Patients with advanced cancer typically experience symptom clusters or multiple concurrent symptoms, which have a detrimental impact on patient outcomes. Research in symptom management has predominantly focused on investigating single symptoms in isolation. Although the literature on symptom clusters is growing, the composition of symptom clusters differs depending on the various clinical variables and the method of their assessment and statistical analysis. Effective management of multiple concurrent symptoms in advanced cancer patients remains a clinical challenge across healthcare settings. Minimal attention has been given to gaining a broad and in-depth understanding about the experiences, perspectives, and attitudes of patients with multiple symptoms and clinicians treating symptom clusters. This thesis describes a systematic review of symptom clusters in advanced cancer (Study 1) and three empirical studies that aimed to explore: the composition of symptom clusters in advanced cancer and their influence on patient outcomes (Study 2); patients’ experiences of living with multiple symptoms (Study 3); and multidisciplinary clinicians’ attitudes and strategies towards managing symptom clusters in advanced cancer (Study 4). The overarching purpose of this thesis was to qualitatively investigate the experience of multiple concurrent symptoms from patients’ and clinicians’ perspectives, whilst simutaneously examine how this converges with and diverges from a quantitative investigation of symptom clusters in advanced cancer patients. This mixed methods study design allows for a complete understanding of the impact of symptom clusters on both qualitative and quantitative accounts of quality of life and functioning. Chapter 3 – Systematic review Method: In Study 1, to understand what is known about the composition, stability, consistency, and impact of symptom clusters in advanced cancer patients, the relevant literature was systematically reviewed. Medline, CINAHL, Embase, Web of Science, and PsychINFO were searched to identify studies investigating variants of symptom clusters, cancer, and palliative care. After screening 977 potentially eligible articles, 33 articles were systematically reviewed and assessed for quality. Results: Four common groupings of symptom clusters were found: anxiety-depression, nausea-vomiting, nausea-appetite loss, and fatigue-dyspnea-drowsiness-pain. Symptom clusters in most cases were not stable longitudinally and the various statistical methods used tended to reveal different symptom clusters. The predictors and outcomes of symptom clusters and measurement tools used were also inconsistent across studies. Future studies need to explore the influence of statistical methods on symptom cluster composition, which symptom clusters predict patient outcomes, and patients’ subjective experience of symptom clusters. Chapter 5 – Quantitative study Method: Study 2 examined the extent to which different statistical methodologies differ in the symptom cluster composition solutions they produce across five primary cancer sites, and determine which symptom clusters predict patient outcomes. One hundred and fifty variations of principal component analysis, exploratory factor analysis, and hierarchical cluster analysis were used on an existing data set (N = 1562) of advanced cancer patients who completed the European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire–Core 30. Results: Four clusters consistently formed for many of the methods and cancer sites: tense-worry-irritable-depressed (emotional cluster), fatigue-pain, nausea-vomiting, and concentration memory (cognitive cluster). The emotional cluster was a stronger predictor of overall quality of life than the other clusters. Fatigue-pain was a stronger predictor of overall health than the other clusters. The cognitive cluster and fatigue-pain predicted physical functioning, role functioning, and social functioning. Chapter 6 – Qualitative study on patients with advanced cancer Method: Study 3 examined advanced cancer patients’ experiences of multiple concurrent symptoms using thematic analysis and an adapted grounded theory approach to data collection and analysis. Semi-structured interviews (N = 58) were conducted with 23 inpatients and 35 outpatients recruited purposively from two palliative care centres and two hospital-based oncology departments in Sydney, Australia. Participants were sampled to include a range of cancers and phases in advanced cancer. Results: Six major themes were identified: imminence of death and deterioration; overwhelming loss of control; impinging on autonomy and identity; psychological adaptation; burden of self-management responsibility; and valuing security and empowerment. Multiple symptoms have a profound impact on patients’ autonomy, function, and psychological state and patients transitioning from oncology to palliative care settings were more vulnerable to self-management burden. Chapter 7 – Qualitative study on clinicians managing symptom clusters in advanced cancer Method: Study 4 examined clinicians’ experiences, strategies, and attitudes towards the management of multiple concurrent symptoms in advanced cancer patients using thematic analysis and adapted grounded theory. In-depth semi-structured interviews (N = 48) were conducted with 10 palliative care physicians, 6 oncologists, 6 general practitioners, 12 nurses, and 14 allied health providers, purposively recruited from two acute hospitals, two palliative care centres, and four community general practices in Sydney, Australia. Results: Six themes were identified: uncertainty in decision making; attunement to patient and family; deciphering cause to guide intervention; balancing complexities in medical management; fostering hope and empowerment; and depending on multidisciplinary expertise. Managing symptom clusters, is both an art and a science currently fraught with uncertainty in decision making. Increased scientific evidence for treating symptom clusters and effective collaboration across settings is vital. Conclusions Integration of symptom cluster research into clinical practice is in its infancy. A psychosocial pathway in the management of symptom clusters was proposed as possibly improving quality of life, and biological mechanisms underpinning symptom clusters require further investigation. Multiple symptom management and integrated care is needed to empower advanced cancer patients and reduce their struggles with self-management burden, particularly as they transition between oncologic and palliative care. Strengthening multidisciplinary collaboration, continuity of care, more pragmatic planning of clinical trials to address the multiple symptom experience, and training in symptom cluster assessment and management is crucial. Future research needs to target translating the body of symptom cluster literature into clinically relevant guidelines and interventions across settings, to support a move towards advancing healthcare and research for symptom management in advanced cancer patients.