2.1 Ethics statement

This study was approved by the First Affiliated Hospital of Zhejiang University School of Medicine (FAHZU) (Grant No. 2021IIT No. 844) and was conducted in accordance with the Declaration of Helsinki. Written informed consent was obtained from all patients before all the treatments.

2.2 Study participants

This retrospective study identified all stage II-III NSCLC patients who underwent tislelizumab plus platinum-based dual-drug chemotherapy (T) or received platinum-based dual-drug chemotherapy alone (C) from the patient cohort at the Department of Thoracic Surgery, FAHZU. Comprehensive patient data, encompassing demographic and clinical information, laboratory findings, imaging data, and surgical details gathered from the hospital's electronic medical record system were recorded in pre-designed tables.

The inclusion criteria were as follows: (1) age of 18 years or older; (2) histopathological confirmation of NSCLC before medication; (3) TNM stage II or III; (4) Eastern Cooperative Oncology Group—Performance Status (ECOG-PS) score < 2; (5) receipt of tislelizumab plus chemotherapy or chemotherapy alone; (6) upon initial consultation, the medical team assessed the mass to ascertain its potential resectability or the probability of benefiting from preoperative medication.

The exclusion criteria were as follows: (1) participants who lacked pre-medication chest imaging data, including computed tomography (CT) or positron emission tomography-computed tomography (PET-CT), or those who had only one imaging data throughout the entire follow-up period in the hospital’s system; (2) patients who had previously undergone radiotherapy, interventional therapy, targeted therapy, other forms of immunotherapy, or surgery; (3) individuals who had previously undergone genetic testing that identified gene mutations potentially targeted by targeted therapy, including EGFR, KRAS, NRAS, BRAF, HER-2, MET, PIK3CA, ALK, ROS1, and RET; (4) patients with active pulmonary tuberculosis, hepatitis C, or autoimmune diseases; (5) patients with severe ventilatory disorders or significant gas exchange defects; (6) individuals who were immunosuppressed or immunodeficient, such as those receiving steroid therapy or diagnosed with HIV infection; (7) patients who exhibited allergies or intolerance to any component of tislelizumab or chemotherapy drugs; (8) participants involved in other concurrent clinical trials.

The follow-up period is extended for a minimum of one year after the administration of treatment. Progression-free survival (PFS) was defined as the duration from the initiation of treatment until the occurrence of disease progression or mortality due to any cause. Overall survival (OS) was defined as the duration from the initiation of treatment to the date of death resulting from any cause.

2.3 Treatment procedures

The enrolled patients in this study underwent intravenous administration of tislelizumab (200 mg) plus chemotherapy or chemotherapy alone for 2–4 cycles before proceeding to assessment about surgical resection. Each treatment cycle lasts about 3 weeks, and the chemotherapy regimens employed consisted of platinum-based dual-drug combinations. Specifically, patients diagnosed with histopathologically confirmed lung squamous cell carcinoma (LUSC) received nab-paclitaxel (260 mg/m2) plus carboplatin (AUC = 5), whereas those with lung adenocarcinoma (LUAD) were administered pemetrexed (500 mg/m2) plus carboplatin (AUC = 5). Considering the relevantly advanced tumor staging, individual variations in treatment responsiveness, and the non-standardized nature of the combined immunotherapy and surgical protocols, the selection of each patient’s treatment plan was jointly determined by the surgeons and the patients themselves. Generally, patients who undergo surgery continue with preoperative treatment until completion of a 6-cycle regimen, followed by regular follow-up. For patients who were not eligible for surgery, a recommendation was made for subsequent treatment with radiotherapy plus chemotherapy, along with regular follow-up.

2.4 Tumor response evaluation

The patients underwent chest CT scans every 2 cycles before surgical resection assessment. Tumor staging was assessed utilizing the 8th edition of the American Joint Committee on Cancer TNM staging system [15] at baseline. Tumor treatment response in the target lesions was evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) [16]. Complete response (CR) was defined as the complete disappearance of all target lesions, while partial remission (PR) was defined as a minimum 30% reduction in the overall diameter of the target lesions. Stable disease (SD) was characterized by a change in the target lesion size between -30% and 20% without the formation of new lesions, whereas progressive disease (PD) was defined as a 20% or greater increase in the overall diameter of target lesions or the emergence of new lesions.

2.5 Treatment-related adverse events evaluation

The investigation utilized the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 to evaluate adverse events (AEs). Blood routine tests and serum biochemical tests were routinely conducted to evaluate potential blood system disorders, endocrine disorders, hepatic function, and renal function abnormalities. Additionally, patients’ self-reported complaints were carefully considered to evaluate occurrences of gastrointestinal reactions, sensory neural disorders, and skin reactions.

2.6 Surgical treatment procedures

Within 4–6 weeks following the completion of preoperative therapy, patients were subjected to a thorough reevaluation by the medical team to ascertain their eligibility for surgical intervention. The surgical procedures employed in this study encompassed open surgery and video-assisted thoracoscopic surgery (VATS), including lung wedge resection, lung lobectomy, lung sleeve resection, pneumonectomy, and thoracal exploration, all of which were accompanied by standardized lymph node dissection or sampling. While the preoperative CT images served as the basis for the initial surgical approach, modifications were introduced during the surgical procedure as dictated by pertinent factors, such as the presence of dense adhesions or complex anatomical structures.

2.7 Pathological reaffirmation

Pathological data, including pathological type, degree of differentiation, depth of invasion, resection margin, lymph node metastasis, and tumor regression grade, were extracted by two independent investigators. Pathological complete response (pCR) was defined as the absence of cancer cells, determined by assessing the proportion of remaining viable tumor cells in the original lesion area. Major pathological response (MPR) was defined as the presence of less than 10% residual viable cancer cells.

2.8 Statistical analysis

The sample size was determined using the module for log-rank tests in the Power Analysis and Sample Size (PASS) software (version 15.0.5). Despite the categorization into four groups, previous data regarding survival comparisons between neoadjuvant immunochemotherapy and neoadjuvant chemotherapy followed by surgery was applied for sample size estimation [17]. The specified parameters included a hazard ratio for survival of 0.55, accrual time of 3 years, total time of 4 years, a two-sided test at a significance level of P = 0.05, a desired statistical power of 0.80, and equal participant allocation for groups. With these specifications, PASS indicated that at least 112 participants in total were required.

Continuous variables following normal distribution were presented as mean (standard deviations) while variables with non-normally distributed data were presented as median (ranges), and categorical variables were presented as frequencies (percentages). Measures of analysis of variance, Student’s t-test, Chi-squared test, and independent samples Kruskal–Wallis test were performed to examine the demographical and clinical differences after surgery / tislelizumab stratification. Significant group effects were further evaluated with Bonferroni-adjusted or Dunnett-adjusted pairwise comparisons.

Cox proportional hazards models were computed to examine the groups’ independent and interactive effects for PFS and OS, adjusting for significant demographical and clinical covariates. Significant group effects were further evaluated with Bonferroni-adjusted log-rank pairwise comparisons. Kaplan–Meier curves with the log-rank test were applied for survival analysis. Two-tailed p-value < 0.05 was considered statistically significant. Statistical analysis was performed using R 4.2.1.