From tradition to transformation: evolving paradigms in surgical lung cancer treatment

Lung cancer continues to be one of the most prevalent forms of cancer and is most often diagnosed at advanced stages, limiting treatment options. Surgery for lung cancer holds a long history, with the first successful pneumonectomy for bronchogenic carcinoma performed by Evarts A. Graham in 1933 (1). This procedure marked the beginning of a surgical approach to treat lung cancer and has been a cornerstone in the treatment of early-stage disease. Its role, however, has evolved significantly over the years. Nowadays, lung cancer surgery plays a crucial part in the multidisciplinary treatment of lung cancer across all stages.

Over the last decades, surgeons were pushed to develop new surgical strategies in response to the evolving complexity of lung cancer cases and the increased percentage of patients with early-stage disease due to lung cancer screening programs. Traditional approaches were no longer considered sufficient, especially not in a world with a growing demand for personalized treatment. This led to the development of minimally invasive techniques, such as video-assisted thoracoscopic surgery (VATS) and robot-assisted thoracic surgery (RATS), as well as lung-sparing surgical approaches, including sublobar and sleeve resections, all while maintaining oncological safety.

The standard surgical procedure for non-small cell lung cancer (NSCLC) has been lobectomy with nodal dissection since the prospective randomized trial by the Lung Cancer Study Group in 1995 (2), but all has changed ever since the JCOG0802/WJOG4607L trial (3) and the CALGB140503 trial (4). Both multicenter randomized trials showed the benefits of sublobar resection over lobar resection for patients with peripheral tumors smaller than 2 cm, with segmentectomy being non-inferior and even superior to lobectomy for overall survival and noninferior for relapse-free survival in the JCOG0802/WJOG4607L trial (3). Locoregional relapse, however, remains a major issue with segmentectomy, as shown by the ad-hoc supplemental analysis of the JCOG0802/WJOG4607L trial, and is associated with pure-solid appearance on thin-section computerized tomography (CT) and a margin distance that is less than the tumor size (5). Hence, indications for patient selection for segmentectomy should be better nuanced, with a likely role for three-dimensional imaging in the future, as this can aid in clinical decision-making between segmentectomy and lobectomy (6,7).

The CALGB140503 trial also showed that sublobar resection—segmentectomy and wedge resection—was not inferior to lobectomy with respect to disease-free survival (4), raising the question whether the even more lung-sparing approach, the non-anatomical wedge resection, is comparable to the more technically demanding segmentectomy. Typically, wedge resection serves as a diagnostic procedure, when preoperative CT-guided biopsies are inconclusive or not possible. Data from the Society of Thoracic Surgeons General Thoracic Surgery Database has shown though that wedge resection is comparable to segmentectomy in terms of overall survival for the broader population with clinical stage IA, and not only for those at risk for surgical complications (8). However, a post-hoc analysis of the CALGB140503 trial did show that locoregional recurrence was numerically, but not statistically, higher after wedge resection compared to segmentectomy (9). As there is a lot of heterogeneity within the sublobar resection group, future steps should be to evaluate when wedge resection is appropriate and who are the real candidates for wedge resection.

Lung sparing surgery is particularly crucial for patients with limited pulmonary reserve or a compromised lung function as it helps preserve postoperative respiratory capacity and lowers the risk of complications. Furthermore, salvage surgical interventions are still a possibility in case of (locoregional) recurrence. Nonetheless, it remains pertinent to consider whether other advanced treatment modalities instead of surgery, such as stereotactic ablative radiotherapy and image-guided thermal ablation, may represent a more suitable option for high-risk patients with stage I NSCLC (10). Nevertheless, the choice of treatment to the patient should be individualized after a multidisciplinary team discussion, taking several patient- and tumor-related factors into account, as well as institutional experience. Growing evidence on the prognostic impact of cancer cachexia (11) further underscores the need to include assessment of frailty and body composition into the therapeutic decision-making process. Not to forget, surgeons, oncologists and pulmonologists should always consider the patient’s needs and personal goals throughout their cancer journey when planning therapeutic interventions.

The most frequently used treatment option for surgically fit patients with early-stage disease has been curative-intent surgery with adjuvant chemo- and/or radiotherapy. However, recurrence occurs in most patients, and more than half of stage II patients do not survive the first 5 years. Hence, other treatment approaches have come into play the last few years, with targeted therapies, such as monoclonal antibodies that target the specific immune checkpoint axis programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1), or small-molecule inhibitors that target the epidermal growth factor receptor (EGFR), at the forefront of individualized care. Neo-adjuvant chemo-immunotherapy has shown promising effects in for example the CheckMate 816 trial (12), and has the potential to downstage cancer, permitting resection that was previously not possible, or target micrometastatic disease, aiming to reduce recurrence rates. Perioperative immune checkpoint inhibitor-based treatment (i.e., neo-adjuvant therapy followed by surgery and adjuvant therapy) as investigated in the KEYNOTE-671 trial (13) results in even more favorable clinical outcomes.

But what about surgery for stage IV disease? Historically, metastatic disease has been considered incurable. Many institutions and hospitals are still not in the game and are questioning whether we are pushing the envelope with operating on patients who have extensive systemic disease. Several reasons exist though why to operate on otherwise healthy patients. For example, with surgery, one can obtain tissue for histopathological analysis, enabling precise tumor characterization and molecular profiling, guiding treatment decision processes. Surgery can also remove any residual cells that stayed behind after radiation therapy. Furthermore, upfront resection could also be used as a strategy to prevent complications of concurrent chemoradiotherapy in the case of a large volume or cavitating tumor (14). With the latest guidelines on surgical management of oligometastatic NSCLC, the Society of Thoracic Surgeons aimed to guide multidisciplinary teams on the evidence-based implementation of treatment plans for stage IV disease (15). So far, there is however insufficient evidence to support any surgical approach (i.e., VATS/RATS over thoracotomy) or procedure (i.e., lobar versus sublobar resection).

While we have come a long way in lung cancer surgery, it still involves considerable risks that cannot be ignored. In recognition of these risks, enhanced recovery after surgery (ERAS) guidelines have become widely available to standardize perioperative care in thoracic surgery and prevent postoperative morbidity and mortality. Instead of implementing all 45 individual recommendations, surgeons should focus on the key elements for recovery; early mobilization, the limited use of opioids and early removal of chest tubes (16). Currently, new and even more progressive chest tube protocols are being implemented in clinical practice. Furthermore, to achieve faster recovery of respiratory muscle function and lower operative morbidity, techniques such as intravenous anesthesia with spontaneous ventilation have been increasingly employed in the last few years to avoid the adverse affects of mechanical ventilation and the residual effects of muscle relaxants (17). All are considered important landmarks in the study after surgical treatment of lung cancer. Given the revolutionary nature of lung cancer surgery, the goal of the present special series on lung cancer surgical treatment is to provide a comprehensive overview of the present state by a group of worldwide leading experts in the field and initiate future research.

Acknowledgments

None.

Footnote

Provenance and Peer Review: This article was commissioned by the editorial office, Translational Lung Cancer Research for the series “Current Advances and Innovations in Surgical Lung Cancer Treatment”. The article did not undergo external peer review.

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2025-732/coif). The series “Current Advances and Innovations in Surgical Lung Cancer Treatment” was commissioned by the editorial office without any funding or sponsorship. E.R.d.L., P.B.L. and A.J.P.M.F. served as the unpaid Guest Editors of the series. The authors have no other conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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