Randomized Trial of a Novel Approach to Addressing Fear of Progression in Advanced Cancer

ABSTRACT Precision oncology has led to a growing population of adults with advanced cancer living increasingly longer lives in the face of profound uncertainty about the future, with over half reporting moderate to high fear of cancer progression (FoP)—anxiety about the high risk or certainty of disease progression. These fears are associated with anxiety and depression, over-use of healthcare, physical symptom burden, higher treatment regret, fatigue, and, in many studies, poorer quality of life. Moreover, FoP is strongly correlated with cancer-related trauma symptoms—physical hyperarousal, intrusiveness of cancer-related thoughts/images, and avoidance of cancer- related thoughts and feelings—which are associated with similarly poor outcomes, suggesting overlapping symptoms and etiology. While behavioral interventions exist to target fear of recurrence in early-stage cancer survivors, there is a notable dearth of behavioral interventions to address FoP or cancer-related trauma symptoms in adults with advanced cancer, and no known published randomized trials of such interventions in the United States. This represents a critical gap in knowledge for the growing community of advanced cancer survivors. In addition, cutting-edge developments for the treatment of trauma in general populations have not been adapted to cancer populations. To address these gaps, we adapted a cutting-edge behavioral treatment for trauma to reduce FoP and cancer-related trauma symptoms among adults with advanced cancer. The intervention, titled EASE, is based on written exposure therapy, a highly efficacious approach for reducing trauma symptoms in general populations that is better accepted and far briefer than other gold-standard approaches. EASE adapts this effective approach to help advanced cancer patients with elevated FoP and cancer-related trauma symptoms to reduce their fear of the future by using written exposure focused on their future worst-case scenario with cancer. Informed by the NIH stage model, we evaluated EASE delivered by telehealth in an open pilot trial for 29 adults with late-stage cancer and elevated FoP and cancer-related trauma symptoms. Pilot findings show strong acceptability, feasibility, and efficacy potential. We now propose to conduct the first randomized trial of EASE, and, thus, first known randomized trial in the United States of a behavioral intervention for FoP and cancer-related trauma symptoms among adults with advanced cancer. Across both community and academic cancer clinics, this 2-arm trial (N=250) will compare EASE delivered by telehealth with Usual Care (UC), with 1:1 randomization. We aim to compare EASE to UC on FoP and cancer-related trauma symptoms (primary outcomes) and anxiety, depression, hopelessness, and quality of life, at post-intervention (Aim 1) and follow-up (Aim 2). We also will evaluate theorized mechanisms for EASE relative to UC (Aim 3). Offering EASE in both English and Spanish, and by telehealth, increases access. Simple content increases scalability. Rigorous evaluation of EASE has the potential to provide a paradigm-shifting intervention ready for dissemination and a solid empirical foundation to inform evidence-based care guidelines for distressed adults with advanced cancer.