Lung Transplant Linked to Better 1-Year Survival in NSCLC

Key Takeaways

• Among selected adults with medically refractory, lung-limited stage IV NSCLC and respiratory failure, lung transplant was associated with higher 1-year survival than medical management alone.
• Early posttransplant survival in the NSCLC transplant cohort was similar to that seen in lung transplant recipients without cancer.
• Deaths were reported during extended follow-up, so the early posttransplant signal does not settle longer-term durability.

Medically refractory, lung-limited stage IV non-small cell lung cancer can progress to fatal respiratory failure even when disease remains confined to the lungs. Lung transplant has historically not been used in this setting because of concern that oncologic outcomes would be poor. That question was examined in a prospective single-center registry.

In a prospective, single-center JAMA registry study of lung transplant for refractory lung-limited stage IV NSCLC, investigators included 404 adults.

Among 98 adults with medically refractory, lung-limited stage IV non-small cell lung cancer (NSCLC), 17 underwent lung transplant and 81 were transplant-eligible but received medical management alone because of nonbiologic barriers.

Another 306 adults without cancer underwent lung transplant for end-stage pulmonary disease. All transplant recipients had respiratory failure, and the transplant approach used contemporary staging and a dissemination-minimizing operative technique. The primary outcome was overall survival from completion of eligibility evaluation in the NSCLC transplant versus medical-management cohorts, with a secondary 1-year posttransplant comparison against recipients without cancer. Enrollment ran from September 1, 2021, through June 30, 2025, with extended follow-up through January 31, 2026.

In the primary comparison, Kaplan-Meier estimated 1-year overall survival was 100% (95% CI 63.1%-100%) among NSCLC transplant recipients versus 40.8% (95% CI 29.6%-53.1%) among medically managed transplant-eligible patients, an absolute difference of 59.2 percentage points (95% CI 46.2-71.7). During the main analysis period, there were 0 deaths in the transplant cohort and 52 in the medically managed cohort.

For the organ-stewardship comparison, 1-year posttransplant survival was 100% (95% CI 63.1%-100%) in the NSCLC cohort versus 88.1% (95% CI 83.7%-91.4%) in recipients without cancer, an absolute difference of 11.9 percentage points (90% CI 9.1-15.5). Extended follow-up through January 31, 2026, recorded 2 deaths among transplant recipients with stage IV NSCLC.

The findings are bounded to a highly selected subgroup with medically refractory, lung-limited stage IV NSCLC and respiratory failure. The transplant-versus-medical-management comparison was observational, single-center, and nonrandomized, and the early survival signal does not answer longer-term durability or quality-of-life questions.

The authors concluded that early survival was favorable among selected patients with medically refractory, lung-limited stage IV NSCLC and respiratory failure who underwent lung transplant, while longer-term follow-up and quality-of-life assessment remain needed.

Clinician Questions

Which patients with stage IV NSCLC were represented in the lung transplant cohort?

The lung transplant cohort was limited to selected adults with medically refractory, lung-limited stage IV NSCLC and respiratory failure. The medical-management comparison group consisted of transplant-eligible patients with the same disease pattern who did not undergo transplant because of nonbiologic barriers, so the finding does not extend to stage IV NSCLC broadly.

From what time point was survival measured in the lung transplant versus medical-management comparison for lung-limited stage IV NSCLC?

Overall survival in medically refractory, lung-limited stage IV NSCLC was measured from completion of transplant eligibility evaluation, not simply from the transplant procedure itself. That starting point defined the comparison clock across both the lung transplant and medical-management groups.

Why were lung transplant recipients without cancer included in this stage IV NSCLC analysis?

Lung transplant recipients without cancer were included for the secondary 1-year posttransplant comparison as an organ-stewardship benchmark. That comparator showed how early posttransplant survival in selected patients with lung-limited stage IV NSCLC related to outcomes in recipients who underwent lung transplant for nonmalignant end-stage pulmonary disease.

What remained unresolved after the early survival findings with lung transplant in lung-limited stage IV NSCLC?

The authors described early survival as favorable in selected patients with medically refractory, lung-limited stage IV NSCLC who underwent lung transplant, but longer-term follow-up and quality-of-life assessment were still needed. Later deaths during extended follow-up also underscored that early survival did not resolve longer-range outcome questions.