Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Sep;170(3):852-863.e6.
doi: 10.1016/j.jtcvs.2025.04.028. Epub 2025 May 4.

Lung cancer recurrence after neoadjuvant immunotherapy

Hao Li  1 , Fatemehsadat Pezeshkian  2 , Yue Xie  3 , Emanuele Mazzola  3 , Rafael Ribeiro Barcelos  2 , Fatemeh Hooshmand  2 , Tianxiao Han  4 , Sanna Laaksonen  5 , Lynette Sholl  5 , Carla Vega  2 , Elias Bou Farhat  2 , Raphael Bueno  2 , Paula Ugalde Figueroa  2 , Scott Swanson  2
Affiliations

Lung cancer recurrence after neoadjuvant immunotherapy

Hao Li et al. J Thorac Cardiovasc Surg. 2025 Sep.

Abstract

Objectives: To investigate recurrence risk and patterns following neoadjuvant immunotherapy (Neo-IO) for resectable lung cancer, with a focus on identifying optimal cutoffs of residual viable tumor percentage (%RVT) of the primary tumor as a prognostic indicator.

Methods: We conducted a retrospective analysis of patients with resectable non-small cell lung cancer who received Neo-IO with or without chemotherapy followed by lung resection, using data from our prospectively maintained clinical database. The %RVT of the primary tumor in the surgical specimen was quantified (0%-100%) according to pan-tumor immune-related pathologic response criteria. The optimal %RVT cutoffs, as a continuous covariate for recurrence-free survival (RFS), were determined using the Rhier function in the rolr R package.

Results: A total of 94 patients treated between October 2017 and April 2024 met the study's inclusion criterion, with a median follow-up of 16.3 months. Seventy-nine patients received Neo-IO combined with chemotherapy, and 15 patients received Neo-IO only. A pathologic complete response (pCR) was observed in 21 patients (22.3%), and a major pathologic response (MPR) was noted in 41 (43.6%). The median %RVT was 20.0% (range, 0%-100%). The estimated optimal %RVT cutoffs were 5% and 40%. Patients with ≥40% RVT demonstrated worse RFS compared to those with 5% to 40% RVT (P = .006) and those with <5% RVT (P = .001). Multivariable analyses identified %RVT as an independent risk factor for RFS (hazard ratio, 3.96; 95% confidence interval, 1.30-12.01; P = .015). Only 3 patients with pCR (12.5%) developed recurrence; all were distant recurrences. The mediastinal lymph node (LN) recurrence rate increased progressively with advancing ypN stage (ypN0, 3.8%; ypN1, 15.0%; ypN2, 25.0%; P = .007).

Conclusions: Primary tumor %RVT in the surgical specimen is an independent risk factor for lung cancer recurrence following Neo-IO and resection, with optimal cutoffs identified at 5% and 40%. The likelihood of mediastinal LN recurrence increases progressively with advancing ypN stage. Given the high rate of mediastinal LN recurrence in ypN2 patients, planned postoperative radiotherapy may be considered.

Keywords: chemoimmunotherapy; lung cancer; neoadjuvant immunotherapy; recurrence; residual viable tumor.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Statement H.L. is supported by the Evarts A. Graham Memorial Traveling Fellowship from the AATS Foundation. All other authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest.

MeSH terms