Developments in Early Stages of Lung Cancer 

Article Information

Developments in Early Stages of Lung Cancer

Jack A. Kastelik*
Department of Respiratory Medicine, Castle Hill Hospital, Hull University Teaching Hospitals NHS Trust, University of Hull and Hull York Medical School, UK

*Correspondence to: Dr. Jack Kastelik BSc, MD, FRCP, Consultant Respiratory and General Internal Medicine, Honorary Reader, Department of Respiratory Medicine, Castle Hill Hospital, Hull University Teaching Hospitals NHS Trust, University of Hull and Hull York Medical School, Cottingham, East Yorkshire, UK, Tel:+44 1482 624067; E-mail: jack.kastelik@hey.nhs.uk

Received: December 30, 2019; Accepted: January 05, 2020; Published: January 08, 2020
Copyright: ©2020 Kastelik JA. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Citation: Kastelik JA. Developments in Early Stages of Lung Cancer. J Clin Pulmonol. 2020; 1(1). 001

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Abstract

Lung cancer remains a major health issue.Survival for the early stages of lung cancer is significantly better than for those with the advanced disease. In order to diagnose lung cancer earlier, an improvement would be required in patients’ awareness of the disease.Another approach to increase diagnosis of the early stages of lung cancer would be through a selected lung cancer screening. The investigational protocols should allow for the rapid staging and histological diagnosis of lung cancer. This requires imaging in the form of computed tomography and positron emission tomography which provide important staging information. In addition, new bronchoscopic techniques such as endobronchial ultrasound for mediastinal staging and navigational bronchoscopy for sampling lung lesions have become more widely used. The treatment options for the early stages of lung cancer are evolving with new radiotherapy and surgical approaches.Therefore, the aim should be for higher rates of early lung cancer diagnosis, which would result in improved treatment and survival outcomes.

Keywords

Lung cancer, Radiotherapy, Bronchoscopy

Article Details

Lung cancer remains a major health issue, considered to be the most important cause of cancer related deaths worldwide, with around 18 million people diagnosed each year [1]. Whilst there have been improvements in diagnosis and therapeutic options, the overall 5 year lung cancer survival has been reported at around 17% [1]. The main reason for the poor survival outcomes in lung cancer are related to the fact that the majority of cases are diagnosed with the advanced disease [1]. Survival for the early stages of lung cancer is significantly better than for those with advanced disease with a reported one year survival for stage 1 of 72% to 86% and for stage 2 between 59% and 78% compared to that of 35% to 46% for stage 3 and 16.8% for stage 4 disease [2]. Therefore, in order to provide the best prognostic outcomes, lung cancer should be diagnosed at the early stages, which allows for the radical options of treatment however, the epidemiological data reveals that only a small proportion, around 17% of cases, are diagnosed at stage I or II [3,4]. The importance of detecting lung cancer at an early stage relates to the wider range of treatment options, which may provide a cure.

Lung cancer from a histology aspect can be divided into small cell (accounting for 10 to 15% of cases) and non-small cell diagnosed in 85 to 90% of cases and is further subdivided into squamous cell cancer and non-squamous cell of which the majority are adenocarcinoma type [1]. Most lung cancers in the early stages would be of non-small cell type. In the modern era of managing lung cancer molecular testing allows for the use of the targeted systemic anti-cancer therapy [1]. The outcomes for patients with advanced lung cancer even when newer systemic anticancer treatments are employed are still relatively poor. The systemic anti-cancer therapy includes cytotoxic chemotherapy, targeted agents which include monoclonal anti-bodies or tyrosine kinase inhibitors and immunotherapy which work through the blockage of checkpoint [5,6]. For patients with advanced cancer, the therapeutic options include systemic anti-cancer treatment. In the context of the early stages of lung cancer, systemic anti-cancer therapy may be given in the neo-adjuvant or adjuvant setting [1,7,8]. The latter is more established with cancers of diameter of 4 cm or more in patients with no nodal involvement [1,7,8]. These approaches would require careful patient assessment and close surgical and oncological collaboration.

An increase in patient awareness of symptoms of lung cancer may be one of the factors for earlier diagnosis.For example, the Chest Australia study showed a 40% increase in consultations through improved awareness amongst the high risk population [9]. Similarly, lung cancer awareness campaigns, mainly as a result of a higher proportion of community chest radiographs being undertaken, were shown to result in higher rates of the early stages of lung cancer being diagnosed [10]. Another approach to improve the rates of diagnosis of the early stages of lung cancer would be through selected lung cancer screening. The NLST trial compared, in 53,454 high risk group of patients defined as those of more than 30 pack-year smoking history and aged 55 to 74 years old, low-dose (computed tomography) CT scanning with chest radiography and revealed that 24.2% of CT scans were positive in contrast to 6.9% chest radio graphs with 320 CT scans required to detect one lung cancer [11]. In the low dose CT scan group,there was also reported a 20% reduction in mortality. In the Dutch Belgian Lung Cancer Screening Trial NELSON, recently presented results showed lung cancer detection rates of 0.9% among-st 16,000 people aged 50 to 74 years with a history of smoking [12]. There was a 26% reduction in lung cancer death over the 10-year period. In the screening arm, 50% of cancers were diagnosed at an early stage compared to 10% in the control arm. Similar findings were confirmed in the Multicentric Italian Lung Detection (MILD) study, which reported on 10 year prolonged active low dose CT scan biennial screening a 39% reduction in the lung cancer mortality [13]. In a recent Manchester community-based Lung Health Check, which targeted high risk individuals in deprived areas, of the 1384 screened individuals 3% had lung cancer of which 80% were of an early stage with the surgical resection rates of 65% [14,15]. The easy access to the low dose CT scanning and the engagement of the high risk group were probably the most important two factorsto explain the findings. In addition, to the low dose CT there has been interest in using biomarkers for an early detection of lung cancer. Currently the value of blood microRNAs in addition to the low dose CT is under investigations in the bio MILD trial [16]. This approach may possibly provide more information whether there is a role for combining biomarkers with low dose CT for an early detection of lung cancer.

The rapid diagnostic pathway remains an important aspect of managing patients with lung cancer. A recent Lung-BOOST trial revealed that by adopting the rapid diagnostic pathway, the lung cancer diagnosis was reached within 15 days and when compared to standard investigational approach this resulted in the increase of median survival by 191 days [17]. The important aspects of the investigations of lung cancer include imaging modalities in the form of CT and positron emission tomography (PET) scanning. One of the aspects of PET, which makes it more superior to the CT scanning, is it’s higher accuracy for assessment of the mediastinal lymph nodes with reported sensitivity of 77.4% and specificity of 90.1% [18]. The accurate mediastinal staging forms an important aspect of managing of lung cancer. Whilst mediastinoscopy remains a gold standard endobronchial ultrasound (EBUS) and endoscopic ultrasound (EUS) have become more commonly used techniques for the mediastinal lymph node sampling with EBUS accuracy reported at 91% and even higher of 97% when combined with the EUS [19]. Another technique, the radial EBUS, gives 360o ultrasound visualisation of solid lesions with reported diagnostic yield of peripheral lesions of 20 mm diameter or greater of 78% and for smaller lesion of less than 20 mm of 56% [20,21]. Therefore, providing an additional investigational procedure complementing the CT guided biopsy for diagnosing peripheral lung lesions.Another new technique for sampling peripheral lung lesions is the electromagnetic navigational bronchoscopy which allows for precise guidance of the biopsy applying thin slice CT images and electromagnetic field. Using bronchoscopy working channel a sensor probe is guided to the site of biopsy and once located the biopsy and brush can be inserted through a sheath [5,22]. A large study NAVIGATE reported a 73% diagnostic yield using electromagnetic navigational bronchoscopy [23]. Another technique, the auto fluorescence bronchoscopy, which uses blue light at 442 Nm, which stimulates different fluorescence in dysplasia allowing for the early detection of pre-invasive and malignant lesions [24,25]. The auto fluorescence bronchoscopy and the newer techniques such as the high magnification bronchoscopy may prove to gain wider application for the diagnosis of an early lung cancer or post operatively to assess for early signs of the disease re-occurrence [25,26].

Radiotherapy in the context of the early stages of non-small cell lung cancer can be used as the main therapy with curative intend.Radiotherapy can be used in combination with systemic treatment or with surgery. Radical radiotherapy delivers the total radiotherapy dose of 60 to 70 Gy in 30 to 35 fractions [6]. An alternative is hypo-fractionated radiotherapy with doses of 50 to 55 Gy in 20 fractions [6]. These forms of radiotherapy use 3D technique allowing to calculate the dose across the three dimensions, which is more accurate compared to older 2D techniques which used central plane. In addition, the newer intensity modulated radiotherapy (IMRT) has acquired wider use due to its improved normal organ sparing [6]. Stereotactic ablative body radiotherapy (SABR), which is used to treat mainly peripheral early non-small lung carcinoma by delivering focused radiation in the form of high fractionation doses every 2 to 3 days with the total doses of 60 to 50 Gy in 3 to 8 fractions [27]. SABR can be used to treat tumours located within 2 cm in all directions of any mediastinal critical structure, including the bronchial tree and moderately central tumours located in the hilar region [27]. SABR was reported to result in overall survival at 12 months of around 83% and at 24 months of around 65% [27]. Other therapeutic options include the use of chemotherapy and radiotherapy in sequential or concurrent settings. Moreover, a recent report showed that Durvalumab, an immunotherapy agent, in addition to chemo-radiotherapy improved overall survival [28].

The proportion of patients undergoing surgery for lung cancer has increased between 1980 and 2015 by 94% [29]. However, there remains geographical variation in the surgical resection rates, which has been reported to range between 9% and 17% [4]. These variations were also observed in the systemic anti-cancer treatments and radical radiotherapy with evidence suggesting that improved resources are related to better lung cancer outcomes [30]. The Lung Cancer Group Study provided evidence from the randomised trial that lobectomy compared to the limited lung resection should be the treatment of choice for the early stage of lung cancer [31]. The patients undergoing limited resection compared to those who had lobectomy had 75% increase in recurrence rates, a 30% increase in the overall death and a 50% increase in the lung cancer death [31]. Therefore, the rates of pneumonectomy have reduced from 40% in 1980 to 5% in 2015 and at the same time the rates of lobectomy have increased from 55% to 79% [29]. Similarly, less invasive forms of surgery such as the video assisted thoracic surgery (VATS) and more recently robotic surgery have become more preferable to the open surgical procedures. There are numerous benefits of the VATS as it is associated with a reduction in the length of hospital stay, chest tube drainage duration and pain [32]. Over recent years, robotic surgery, of which da Vinci Robotic system is the most commonly used, has started to gain wider usein the context of thoracic surgery including the management of the early lung cancer [33,34]. Robotic surgery systems allow for a minimally invasive surgery using a surgical manipulator with a camera and three instrumental arms connected to a master remote control [33]. So far, the majority of the evidence using robotic surgery comes from the management of stage 1 and 2 lung cancer with lobectomy being the most common type of operation. Reassuringly robotic surgery for lung cancer has been shown to have reproducible outcomes and safety profile with costs being the main limiting factor [33]. Undoubtedly, robotic surgery will become more widely used in the future.

In conclusion, the early stages of lung cancer have better outcomes due to wider range of therapeutic and potentially curative treatment options. Therefore, in order to improve the outcomes strategiesare required to increase the proportion of patients diagnosed with the early stages of lung cancer. This potentially can be achieved through the campaigns to increase lung cancer awareness, the introduction of screening of the high risk groups of patients together with the rapid diagnostic investigational protocols.

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