Existential Distress in Advanced Cancer: Comparing a Short-term Psychodynamic Psychotherapy (ORPHYS) to Treatment as Usual (TAU)

Official title

Existential Distress in Advanced Cancer: Pragmatic Randomized Controlled Trial of a Short-term Psychodynamic Psychotherapy (ORPHYS) Compared to Treatment as Usual (TAU)

Overview

The psychological challenges faced by patients with incurable cancer and their caregivers include an uncertain future, fear of dying and uncontrollable suffering, grief, and loneliness. In a significant subgroup, this challenge is associated with significant fear and existential distress. This distress can manifest itself, for example, in the form of demoralization, a state of despair and hopelessness in which the possibilities for coping seem exhausted. Although open discussions about fears at the end of life are becoming increasingly important, little is known about how patients with high existential distress can best be supported to promote quality of life. The aim of the study is to test the effectiveness of the newly developed individual psychotherapy ORPHYS (ShORt-term psychodynamic psychotherapy in serious PHYSical illness) in reducing existential distress. To this end, a randomly selected half of the participants who receive ORPHYS treatment will be compared with a second group who receive the standard routine psycho-oncological treatment TAU (Treatment As Usual). The level of distress caused by demoralization will be used for the comparison. A total of 160 patients with advanced cancer will be included in the study. Due to improved treatment options, life expectancy for advanced cancer has increased significantly. This means that patients and their families must deal with the existential tension between uncertainty and a focus on life. The treatment is intended to contribute to providing the best possible support for patients who suffer from uncertainty and fears at the end of life.

Detailed description

Background: As improvements in systemic anti-cancer treatments have extended survival, patients with advanced cancer and their family caregivers face the existential tension between engaging in life and coping with uncertainty about illness trajectory and course of treatment. For a subgroup, this tension is associated with overwhelming fear and existential distress. Existential distress is often characterized by demoralization, a state of despair and hopelessness in which coping skills are exhausted and patients are unable to see something positive in the future. Such adjustment difficulties may increase the risk of poor quality of life and suicidality, as well as impair prognostic awareness and patient-clinician communication. Despite growing interest in open conversations about end-of-life issues, little is known about how clinicians can best support patients experiencing high levels of existential distress in order to facilitate psychological adaptation at the end of life.

Objective: To evaluate the effectiveness of ORPHYS (ShORt-term psychodynamic psychotherapy in serious PHYSical illness) in a pragmatic randomized controlled trial. The intervention group receives 15-31 sessions of ORPHYS, a manualized individual psychotherapy that flexibly integrates uncovering and holding treatment elements. The control group receives usual psycho-oncological care (TAU). The primary outcome is demoralization as assessed by the Demoralization Scale-II. Secondary outcomes include diagnosis of affective, anxiety and stress-related disorders, death anxiety, dignity-related distress, and quality of life.

Methods: The investigators will conduct a two-arm parallel randomized controlled trial with an active control group. Patients will be assessed pre-intervention and after 3, 6, 9, and 12 months. The target sample size is 160 participants before randomization. The investigators will 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. Outcome assessments will be conducted via diagnostic interviews and self-report questionnaires. Linear mixed models will examine outcome differences between trial arms. A confirmatory test of the group contrast at 6 months-follow-up will be conducted.

Discussion: Due to an aging population and prolonged survival, there is a growing demand to help patients deal with existential challenges. 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.

Interventions

• Behavioral ORPHYS (ShORt-term psychodynamic psychotherapy in serious PHYSical illness)
  ORPHYS is a manualized individual psychotherapy that was specifically designed for patients with serious physical illness (Philipp et al., 2024). Patients receive 15-31 weekly therapy sessions of 50 minutes length. ORPHYS takes into account the individual meaning of illness in the context of internalized motives and fears. ORPHYS aims to help patients gain consciousness of related existential conflict. The treatment supports reflection on current relational experiences in the context of realisti
• Behavioral TAU (Treatment As Usual: Standard psycho-oncological care)
  Patients receive routine psycho-oncological care as provided by the study centers. TAU includes individual sessions provided by physicians or master-level psychologists with experience in psycho-oncological care. There is no restriction on the minimum or maximum number of sessions.

Primary outcome measures

• Demoralization assessed via the Demoralization Scale-II (DS-II; Robinson et al., 2016; Koranyi et al., 2021) [Time frame: Day 0, Month 3, Month 6, Month 9, Month 12]

Secondary outcome measures (6)

• Diagnosis of affective disorders, anxiety disorders, trauma- and stressor-related disorders assessed via Diagnostic and Statistical Manual of Mental Disorders-5 (SCID-5; Beesdo-Baum, 2019) [Time frame: Day 0, Month 6, Month 12]
• Diagnosis of stressor-related disorders assessed via CIDI Adjustment Disorder Module (Perkonigg et al., 2019) [Time frame: Day 0, Month 6, Month 12]
• Death anxiety assessed via Death and Dying Distress Scale (DADDS; Lo et al., 2011) [Time frame: Day 0, Month 3, Month 6, Month 9, Month 12]
• Dignity-related distress assessed via the Sense of Dignity Item (SDI; Chochinov et al., 2002) [Time frame: Day 0, Month 3, Month 6, Month 9, Month 12]
• Dignity-related distress assessed via the Patient Dignity Inventory (PDI; Chochinov et al., 2008) [Time frame: Day 0, Month 3, Month 6, Month 9, Month 12]
• Quality of life assessed via the Quality of Life at the End of Life-Cancer-Psychosocial Questionnaire (QUAL-EC-P) [Time frame: Day 0, Month 3, Month 6, Month 9, Month 12]

Eligibility criteria

Inclusion criteria

• UICC stage III/IV solid tumor or advanced hematological cancer
• Physical condition at beginning of treatment sufficient for outpatient treatment
• Existential distress due to at least one of the following concerns: loss of hope, demoralization, fear of the future, loneliness, death anxiety, sense of isolation, death wishes
• Severity of distress: significant subjective distress and impairment in functioning

Exclusion criteria

• Acute suicidality with concrete or impending intent to follow through (suicide plan)
• diagnosis of a substance dependence, substance abuse, or psychotic disorder (exception: tobacco-related disorders)
• Inability to adhere to a psychotherapeutic setting
• Other current psychotherapeutic or psycho-oncological treatment according to TAU definition
• Insufficient German to give informed consent and complete self-report questionnaires

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Treatment

Study locations

Germany · 3 centers

• Clinical Institute for Psychosomatic Medicine and Psychotherapy, University Medical Center — Düsseldorf
• University Medical Center Hamburg-Eppendorf — Hamburg
• Psychosomatics, Psychotherapy and Psychooncology, Medicine II, University of Würzburg — Würzburg

Publications

• Philipp R, Walbaum C, Lindner R, Karger A, Maatouk I, Dinger U, Vehling S. [ORPHYS - Treatment Manual for a Short-Term Psychodynamic Psychotherapy in Patients with Serious Physical Illness]. Psychother Psychosom Med Psychol. 2024 Aug;74(8):345-351. doi: 10.1055/a-2322-8596. Epub 2024 Jun 17. German. PMID 38885656
• Perkonigg A, Strehle J, Beesdo-Baum K, Lorenz L, Hoyer J, Venz J, Maercker A. Reliability and Validity of a German Standardized Diagnostic Interview Module for ICD-11 Adjustment Disorder. J Trauma Stress. 2021 Apr;34(2):275-286. doi: 10.1002/jts.22597. Epub 2020 Nov 5. PMID 33151596
• Huber J, Nikendei C, Ehrenthal JC, Schauenburg H, Mander J, Dinger U. Therapeutic Agency Inventory: Development and psychometric validation of a patient self-report. Psychother Res. 2019 Oct;29(7):919-934. doi: 10.1080/10503307.2018.1447707. Epub 2018 Mar 20. PMID 29557306
• Brahler E, Horowitz LM, Kordy H, Schumacher J, Strauss B. [Validation of the Inventory for Interpersonal Problems (IIP). Results of a representative study in East and West Germany]. Psychother Psychosom Med Psychol. 1999 Nov;49(11):422-31. German. PMID 10593141
• Galushko M, Strupp J, Walisko-Waniek J, Hahn M, Loffert S, Ernstmann N, Pfaff H, Radbruch L, Nauck F, Ostgathe C, Voltz R. Validation of the German version of the Schedule of Attitudes Toward Hastened Death (SAHD-D) with patients in palliative care. Palliat Support Care. 2015 Jun;13(3):713-23. doi: 10.1017/S1478951514000492. Epub 2014 May 22. PMID 24849188
• El-Jawahri A, Forst D, Fenech A, Brenner KO, Jankowski AL, Waldman L, Sereno I, Nipp R, Greer JA, Traeger L, Jackson V, Temel J. Relationship Between Perceptions of Treatment Goals and Psychological Distress in Patients With Advanced Cancer. J Natl Compr Canc Netw. 2020 Jul;18(7):849-855. doi: 10.6004/jnccn.2019.7525. PMID 32634779
• Conrad M, Engelmann D, Friedrich M, Scheffold K, Philipp R, Schulz-Kindermann F, Harter M, Mehnert A, Koranyi S. [Assessment of Couples' Communication in Patients with Advanced Cancer: Validation of a German Version of the Couple Communication Scale (CCS)]. Psychother Psychosom Med Psychol. 2019 May;69(5):189-196. doi: 10.1055/a-0583-4837. Epub 2018 Apr 13. German. PMID 29653458
• Hack TF, McClement SE, Chochinov HM, Cann BJ, Hassard TH, Kristjanson LJ, Harlos M. Learning from dying patients during their final days: life reflections gleaned from dignity therapy. Palliat Med. 2010 Oct;24(7):715-23. doi: 10.1177/0269216310373164. Epub 2010 Jul 6. PMID 20605851

Identifiers

NCT: NCT07312760 · DKH70116803

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗