Salvage surgery for advanced non-small cell lung cancer after induction therapy with selective RET inhibitors: safety and feasibility.
4 affiliations
- 1Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, China.
- 2Lung Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
- 3West China School of Medicine, Sichuan University, Chengdu, China.
- 4Department of Thoracic Surgery, Fushun People's Hospital, Zigong, China.
Abstract
Non-small cell lung cancer (NSCLC) harboring rearranged during transfection (RET) gene fusions represents a rare molecular subset associated with an unfavorable prognosis. The advent of selective RET inhibitors has substantially reshaped the therapeutic landscape for RET fusion-positive NSCLC; nevertheless, acquired resistance remains an unmet clinical challenge, underscoring the need for alternative or combinatorial strategies. Here, we evaluate a novel therapeutic approach integrating salvage surgery with induction therapy using selective RET inhibitors. We retrospectively identified patients with advanced RET fusion-positive NSCLC who underwent salvage resection following induction therapy with selective RET inhibitors at West China Hospital, Sichuan University. Clinicopathological characteristics were systematically reviewed. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Between January 2022 and June 2025, 17 patients who received induction therapy with selective RET inhibitors followed by salvage surgery were enrolled. The mean age was 42.3 years, and 15 patients (88.2%) presented with advanced-stage disease. Induction therapy consisted of first- or second-line selective RET inhibitor treatment for a mean duration of 12 months (range, 3-34 months). All patients underwent salvage resection, with uneventful postoperative recovery and no major complications. No 30-day mortality was observed. Eight patients (47.1%) achieved a pathological complete response (pCR), while 13 patients (76.5%) achieved a major pathological response (MPR) including pCR. At a median follow-up of 26 months, the 3-year PFS and OS rates after salvage surgery were 75% and 100%, respectively. Salvage surgery following selective RET inhibitor therapy was feasible in this highly selected cohort and was associated with favorable pathological responses and short-term outcomes. Comparative studies with longer follow-up are required to determine its oncological benefit.
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BibTeX
@article{deng2026salvage,
title = {{Salvage surgery for advanced non-small cell lung cancer after induction therapy with selective RET inhibitors: safety and feasibility.}},
author = {Han-Yu Deng and Jia-Hao Li and Xiao-Long Chen and Lu Li and Xiao-Jun Tang and Qinghua Zhou},
journal = {Journal of thoracic disease},
year = {2026},
month = sep,
doi = {10.21037/jtd-2026-1909},
url = {https://europepmc.org/article/MED/42996952},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Salvage surgery for advanced non-small cell lung cancer after induction therapy with selective RET inhibitors: safety and feasibility.
AU - Han-Yu Deng
AU - Jia-Hao Li
AU - Xiao-Long Chen
AU - Lu Li
AU - Xiao-Jun Tang
AU - Qinghua Zhou
PY - 2026
DA - 2026/09/28
JO - Journal of thoracic disease
DO - 10.21037/jtd-2026-1909
UR - https://europepmc.org/article/MED/42996952
AB - Non-small cell lung cancer (NSCLC) harboring rearranged during transfection (RET) gene fusions represents a rare molecular subset associated with an unfavorable prognosis. The advent of selective RET inhibitors has substantially reshaped the therapeutic landscape for RET fusion-positive NSCLC; nevertheless, acquired resistance remains an unmet clinical challenge, underscoring the need for alternative or combinatorial strategies. Here, we evaluate a novel therapeutic approach integrating salvage surgery with induction therapy using selective RET inhibitors. We retrospectively identified patients with advanced RET fusion-positive NSCLC who underwent salvage resection following induction therapy with selective RET inhibitors at West China Hospital, Sichuan University. Clinicopathological characteristics were systematically reviewed. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Between January 2022 and June 2025, 17 patients who received induction therapy with selective RET inhibitors followed by salvage surgery were enrolled. The mean age was 42.3 years, and 15 patients (88.2%) presented with advanced-stage disease. Induction therapy consisted of first- or second-line selective RET inhibitor treatment for a mean duration of 12 months (range, 3-34 months). All patients underwent salvage resection, with uneventful postoperative recovery and no major complications. No 30-day mortality was observed. Eight patients (47.1%) achieved a pathological complete response (pCR), while 13 patients (76.5%) achieved a major pathological response (MPR) including pCR. At a median follow-up of 26 months, the 3-year PFS and OS rates after salvage surgery were 75% and 100%, respectively. Salvage surgery following selective RET inhibitor therapy was feasible in this highly selected cohort and was associated with favorable pathological responses and short-term outcomes. Comparative studies with longer follow-up are required to determine its oncological benefit.
SN - 2072-1439
SN - 2077-6624
ER -