Lung resection after initial nonoperative treatment for non-small cell lung cancer (NSCLC) was safe and led to significantly improved survival in select patients previously treated with nonoperative therapies, according to a study by Memorial Sloan Kettering Cancer Center (MSK) investigators.
Three-year event-free survival (EFS) and overall survival (OS) were 39% and 73%, respectively, among 120 patients previously treated with chemotherapy, immunotherapy, targeted therapy, radiation therapy, or any combination of these treatments. Further, patients with stage 4 disease who underwent salvage resection had a significantly greater OS than patients in a comparison cohort treated with subsequent systemic therapy. The study was published recently in The Journal of Thoracic and Cardiovascular Surgery. (1)
“Our real-world study is the largest series to date evaluating salvage surgery outcomes across different forms of complicated NSCLC treated initially with a range of nonsurgical therapies,” said lead author Elizabeth Dunne, MD, a research fellow in the David Jones Lab at MSK. Dr. Dunne is a general surgery resident at NewYork-Presbyterian Hospital/Weill Cornell Medical Center and is completing her final year of research in the Jones lab.
“While the percentage of patients receiving salvage surgery of their primary lung cancer after initial nonoperative treatment is small, we were able to evaluate survival benefits of this approach given the high volume of patients we treat at MSK,” said thoracic surgeon David R. Jones, MD, Chief of the Thoracic Service, Department of Surgery and Co-Director of the Druckenmiller Center for Lung Cancer Research at MSK.
“We hope our findings will increase the consideration of salvage surgery for appropriately-selected patients to improve outcomes.”
The Knowledge Gap: Does Salvage Surgery Improve Survival?
The efficacy of local consolidative therapy with radiation after systemic treatment has been clearly established for several solid tumors, including lung cancer. However, few studies have investigated lung resection for oligometastatic or oligoprogressive disease after systemic treatment. (2) (3) (4)
Surgical resection is the primary treatment for early-stage NSCLC. However, up to 30% of patients are diagnosed with locoregional disease, and about 50% have metastasis at diagnosis. Reasons for patients with NSCLC receiving nonsurgical first-line treatments include cancer that is too extensive to be surgically removed or invading vital structures. The standard of care for patients with stage 4 NSCLC includes systemic therapy or radiation, not surgery. (1)
Although previous studies have demonstrated the safety of salvage surgery for patients with recurrent disease, they were mostly small in scope and did not identify prognostic factors for patient selection. (6) (7) Moreover, only a few case reports have reported salvage surgery outcomes after targeted therapy and immunotherapy. (8) (9) (10)
MSK Study Design
Dr. Dunne and colleagues evaluated MSK’s prospectively maintained database and identified patients with NSCLC who had chemotherapy, immunotherapy, targeted therapy, radiation therapy, or any combination of these treatments, with no upfront surgical plan, and subsequently underwent resection of their primary lung tumor from January 2010 to May 2022. (1)
The primary endpoints were event-free survival (EFS) and overall survival (OS), and the secondary endpoints were the incidence of recurrence and perioperative morbidity and mortality. The investigators also evaluated patient and clinical characteristics associated with prognosis. (1)
Finally, the researchers compared outcomes for patients who underwent salvage surgery with a cohort of similar patients treated at MSK who received a second-line nonoperative treatment. MSK patients included in the American Association for Cancer Research Project Genomics Evidence Neoplasia Information Exchange BioPharma Collaborative (GENIE BPC) comprised the comparision group. Since all of the MSK patients in GENIE BPC had stage 4 disease at diagnosis, the cohort analysis compared only patients with stage 4 disease who underwent salvage surgery. (1)
MSK Study Findings
A total of 120 patients, representing 2% of lung resections for NSCLC performed at MSK during the study period, were included in the analysis. Two-thirds of these patients were initially treated at MSK and one-third were referrals from other centers. The initial cancer stage before any treatment was stage I in 10%, stage II in 6%, stage III in 25%, and stage IV in 59% of patients. (1)
Patients had received a wide range of nonoperative treatments, including chemotherapy (59%), targeted therapy (45%), immunotherapy (17%), radiation therapy (39%), and stereotactic body radiation therapy (13%). The median duration of initial nonoperative treatment was eight months. (1)
The most common indication for surgery was local control of oligometastatic disease, followed by persistent disease, oligoprogression, and recurrent disease. Salvage surgery consisted of lobectomy for 67% of patients. A minimally invasive approach was employed for 45% of patients, with an increasing trend over the study period. Thoracic surgery accomplished a complete or R0 resection in 88% or 105 of 120 patients. (1)
Patients were followed for a median of 57 months. The three- and five-year cumulative incidences of NSCLC recurrence were 53% and 61%, respectively, and most recurrences occurred at distant locations. The median EFS was 17 months, and three- and five-year EFS were 39% and 29%, respectively. The median OS was 72 months, and three- and five-year OS were 73% and 61%, respectively. (1)
Notably, for stage 4 patients, the OS rate at five years was 75% for those who underwent salvage surgery compared to 25% for the comparison cohort of stage 4 patients who underwent subsequent systemic therapy. (1)
Factors Associated with Improved Outcomes
Male sex and lymphovascular invasion were associated with shorter EFS and OS. By contrast, younger age at diagnosis and prior radiation therapy were associated with shorter OS only.1 “While the latter finding was counterintuitive, the small sample size led us to hypothesize a history of radiation therapy was an indication ofa larger, more central tumor at initial presentation,” said Dr. Dunne. “Importantly, the present study was not intended nor powered to compare cancer-related deaths by modality.”
“It was very exciting for us to see that salvage surgery provided clinically meaningful improvements in survival in appropriately selected patients,” said Dr. Dunne. “At MSK, patients are selected for resection based on their initial response to nonoperative treatment, resectability of the tumor, cancer control prognosis for disease sites, and pulmonary and performance status.”
“Our study findings indicate that patients with initially oligometastatic disease for whom immunotherapy and targeted therapy eradicates their metastasis should be considered candidates for salvage surgery for persistent disease in the lung,” Dr. Dunne said.
MSK’s Multidisciplinary Approach to Lung Cancer Care
“Patient selection for salvage surgery after initial nonoperative treatment for NSCLC is crucial,” Dr. Dunne said. “MSK’s multidisciplinary experts, including thoracic surgeons, radiation oncologists, medical oncologists, and radiologists, discuss complex cases at weekly tumor board meetings and collaborate to develop an individualized treatment plan for each patient.”
Learn more about MSK clinical trials for patients with lung cancer.
The study was supported by funding from the National Institutes of Health/National Cancer Institute (grants RO1CA217169 and RO1CA240462 to Dr. Jones, Cancer Center Support Grant P 30 CA008748 to MSK, and RO1CA24966 to Dr. Bob Li). Dr. Dunne reports no relationships or financial interests with external entities. Access disclosures for Dr. Jones.