Many advanced-stage patients of the disease are experiencing long-lasting remissions along with longer survival rates through the apt use of newer immunotherapies

The GLOBOCAN 2020 reports the number of lung cancer cases at 2.21 million, making it the second highest contributor to cancer cases worldwide. It is also the leading cause of cancer-related deaths with around 1.80 million people succumbing to the disease every year.

Non-small-cell lung cancer (NSCLC) is the most common type. Two third of lung cancers are detected at an advanced stage, and the 5-year survival rate of this frightening disease is very bleak.

Signs and Symptoms of NSCLC

The most common signs and symptoms of lung cancer include a history of cough (2-3 weeks), worsening of cough, hemoptysis (coughing up blood), pain in breathing or coughing, hoarseness of voice, wheezing, persistent breathlessness, unexplained weight loss, and persistent fatigue or lack of energy, etc.

Risk Factors of NSCLC

There are both modifiable and non-modifiable risk factors for developing lung cancer. The non-modifiable risk factors include biological risk factors that a person has no control over, such as certain genetic mutations, family history, age as two out of three lung cancers are diagnosed over the age of 65, gender as female sex is an independent risk for most types of lung cancers, race, and ethnicity.

The modifiable risk factors refer to health behaviours and lifestyle choices that can be changed to cut down the risk. These include cessation  of smoking and tobacco, alcohol abstinence, maintaining a healthy body weight, and preventing exposure to second and third-hand smoke, asbestos, and other cancer-causing chemicals.

With the adoption of molecular profiling-based targeted therapies, the overall survival, as well as treatment outcomes in NSCLC, have improved significantly. As compared to the period from 1995 to 2001, when the patients with NSCLC had just a 15 percent chance of being alive after five years, the percentage has jumped significantly to 50 percent or more with the advancement of targeted treatments.

Staging NSCLC

Based on the size of the tumour and its location, NSCLC can be classified into four stages (I to IV). In stage I, the tumour remains restricted to the lung tissues, whereas in stage II, it spreads to the nearby lymph nodes. In stage III, the disease further spreads into the lymph nodes and the middle of the chest, whereas in stage IV, the disease spreads or metastasises to distant parts of the body.

Molecular Characterisation and Management of NSCLC

Management of NSCLC involves a multimodality treatment approach with surgical resection for early stages, combined radiotherapy and chemotherapy for locally advanced stages and palliative chemotherapy and radiotherapy for advanced or metastatic disease. Scientific advancements in molecular biology and cancer genetics have triggered the discovery of novel approaches for an improved diagnosis as well as the management of this disease. The molecular characterisation of advanced NSCLC has unveiled different genomic alterations that, in turn, are paving the way for a new era of improved treatment outcomes and personalised treatment of the individual patient.

The most common driver mutations that have been identified so far include EGFR gene mutations, KRAS gene mutations, EML4-ALK rearrangements, and altered MET signalling and ROS1 gene rearrangements. Biomarker tests for immunotherapy can help identify patients that may respond to immunotherapy.

Immunotherapy can be used either alone or in combination with chemotherapy or targeted therapies for better outcomes in lung cancer patients. A number of targeted oral therapies based on specific genetic alterations have been introduced to work better than conventional chemotherapy in recent times. Further, the use of CRISPR/Cas9 gene editing technology to alter the DNA sequences and modify gene function eliminates drug resistance issues in lung cancer.

Prevention of NSCLC

"Cessation of smoking significantly reduces the risk of lung and other cancers. Compared with smokers, lung cancer mortality is lower for individuals who quit smoking by age 50 and even lower for individuals who quit smoking by age 30. Newer smokers have the lowest cumulative lung cancer mortality."

For non-smokers, the prevention strategy is to avoid second-hand (environmental tobacco smoke) and third-hand smoke (residual nicotine and other chemicals left on indoor surfaces by tobacco smoke).

With the adoption of molecular profiling-based targeted therapies, the overall survival, as well as treatment outcomes in NSCLC, have improved significantly. As compared to the period from 1995 to 2001, when the patients with NSCLC had just a 15 percent chance of being alive after five years, the percentage has jumped significantly to 50 percent or more with the advancement of targeted treatments. Many advanced-stage lung cancer patients are witnessing long-lasting remissions along with longer survival rates through the apt use of newer immunotherapies.

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