For a carefully selected group of patients with medically refractory, lung-limited, stage IV non-small cell lung cancer (NSCLC), bilateral lung transplant appears beneficial, being associated with favourable early survival outcomes, as shown in a study.
The estimated 1-year overall survival (OS) rates were 100 percent among lung transplant recipients and only 40.8 percent among those who did not undergo transplant and received medical treatment alone (absolute difference, 59.2 percentage points, 95 percent confidence interval [CI], 46.2–71.7). [JAMA 2026;doi:10.1001/jama.2026.8717]
First study author Dr Ankit Bharat and co-authors from the Northwestern University Feinberg School of Medicine in Chicago, Illinois, US, noted that the lung transplant cohort achieved longer early OS than the medically managed cohort, despite the presence of severe respiratory failure and worse functional status at baseline among the transplant recipients.
Of note, lung transplant recipients with NSCLC also had a higher 1-year post-transplant survival rate when compared with lung transplant recipients without cancer (100 percent vs 88.1 percent; absolute difference, 11.9 percentage points, 90 percent CI, 9.1–15.5).
“With longer descriptive follow-up, deaths occurred over time, underscoring that lung transplant should not be interpreted as restoring normal life expectancy in this population,” said Bharat and colleagues.
“The current study reframes lung transplant as deliberate organ-level removal of gross pulmonary disease in a defined subset of patients rather than as nonspecific escalation of therapy for biologically unselected cancer,” they added.
Accordingly, the authors restricted enrolment to patients with rigorously confirmed lung-limited disease, established through contemporary cross-sectional and functional imaging coupled with systematic invasive mediastinal staging. They also positioned transplant as a salvage intervention by requiring patients to have documented refractoriness to guideline-directed systemic therapies.
Finally, the operative technique used was modified to incorporate early pulmonary vein control, bilateral pneumonectomy prior to implantation, and extensive airway and cavity irrigation. The aim was to minimize intraoperative tumour dissemination.
“These modifications and biologic considerations distinguish the results from the present study from historical reports, which largely predated modern staging standards and effective systemic therapies and typically used conventional sequential bilateral transplant,” Bharat and colleagues pointed out.
“Within [such a] framework, early post-transplant survival in patients with lung-limited, medically refractory stage IV NSCLC was not materially worse and may be superior to that observed after transplant for non-malignant disease during the first year after transplant,” they added.
In an accompanying editorial, Drs Ece Cali Daylan and Ramaswamy Govindan from Washington University in St Louis in Missouri, US, wrote: “The study by Bharat and colleagues has brought the issue of bilateral lung transplant to the forefront, albeit for a unique and rare subset of patients with advanced NSCLC. [JAMA 2026;doi:10.1001/jama.2026.11478]
“Before widespread adoption, it is critical to confirm these results in larger, multicentre, well-controlled, randomized studies including carefully selected patients with lung-confined metastatic, refractory NSCLC without evidence of mediastinal nodal or extra thoracic disease determined using state-of-the-art imaging and ultrasensitive cell-free DNA analyses,” Cali Daylan and Govindan concluded.
The study included 98 patients with stage IV NSCLC and 306 lung transplant recipients without cancer (median age 63 years, 37 percent female, median follow-up from transplant 200 days). Of the NSCLC patients, 17 underwent lung transplant (median age 61 years, 59 percent female, median follow-up 343 days) and 81 received medical treatment alone (median age 63.4 years, 52 percent female, median follow-up 221 days).