. 2025 Jan 29;25(1):171.

doi: 10.1186/s12885-025-13506-4.

Solving unknown primary cancer with earlier diagnosis - the SUPER-ED trial: study protocol for a stepped-wedge cluster randomised controlled trial to support earlier diagnosis for people presenting with malignancy of undefined primary origin

Anna Ugalde¹, Richard W Tothill^{2

3

4}, Stephen Quinn⁵, Hui-Li Wong^{2

3}, Owen Prall², Catherine Mitchell^{2

3}, Nilmini Wickramasinghe^{5

6}, Clare Fedele⁷, Natalie Richards², Elizabeth Todio^{2

5}, Cindy Bryant⁵, Louisa G Collins^{8

9}, Sarah McLean², Hyun Soo Ko^{3

10

11}, Tim Akhurst², Christopher Steer¹², Bo Gao^{13

14}, Mark Wong¹⁴, Chloe Georgiou¹⁵, Narayan Karanth¹⁶, Anna Kuchel¹⁷, Louise Nott¹⁸, Shamsudheen Padinharakam¹⁹, Mark Shackleton^{20

21}, Ian M Collins^{22

23}, Madhu Singh²⁴, Rachel Wong²⁵, Zee Wan Wong²⁶, Alexis Butler², Tharani Sivakumaran^{2

3}, Penelope Schofield^#^{3

5

27}, Linda Mileshkin^#^{2

3}

Affiliations

¹ Institute for Health Transformation, Faculty of Health, Deakin University, 221 Burwood Highway, Burwood, Geelong, Victoria, 3125, Australia. a.ugalde@deakin.edu.au.
² Peter MacCallum Cancer Centre, Parkville, Victoria, Australia.
³ Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria, Australia.
⁴ Department of Clinical Pathology and Centre for Cancer Research, University of Melbourne, Parkville, Victoria, Australia.
⁵ Swinburne University of Technology, Hawthorn, Victoria, Australia.
⁶ Latrobe University, Bundoora, Victoria, Australia.
⁷ CSL Innovation, Melbourne, Victoria, Australia.
⁸ QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
⁹ Viertel Cancer Research Centre, Cancer Council Queensland, Queensland, Australia.
¹⁰ Department of Cancer Imaging, Peter MacCallum Cancer Centre, Melbourne, Australia.
¹¹ Department of Diagnostic and interventional Radiology, University Hospital Bonn, Bonn, Germany.
¹² Border Medical Oncology, Albury Wodonga Regional Cancer Centre, Albury, New South Wales, Australia.
¹³ University of Sydney, Sydney, New South Wales, Australia.
¹⁴ Department of Medical Oncology, Westmead Hospital, Sydney, New South Wales, Australia.
¹⁵ Department of Medical Oncology, Bendigo Health, Bendigo, Victoria, Australia.
¹⁶ Department of Medical Oncology, Royal Darwin Hospital, Darwin, Northern Territory, Australia.
¹⁷ University of Queensland, Brisbane, Queensland, Australia.
¹⁸ Department of Medical Oncology, Royal Hobart Hospital, Hobart, Tasmania, Australia.
¹⁹ Launceston General Hospital, Launceston, Tasmania, Australia.
²⁰ Department of Oncology, Alfred Hospital, Melbourne, Victoria, Australia.
²¹ School of Translational Medicine, Monash University, Melbourne, Victoria, Australia.
²² Institute for Health Transformation, Faculty of Health, Deakin University, 221 Burwood Highway, Burwood, Geelong, Victoria, 3125, Australia.
²³ Southwest Healthcare, Warrnambool, Victoria, Australia.
²⁴ Barwon Health, Geelong, Victoria, Australia.
²⁵ Eastern Health, Melbourne, Victoria, Australia.
²⁶ Monash Health, Clayton, Victoria, Australia.
²⁷ School of Computing, Engineering and Mathematical Sciences, La Trobe University, Melbourne, Australia.

^# Contributed equally.

PMID: 39881222
PMCID: PMC11776227
DOI: 10.1186/s12885-025-13506-4

Solving unknown primary cancer with earlier diagnosis - the SUPER-ED trial: study protocol for a stepped-wedge cluster randomised controlled trial to support earlier diagnosis for people presenting with malignancy of undefined primary origin

Anna Ugalde et al. BMC Cancer. 2025.

. 2025 Jan 29;25(1):171.

doi: 10.1186/s12885-025-13506-4.

Authors

Affiliations

¹ Institute for Health Transformation, Faculty of Health, Deakin University, 221 Burwood Highway, Burwood, Geelong, Victoria, 3125, Australia. a.ugalde@deakin.edu.au.
² Peter MacCallum Cancer Centre, Parkville, Victoria, Australia.
³ Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria, Australia.
⁴ Department of Clinical Pathology and Centre for Cancer Research, University of Melbourne, Parkville, Victoria, Australia.
⁵ Swinburne University of Technology, Hawthorn, Victoria, Australia.
⁶ Latrobe University, Bundoora, Victoria, Australia.
⁷ CSL Innovation, Melbourne, Victoria, Australia.
⁸ QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
⁹ Viertel Cancer Research Centre, Cancer Council Queensland, Queensland, Australia.
¹⁰ Department of Cancer Imaging, Peter MacCallum Cancer Centre, Melbourne, Australia.
¹¹ Department of Diagnostic and interventional Radiology, University Hospital Bonn, Bonn, Germany.
¹² Border Medical Oncology, Albury Wodonga Regional Cancer Centre, Albury, New South Wales, Australia.
¹³ University of Sydney, Sydney, New South Wales, Australia.
¹⁴ Department of Medical Oncology, Westmead Hospital, Sydney, New South Wales, Australia.
¹⁵ Department of Medical Oncology, Bendigo Health, Bendigo, Victoria, Australia.
¹⁶ Department of Medical Oncology, Royal Darwin Hospital, Darwin, Northern Territory, Australia.
¹⁷ University of Queensland, Brisbane, Queensland, Australia.
¹⁸ Department of Medical Oncology, Royal Hobart Hospital, Hobart, Tasmania, Australia.
¹⁹ Launceston General Hospital, Launceston, Tasmania, Australia.
²⁰ Department of Oncology, Alfred Hospital, Melbourne, Victoria, Australia.
²¹ School of Translational Medicine, Monash University, Melbourne, Victoria, Australia.
²² Institute for Health Transformation, Faculty of Health, Deakin University, 221 Burwood Highway, Burwood, Geelong, Victoria, 3125, Australia.
²³ Southwest Healthcare, Warrnambool, Victoria, Australia.
²⁴ Barwon Health, Geelong, Victoria, Australia.
²⁵ Eastern Health, Melbourne, Victoria, Australia.
²⁶ Monash Health, Clayton, Victoria, Australia.
²⁷ School of Computing, Engineering and Mathematical Sciences, La Trobe University, Melbourne, Australia.

^# Contributed equally.

PMID: 39881222
PMCID: PMC11776227
DOI: 10.1186/s12885-025-13506-4

Abstract

Background: People with malignancy of undefined primary origin (MUO) have a poor prognosis and may undergo a protracted diagnostic workup causing patient distress and high cancer related costs. Not having a primary diagnosis limits timely site-specific treatment and access to precision medicine. There is a need to improve the diagnostic process, and healthcare delivery and support for these patients. This trial aims to implement and evaluate an optimal model of care for people presenting with MUO to reduce time to diagnosis, improve patient experiences and reduce healthcare costs.

Methods/design: This is a pragmatic stepped-wedge cluster randomised trial comparing a control phase of standard practice with an intervention phase. Patient inclusion criteria are: 1) age 18 years or older, 2) presenting with suspected metastatic malignancy without an obvious primary site on imaging, 3) clinically appropriate to undergo diagnostic work-up and 4) able to provide written or verbal consent. The intervention is a new model of care comprising four key components: standardised diagnostic workup, dedicated cancer care coordinators, virtual multidisciplinary meetings and a website resource for patients, carers and clinicians. The primary endpoint is the time to completion of minimum diagnostic workup. Secondary outcomes are whether the type of tumour is diagnosed, clinical trial participation, referral to palliative care, patient-reported physical, social and mental health, patient-reported understanding and uncertainty. Implementation outcomes include acceptability, feasibility, fidelity and adoption and health care use and costs. Intervention implementation will be supported using clinical leadership, education and reinforcement. Patients who consent to having their data collected will receive the model of care active at the site at the time of recruitment. Patients will complete a patient-reported outcomes questionnaire four months after study enrolment. A health economic analysis will be included. Across 15 hospitals, a total sample size of 240 is planned.

Discussion: There is a lack of intervention research for people presenting with MUO. The stepped-wedge design seeks to mitigate the potential challenge of enrolling people with a poor prognosis and high symptom burden in trials. This research will generate important evidence with scalability for future research at trial completion.

Trial registration: ACTRN12622001504707.

Keywords: Cancer; Care; Diagnosis; Stepped-wedge cluster; Support; Unknown primary cancer.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: Ethical approval was obtained from Peter MacCallum Cancer Centre Human Research Ethics Committee (number 22/141). All methods will be performed in accordance with relevant guidelines and regulations. Participants will provide informed consent. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.

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References

1. NICE. NICE Clinical Guideline. Metastatic Malignant Disease of Unknown Primary Origin. London: National Institute for Health and Clinical Excellence; 2010. - PubMed
1. Fizazi K, Greco FA, Pavlidis N, Daugaard G, Oien K, Pentheroudakis G. Cancers of unknown primary site: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2015;26:v133–8. - DOI - PubMed
1. Pavlidis N, Pentheroudakis G. Cancer of unknown primary site. The Lancet. 2012;379(9824):1428–35. - DOI - PubMed
1. Australian Institute of Health and Welfare 2021. Cancer in Australia 2021. Cancer series no. 133. Cat. no. CAN 144. Canberra: AIHW.
1. Mileshkin L, Bochtler T, Gatta G, Kurzrock R, Beringer A, Müller-Ohldach M, Surinach A, Perret C, Thomas M, Gondos A. Cancer-of-unknown-primary-origin: A SEER–medicare study of patterns of care and outcomes among elderly patients in clinical practice. Cancers. 2022;14(12):2905. - DOI - PMC - PubMed

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Solving unknown primary cancer with earlier diagnosis - the SUPER-ED trial: study protocol for a stepped-wedge cluster randomised controlled trial to support earlier diagnosis for people presenting with malignancy of undefined primary origin

Affiliations

Solving unknown primary cancer with earlier diagnosis - the SUPER-ED trial: study protocol for a stepped-wedge cluster randomised controlled trial to support earlier diagnosis for people presenting with malignancy of undefined primary origin

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources