Abstract

Lung cancer remains one of the leading causes of cancer-related mortality globally, accounting for millions of deaths annually.

It is broadly categorized into Non-Small Cell Lung Cancer (NSCLC) and Small Cell Lung Cancer (SCLC), each with distinct pathological and clinical features. Key risk factors include tobacco smoking, exposure to carcinogens, genetic predispositions, and environmental pollution.

Early diagnosis significantly improves prognosis, but most cases are diagnosed at an advanced stage. This study explores the etiology, classification, diagnostic approaches, clinical manifestations, and current treatment modalities of lung cancer.

Introduction

Lung cancer is a malignant condition that originates in the tissues of the lungs, commonly in the lining of the air passages. It is primarily divided into:

• Non-Small Cell Lung Cancer (NSCLC): Comprising about 85% of cases, including adenocarcinoma, squamous cell carcinoma, and large cell carcinoma.

• Small Cell Lung Cancer (SCLC): A more aggressive form with rapid growth and early metastasis.

Major risk factors:

• Cigarette smoking (primary cause)

• Secondhand smoke

• Exposure to asbestos, radon gas, and industrial pollutants

• Genetic mutations and family history

• Air pollution

Methods

A comprehensive and systematic literature review was conducted to gather current and clinically relevant information regarding the diagnosis and management of lung cancer.

The search was performed across major scientific and medical databases, including PubMed, Scopus, Google Scholar, and the Cochrane Library.

The time frame for the selected literature spanned the past 10 years (2013–2023) to ensure the inclusion of the most recent advances in diagnostics, therapeutics, and screening protocols.

Keywords and Search Strings:

A combination of MeSH terms and Boolean operators was used, including:

“lung cancer,” “non-small cell lung cancer (NSCLC),” “small cell lung cancer (SCLC),” “lung cancer screening,” “LDCT,” “biopsy,” “EGFR mutation,” “ALK translocation,” “targeted therapy,” “immunotherapy,” “chemotherapy,” and “oncogene testing.”

Inclusion Criteria:

• Peer-reviewed articles from indexed journals

• Meta-analyses, systematic reviews, and randomized controlled trials

• Clinical guidelines from reputable bodies such as NCCN (National Comprehensive Cancer Network), ASCO (American Society of Clinical Oncology), and WHO

• Studies focusing on human subjects

• Articles written in English

• Research addressing diagnosis, risk factors, treatment modalities, and patient outcomes in lung cancer

Exclusion Criteria:

• Case reports, letters to the editor, and studies with insufficient sample size

• Animal studies

• Duplicated or outdated information not aligned with current clinical practice

Diagnostic Techniques Explored and Their Clinical Relevance:

1. Low-Dose Computed Tomography (LDCT):

Proven to reduce lung cancer mortality by enabling early detection in asymptomatic individuals at high risk (e.g., long-term smokers aged 50–80).

LDCT has been endorsed by USPSTF (U.S. Preventive Services Task Force) as the standard screening modality for eligible patients.

Compared to standard chest X-rays, LDCT detects small nodules with higher sensitivity, improving early-stage cancer diagnosis.

2. Chest X-rays and Conventional CT Scans:

Widely used as initial imaging tools in symptomatic patients. Although less sensitive than LDCT, they are useful in detecting masses, consolidation, or pleural effusions that may suggest malignancy.

High-resolution CT scans offer detailed visualization of lesion morphology and lymph node involvement.

3. Bronchoscopy with Transbronchial Biopsy and Endobronchial Ultrasound (EBUS):

Essential for obtaining tissue samples from central lung tumors and mediastinal lymph nodes.

EBUS-guided biopsy enhances diagnostic yield and staging accuracy, minimizing the need for more invasive procedures.

Allows simultaneous cytology, histopathology, and molecular testing.

4. Transthoracic Needle Aspiration (TTNA) and Core Biopsy:

Utilized for peripheral lesions or masses not accessible via bronchoscopy. CT-guided needle biopsy is preferred for accurate targeting, especially in small or deeply located nodules.

5. Molecular and Genetic Testing:

Molecular profiling is now a standard of care in NSCLC to guide targeted therapy.

Tests include:

·         EGFR mutations: Predict response to tyrosine kinase inhibitors (TKIs) like erlotinib or osimertinib.

·         ALK and ROS1 rearrangements: Respond well to ALK inhibitors (crizotinib, alectinib).

·         PD-L1 expression: Determines eligibility for immunotherapy with agents like pembrolizumab.

Next-Generation Sequencing (NGS) panels are increasingly used for comprehensive mutation analysis.

Results

1. Epidemiology and Risk Profile

·         Lung cancer is the leading cause of cancer death globally.

·         Smokers are 15–30 times more likely to develop lung cancer than non-smokers.

·         Increased incidence in developing countries due to rising smoking rates and industrial exposure.

2. Clinical Presentation

·         Persistent cough, hemoptysis (coughing up blood), chest pain, hoarseness, and weight loss.

·         Late-stage symptoms include bone pain, neurological deficits, and difficulty breathing due to metastasis.

3. Histological and Molecular Classification

·         NSCLC Subtypes:

o   Adenocarcinoma: Most common in non-smokers

o   Squamous cell carcinoma

o   Large cell carcinoma

·         SCLC: Rapid doubling time, associated with paraneoplastic syndromes.

·         Genetic markers like EGFR, ALK, KRAS, and PD-L1 influence treatment decisions.

4. Treatment Outcomes

·         Surgery: Most effective in early-stage NSCLC.

·         Chemotherapy & Radiation: Standard for advanced SCLC and unresectable NSCLC.

·         Targeted Therapy: EGFR inhibitors (e.g., erlotinib), ALK inhibitors (e.g., crizotinib)

·         Immunotherapy: PD-1/PD-L1 inhibitors like pembrolizumab show promise in advanced NSCLC.

·         Five-year survival rate is <20% overall, but early detection can improve prognosis significantly.

Discussion

Lung cancer continues to pose a significant global health burden. Despite advancements in treatment, the high mortality rate is largely due to late-stage diagnosis.

The integration of molecular diagnostics has revolutionized personalized treatment, allowing for targeted therapies and immunotherapies with improved outcomes.

However, disparities in healthcare access, lack of awareness, and smoking prevalence remain major challenges. Emphasis should be placed on:

·         Smoking cessation programs

·         Public health education campaigns

·         Enhanced screening protocols for high-risk populations

·         Wider accessibility of targeted and immunotherapy options

Conclusion

Lung cancer is a deadly yet largely preventable disease with early intervention. The increasing adoption of LDCT screening, precision medicine, and improved therapeutic modalities have enhanced outcomes for many patients.

However, sustained efforts in prevention, early diagnosis, and equitable treatment access are critical to reduce global morbidity and mortality.

Improving patient awareness, healthcare infrastructure, and continued research are essential for combating this disease effectively.

Reference

1. Siegel RL, Miller KD, Fuchs HE, Jemal A. (2022). Cancer Statistics, 2022. CA: A Cancer Journal for Clinicians, 72(1), 7–33.

https://doi.org/10.3322/caac.21708

2. National Lung Screening Trial Research Team. (2011). Reduced lung-cancer mortality with low-dose computed tomographic screening. New England Journal of Medicine, 365(5), 395–409.

https://doi.org/10.1056/NEJMoa1102873

3. Travis WD, Brambilla E, Burke AP, Marx A, Nicholson AG. (2015). WHO Classification of Tumours of the Lung, Pleura, Thymus and Heart (4th ed.). IARC: Lyon.

4. Hanna NH, Robinson AG, Temin S, et al. (2020). Therapy for Stage IV Non–Small-Cell Lung Cancer Without Driver Alterations: ASCO and OH (CCO) Guideline. Journal of Clinical Oncology, 38(14), 1608–1632.

https://doi.org/10.1200/JCO.19.03022

5. Mok TS, Wu YL, Ahn MJ, et al. (2017). Osimertinib or Platinum–Pemetrexed in EGFR T790M–Positive Lung Cancer. New England Journal of Medicine, 376(7), 629–640.

https://doi.org/10.1056/NEJMoa1612674

6. Reck M, Rodriguez-Abreu D, Robinson AG, et al. (2016). Pembrolizumab versus Chemotherapy for PD-L1–Positive Non–Small-Cell Lung Cancer. New England Journal of Medicine, 375(19), 1823–1833.

https://doi.org/10.1056/NEJMoa1606774

7. Govindan R, Ding L, Griffith M, et al. (2012). Genomic landscape of non–small cell lung cancer in smokers and never-smokers. Cell, 150(6), 1121–1134.

https://doi.org/10.1016/j.cell.2012.08.024

8.      Tan DS, Yeo WL, Zhang Z. (2021). Predictive biomarkers for immune checkpoint blockade in non–small cell lung cancer (NSCLC). Cancer Treatment Reviews, 98, 102175.

https://doi.org/10.1016/j.ctrv.2021.102175

9.      Rolfo C, Mack P, Scagliotti GV, et al. (2018). Liquid Biopsy for Advanced Non–Small Cell Lung Cancer: A Consensus Statement From the International Association for the Study of Lung Cancer (IASLC). Journal of Thoracic Oncology, 13(9), 1248–1268.

https://doi.org/10.1016/j.jtho.2018.05.030

10.  Paz-Ares L, Vicente D, Herbst RS, et al. (2020). Pembrolizumab plus chemotherapy for squamous non-small-cell lung cancer. New England Journal of Medicine, 379(21), 2040–2051.

https://doi.org/10.1056/NEJMoa1810865