Pneumonectomy—a necessary evil?

Bronchial sleeve lobectomy, when feasible, is the preferred parenchyma-sparing surgical intervention of lung cancer patients with centrally located tumors, through a minimally invasive approach whenever achievable. However, pneumonectomy remains an important surgical option to achieve radical treatment for selected lung cancer patients when sleeve lobectomy is not feasible, though the indications for pneumonectomy remain subjective (1). Notably, there is no specific tumor node metastasis (TNM) classification for central lung tumors, complicating the prediction of prognosis and determining optimal patient-tailored treatment (2). Moreover, the definition of a central tumor is not clearly established and incorporated in current guidelines (3).

In a recent issue of Translational Lung Cancer Research, Wang and colleagues analyzed data from the Surveillance, Epidemiology, and End Results (SEER) database to investigate the impact of laterality on postoperative complications and survival following pneumonectomy (4). They found that right-sided pneumonectomy is associated with increased mortality within the first six months after surgery, compared to left-sided surgery. Beyond this high-risk phase, laterality did not affect long-term survival or prognosis. This finding raises critical interrogatives on post-operative management and underscores the need for targeted follow-up strategies.

Wang and colleagues advocate for an extended follow-up period, particularly for patients undergoing right-sided pneumonectomy. However, several key questions arise: how should extended follow-up be structured? who would be responsible for its implementation? and would it have a measurable impact on survival? Currently, surveillance following curative-intent treatment for lung cancer is managed by pulmonologists or oncologists, with thoracic computed tomography (CT) scans at six-month intervals for the first 2 years, followed by annual scans for an additional 3 years (5).

Regarding mortality, Wang and colleagues report that most deaths occur within the first six months after pneumonectomy, although they do not elaborate on the actual causes of death. Available literature on 30- and 90-day mortality states that the most frequently encountered complications include respiratory complications like pneumonia, cardiac complications like arrhythmia, and other complications like bronchopleural fistula (6,7). It is essential to identify which complications contribute to early morbidity and mortality, determine their timing, and establish strategies for prompt recognition and effective management. While most of these complications occur during hospitalization, they remain relevant post-discharge. This raises the question whether these patients should be monitored by a multidisciplinary team, including pulmonologists, cardiologists, and thoracic surgeons. Additionally, should all postoperative patients be monitored with such intensive follow-up, or can we select and target on individual high-risk patients? The recent development of risk assessment scores that predict mortality in pneumonectomy patients could aid in this matter. The RESECT-90 is a validated logistic regression model that combines age, sex, performance status, blood tests (creatinine and hemoglobin), diffusion capacity of the lungs for carbon monoxide (DLCO), laterality, and surgical approach to estimate 90-day mortality (8). In concordance with these risk factors, Wang and colleagues identified right-sided pneumonectomy and advanced-stage disease as risk factors for mortality. It could be argued that patients with these adverse prognostic characteristics and a high RESECT-90 score may benefit from more intensive follow-up.

Accurate staging is paramount for determining prognosis and is considered the cornerstone of decision-making in lung cancer treatment (9). Wang and colleagues report that stage III or higher is associated with a more than twofold increased risk for mortality within the first three months postoperatively. Therefore, meticulous patient selection based on disease stage could improve survival outcomes and reduce complication rates. Especially when it concerns a surgical procedure with high morbidity and mortality rates, like pneumonectomy. Some patients, specifically with advanced-stage disease, could therefore benefit more from (neoadjuvant) strategies like chemoradiation, targeted therapy, chemo-immunotherapy, or definitive non-surgical treatment strategies. Neoadjuvant chemo-immunotherapy has yielded promising outcomes in survival compared to chemotherapy alone and may represent the future direction of neoadjuvant treatment in non-small cell lung cancer (10).

With the newest promising neoadjuvant therapies available, investigated in studies such as the KEYNOTE-671 study and the Checkmate 816 study (11,12), one could aim to downstage the initial tumor, possibly resulting in the option of a less invasive surgical treatment modality such as sleeve lobectomy or even (bi)lobectomy, which could greatly improve short- and long-term survival compared to pneumonectomy (13). In some cases, patients even show pathological complete response after neoadjuvant therapy, which results in better prognosis for these patients (14). However, a pathological complete response is less likely in extensive tumors that require pneumonectomy. Consequently, as neoadjuvant treatments evolve, the role of pneumonectomy may diminish further. In the future, a wait-and-see policy, like in other types of cancer like colorectal and esophageal cancer, could even be proposed for these patients (15). However, this remains to be studied in lung cancer patients and is probably still a long way from implementation in our current practice.

If pneumonectomy remains the only viable curative-intent treatment modality for specific patients, it should be performed under the most optimal conditions. Prehabilitation programs, especially high-intensity interval training two to six weeks prior to surgery, have shown positive effects on exercise capacity and pulmonary function, in turn resulting in improved postoperative outcomes after lung cancer surgery (16). In addition, the enhanced recovery after thoracic surgery guidelines stipulate pre- and peri-operative recommendations like optimization of nutrition, smoking and alcohol cessation, pain and nausea management, fluid management, chest drain management, and postoperative early mobilization and physical therapy to improve postoperative outcomes (17).

In conclusion, specific causes of death after pneumonectomy remain unclear and are not extensively described in the current literature. These causes should be further studied to allow for more patient-tailored postoperative monitoring and follow-up, possibly resulting in improved treatment strategies for the currently very high morbidity and mortality rates after pneumonectomy. It could even be argued that pneumonectomy may no longer be considered a curative treatment modality if cancer-related mortality turns out to be the primary cause of death following the procedure. Be that as it may, pneumonectomy, and in particular right-sided pneumonectomy, should be avoided whenever possible by considering lung-sparing alternatives, such as (sleeve) lobectomy, that could be facilitated through neoadjuvant therapies like chemo-immunotherapy. Careful patient selection is essential and should be guided by specific preoperative diagnostic modalities such as a quantitative ventilation perfusion scan or pulmonary function tests like DLCO, forced expiratory volume in 1 second (FEV₁), and maximal oxygen consumption (VO₂max) (18). Moreover, definitive chemoradiation could be considered as alternative in elderly patients with advanced-stage disease. Given the heightened perioperative risk associated with (right-sided) pneumonectomy, referral of these patients to high-volume centers with extensive thoracic surgery expertise may also help optimize patient selection, improve perioperative management, and potentially mitigate postoperative morbidity and mortality. As for select patients, pneumonectomy remains a necessary evil, being the only curative-intent treatment available for now.

Acknowledgments

None.

Footnote

Provenance and Peer Review: This article was commissioned by the editorial office, Translational Lung Cancer Research. The article has undergone external peer review.

Peer Review File: Available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2025-233/prf

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-2025-233/coif). The authors have no conflicts of interest to declare.

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