The study, led by Xun Jiang, Guoliang Liao, Xin Yan, and colleagues at Fujian Medical University Union Hospital and collaborating institutions, followed 167 patients with clinical stage IB to IIIB NSCLC who received neoadjuvant therapy followed by curative-intent surgical resection between 2018 and 2022. Rather than measuring distress at a single moment, the team assessed it at three critical junctures: before the start of neoadjuvant therapy, immediately before surgery, and three months after the operation. This longitudinal design is what sets the work apart, because it captures not just whether patients are distressed, but how their distress behaves across the most demanding phases of multimodality cancer treatment.

To quantify emotional distress, the researchers deployed four well-validated screening instruments: the anxiety and depression subscales of the Hospital Anxiety and Depression Scale (HADS-A and HADS-D), the Generalized Anxiety Disorder-7 questionnaire (GAD-7), and the Patient Health Questionnaire-9 (PHQ-9). For the primary analyses, a patient was considered positive for emotional distress if they scored positively on any of these measures at a given time point. This broad definition deliberately casts a wide net, capturing the full spectrum of anxiety and depressive symptoms rather than requiring a formal psychiatric diagnosis. The approach reflects a growing consensus in psycho-oncology that subthreshold distress, while less visible, can still carry clinical weight.

The central analytical move was to classify each patient into one of three trajectory groups based on their pattern of distress across the three assessments. Patients who never screened positive were labeled persistently negative (ED0); those who screened positive at some but not all time points were labeled intermittently positive (ED1); and those who screened positive at every assessment were labeled persistently positive (ED2). The distribution was revealing: 47.3 percent of patients remained persistently negative, 29.9 percent were intermittently positive, and 22.8 percent — nearly one in four — carried persistent distress through the entire treatment arc. Median follow-up extended to 46 months, long enough to observe meaningful differences in survival outcomes.

The survival curves diverged dramatically. Three-year overall survival was 89.9 percent in the persistently negative group, 71.9 percent in the intermittently positive group, and just 57.9 percent in the persistently positive group, a gradient that was highly statistically significant across the cohort. In other words, patients whose emotional distress never lifted fared substantially worse than those who remained psychologically resilient throughout treatment, with the intermittent group occupying an intermediate position. This dose-response-like pattern — where worse distress trajectories correspond to progressively worse survival — strengthens the plausibility of a genuine association rather than a statistical fluke.

The association survived rigorous statistical adjustment. In multivariable Cox regression models that accounted for established clinicopathologic prognostic factors, persistent emotional distress remained independently associated with poorer overall survival, with a hazard ratio of 5.04 (95 percent confidence interval, 2.55 to 9.99) compared with persistently negative patients. The effect on progression-free survival was similarly robust, with a hazard ratio of 3.26 (95 percent confidence interval, 1.87 to 5.69). A hazard ratio of five is a large effect by oncology standards, comparable in magnitude to some of the strongest clinicopathologic predictors, which is precisely why the finding demands attention — and, the authors caution, further validation before distress screening is elevated to a formal prognostic tool.

The researchers also explored whether distress data could improve predictive performance when combined with conventional clinical variables. Models integrating the emotional distress trajectory with clinicopathologic factors achieved an area under the curve (AUC) of 0.86 for predicting overall survival and 0.80 for progression-free survival. These are respectable discrimination values, suggesting that psychological trajectories carry information that complements, rather than merely duplicates, what tumor stage, histology, and treatment response already reveal. The authors are careful, however, to note that the added prognostic value of distress assessment beyond standard variables requires confirmation in independent cohorts before it can inform clinical decision-making.

Why might persistent emotional distress be biologically linked to cancer outcomes? The study itself is observational and cannot establish causation, but the surrounding literature offers several plausible mechanisms. Chronic psychological stress activates the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system, elevating cortisol and catecholamines that can reshape the tumor microenvironment, modulate immune surveillance, and potentially blunt the efficacy of treatments — including the immunotherapies and chemotherapies now standard in neoadjuvant NSCLC protocols. Recent work has even suggested that pretreatment distress may influence response to immune checkpoint inhibitors in lung cancer, hinting that the cancer-immune dialogue is sensitive to the patient’s psychological state. Persistent distress may also reflect or exacerbate behaviors that affect outcomes, from reduced adherence to follow-up care to diminished resilience during postoperative recovery.

There is also the possibility of reverse causation — that persistent distress is a marker, not a driver, of underlying disease severity. Patients whose cancer is biologically more aggressive may feel worse, respond less well to neoadjuvant therapy, and experience more complications, generating distress that merely mirrors their prognosis. The multivariable adjustment for clinicopathologic factors partially addresses this concern, and the fact that distress was measured before treatment outcomes were known helps with temporality, but only prospective interventional studies — for example, trials testing whether effective psychological treatment improves survival — could settle the question of causality. Such trials would be ambitious but not unprecedented, given prior evidence that psychological interventions can influence immune parameters and quality of life in cancer patients.

The practical implications are nonetheless immediate. Clinical guidelines from the National Comprehensive Cancer Network and the American Society of Clinical Oncology already recommend routine distress screening in cancer care, yet screening is often performed once, at diagnosis, and its results rarely feed into prognostic discussions. This study suggests that a single snapshot may miss the patients who matter most: the roughly one in five whose distress persists across the treatment journey. Repeated, brief screening with instruments like the HADS, GAD-7, or PHQ-9 at each treatment milestone is feasible in busy thoracic oncology clinics, and patients flagged with persistent positivity could be prioritized for psycho-oncology referral, pharmacologic treatment, or intensified supportive care. As neoadjuvant immunotherapy transforms the standard of care for resectable NSCLC, the patients undergoing this demanding treatment sequence may represent a group in whom psychological monitoring is not just compassionate care, but a potential component of prognostic evaluation — one that costs little to implement and could meaningfully change how clinicians see the whole patient.

Subject of Research: Longitudinal emotional distress trajectories and survival outcomes in patients with resectable non–small cell lung cancer treated with neoadjuvant therapy and surgery

Article Title: Prognostic significance of dynamic emotional distress during neoadjuvant therapy and surgery for resectable non–small cell lung cancer

Article References: Jiang, X., Liao, G., Yan, X., Lin, Y., Huang, R., Cheng, L., Xu, G., Zheng, B., Chen, C., & Yang, Z. (2026). Prognostic significance of dynamic emotional distress during neoadjuvant therapy and surgery for resectable non–small cell lung cancer. Supportive Care in Cancer, 34(10), Article 1027. https://doi.org/10.1007/s00520-026-11260-2

Image Credits: AI Generated

DOI: 10.1007/s00520-026-11260-2

Keywords: non-small cell lung cancer, emotional distress, neoadjuvant therapy, prognosis, overall survival, progression-free survival, HADS, GAD-7, PHQ-9, psycho-oncology, distress screening, supportive care