Surgery for advanced lung cancer

Understanding advanced lung cancer and radical treatment

For patients with advanced (stage IV) non-small cell lung cancer seeking active treatment, the current standard of care is systemic anti-cancer treatment that involves chemotherapy, targeted treatments (for those with EGFR or ALK positive tumors) and/or immunotherapy.

Some patients are fortunate in that the number of disease sites are small (typically less than five) at the point of diagnosis - known as de novo oligometastatic disease. Survival outcomes are so good with treatments today that many are expected to live much longer with their disease held at bay, and even in multiple site setting at the outset, targeted treatments or immunotherapy can potentially reduce the number and sites of disease - this is known as induced oligometastatic disease.

Ultimately when only a few sites of disease remain, the question on most patients minds is if further (local consolidative) treatment such as surgery, radiotherapy, ablation to all residual sites of disease can improve survival?

Evolving role of surgery as local consolidation treatment

Small studies have reported improved survival with radiotherapy[1] and a study by Gomez reported that surgery, radiotherapy and/or ablation improved survival by 54% in this setting increasing to 85% in the presence of EGFR or ALK genetic abnormalities.[2] As the trial was relatively small, we need to know if this is a consistent finding with a greater degree of certainty.

Currently American and European joint radiation guidelines[3], American surgical guidelines[4], and European medical oncology guidelines[5], uniformly recommend and support surgery as part of multi-modality management where appropriate in this setting.

Eligibility for Lung Cancer Surgery in Advanced Stages

Radiotherapy, ablation or surgery are usually undertaken as option for local control and are complimentary options rather than competing for example there are limits as to how much radiation one can receive, and surgery may not be easily performed in technically difficult sites.

Tumour and disease characteristics

To be eligible for local therapies, one general rules applies in that ALL sites are amenable to treatment, if not then then you may undergo the risks of complications of the treatments without any benefit if all the disease cannot be controlled.

Currently there is no consensus on how many deposits and when local treatment should be administered. In 2021, I led a UK wide multi-center trial called RAMON designed to answer this question but it was not possible to recruit to completion, however we did learn a lot. In this study, we defined “oligometastatic” as all sites are treatable, without a regard for the specific number of deposits. We specified that 3 months of initial systemic treatment should be given to assess stability, and recommended PET/CT and MRI of the head to evaluate the disease extent (early local consolidation). We also allowed patients to participate if they had good control for a period longer than 3 months (late local consolidation).

Key patient factors for surgery and radical treatment

For surgery there are additional considerations of reasonable health status and lung function before any operation and specific considerations for radiotherapy.

When not to have surgery

Surgery would not be recommended if all the disease cannot be removed, if you have very poor lung function or in such a poor state of health where the risks of the operation outweigh any potential benefits.

Extent of surgery for advanced lung cancer

The treatment plan for all sites of disease is usually undertaken by a tumour board or multi-disciplinary team to ensure that all sites are treated with the least risk and disruption to you. Currently there is no consensus as to how much lung should be removed and in the RAMON trial, we recommended resection of the lesion itself with a margin rather than entire segments, lobes or lung. In addition we specified that lymph node where feasible should be removed.

Benefits and potential outcomes of surgery

Apart from complete resection, surgery also had the advantage of obtaining more tissue for biomarker analysis, and the profile of your tumour can change with time (clonal evolution), and after treatment (clonal selection) and new biomarkers may also be detected.

All operations carry risks, such as death, pain, bleeding and infection. It is important to note that the perceived outcome of improved survival were only suggested in small studies. In 2024 the results of a larger study NRG LU002 was presented suggesting no survival benefit (the published results are awaited) so uncertainty exists (in the thoracic oncology community) whether to routinely recommend local consolidative therapy.

Key takeaways and future outlook

Surgery as part of local consolidation treatment is highly individualised and required the support of a highly functional and supportive multi-disciplinary team. Surgery has the potential to improve survival, prevent further disease progression and provide tissue for updated biomarker analyses. However survival benefits have recently been called into question for (biomarker) unselected patients and therefore a detailed discussions are required.

If you would like to discuss your individual management, do not hesitate to contact me.

References

1. Gomez DR, Tang C, Zhang J, Jr GRB, Hernandez M, Lee JJ, Ye R, Palma DA, Louie AV, Camidge DR, et al. Local Consolidative Therapy Vs. Maintenance Therapy or Observation for Patients With Oligometastatic Non–Small-Cell Lung Cancer: Long-Term Results of a Multi-Institutional, Phase II, Randomized Study. Journal of Clinical Oncology. 2019;37:1558-1565. doi: 10.1200/jco.19.00201

2. Iyengar P, Wardak Z, Gerber DE, Tumati V, Ahn C, Hughes RS, Dowell JE, Cheedella N, Nedzi L, Westover KD, et al. Consolidative Radiotherapy for Limited Metastatic Non-Small-Cell Lung Cancer: A Phase 2 Randomized Clinical Trial. JAMA Oncol. 2018;4:e173501. doi: 10.1001/jamaoncol.2017.3501

3. Iyengar P, All S, Berry MF, Boike TP, Bradfield L, Dingemans A-MC, Feldman J, Gomez DR, Hesketh PJ, Jabbour SK, et al. Treatment of Oligometastatic Non-Small Cell Lung Cancer: An ASTRO/ESTRO Clinical Practice Guideline. Practical Radiation Oncology. 2023;13:393-412. doi: 10.1016/j.prro.2023.04.004

4. Antonoff MB, Mitchell KG, Kim SS, Salfity HV, Kotova S, Ripley RT, Neri AL, Sood P, Gandhi SG, Elamin YY, et al. The Society of Thoracic Surgeons (STS) Clinical Practice Guideline on Surgical Management of Oligometastatic Non-small Cell Lung Cancer. The Annals of Thoracic Surgery. 2025;119:495-508. doi: https://doi.org/10.1016/j.athoracsur.2024.11.010

5. Hendriks LEL, Cortiula F, Martins-Branco D, Mariamidze E, Popat S, Reck M, Committee EG. Updated treatment recommendations for systemic treatment: from the ESMO non-oncogene addicted-metastatic NSCLC Living Guideline(dagger). Ann Oncol. 2025. doi: 10.1016/j.annonc.2025.06.004