The time-to-surgery interval and its effect on pathological response after neoadjuvant chemoimmunotherapy in non-small cell lung cancer: a retrospective cohort study

Background: The time to surgery (TTS) after the completion of the final cycle of neoadjuvant chemoimmunotherapy in patients with non-small cell lung cancer (NSCLC) is inconsistent. Pathological complete response (pCR) and major pathological response (MPR) are associated with enhanced survival in those with NSCLC. The optimal TTS interval remains to be determined, some studies indicated that TTS ≤6 weeks has a vital role in NSCLC prognosis. Therefore, this study aimed to determine whether TTS is correlated with pathological outcomes and to identify the factors associated with TTS.

Methods: We retrospectively analyzed 82 individuals who had surgery after neoadjuvant chemoimmunotherapy for NSCLC between January 2020 and December 2023. Fifty participants were included in this study after inclusion and exclusion criteria. Participants were categorized into two groups: TTS ≤4 weeks and TTS >4 to 6 weeks. Univariate and multivariate regression analyses were employed to determine the impact of TTS on pathological response and to identify the variables associated with TTS. Variables that showed their P value <0.2 in univariate analyses were included in the multivariate analysis. Kaplan-Meier analysis was used to analyze disease-free survival (DFS).

Results: Our study evaluating 50 patients revealed that patients in the TTS ≤4 weeks group achieved pCR or MPR compared to patients in the >4 to 6 weeks group (P=0.01). In univariate analyses, TTS ≤4 weeks was more correlated with achieving pCR or MPR than TTS >4 to 6 weeks [odds ratio (OR) =0.211; 95% confidence interval (CI): 0.062-0.711; P=0.01] The multivariate analysis showed that cT1 stage (compared to cT4), and cN1 stage (compared to cN0) showed statistical correlation with achieving pCR or MPR. cN1 stage was independent predictor of achieving pCR or MPR (OR =27.817; 95% CI: 1.536-503.88; P=0.02). Concerning to the DFS, TTS ≤4 weeks group and TTS >4 to 6 weeks group showed no statistical differences (2-year DFS rate were 70.6% and 72.6%, respectively). Regarding the tendency of being patients' TTS ≤4 weeks, patients with ventilatory impairment (OR =0.203; 95% CI: 0.04-0.98; P=0.047) were more tending to prolong the TTS to >4 to 6 weeks.

Conclusions: TTS ≤4 weeks was associated with a significant improvement of pathological response. Therefore, patients with NSCLC should undergo surgery within 4 weeks after the last cycle of neoadjuvant chemoimmunotherapy.