EMOTIONAL distress before treatment is strongly associated with poorer responses to immunotherapy in patients with advanced non-small cell lung cancer (NSCLC), according to new research. The findings highlight the need to consider psychological health as a factor that can directly influence treatment efficacy.
The STRESS-LUNG-1 study evaluated 227 patients receiving immune checkpoint inhibitors (ICIs) and found nearly half met diagnostic criteria for emotional distress, as measured by PHQ-9 and GAD-7 questionnaires. These patients experienced significantly shorter progression-free survival compared with those without distress, with median survival at 7.9 months versus 15.5 months. They also had lower response rates to immunotherapy, at 46.8% compared with 64.9% in patients without distress. These effects remained consistent across subgroups, suggesting emotional distress itself may impair immune response and treatment outcomes.
Emotional distress in cancer is common, with close to half of patients reporting it at diagnosis. Its effects extend beyond quality of life, influencing immune regulation and increasing suicide risk. Chronic stress activates the hypothalamic-pituitary-adrenal axis, leading to immune suppression, reduced CD8 T cell function, and diminished natural killer cell activity. These immune disruptions may explain the reduced effectiveness of immunotherapy observed in patients experiencing psychological stress.
Despite its important findings, the study has several limitations. It was conducted at a single center in China, where the patient cohort was predominantly male and with a smoking history, raising questions about generalizability to other populations. The use of multiple ICIs also introduced variability, and self-reported questionnaires may have overestimated or underestimated emotional distress in this population.
Nevertheless, the study represents the first large-scale effort to examine the relationship between emotional distress and immunotherapy outcomes in advanced NSCLC. Ongoing trials, including the STRESS-LUNG-2 and STRESS-LUNG-3 cohorts, are expected to expand understanding of this relationship across small cell lung cancer, resectable disease, and surgical outcomes. These findings may encourage clinicians to integrate mental health screening and support into cancer care, ensuring that emotional well-being is recognized as a key component of treatment success.
