Adolescents and young adults (AYAs) with cancer are at risk for poor psychosocial outcomes. This study aimed to determine whether a novel intervention targeting resilience resources would improve patient‐reported resilience, quality of life, and psychological distress.

In this parallel, phase 2 randomized controlled trial, English‐speaking AYAs (12‐25 years old) with cancer were randomized to the Promoting Resilience in Stress Management (PRISM) intervention or usual care (UC). PRISM is a brief, skills‐based intervention targeting stress management, goal setting, cognitive reframing, and meaning making. Participants completed surveys at enrollment and 6 months. Mixed effects regression models evaluated associations between PRISM and the primary outcome (10‐item Connor‐Davidson Resilience Scale scores) and secondary outcomes (generic and cancer‐related quality of life [Pediatric Quality of Life modules], psychological distress [Kessler‐6], and anxiety/depression [Hospital Anxiety and Depression]) at 6 months.

Ninety‐two AYAs were enrolled, were randomized, and completed baseline surveys (48 in the PRISM group and 44 in the UC group); 73% were 12 to 17 years old, and 62% had leukemia or lymphoma. Attrition was primarily due to medical complications and/or death; 36 PRISM participants and 38 UC participants completed 6‐month surveys. PRISM was associated with improved resilience (+3.0 points; 95% confidence interval [CI], 0.5‐5.4; P = .02) and cancer‐specific quality of life (+9.6; 95% CI, 2.6‐16.7; P = .01) and reduced psychological distress (–2.1; 95% CI, –4.1 to –0.2; P = .03) but not generic quality of life (+7.2; 95% CI, –0.8 to 15.2; P = .08). Although anxiety was similar between the groups, 2 PRISM participants (6%) and 8 UC participants (21%) met the criteria for depression at 6 months (odds ratio, 0.09; 95% CI, 0.01‐1.09; P = .06).

PRISM was associated with improved psychosocial outcomes in comparison with UC, suggesting that brief, skills‐based interventions for AYAs may provide a benefit.