Subsequent surgical treatment or maintenance immunotherapy in stage III lung cancer patients achieving a favorable response following neoadjuvant immunotherapy: A matched retrospective cohort study from the surgical perspective

Abstract

Background: Current treatment strategies for advanced non-small cell lung cancer (NSCLC) are highly individualized and subject to ongoing debates. In the era of immunotherapy, surgery assumes a critical role. The aim of this study was to investigate if subsequent surgical intervention, following a favorable response to immunotherapy and chemotherapy, could yield a more favorable prognosis for patients with advanced stage III NSCLC compared to the continuation of immunotherapy and chemotherapy.

Methods: We included patients whose tumors exhibited a favorable response (including partial response [PR] and complete response [CR]) to immunotherapy and chemotherapy. These patients were categorized into two groups based on their subsequent treatment plans: surgical and nonsurgical (continuation of maintenance immunotherapy and chemotherapy). The efficacy and long-term prognosis of these groups were compared after matching them in a 1:1 ratio using propensity scores.

Results: In total, 186 patients (93 in each group) were included in this study after matching via propensity scores. The 1- and 3-year overall survival (OS) and progression-free survival (PFS) rates were 96.0%, 88.5%, and 93.1%, 80.7% in the surgical group, and 93.2%, 83.1%, and 57.7%, 50.4% in the nonsurgical group, respectively. Patients in the surgical group exhibited significantly superior PFS and OS compared to those in the nonsurgical group (p = 0.025 and p = 0.00086). Univariate and multivariate analyses confirmed ΔBMI, Δtumor size reduction, tumor response, earlier clinical stage (IIIb vs. IIIa), and surgery as independent protective factor for patient prognosis. We further selected 101 patients with CR (39 in the surgical group and 62 in the nonsurgical group) and found that patients in the surgical group were significantly better in both PFS and OS. Our subgroup analysis in postoperative patients demonstrated that different surgical strategies did not significantly affect the long-term prognosis of patients (PFS and OS) but could impact their perioperative experience.

Conclusion: Patients with advanced stage III NSCLC, whose tumors achieved PR and CR after 2-4 cycles of immunotherapy combined with chemotherapy, experience a more promising prognosis with subsequent surgical intervention compared with the continued immunotherapy. Despite encountering formidable obstacles, such as protracted surgical procedures and associated trauma, we must rise to the challenge and unleash the power of surgery after immunotherapy in advanced NSCLC.

Keywords: advanced stage III non‐small cell lung cancer; immunotherapy and chemotherapy; promising prognosis; surgery intervention.

FIGURE 1

Flow chart summarizing the process of enrollment and prognostic analysis of surgical and nonsurgical groups after immunotherapy in patients with advanced stage III non‐small cell lung cancer. PFS, progression‐free survival; OS, overall survival; PR, partial response; CR, complete response; RECIST, response evaluation criteria in solid tumors; ECOG, Eastern Cooperative Oncology Group.

FIGURE 2

Kaplan–Meier curves for survival before and after propensity score matching between surgical and nonsurgical groups. (a) PFS between surgical and nonsurgical groups before PSM. (b) OS between surgical and nonsurgical groups before PSM. (c) PFS between surgical and nonsurgical groups after PSM. (d) OS between surgical and nonsurgical groups after PSM. PFS, progression‐free survival; OS, overall survival; PSM, propensity score matching.

FIGURE 3

Kaplan–Meier curves for survival before and after propensity score matching between surgical and nonsurgical groups in the complete subset. (a) PFS between surgical and nonsurgical groups before PSM in CR subset. (b) OS between surgical and nonsurgical groups before PSM in CR subset. (c) PFS between surgical and nonsurgical groups after PSM in CR subset. (d) OS between surgical and nonsurgical groups after PSM in CR subset. PFS, progression‐free survival; OS, overall survival; PSM, propensity score matching; CR, complete response.

FIGURE 4

Comparisons of postoperative results between minimally invasive surgery and open thoracotomy group. (a) Operative duration (min). (b) intraoperative blood loss (mL). (c) Lymph nodes removed (n). (d) Postoperative hospital stay (days). (e) Rate of postoperative complications (%). (f) Kaplan–Meier curves for PFS. (g) Kaplan–Meier curves for OS. MIS, minimally invasive surgery; Thora., open thoracotomy; PFS, progression‐free survival; OS, overall survival.

FIGURE 5

Comparison of postoperative results between lobectomy and extended lobectomy. (a) Operative duration (min). (b) Intraoperative blood loss (mL). (c) Lymph nodes removed (n). (d) Postoperative hospital stay (days). (e) Rate of postoperative complications (%). (f) Kaplan–Meier curves for PFS. (g) Kaplan–Meier curves for OS. PFS, progression‐free survival; OS, overall survival.

FIGURE 6

Comparison of postoperative results stratified by lymph node removals. (a) Operative duration (min). (b) Intraoperative blood loss (mL). (c) Postoperative hospital stay (days). (d) Rate of postoperative complications (%). (e) Rate of positive lymph nodes (%). (f) Rate of pCR (%). (g) Kaplan–Meier curves for PFS among two groups. (h) Kaplan–Meier curves for OS among two groups. PFS, progression‐free survival; OS, overall survival.

FIGURE 7

Kaplan–Meier survival curves for each subgroup after propensity score matching. (a) PFS between male and female. (b) OS between male and female. (c) PFS between squamous cell carcinoma and adenocarcinoma. (d) OS between squamous cell carcinoma and adenocarcinoma. (e) PFS between PD‐L1 positive and negative. (f) OS between PD‐L1 positive and negative. (g) PFS stratified by immunotherapy. (h) OS stratified by immunotherapy. PFS, progression‐free survival; OS, overall survival; PSM, propensity score matching; PD‐L1, programmed death‐ligand 1.