Study Hints at Survival Benefit With Transplant for Metastatic Lung Cancer

Lung transplant for selected metastatic non-small cell lung cancer (NSCLC) patients was associated with better early survival outcomes in a prospective, single-center study.

Among 98 patients with lung-only involvement despite having medically refractory stage IV NSCLC, the estimated 1-year overall survival rates were 100% for the transplant recipients and 40.8% for the remaining patients treated with medical management alone.

The longer survival in the transplant group was observed “despite more severe respiratory failure and worse functional status at baseline,” reported researchers led by Ankit Bharat, MD, of the Feinberg School of Medicine at Northwestern University in Chicago.

At 1 year, 92.3% versus 5.6% of the two groups were alive and free of recurrence or progression, and the 1-year survival rate among the transplant recipients was similar to a group of patients without cancer who underwent lung transplantation for end-stage pulmonary disease (88.1%), according to the study in JAMA.

“This work changes what we can imagine for a highly selected group of patients who were previously considered beyond the reach of curative-intent intervention,” Bharat said in a press release.

“We are not saying lung transplant is appropriate for every patient with stage IV lung cancer,” Bharat cautioned. “We are saying that when the cancer is rigorously proven to be confined to the lungs, when standard therapies have been exhausted, and when the lungs themselves have become the life-limiting organ, transplantation may offer a new path forward.”

A rare subset of NSCLC patients have lung-only metastatic disease even after multiple lines of treatment. This patient population often dies because of respiratory failure, with surgical resection impossible because of diffuse bilateral involvement, the researchers explained.

Lung transplantation in lung cancer has been contraindicated based on past research suggesting high recurrence rates and poor survival outcomes, though prior studies predated current staging methods and systemic treatments and used transplant techniques that carried the risk of tumor spread.

“Before widespread adoption, it is critical to confirm these results in larger, multicenter, well-controlled, randomized studies,” according to Ece Cali Daylan, MD, PhD, and Ramaswamy Govindan, MD, both of Washington University in St. Louis.

Importantly, the patients selected for the study had to meet highly restrictive criteria, they noted in an accompanying editorial. Beyond the requirement for lung-limited disease, patients needed to have documented progression after guideline-directed systemic treatment and be staged with 18F-fluorodeoxyglucose PET, brain MRI, and systematic invasive mediastinal evaluation.

Also, “the study used a surgical technique to minimize dissemination (incorporating early pulmonary vein ligation and airway decontamination) and reduce intraoperative tumor spread,” wrote Cali Daylan and Govindan.

The editorials also pointed to several caveats of the research, including that the proportion of never smokers in the NSCLC transplant group was “strikingly” high at 59%, younger (61 years), and had fewer comorbidities compared with what is generally seen in metastatic NSCLC patients.

Bharat and colleagues evaluated outcomes from the Double Lung Transplant Registry for Lung-Limited Malignancies (DREAM).

The prospective, single-center study, conducted at Northwestern Medicine from September 2021 to June 2025, included 404 adults with end-stage pulmonary disease, including 98 with stage IV lung cancer — 17 underwent lung transplant while 81 received medical management as nonbiologic barriers (logistical, financial, or geographic) prevented transplant.

Among the 17 stage IV NSCLC patients who underwent transplant (94% bilateral), the median age was 61 years, 59% were women, 41% had hypertension, and 41% had a history of smoking. Most had undergone multiple lines of therapy for their NSCLC, including one patient who underwent seven lines, including immunotherapy, targeted therapy, and a clinical trial. Seven had received prior surgery.

For the 81 NSCLC patients who received medical management alone, the median age was 63 years, 52% were women, and 61% were former smokers. Comorbidities were more frequent in this group: 53% had hypertension, 28% had diabetes, and one-fifth had chronic kidney disease.

Disease progression ultimately occurred in four NSCLC transplant patients (over 343 days of median follow-up), as compared with 74 of the NSCLC patients who received medical management alone (over 221 days follow-up).

“Deaths occurred over time, underscoring that lung transplant should not be interpreted as restoring normal life expectancy in this population,” wrote Bharat and colleagues. “Rather, the clinically relevant question is whether transplant may offer longer survival than the non-transplant alternative for carefully selected patients facing otherwise poor near-term prognosis.”

The authors acknowledged their study had limitations, including the fact that it was a single-center study, and said that assessments of longer-term outcomes and quality of life are needed.