BackgroundCancer negatively affects patients’ physical and mental health. This work sought to analyze the sociodemographic and clinical variables that modulate psychological distress in individuals with resected vs unresectable cancer before and after receiving systemic antineoplastic treatment, and to evaluate how different coping strategies and spiritual well-being influence psychological distress in these subjects.MethodsObservational, prospective, consecutive study performed in 15 hospitals in Spain. The study consists of two cohorts: patients with resected locally and locally advanced cancer receiving adjuvant chemotherapy (NEOcoping study, 2016 and 2018) and those with unresectable locally advanced and advanced cancer, eligible for systemic treatment (NEOetic study, 2020 and 2021). Participants completed the following scales: BSI-18 (psychological distress) at baseline and after antineoplastic treatment; MINI-MAC (coping), and FACIT-sp (spirituality), before initiating systemic treatment.ResultsFourteen hundred and fifty patients were recruited; 941 had resected cancer and 509 had advanced cancer. The advanced cancer sample included more males, older, less educated, and more unemployed individuals. Before starting systemic treatment, the advanced, unresectable disease group suffered more psychological distress than those with resected cancer (66.9 vs. 63.7, p=0.001) and used more coping strategies, especially positive attitude (79.1 vs. 75.6, p=0.001) and cognitive avoidance (64.3 vs. 53.6, p=0.001). Participants with resected cancer displayed greater spiritual well-being (36.5 vs 33.2, p=0.001). After receiving systemic treatment, psychological distress decreased in cases of advanced cancer and increased in resected cancer, albeit still higher in subjects with advanced cancer, particularly anxiety (61.4 vs 60.9) and depression (61.0 vs 60.6), (p=0.001 in both cases).ConclusionPatients with advanced cancer exhibit greater psychological distress, use more coping strategies, and have less spiritual well-being, but their psychological distress improves with antineoplastic treatment.