A patient with stage IV non–small cell lung cancer (NSCLC) sits with her oncology team reviewing her latest imaging results. She has exhausted chemotherapy, targeted therapy, immunotherapy, and available clinical trial options. The scans show progressive disease, but with one important distinction: the cancer remains confined to the lungs. As her respiratory symptoms worsen, she asks a difficult question: Could a lung transplant be an option?

Historically, the answer has been no. Active lung cancer has long been considered a contraindication to transplantation due to concerns about cancer recurrence and poor outcomes. However, advances in cancer staging, systemic therapies, molecular characterization, and transplant techniques have prompted investigators to reconsider whether a carefully selected group of patients with lung-limited metastatic disease may benefit from transplantation.

Reconsidering Lung Transplantation in Advanced NSCLC

A recent prospective registry study, the Double Lung Transplant REgistry Aimed for Lung-limited Malignancies (DREAM), challenges this longstanding belief by evaluating whether bilateral lung transplantation may offer a potential treatment strategy for a highly selected population of patients with lung-limited, medically refractory stage IV NSCLC.

In the DREAM study, investigators evaluated patients with stage IV NSCLC whose disease was restricted to the lungs despite guideline-directed systemic therapies, including chemotherapy, targeted therapies when appropriate, immunotherapy, and clinical trial participation.

The study included three patient cohorts. The primary cohort consisted of 17 patients with lung-limited stage IV NSCLC who underwent lung transplantation. These patients were compared with 81 patients who met transplant eligibility criteria but did not undergo transplantation because of nonmedical barriers, including geographic, logistical, or financial barriers, and instead received medical management alone. A third cohort included 306 patients without cancer who underwent lung transplantation for end-stage pulmonary disease and served as a comparison group.

Importantly, the patients selected for transplantation represented an extremely ill population. All 17 transplant recipients had respiratory failure at the time of evaluation, with many requiring high-flow oxygen, mechanical ventilation, or extracorporeal membrane oxygenation (ECMO), a form of life support that temporarily provides oxygenation and removal of carbon dioxide when lung function is severely impaired. Their functional status was significantly worse than that of the medically managed comparison group.

A key component of the study was a modified surgical approach designed to minimize the risk of cancer spread during transplantation. Because traditional transplant techniques raised concerns about releasing tumor cells during removal of cancer-containing lungs, the DREAM protocol incorporated strategies to reduce this risk, including early blood vessel control, removal of both diseased lungs before donor lung implantation, and thorough airway irrigation.

Survival outcomes were encouraging. During follow-up, none of the 17 patients who underwent transplantation died, compared with 52 of 81 patients receiving medical management alone. Estimated 1-year overall survival was 100% in the transplant group compared with 40.8% in the nontransplant group.

Disease control was also notable. Only four transplant recipients experienced progression of NSCLC during follow-up, compared with 74 of 81 patients in the medical management group. One-year survival free from progression was estimated at 92.3% among transplant recipients compared with 5.6% among medically managed patients.

Concerns regarding appropriate use of donor organs are an important consideration whenever transplantation is considered for patients with active malignancy. To address these concerns, investigators compared outcomes among transplant recipients with NSCLC with those of patients receiving transplantation for nonmalignant lung disease. One-year posttransplant survival was 100% among patients who underwent transplant for NSCLC compared with 88.1% among standard lung transplant recipients.

Nursing Considerations

Oncology nurses may play an important role in identifying patients who have exhausted standard treatment options but continue to have disease limited to the lungs. As transplant oncology continues to evolve, recognizing when referral to specialized multidisciplinary transplant programs may be appropriate will become increasingly important.

Caring for these patients requires an understanding of both oncology and transplant principles. Before transplantation, nurses support patients through complex staging evaluations, treatment transitions, symptom management, and goals-of-care discussions. After transplantation, nursing priorities include monitoring for infection, rejection, immunosuppression-related toxicities, medication adherence challenges, and potential cancer recurrence.

It is important to note that the DREAM registry represents a small, single-center experience involving only 17 transplant recipients. The study was not randomized, and longer-term outcomes related to late recurrence, chronic rejection, and overall survival remain unknown.

Nevertheless, the DREAM study represents an important advancement in transplant oncology. For a carefully selected population of patients with stage IV NSCLC, bilateral lung transplantation may offer a potential therapeutic option where none previously existed.