Objective: The demanding nature of oncological therapies may affect treatment motivation and adherence, leading to an increased risk of premature death. Exploring the interaction between depressive episodes and treatment adherence is essential, considering how depression may influence patients' willingness to continue treatment. This study aims to investigate the association between depressive episodes, low treatment adherence, and premature death in individuals with cancer. The study also assessed whether low adherence to therapy acted as a mediator in the relationship between depression and the risk of early death.

Participants and Methods: This is a 9-month cohort study in which participants were enrolled in two Italian Oncology hospital units. The Patient Health Questionnaire (PHQ-9) was used for depression screening. Stratified analyses were conducted to explore the relationship between depression, low adherence, and premature death.

Results: Out of 263 subjects, depressive episode frequency was 48.2% and low adherence was 9.9%. After 9 months, 13.7% had died. There was a significative association between experiencing a depressive episode (RR=2.14, 95% CI: 1.08-4.39) and low adherence (RR=2.2, 95% CI: 1.01-4.48) upon cohort entry and being deceased at month 9 of observation. The risk associated with depression was found to persist even after accounting for the level of adherence to therapy through standardization (MH-OR=3.11; 95% CI: 1.52-6.34).

Conclusions: Individuals with cancer who experience a depressive episode or demonstrate low adherence to therapy are at risk for premature death. Early intervention targeting depressive symptoms and treatment adherence may improve oncological-related outcomes.