Background: ACP and their SC experience psychological distress living with future uncertainty regarding their cancer. Yet, little is known how existential DA adversely impacts the psychological well-being and overall survival of ACP participating in Phase I trials and their SC. Methods: A prospective study of ACP enrolling in phase I trials and their SC were assessed at baseline (T1) and one month (T2) using quantitative symptom measures including: depression (CES-D), state anxiety (STAI-S), quality of life/qol (FACIT-Pal), and global health (SF-36). Semi-structured interviews evaluated DA: suffering; meaning, and worry re death. Results: To date, 158 participants (79 Phase I ACP and 79 SC) have been separately interviewed at T1 and T2. For the total population: median age 62 (28-79y); 50% male; 100% married; 89% Ca; 69% > HS educ; 59% GI dx; ACP median survival 8.2 month (.51-18.8) 53% income < $65,000 yr. At T1, 83% of ACP experienced worry re death, and 77% reported suffering. For SC at T1, 75% reported worry re ACP death; 88% worried re own death; and 85% reported experiencing suffering and 84% lost meaning during the ACP illness. For both ACP and SC, rates remained consistent for both ACP and SC. At T2, ACP with worry re death had higher STAI-S (32±11 v. 28±9, p = 0.04) and CES-D scores (12±10 v. 11±10, p = 0.03). SC with self-reported suffering had higher STAI-S anxiety (38±15 v. 34±12, p = 0.02) at T2. Regression analyses revealed ACP with worry had worsening FACIT-Pal QOL over time. Also, SC with suffering at T2 was negatively associated with SF-36 scores. Regarding survival, ACP with DA had shorter survival compared to ACP without DA (4.4 v. 6.9 months, p = 0.02). Conclusions: Phase I ACP and SC report worry re death and suffering negatively impacting their psychological well-being and survival. Supportive couple-based, dyadic psychological interventions for ACP-SC designed to address DA coping are needed.