Clinical FeaturesOncology

Lung Cancer – a Brief Overview

Written by Mr Gerard J. Fitzmaurice MSc FRCSI (CTh), Consultant Cardiothoracic Surgeon s.i. Thoracic Surgical Oncology, St. James’s Hospital, Dublin

Lung cancer is the leading cause of cancer related mortality amongst both men and women in Ireland. Based on median projections from the National Cancer Registry, annual cases of lung cancer are projected to increase to 2,633 (+94%) in men and to 3,124 (+176%) in women by 2045. That is an overall increase to 5,757 cases annually for men and women combined (+132%) highlighting the importance of optimising the prevention, early diagnosis, and treatment of lung cancer in Ireland (Figure 1).

Lung cancer comprises two broad types namely small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) representing about 15% and 85% of lung cancer cases respectively. Small cell lung cancer is a particularly aggressive malignancy that is generally managed with systemic cytotoxic chemotherapy and radiotherapy; there is a limited role for surgery except in very select cases.

Non-small cell lung cancer, being the more common, can be considered any type of epithelial lung cancer that is not smallcell. There are a variety of types with the most common being Squamous cell carcinoma and Adenocarcinoma; other tumour types include large cell carcinoma and pleomorphic carcinoma. Although they are heavily associated with cigarette smoking, Adenocarcinoma may be found in non-smokers, something that is becoming slightly more common. Our latest three-year cancer audit report 2018-2020 highlighted only 8% of patients who underwent treatment for lung cancer at St. James’s were never smokers.

One of the major problems historically with lung cancer is delayed diagnosis with the majority of patients presenting with advanced disease that is not amenable to curative intent treatment. To counter this, the National Cancer Control Programme (NCCP) was established in Ireland in 2007 following the publication of the second National Cancer Strategy and led to the establishment of 8 cancer centres with rapid access lung cancer clinics (RALC) in each. General practitioners, as the gatekeepers to secondary care, were provided with a referral guideline to RALCs, which includes:

An abnormal chest x-ray suspicious for lung cancer, or a patient with haemoptysis and / or other concerning symptom, even with a normal chest x-ray

Indications for urgent chest x-ray include:

– Haemoptysis

– Persistent cough (> 3 weeks) or alteration of chronic cough

– Unexplained chest pain or dyspnoea

– Unexplained weight loss

– Unexplained bone pain / neurological symptoms

– Clinical signs such as finger clubbing, lymphadenopathy, focal chest signs, or hepatomegaly

There is also a greater awareness of the risk factors for lung cancer that include smoking (including a history of passive smoking, be that occupational or partner / family member), family history, radon exposure, prior radiation exposure, known or suspected exposure to asbestos, and / or a history of prior cancer. Patients referred via the RALC pathway will be assessed within 2 weeks of the receipt of a request by the referring clinician which has streamlined patients prompt access to appropriate secondary care, however patients do present via numerous other pathways.

Once a patient enters the RALC pathway, they will be assessed by a respiratory physician with a special interest in the diagnosis and management of lung cancer. Initial investigations include radiological imaging that is typically a CT Thorax to accurately delineate any abnormality in the chest and endoscopic assessment via a flexible bronchoscopy to assess the patient’s airway and obtain basic cytological and microbiological samples. If the patient has a concerning abnormality identified, then they will proceed to a tissue diagnosis. At St James’s we have a special expertise and interest in complex thoracic malignancies and hence we have a variety of options to obtain tissue, including a CT-guided biopsy, ultrasoundguided biopsy, transbronchial biopsy under fluoroscopic guidance, Endobronchial ultrasound (EBUS), and in certain cases surgical biopsy.

When a diagnosis of lung cancer has been made, the patient will complete staging. For early-stage lung cancers, that can generally involve a PET-CT whereas more advanced cancers may need invasive staging modalities to accurately determine their clinical stage and guide treatment. These include advanced bronchoscopic techniques (EBUS), and in certain cases surgical staging via mediastinoscopy or video-assisted thorascopic surgery (VATS).

All patients diagnosed with lung cancer via the RALC at St James’s are discussed at the multi-disciplinary meeting where the clinical stage is determined following completion of all investigations and a treatment plan decided. The optimal treatment for lung cancer is surgical resection if that’s possible and appropriate. The more advanced the stage, the type of treatment offered will change. For patients with evidence of systemic disease, systemic treatment options are offered including systemic cytotoxic chemotherapy and / or immunotherapy. More recently there have been advances in the genetic evaluation of lung cancer with identification of mutations that may be amenable to targeted therapy such as third generation tyrosine kinase inhibitors (TKIs) for EGFR mutant NSCLC.

For patients with early-stage disease who are not fit or otherwise decline surgical resection, there is the option of stereotactic ablative radiotherapy which has clear benefits and a very acceptable risk profile. In some select cases, there may also be the option of radiofrequency ablation which is a local control treatment strategy.

At St James’s we perform approximately 55% of all curativeintent lung cancer surgery in Ireland and consequently we have a special expertise in lung cancer care. We have a special interest and experience in the management of advanced malignancies, such as proximal airway tumours, tumours involving the major blood vessels, and chest wall tumours including Pancoasts (superior sulcus tumours). That experience can allow optimal preservation of lung parenchyma in “lung sparing” surgery. In certain cases, patients may undergo neoadjuvant treatment to include systemic chemotherapy and in some cases radiotherapy in preparation for surgical resection.

All patients who are considered potential candidates for surgery are seen by a cardiothoracic surgeon specialising in thoracic surgical oncology and a decision is made, in consultation and discussion with the patient, regarding the optimal management approach. Should they be fit for surgery, then they will be enrolled in our prehabilitation program to optimise their fitness for surgery under the guidance of a thoracic physiotherapist. We are currently involved in a more detailed prehabilitation trial (PREHIIT) in conjunction with our upper gastrointestinal surgery colleagues, to evaluate the benefit of high intensity interval training in preparation for major thoracic surgery. These interventions improve patients fitness for surgery reducing post-operative complications and optimising their overall journey. All patients who continue to smoke are offered review by the smoking cessation clinical nurse specialist to optimise their chances of stopping smoking at what is an opportune time. We also provide a pre-assessment clinic for detailed evaluation of moderate and highrisk surgical candidates.

At St. James’s, we offer a comprehensive minimally invasive thoracic surgical program – about 70% of all resections for lung cancer are undertaken via a minimally invasive approach. We offer both video-assisted and more recently robotic-assisted thoracic surgery using the latest da Vinci Xi model. We have an enhanced recovery after thoracic surgery (ERATS) program to optimise our patient’s peri-operative journey with an average length of stay of 4-days.

For patients with advanced malignancies involving part of their airway or major vascular structures or chest wall, surgery is generally offered via a posterolateral thoracotomy to facilitate resection and reconstruction of the involved structure(s). That may involve a sleeve bronchoplastic repair, resection and reconstruction of the pulmonary artery, and / or resection and reconstruction of the chest wall with a variety of materials used to optimise the patients function and recovery.

Adjuvant treatment, which is additional treatment delivered following surgery in patients with stage IIA – III disease, comprises systemic cytotoxic chemotherapy. This, as with neoadjuvant treatment, is a platinum-based doublet that generally includes cisplatin or carboplatin and an additional agent. In general, patients are assessed by a medical oncologist with a special expertise in lung cancer care and appropriate treatment is delivered once they have fully recovered from surgery. This can provide a 5-year additional survival benefit of about 5.3% in appropriate patients. There is currently great debate about the role of adjuvant radiotherapy amongst this patient group and in general, it is only recommended in very select cases.

As the largest centre for lung cancer surgery in Ireland, we are also involved in regular trials including neoadjuvant surgical trials using immunotherapy. We have a clear interest in research and have an active biobanking program to facilitate translational research. Patients will find that they are approached to be involved in research opportunities, should they wish, during their journey at St. James’s with an aim to improve overall lung cancer care.

The future of lung cancer management is very dynamic at present. The landscape for neoadjuvant treatment strategies is evolving and in the next 6-12 months there should be definite changes to the treatment strategy to optimise patients access to optimal curative intent care in Ireland. The recent seminal paper by Forde et al (NEJM 2022) demonstrating the significantly longer event-free survival and pathological complete response rates with neoadjuvant Nivolumab and chemotherapy in resectable lung cancer is practice changing. Screening for lung cancer is also moving to centre stage following the Dutch-Belgian NELSON study that evaluated 50 – 74 year olds with a history of smoking who underwent a screening CT Thorax at 1, 3, and 5.5 years. At ten years follow-up, they demonstrated a 24% reduction in lung cancer mortality amongst the screened population. The clear benefit of screening is the detection of more patients with early-stage disease who could be offered curative intent treatment and consequently it is an important area of development in Ireland. Save the date: The 10th All Ireland Lung Cancer Conference September 23rd / 24th Barberstown Castle, Straffan, Co Kildare

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