Lung volume reduction surgery vs. endobronchial valve revisited—another piece in the puzzle for good evidence

Lung volume reduction surgery (LVRS) and endobronchial valve procedure (EBV) are therapeutic options for patients with lung emphysema either as a definite treatment or as a bridge to lung transplantation. In 2003, the National Emphysema Treatment (NET) Trial, a randomized controlled trial evaluating the effect of LVRS against medical therapy, was released with more than 1,000 patients enrolled (1). Results from this trial preset defined patient selection criteria for LVRS, these are patients with upper lobe disease and low exercise tolerance, as this group of patients demonstrated decreased mortality compared to no surgery. Since then, these criteria guide patient selection and Medicare reimbursement in accredited centers in the United States (US). Inside but also outside US, LVRS procedures are underrepresented due to a feared high morbidity and mortality by surgeons reported from the NET trial and the lack of particularly specialized centers.

The reported high morbidity and mortality within subgroups of patients from the NET trial paved the way for boosting endobronchial valve therapy for the treatment of advanced lung emphysema. This culminated in a series of randomized clinical trials within the last 15 years comparing valves versus controls, such as the VENT trial in 2010 (2), the IMPACT trial in 2016 (3), the LIBERATE trial in 2018 (4), and the EMPROVE trial in 2024 (5). These trials included in part selection criteria for patients that were beyond the NET trial criteria formulated in and since 2003 such as homogenous distribution and lower lobe emphysema. The maximum follow-up period applied in these trials was 24 months. The results from these trials clearly favored EBVs having a safe profile with durable improvements in lung function, respiratory symptoms, quality of life and a significant reduction in dyspnea,

In the article “Endobronchial Valve Therapy vs Lung Volume Reduction Surgery in the United States” by Hayanga and colleagues, authors conducted a retrospective observational analysis comparing EBV with upper lobe wedge resection for LVRS between 2018 and 2020 in patients with advanced emphysema (6). Having included 3,222 patients undergoing LVRS and 841 patients treated with endobronchial valves, this study is one of the largest retrospective comparative studies of its kind. The main and most important findings of this study were, as opposed to all studies available on EBV, that (I) it defines mortality as an endpoint, (II) the mortality in the LVRS group is lower than in the NET trial, (III) the observation period extends up to 3 years and (IV) within this time period, patients receiving endobronchial valves demonstrate a higher perioperative morbidity and mortality though having a lower comorbidity profile (6). One important reason why the mortality is reported to be lower in the LVRS group in this study compared to the LVRS mortality reported in the NET trial is that in the latter, a relevant number of LVRS were performed via median sternotomy, which is not comparable to the development of minimal invasive advances within the last 20 years and in which setting LVRS is performed thoracoscopically today in specialized centers.

Very few retrospective reports exist comparing LVRS vs. EBV. In a retrospective comparative study by Lee and colleagues comparing bronchoscopic lung volume reduction with robotic-assisted lung volume reduction surgery, it was found that valve placement indeed uses less hospital resources than the robotic procedure; however, only if recovery is uncomplicated (7). When adjusting for the costs of the treatment of complications and revisional procedures in the EBV group, both procedures do not differ in terms of costs. This is in agreement with the current study in which re-admission and re-intervention rates are higher in the bronchoscopy group in the 30-day as well as within the 3-year observation period while costs do not differ significantly in both groups. In general, the EBV would possibly be the method of choice if no complications occur during the post-interventional course; however, this is normally not the case.

While there is a series of randomized clinical trials for EBVs, there is only one randomized clinical trial that compares LVRS with EBV since the NET trial up to now (8). No significant functional or peri-procedural difference could be seen between the LVRS and bronchoscopic valve procedure group, but mortality was not considered in the study design and the follow-up period was limited to 12 months.

While EBV is applied to heterogenous, homogenous as well as upper and lower lobe disease, LVRS is still confined to the NET selection criteria clearly revealing a gap of research. There is evidence that also patients with homogeneously distributed emphysema can profit from LVRS in well selected cases. Weder and co-authors described that patients with homogenous emphysema profit from LVRS with a perioperative mortality of less than 1%, an 35% improvement in forced expiratory volume in one second (FEV₁) and the same 1-year survival compared to LVRS in heterogenous emphysema (9). Nevertheless, there is no doubt that, as postulated by the NET trial, patients with heterogenous, upper lobe disease carry the best outcome after LVRS. However, to the best of my knowledge and what is known from the literature, there is no center except for the Zurich emphysema program led by Weder and colleagues that is successfully performing LVRS on homogenous emphysema. If there is strict adherence to key indications such as severe hyperinflation, adequate lung function with a diffusing capacity for carbon monoxide not less than 20% and no pulmonary hypertension, patients with homogenous emphysema should not a priori excluded from LVRS and should be evaluated as a subgroup of patient analyzed, as they can profit from the procedure with a low surgical mortality (10).

We have learned important aspects from this large retrospective study by Hayanga and colleagues. But if we want to add further and good evidence to the discussion about LVRS vs. EBV, a randomized controlled trial comparing LVRS with EBV in today’s era and under today’s minimally invasive surgical conditions is needed. This trial should consider relevant issues such as the inclusion of mortality as an endpoint and an adequate long follow-up period of patients. Considering the higher re-admission and re-intervention rate in most of the EBV studies available, particularly longer follow-up period on patients is needed. Patients should undergo rigorous discussion and selection for either procedure by an experienced team consisting of thoracic surgeons, pulmonologists, anesthesiologists, trained nurses, pre- and rehabilitation specialist, and pharmacologists. Also, the general belief that patients irrespective of their emphysema type should by default undergo primarily EBV before considering LVRS should be re-discussed. In this setting, also homogenous emphysema should not a priori be excluded as an indication for LVRS for well selected patients.

In summary, the current report provides the ideal platform to request for an actual standing. This would be best evaluated by a randomized controlled trial comparing LVRS vs. EBV under today’s practice considering morbidity, mortality and costs during an adequate follow-up period.

Acknowledgments

None.

Footnote

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