Perioperative anxiety and depression predict long-term survival after neoadjuvant therapy in non-small cell lung cancer: a multicenter analysis.

BACKGROUND

Anxiety and depression are common yet not timely valued in thoracic oncology. The prognostic value of perioperative trajectories of anxiety and depression has not been well-quantified in neoadjuvant-treated. This study aimed to evaluate whether perioperative anxiety and depression independently predict overall survival (OS) in non-small cell lung cancer (NSCLC) patients receiving neoadjuvant therapy and surgery, and to build a pragmatic prognostic nomogram.

METHODS

We retrospectively analyzed 167 consecutive NSCLC patients from three tertiary centers (Jan 2018 to Feb 2024). Psychological status was assessed at baseline, preoperatively, and 3-month postoperatively using the Hospital Anxiety and Depression Scale (HADS). Receiver operating characteristic (ROC) analyses defined high-risk cut-offs. OS was estimated by Kaplan-Meier and compared by log-rank; predictors were assessed with Cox models. A nomogram integrating psychological and pathological variables underwent internal validation (bootstrap, calibration, time-dependent ROC, decision-curve analysis).

RESULTS

Optimal HADS-Anxiety (HADS-A) thresholds were 5.5 (baseline), 4.5 (preoperative), and 7.5 (3-month postoperative); HADS-Depression (HADS-D) thresholds were 3.5, 5.5, and 7.5 (all P<0.001). During follow-up, 45 patients recurred and 27 died (all cancer-related); mean follow-up was 38.65 months, and estimated 1-, 3-, and 5-year OS was 95.81%, 86.23%, and 83.83%. In multivariable analysis, post-neoadjuvant pathologic tumor lymph nodes metastasis (ypTNM) stage III [hazard ratio (HR) =5.72; 95% confidence interval (CI): 2.05-15.97; P<0.001], baseline HADS-A >5.5 (HR =4.59; 95% CI: 1.01-20.77; P=0.048), and 3-month HADS-A >7.5 (HR =7.50; 95% CI: 2.85-19.71; P<0.001) independently predicted worse OS, whereas HADS-D did not. The nomogram achieved areas under the curves (AUCs) of 0.89, 0.90, and 0.89 for 1-, 2-, and 3-year OS and outperformed ypTNM alone [concordance index (C-index) 0.85 vs. 0.64], with good calibration and higher net clinical benefit.

CONCLUSIONS

Perioperative anxiety, particularly at baseline and 3-month postoperatively, provides independent prognostic information beyond staging in neoadjuvant-treated NSCLC. Incorporating perioperative anxiety assessment into oncologic pathways may improve prognostic precision and inform personalized perioperative interventions.