Existential distress in advanced cancer: study protocol of a pragmatic randomized controlled trial of a short-term psychodynamic therapy (ORPHYS) compared to usual psycho-oncological treatment (TAU).

Abstract

Background: As improvements in anti-cancer treatments have extended survival, patients with advanced cancer and their family caregivers face existential tension between engaging in life and coping with uncertainty about illness trajectory and the course of treatment. For a subgroup, this tension is associated with overwhelming fear and existential distress. Such adjustment difficulties may increase the risk of mental disorders, poor quality of life, and suicidality, and impair prognostic awareness and patient-clinician communication. Despite growing interest in open conversations about end-of-life issues, systematic evidence on effective psychotherapies to best support psychological adaptation in patients with high levels of existential distress is still scarce. We aim to evaluate the effectiveness of a short-term psychodynamic therapy (ORPHYS) to mitigate existential distress compared to usual psycho-oncological treatment (TAU).

Methods: We conduct a two-arm parallel randomized controlled trial with an active control group. ORPHYS is a manualized individual face-to-face psychotherapy focusing on emotional and relational conflicts specific to cancer patients' illness situation. Treatment lasts between 5 and 11 months with 15 to 31 weekly sessions (50 min). TAU includes at least one individual session provided by physicians or psychologists with experience in psycho-oncological care. Patients will be assessed pre-intervention and 3, 6, 9, and 12 months after baseline. Target sample size is 160 randomized participants. We recruit patients with stage III/IV solid tumors or advanced hematological cancer and clinically significant existential distress from psycho-oncology clinics and referring oncologists at Hamburg, Düsseldorf, and Würzburg Comprehensive Cancer Centers, Germany. The primary outcome is demoralization (Demoralization Scale-II). Secondary outcomes include diagnoses of affective, anxiety and stress-related disorders, death anxiety, dignity-related distress, and quality of life. Outcome assessments are conducted via self-report questionnaires and diagnostic interviews. Linear mixed models examine outcome differences between trial arms. A confirmatory test of the group contrast at 6-month follow-up after baseline is conducted.

Discussion: Due to an aging population and prolonged survival, there is a growing demand to help patients deal with existential challenges undergoing palliative cancer care. The study will contribute to knowledge about how clinicians can best help patients with advanced cancer who substantially struggle with uncertainty at the end of life.

Trial registration: German Clinical Trials Registry, DRKS00038173. Registered October 20th, 2025, https://drks.de/search/en/trial/DRKS00038173 .

Clinicaltrials: gov, NCT07312760. Registered December 30, 2025, https://clinicaltrials.gov/study/NCT07312760 .