Lung Cancer Diagnosis and Treatment Modalities

Lung cancer remains the leading cause of cancer mortality worldwide, with non-small cell lung cancer (NSCLC) accounting for the majority of cases. Advances in early detection include low-dose computed tomography screening programmes and the integration of molecular biomarkers, such as circulating tumour DNA (ctDNA), into diagnostic algorithms. Radiographic techniques have been refined by the application of positron emission tomography–computed tomography (PET-CT) and radiomic analysis, improving lesion characterisation and staging accuracy. Histopathological evaluation continues to rely on tissue biopsy, while emerging liquid-biopsy approaches offer minimally invasive insights into tumour genomics and treatment response.

Treatment strategies for lung cancer have evolved into a multidisciplinary paradigm. Surgical resection remains the cornerstone for early-stage disease, complemented by stereotactic body radiotherapy for inoperable patients. Systemic therapy encompasses platinum-based chemotherapy, targeted agents against driver mutations (EGFR, ALK, ROS1), and immune checkpoint inhibitors targeting PD-1, PD-L1 and CTLA-4 pathways. In locally advanced disease, concurrent chemoradiotherapy achieves superior outcomes but requires careful management of toxicities. Neoadjuvant and adjuvant approaches are increasingly personalised, informed by molecular profiling and perioperative ctDNA dynamics. The integration of immunotherapy into perioperative regimens has shown promising pathological responses and survival benefits, reshaping the management of operable NSCLC.

Research from Nature Portfolio

Recent studies have demonstrated that combining immunotherapy with chemotherapy in the neoadjuvant setting significantly enhances pathological tumour regression. A phase 2 platform trial compared neoadjuvant nivolumab plus platinum-based chemotherapy with the addition of ipilimumab in operable NSCLC. The dual-checkpoint regimen achieved major pathological responses in half of treated patients and revealed enriched immune cell populations, including effector memory CD8+ T cells and tertiary lymphoid structures, suggesting mechanistic insights into improved tumour eradication. Baseline gut microbiota composition was also correlated with response, highlighting the influence of host microbiome on immunotherapy efficacy.

Another large single-arm study evaluated neoadjuvant monotherapy with an anti-PD-L1 antibody in resectable NSCLC. Two preoperative doses yielded a major pathological response rate exceeding the prespecified threshold and an encouraging three-year survival of 80%. Exploratory immunophenotyping identified peripheral blood and tumour-infiltrating innate immune subsets predictive of pathological response, paving the way for biomarker-driven patient selection and optimisation of neoadjuvant immunotherapy.

Lung Cancer Diagnosis and Treatment Modalities publication trend

The graph below shows the total number of articles in lung cancer diagnosis and treatment modalities across all publications each year (not limited to Nature Index journals).

Technical terms

Major pathological response (MPR): Reduction to ≤10% viable tumour cells in resected specimen following neoadjuvant therapy.

Pathologic complete response (pCR): Absence of viable tumour cells in all resected tissue after preoperative treatment.

Neoadjuvant therapy: Treatment administered before surgical resection to downstage tumours and eradicate micrometastases.

Circulating tumour DNA (ctDNA): Fragmented tumour-derived DNA in the bloodstream used as a biomarker for disease burden and treatment response.

Immune checkpoint inhibitor: Monoclonal antibody targeting regulatory pathways (PD-1, PD-L1, CTLA-4) to enhance antitumour immunity.

References

1. Neoadjuvant nivolumab with or without platinum-doublet chemotherapy based on PD-L1 expression in resectable NSCLC (CTONG1804): a multicenter open-label phase II study. Signal Transduction and Targeted Therapy (2023).
2. Neoadjuvant chemotherapy plus nivolumab with or without ipilimumab in operable non-small cell lung cancer: the phase 2 platform NEOSTAR trial. Nature Medicine (2023).
3. Neoadjuvant atezolizumab for resectable non-small cell lung cancer: an open-label, single-arm phase II trial. Nature Medicine (2022).
4. Effect of Postoperative Radiotherapy for Patients With pIIIA-N2 Non–Small Cell Lung Cancer After Complete Resection and Adjuvant Chemotherapy. JAMA Oncology (2021).