Salvage Surgery a Possible Approach in NSCLC After Immunotherapy

Select patients who respond to target therapy or immunotherapy for non–small cell lung cancer (NSCLC) could be further treated using salvage surgery, according to a new study published in the Journal of Thoracic Disease.¹ Further research would be needed on long-term survival outcomes.

NSCLC has undergone changes in treatment over the years, with molecular target therapies and immune checkpoint inhibitors acting as methods of improving outcomes in patients.² Salvage therapy may be a potential next step after immunotherapy or targeted therapy due to acquired resistance to therapies or to remove any residual cells. The aim of the study was to determine the characteristics of the patients who had salvage surgery after therapy for NSCLC that was initially nonresectable.¹

Salvage surgery is a potential option for patients who responded well to immunotherapy or target therapy | Image credit: steph photographies - stock.adobe.com

Patients who had salvage surgery after either target therapy or immunotherapy between January 1, 2015, and December 31, 2022, at multiple health centers were considered for this study. Patients needed to have NSCLC that was not able to be directly operated on, had an evaluation of PD-L1 expression rate, had surgery that was performed for radical intent, and had a pathologically proven mutation that was susceptible to target therapy. An absence of chemo or radiotherapy before target therapy, disease progression during therapy, an operable tumor, surgery performed with intent for biopsy, or stage IV cancer with pericardial or pleural effusion were all reasons for exclusion.

All participants had physical examinations, CT scans, and blood testing as well as tissue biopsy. Fitness for surgical resection was evaluated by doctors prior to the surgery, and all surgeries were conducted either through thoracotomy, thoracoscopic, or robotic means. Absence of residual tumor cells was considered a pathological complete response (pCR). Rate of pCR and surgical feasibility acted as primary end points.

There were 30 patients included in the study, with 22 presenting with stage III cancer and 8 presenting with stage IV distant metastases. Immunotherapy was administered to 22 patients either alone or after chemotherapy, and target therapy was given in 8 cases. Clinical downstaging occurred in 22 patients, with all but 1 patient with stage IIIA disease having a partial or complete response to therapy. A total of 10 patients had nonnegligible tumor shrinkage after therapy after being judged inoperable.

All but 2 patients were approved for anatomical resection after therapy. Lymphadenectomy was performed in all cases. Perioperative mortality was not reported. A total of 6 cases had complications, and the length of stay was a mean (SD) of 5.9 (2.8) days. There were no deaths through 60 days. Downstaging was confirmed in 26 patients, and 11 patients had pCR. A total of 10 of the 22 patients who were treated with immunotherapy achieved pCR.

There were 5 patients who experienced a recurrence, and 4 died due to causes related to cancer during the median (range) follow-up time of 12 (2-83) months. These recurrences occurred after 2, 5, 9, 10, and 21 months in the respective patients.

There were some limitations to this study. The sample size was small and was retrospective in design, which may limit generalizability. Variations in the way each center approached surgery make it hard to draw conclusions across all patients. The follow-up periods were shorter, which led to no calculation of survival rates in the statistical analysis to reduce bias.

The researchers concluded that salvage surgery was a feasible approach for patients with NSCLC who responded to target therapy or immunotherapy.

“Although the pCR rate of about 36% is encouraging, survival outcomes need to be evaluated with longer follow-up times,” the authors concluded.

References

1. Chiappetta M, Sassorossi C, Lococo F, et al. Short-term results of salvage surgery after immune and target therapies in non-small cell lung cancer. J Thorac Dis. 2025;17(7):4929-4939. doi:10.21037/jtd-2025-387

2. Non-small cell lung cancer treatment (PDQ®)–patient version. National Cancer Institute. Updated May 16, 2025. Accessed August 14, 2025. https://www.cancer.gov/types/lung/patient/non-small-cell-lung-treatment-pdq