use), different types of brushes (10–30 euro single use), biopsy needles (from 150 euro 22G, 19G single use to 450 euro 22G and 770 euro 19G core biopsy, single use) and cryo probe (1.1–1.7 mm 450 euro, single use). All these tools are free in the NHS, while in the private sector they are not covered. Moreover, we should not forget the service of the equipment. The minimum budget should be considered for the ultrasound catheter which would range from 800 euros per patient if we use the cheap catheter of 12,000 euros for 15 patients to 1200 euros if we use the large ultrasound catheter for 15 patients. The tax is included in these calculations. The radial-ebus equipment itself does not need frequent service, it needs one service per 2 years, and ranges from 500 euros basic to 20,000 euros depending on the damage. We will not calculate this expense for every patient. A radial-ebus biopsy could cost from 1840 euro (biopsy forceps + catheter guiding system figure + ultrasound small catheter reimbursement) to 3000 euro (biopsy needle + catheter guiding system + ultrasound large catheter reimbursement). We can also use a combination of biopsy tools or navigation tools (see section radiology navigation systems). The convex ebus is another endoscopy methodology for the diagnosis of central lesions. There are currently three companies: Pentax, Olympus and Fuji (Figures 1 & 2).
The systems have an endoscope, an ultrasound source and a video source, their mean price is 165,000 euros with tax included. We use 22G, 21G and 19G core biopsy needles, their cost ranges from 450>550>770 euros with tax included. The equipment that definitely needs to be serviced two- to four-times a year is the endoscope and there is always insurance from the hospitals which is up to 40,000 euros per year. Moreover, there is also a balloon inflated with water that provides higher visualization during the biopsy (cost 30 euro tax). The biopsy for each patient ranges from 2130 euros (balloon, 22G needle and equipment compensation) to 2450 euros (balloon, 19G needle and equipment compensation). There is the case were we can use a cryo probe for biopsy, and in order to do this we have to use firstly a 19G needle to open a tunnel and then use the cryo probe (all types of cryo probes cost 450 euros with tax from ERBE). The cost in this case is 2900 euros with tax. The cost can rise even more if we use rapid on site evaluation (see next sections). The cost of this diagnostic procedure is covered by the NHS; however, in the private sector the state does not compensate patients. All patients have to pay 95% of the examination for example 2800 euros out of 2900 euros. CT-guided biopsy is performed with a 18G or 16G needle (cost 30–60 euro with tax included). The cost of a new CT scan ranges between 120,000 and 180,000 euros (with low dose radiation). Each biopsy costs between 1230 and 1260 euros (equipment compensation for CT and needles). The cost of this diagnostic procedure is covered by the NHS; however, in the private sector the state does not compensate the patients and they have to pay again 80% of the examination 250 out of 1230 euros in the private sector. Ultrasound guided biopsy is performed with an ultrasound source with a cost of purchase ranging from 12,000 to 65,000 euros depending on the software and probes, the biopsy tools are 16G needles, 18G needles and 22G needles. The cost of the needles ranges from 30 to 60 euros. The cost of such biopsy ranges from 150 to 690 euros (depends from the ultrasound equipment compensation and biopsy needle). The service is usually every 2–5 years and it ranges from 100 to 5000 euros. The cost is covered in the NHS hospitals, but not in the private hospitals. Therefore, the patient has to pay 80% (590 euros out of 690). All these procedures require mild sedation or rarely general anesthesia. We will not comment on this aspect of the biopsy procedure. However, we have to add that all patients either in a NHS hospital or private hospital they have to have a bed and a peripheral line as it is obligatory by our state law and for their safety this status is called one day clinic.

1.2.
Radiology navigation systems
A portable C-Arm system can be used for fluoroscopy along with the radial-ebus with a cost ranging from 20,000 to 80,000 euros depending of the radiologic capabilities. We can use also Dyna CT (250,000 euros), Cios Spin (150,000 euros) or O-Arm (150,000 euros) as a navigation system raising the cost by 100 euros for each diagnostic procedure since the normal service for these machines is done every 6 months and more than 2000 examinations can be performed without the need for service. The prices that we refer to are for newly purchased equipment with the necessary programs to visualize pulmonary nodules. This equipment has been found to be safe for patients from radiation [13,14] (Figure 3).

1.3.
ROSE techniques
ROSE is a technique that requires a microscope and five different fluids in order to prepare the sample on a cytology glass for evaluation. The cost of the fluids is 50 euros for 200 ml × 5 and they can be used for 50 sample preparations. The cytology glasses cost 100 pieces 20 euro. The type of microscope depends from the user, a minimum of high value equipment would cost 670 euro. The cost per examination is 80 euro with tax per sample. The operator has to be educated with a minimum education time for a pulmonologist of 3 months, with a certified program for 15,000 euros. The cost is not covered in NHS, nor in the private sector, and 80 euro is the lowest price available ranging from 80 to 250 euro based on the number of samples within on diagnostic procedure. Also, the time for each sample preparation is minimum 2 min, with a range from 2 to 5 min based on the operators’ experience. Confocal laser endomicroscopy with the system cellvizio by MAUNA KEA technologies which is the only system that can visualize cells in real time for any type of tissue has a cost of 150,000 euros with tax. Depending on the probe an additional cost of 15,000 euros with tax (1.1 mm probe for lymph node assessment) per 15 patients. So the cost per patient is 1000 euro. However, in order to visualize lymphnode tissue we have to open a tunnel with a 19G Olympus needle which costs 770 euro with tax. Therefore, the cost of this type of examination is raised to 1770 euro, let alone the expenses for immunohistochemistry which will be analyzed later. The cost for service has a range from 500 to 20,000 euro every 2 years. The cost for an endobronchial lesion rages from 1010 euro for using only biopsy forceps to 2220 euro (catheter, 19G needle and cryo probe included) if we want to take a lymphnode biopsy with a cryo probe. In the case that we want to use only miniforceps then the cost is 1030 euros (catheter + minifroceps they can puncture through lymphnode tissue, there is no need for a 19G needle usually to open a tunnel and perform the biopsy). The operator has to be educated with a minimum education time for a pulmonologist of 3 months, with a certified program for 15,000 euros. This equipment provides us with the information were to take biopsy; however, again we need to use different tools based on the location and tissue. These tools are the same that have been presented in the section Diagnostic techniques (Figure 4).

1.4.
Electromagnetic navigation systems
Electromagnetic navigation systems provide a catheter through the bronchoscope and increase the diagnostic yield. There are two major systems on the market the Archemedes, Bronchus and Illumisite™ platform form Medronic [22]. The Archemedes has a cost of 250,000 euros and for every patient we use a single use navigation catheter with a cost of 200 euro. The cost of Illumisite platform is 180,000 euro with a single use catheter with a cost of 1100 euro. The catheter in both systems provide the site for biopsy with an accuracy up to 80% (again there is a variation of efficiency depending on the site and size of the pulmonary nodule). Again biopsy tools have to be used. Service for Archemedes is considered to 10,000 euros annually, while for Illumisite 7000 euros. The minimum cost for a biopsy with Archemedes is 210 euros (navigation catheter + biopsy forceps) to 650 euros (navigation catheter + cryo probe). In a center of excellence where 100 Archemedes procedures are performed we need to add an extra cost of 2500 euro per patient in order to compensate for the equipment (250,000 euro). Then the cost of a biopsy would range from 2710 to 3150 euro. Regarding the Illumisite the cost ranges from 1110 euro per patient (navigation catheter + biopsy forceps) to 1550 euro (navigation catheter + cryo probe). In a center of excellence were 100 Illumisite procedures are performed we need to add an extra cost of 1800 euro per patient in order to compensate for the equipment (180,000 euros). Therefore, the final cost per patient can range from 2910 to 3350 euros. The operator has to be educated with a minimum education time for a pulmonologist of 3 months, with a certified program for 15,000 euros. Until now there is no compensation or reimbursement for this diagnostic technique since there are only two electromagnetic navigation systems in the country one Archemedes and one illumisite, nor in the national health system, nor in the private sector (Figure 5).

1.5.
Robotic endoscopy
There are currently two robotic systems on the market since 2018, Monarch® Platform (Auris Health, Inc, CA, USA) [23] and Ion Endoluminal System (Model IF1000), Intuitive [24]. There is also the Galaxy System™ (Noah Medical, CA, USA), which will have US FDA approval within 2023, we have no price for this unit. The monarch costs 500,000 US dollars, while the Ion costs 450,000 US dollars. We do not have the cost for the education of medical officers since in our country until now there is no such system and no educational program. The technique is not reimbursed nor in the NHS nor private sector since there no system in our country available in order to have additional data.

1.6.
Pathology reports
All samples have to undergo a certain procedure in order to be ready for the operator. Firstly we take the sample from the forceps, brush, needle or cryo probe. The first step is to extract the sample and prepare it in a cytology glass or paraffin block. In the case of mixed samples such as 22G biopsy needles we have both cytology specimen and tissue fragments and cell block preparation is necessary [25]. The cost of cell block preparation is the most expensive with a cost ranging from 120–150 euros tax included. The tissue samples are prepared directly to paraffin blocks with a mean cost of 80 euros tax included, the same price is for cytology specimens when they are prepared in cytology glasses for the microscope. ROSE cost for cytology specimens has been reported before; however, there is also ROSE for tissue samples [26]. The price ranges from 80 to 150 euros with tax included. All ROSEs are not covered by NHS and have to be paid privately. Again, with the ROSE we can establish only whether our material is enough for diagnosis and we can identify if there is cancer in our sample. The next step if cancer is identified is to use immunohistochemistry which range from 60 euro one immunohistochemistry antigen up to 15 (900 euro) in the case for example of a lymphnode with metastatic disease with Hodgkin lymphoma. Immunohistochemistry is covered by NHS and it is for free when conducted in the NHS; however, it covered only by 75% in the private sector. In the case of a Hodgkin lymphoma (900 euros with tax included) a patient would have to pay 225 euro in a private clinic. In our previous sections we did not include in the biopsy procedure this cost and therefore additional calculations have to be made, moreover, also we are referring only to those cases where the possible diagnosis is cancer (Figure 6).

1.7.
Medical officer education
Currently in the official educational system as pulmonologist there is no official program of education for radial-ebus, convex-ebus, biopsy with convex probe ultrasound or use of fluoroscopy (C-Arm) when endoscopy is performed. There is also no official program for education in electromagnetic navigation platform, robotic platforms or Dyna-CT, Cone Beam CT, Cio-Spin or O-Arm. We have only an educational program for bronchoscopy with local anesthesia. In the very few cases where anesthesia is administered it is without the presence of an anesthesiologist and also his presence is obligatory by our state law. Doctors using advanced navigation techniques have been educated in centers in foreign countries. It is also allowed by our national pulmonology society for doctors to use advance diagnostic techniques in patients even if they have only certifications from European Respiratory Society educational programs like EBUS part I, II and III. Therefore, many NHS hospitals or Private have doctors using this equipment with a low learning curve. As a result several patients have to undergo the same diagnostic procedure a second or even third time. Furthermore, the sample in several cases based on the type of biopsy (needle) cell blocks have to be created which in many hospitals is not possible. It has been observed that there is no interaction between cytologists and pathologists for samples with both cells and tissue fragments. There are very few ‘one stop pathology shops’ in the NHS and private sectors. Unfortunately, technology moved forward too fast for several health systems to have properly educated doctors. Finally, it has been observed that there is no interaction between doctors and there are cases where bronchoscopies are performed for small pulmonary nodules ≤1 cm which is impossible to obtain sample at least without a navigation system. The patient loses time from this diagnosis. This situation becomes more frequent in our country for pulmonologist at the age ≥35, because this group did not have the opportunity to learn during their 5 year education as a pulmonary registrar these new diagnostic techniques and to be able to identify which is the right technique for every patient. Educational programs are available only for ROSE and convex ebus in our country during a 3 month period with a cost of 15,000 euro.

2.
Discussion
It has come to our attention during the past 15 years, due to the crisis in our country that the education of pulmonologists has been delayed regarding novel diagnostic equipment in lung cancer. A bloom of novel technical equipment and diagnostic techniques has been introduced in the everyday clinical practice for lung cancer diagnosis. Therefore, the national health system was not able to cost properly all new diagnostic procedures and while the private sector with the proper funding moved forward, the national health system did follow. Although the NHS is responsible for educating young doctors, however, the patients should not undergo a second or even a third time a diagnostic procedure. The state must move forward to quickly compensate for the time that was lost and reimburse properly without claw back and rebait all hospitals, NHS and private. All patients with health insurance should have free biopsies when lung cancer is suspected by proper educated personnel. In our manuscript we did not include the cost of the anesthesia that is required in our diagnostic procedures. Moreover, several private institutes increase the price of a diagnostic procedure every 1 h. After the first hour the patient has to pay additionally 200–250 euro, depending on the private hospital. This type of additional cost does not exist for the NHS system. Proper boards from the national health system should create educational programs. We presented based on current information from several companies in our country the cost of several tools and procedures per patient. There might be small variations since we used data from eight national health systems hospitals and 12 private hospitals. Due to our research we observed that each hospital had a different contract for the buy of diagnostic equipment and compensation of the diagnostic tools. Probably this occurred because equipment was purchased in different years and companies. Finally, we did not include the cost of malignant pleural effusion biopsy (fluid or pleura) because we should include more information from the thoracic surgeons’ perspective which is another specialty. Also, we did not include the cost of pneumothorax or other adverse effects of biopsy procedures as this information should be another special chapter. Finally, we did not discuss cost–effectiveness of non-small-cell lung cancer drugs, since this is another issue. Again the effectiveness of therapy is associated with diagnosis since the initial biopsy sample is of great importance and this is the key factor for treatment administration and patient survival [27–29]. As a major limitation of our study we did not include the following information: construction or renovation costs associated with building a procedure suite to accommodate the new equipment, maintenance costs and personnel because, hospitals have different budgets for these parameters.

3.
Conclusion
Proper education of medical officers involved in the diagnosis of lung cancer is absolutely necessary. There should be a multimodality board between radiologists, pulmonologists, thoracic surgeons and pathologists. Proper education means early lung cancer diagnosis and cost–effectiveness for our health system. The cost of the diagnostic equipment should be closely observed by a national health committee. National health sector and private sector should have the same compensation by the state for all patients with health insurance. The national health system with its current hospitals and equipment cannot cover the demand for lung cancer diagnosis and the private sector capabilities should be used properly and in full. Moreover, with all novel minimal invasive techniques we a lower cost than thoracic surgery. For previous pulmonary nodules we performed thoracic surgeries with a cost ≥20,000 euros with several adverse effects for COPD patients and lengthy hospitalizations. Finally, we did not include the cost of anesthesia as there are no guidelines by our national health system and therefore it is up to the physicians’ opinion what kind anesthesia will be used. Screening program for lung cancer should be free for patients with COPD. Diagnosis should be made only in centers where all diagnostic modalities are available. Private sector should be equally reimbursed from the state for patients using their national health insurance. National health boards should oversee the education of medical officers and should be responsible for creating and evaluating new techniques. National health boards should oversee the cost of the equipment used in all biopsy techniques. National health boards should provide the necessary funding for expensive diagnostic techniques since early diagnosis will provide treatment for most patients.

4.
Future perspective
The Greek government has a different budget for the national health system hospitals and for the private hospitals due to the economic crisis that occurred in 2008. This issue remains unsolved even after several years have passed. There is a central office within the ministry of health that investigates that prices all equipment for all medical specialties and therefore there is a thorough evaluation for misconduct for both national and private sector pricing and this should remain as it is. However, since the budget for the private sector is lower until today it is absolutely necessary that this issue is corrected. Moreover, with the addition of new diagnostic and therapeutic techniques in the everyday practice more budget should be made by the ministry of health for the current health practice.