SUPER: Solving Cancer of Unknown Primary

A diagnosis of ‘Cancer of Unknown Primary’ CUP is made when a patient presents with metastatic disease for which no primary cancer can be identified despite extensive clinical assessment, imaging and pathological evaluation. Currently, there is very little information available to clinicians to help guide diagnostic, treatment, or supportive care practices for patients with CUP.

SUPER is a cohort study that was initiated by a multidisciplinary research team to address the difficulties that both clinicians and patients face when dealing with a diagnosis of CUP.

SUPER is establishing a ‘bio and information bank’ which will be a national information resource of clinical, molecular and patient questionnaire information that is currently being used to identify the supportive care and psychosocial needs of CUP patients, understand the clinical and molecular characteristics of CUP, as well as improving the diagnostic assessment of CUP patients. 

We are also hoping to identify any differences in needs between patients residing in metropolitan versus rural/regional areas as well as comparing the economic, quality of life and psychosocial needs of CUP patients to other patients diagnosed with advanced cancer of a known primary. 

SUPER is currently recruiting at 11 metropolitan sites nationally in Victoria, New South Wales, South Australia, Northern Territory and Australian Capital Territory. The target recruitment for this study is 300 participants. To our knowledge, we are the only translational, cross-disciplinary research group in Australia investigating CUP.

Molecular Tests for CUP patients

As part of the SUPER teams larger body of work, SUPER is providing real-time feedback of molecular data to clinicians treating CUP patients. SUPER hopes to evaluate the impact of performing molecular diagnostic tests and how the feedback of results could influence clinical care of CUP patients. SUPER currently offers participants two molecular tests; SUPERDx has been newly developed by the SUPER team at Peter Mac and is used to potentially identify the likely site of origin. This is used alongside a next generation sequencing mutation profiling test, to identify any genetic information which could potentially be targeted by treatment. The tests together hope to offer more targeted treatment options to CUP patients. The clinical utility of these results is being measured by the impact this information has on clinical decision-making and patient outcomes.

Recruitment sites


Peter MacCallum Cancer Centre
Geelong Hospital –Barwon Health
South West Healthcare – Warrnambool Campus
Bendigo Hospital

New South Wales

Westmead Hospital
Nepean Hospital 
Blacktown Mount Druitt Hospital
Border Medical Oncology
Canberra Hospital - awaiting activation 

South Australia

Flinders Medical Centre

Northern Territory

Darwin Hospital - awaiting activation


  • Provide molecular diagnostic and therapeutically actionable data to clinicians in real-time and assess the impact of this information in order to better understand the place of these tests in the clinical management and costs of care of CUP patients.
  • Compare the supportive care needs, quality of life and communication experiences of CUP patients and advanced cancer patients with known primary sites.
  • Compare the supportive care needs, quality of life and communication experiences of CUP patients treated in rural/regional and metropolitan areas.


This project has three long-term objectives:

  1. To significantly improve the diagnostic assessment of CUP patients;
  2. To integrate new treatment approaches, specifically, molecular therapeutics and treatments for likely site of origin; and
  3. To meet the psychosocial needs of CUP patients.


Peter MacCallum Cancer Centre


The project has received 3 sources of grant funding;

  1. ‘SUPER’ is funded by Cancer Australia. This study establishes a ‘biobank’ of 120 CUP patients, and 120 non-CUP patients which will be a resource of clinical, molecular and patient questionnaire information for future studies. The study is based in NSW, SA and Melbourne Victoria.
  2. ‘SUPER plus’ is funded by the Victorian Cancer Agency. This study expands SUPER by increasing patient numbers, and expanding recruitment sites across regional Victoria. In addition, clinical questionnaires were included here to assess whether receiving timely molecular profiling results would alter patient management and treatment choice.
  3. ‘Recuperate’ is funded by Cancer Australia, and compliments ‘SUPER plus’ by expanding the study nationally to include Northern Territory and the Australia Capital Territory. In addition, Recuperate also is assessing the costs associated with a diagnosis of CUP.

Principal Investigator/s

  • SUPER - CIA: Prof. Penelope Schofield, CIB: Prof David Bowtell, CIC: Assoc/Prof Linda Mileshkin
  • SUPER plus - CIA: Assoc/Prof Linda Mileshkin, CIB: Prof Penelope Schofield, CIC: Prof David Bowtell
  • Recuperate - CIA: Assoc/Prof Linda Mileshkin, CIB: Prof David Bowtell; CIC: Prof Penelope Schofield.

Contact details

Ms Krista Fisher

Research Assistant

Email: [email protected] 

Publications & presentations

Guccione, L., Mileshkin, L., Schofield, P., Bowtell, D. Carcinoma of unknown primary – rare but ripe for help from genomics? Cancer Forum, 2015; 39(1): 44-46

Tothill, R.W., Li, J., Mileshkin, L., Doig, K., Signakis, T., Cowin, P., Fellowes, A., Semple, T., Fox, S., Byron, K., Kowalczyk, A., Thomas, D., Schofield, P., Bowtell, D. (2013). Massively-parallel sequencing assists the diagnosis and guided treatment of cancers of unknown primary. Journal of Pathology.

Moran S, Martínez-Cardús A, Sayols S, Musulén E, Balañá C, Estival-Gonzalez A, Moutinho C, Heyn H, Diaz-Lagares A, de Moura MC, Stella GM, Comoglio PM, Ruiz-Miró M, Matias-Guiu X, Pazo-Cid R, Antón A, Lopez-Lopez R, Soler G, Longo F, Guerra I, Fernandez S, Assenov Y, Plass C, Morales R, Carles J, Bowtell D, Mileshkin L, Sia D, Tothill R, Tabernero J, Llovet JM, Esteller M. Epigenetic profiling to classify cancer of unknown primary: a multicentre, retrospective analysis. Lancet Oncol. 2016 Oct;17(10):1386-1395.