Preoperative immunochemotherapy for locally advanced non-small cell lung cancer: an analysis of the clinical outcomes, optimal number of cycles, and peripheral immune markers

BACKGROUND: This retrospective study aimed to evaluate the real-world efficacy of neoadjuvant immunochemotherapy in locally advanced stage III non-small cell lung cancer (NSCLC), with a particular focus on analyzing the optimal treatment cycle and peripheral immune markers. METHODS: Eligible patients with biopsy-confirmed stage III NSCLC who underwent neoadjuvant immunochemotherapy between January 1(st), 2018 and March 30(th), 2021 were identified, and their oncological outcomes were collected. RESULTS: A total of 115 patients were identified, among whom 61, 51, and three cases were classified as clinical stage IIIA, IIIB, and IIIC at presentation, respectively. The objective response rate was 61.7% (71/115) after immunochemotherapy. The most frequent surgical procedure was lobectomy, performed in 91 (79.1%) cases, and all patients had microscopic-free margins. Major pathological response (MPR) was observed in 64 (55.7%) patients, among whom 44 (38.3%) achieved a complete pathological response; pathological-confirmed lymph node downstage (cN2-3 to ypN0-1) was described in 73.6% (67/91) of patients with cN2-3 diseases. The median disease-free survival (DFS) of all enrolled patients was 23.6 [95% confidence interval (CI): 15.9–31.3] months, while for patients with residual tumors of more than 10%, the median DFS was 18.1 (95% CI: 12.5–23.8) months. The post-hoc multivariable analysis showed that three [odds ratio (OR), 4.78; 95% CI: 1.17–19.55] and four (OR: 6.50; 95% CI: 1.12–37.54) cycles of neoadjuvant immunochemotherapy were prone to higher MPR rates compared to two cycles in patients that were classified as complete/partial response (CR/PR). However, adding over five cycles was not associated with a higher MPR rate (OR, 0.91; 95% CI: 0.15–5.47). The pretreatment lymphocyte count level (1.89±0.68 vs. 1.59±0.63, P=0.019) and monocyte count level (0.71±0.32 vs. 0.59, P=0.020) were significantly higher in MPR patients compared to non-MPR patients. CONCLUSIONS: The present study confirmed a favorable real-world tumor downstage efficacy of neoadjuvant immunochemotherapy in locally advanced NSCLC. Even though CR/PR was achieved, it is still beneficial when extended into 3–4 cycles of neoadjuvant immunochemotherapy.