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Selected journal articles and useful documents on understanding CUP and its treatment

The resources on this page are grouped below by category:

  • General
  • CUP epidemiology
  • Palliative care
  • Patients’ stories
  • (Note: Cup Foundation conferences papers are in the conferences archive)

Further  journal articles on CUP available through the British Library (without hotlinks) are listed here.


2024. A cfDNA methylation-based tissue-of-origin classifier for cancers of unknown primary.
Conway, Alicia-Marie, et al. Nature Communications. 17 April.

2024. Prediction of tumor origin in cancers of unknown primary origin with cytology-based deep learning. Fei Tian et al. Nature Communications (16 Apr)

2023. Outcomes of CUPem: A prospective Phase II multicentre clinical Trial of Pembrolizumab in patients with pre-treated Cancer of Unknown Primary. Abstract. Wasan et al. ESMO Immuno-Oncology Congress. Geneva. 6-8 Dec 2023.

2023.  A randomized phase III trial of site-specific therapy guided by the 90-gene expression assay versus empiric chemotherapy in patients with cancer of unknown primary. Luo Z et al.  Annals of Oncology. Elsevir; [cited Nov 21];34:s712. Available from:

2023. Nivolumab and ipilimumab in recurrent or refractory cancer of unknown primary: a phase II trial. Pouyiourou, Maria et al. Nature Communications (Oct)

2023. Immune and genomic biomarkers of immunotherapy response in cancer of unknown primary. Posner, Atara et al. Journal for ImmunoTherapy of Cancer. (Jan).

2022. Intrahepatic cholangiocarcinoma hidden within cancer of unknown primary. Conway, Alicia-Marie et al. British Journal of Cancer

2022. Comprehensive genomic and epigenomic analysis in cancer of unknown primary guides molecularly-informed therapies despite heterogeneity. Möhrmann, L. et al.
Nature Communications. August.

2022. Systematic review of the CUP trials characteristics and perspectives for next-generation studies. Rassy, Elie et al. Cancer Treatment Reviews. HOT TOPIC| VOLUME 107, 102407, JUNE 01, 2022

2022.  Commentary on: Michael J Fusco et al. Evaluation of Targeted Next-Generation Sequencing for the Management of Patients Diagnosed With a Cancer of Unknown Primary. Greco F. A. PracticeUpdate website. Accessed February 24, 2022.

2021.  Characterisation and outcomes of patients referred to a regional cancer of unknown primary team: a 10-year analysis. Stares et al. British Journal of Cancer.

2021.  AI-based pathology predicts origins for cancers of unknown primary (Abstract only). Ming et al. Nature (5 May).

2021. A Challenging Task: Identifying Patients with Cancer of Unknown Primary (CUP) According to ESMO Guidelines: The CUPISCO Trial Experience. Pauli, Chantal et al. The Oncologist. 09 March.

2020. A deep learning system accurately classifies primary and metastatic cancers using passenger mutation patterns. Wei Jiao et al.  Nat Commun 11, 728

2020. New rising entities in cancer of unknown primary: Is there a real therapeutic benefit? Rassya et al. Critical Reviews in Oncology / Hematology 

2020.  Progress in refining the clinical management of cancer of unknown primary in the molecular era. Rassy, Elie and Pavlidis, Nicholas. Nature. Published online 29 Apr.

2019.  Does Cancer of Unknown Primary (CUP) Truly Exist as a Distinct Cancer Entity? Bochtler, Tilmann & Krämer, Alwin. Front. Oncol., 17 May 2019

2019.  Clinical and immune profiling for cancer of unknown primary site. Haratani, Koji et al. Journal for ImmunoTherapy of Cancer.

2019. A phase III trial of empiric chemotherapy with cisplatin and gemcitabine or systemic treatment tailored by molecular gene expression analysis in patients with carcinomas of unknown primary (CUP) site (GEPCAPI 04). Fizazi K, Maillard A, Penel A, et al. Ann Oncol 2019;30:5S. Presented at ESMO Sep 2019

2019.  Prospective Cohort of Referrals to a Cancer of Unknown Primary Clinic, including Direct Access from Primary Care. Creak. A. Clinical Oncology: a Journal of the Royal College of Radiologists (2019 October 18)

2018. Randomized Phase II Trial Comparing Site-Specific Treatment Based on Gene Expression Profiling With Carboplatin and Paclitaxel for Patients With Cancer of Unknown Primary Site. Hidetoshi Hayashi et al.  Journal of Clinical Oncology. Nov 2018.

2018. Molecular characterisation and liquid biomarkers in Carcinoma of Unknown Primary (CUP): taking the ‘U’ out of ‘CUP’. Conway, Alicia-Marie et al. British Journal of Cancer – online December 2018

2018. Cancer of Unknown Primary Site: New Treatment Paradigms in the Era of Precision Medicine. John D. Hainsworth and F. Anthony Greco. Downloaded from on July 17, 2018. American Society of Clinical Oncology

2018. Renal Cell Carcinoma Presenting as Carcinoma of Unknown Primary Site: Recognition of a Treatable Patient Subset. Greco FA & Hainsworth JD, Clin Genitourin Cancer.  Mar 9 epub ahead of print.

2017. 18F-FDG PET/CT for detection of the primary tumor in adults with extracervical metastases from cancer of unknown primary. A systematic review and meta-analysis. Burglin, Synne Alexandra et al. Medicine (2017) 96:16 Burglin 2017 F-FDG PET CT

2017. Utility of Genomic Analysis In Circulating Tumor DNA from Patients with Carcinoma of Unknown Primary. Shumei Kato et al. American Association for Cancer Research. Published online First June 22, 2017. C Kato et al_

2017. Differences in experiences of care between patients diagnosed with metastatic cancer of known and unknown primaries: mixed-method findings from the 2013 cancer patient experience survey in England . Wagland, R; Bracher, M; Drosdowsky, A; Richardson, A; Symons, J; Mileshkin, L; Schofield, P.  BMJ Open Volume 7, Issue 9

2017. Ten years a CUP charity: is the unknown nearly known? Symons, John. CUP Foundation Paper. June 2017

2017.  Perceptions of Cancer of Unknown Primary site  – A National Survey of Australian Medical Oncologists: Australian Medical Oncologist CUP survey. Christos S Karapetis et al. Internal Medicine Journal. Jan 2017.

2017. Cost-effectiveness of using a gene expression profiling test to aid in identifying the primary tumour in patients with cancer of unknown primary. M B Hannouf et al. The Pharmacogenomics Journal  17, 286–300.

2016. Lung Adenocarcinoma with Anaplastic Lymphoma Kinase (ALK) Rearrangement Presenting as Carcinoma of Unknown Primary Site: Recognition and Treatment Implications. Hainsworth JD, et al. Drugs Real World Outcomes.

2016.  Improved diagnosis, therapy and outcomes for patients with CUP   Nature Reviews, Clinical Oncology. Greco, F. Anthony. Nov. Kandalaft, PL & Gown, AM.

2016. Economopoulou P, Pentheroudakis G. Cancer of unknown primary: time to put the pieces of the puzzle together? Lancet Oncol. Oct;17(10):1339-1340.

2016.  Practical applications in immunohistochemistry: carcinomas of unknown primary site.  Kandalaft, PL & Gown, AM.  Arch. Pathol. Lab. Med. 140, 508–523 (2016).

2016.  Gene expression profiling identifies responsive patients with cancer of unknown primary treated with carboplatin, paclitaxel, and everolimus. Yoon, H. H. et al.  Ann. Oncol. 27, 339–344 (2016).

2015. Paclitaxel/carboplatin with or without belinostat as empiric first-line treatment for patients with carcinoma of unknown primary site: A randomized, phase 2 trial. Hainsworth JD, et al. American Cancer Society

2015. Fotopoulos G, et al. Prognostic significance of WNT and hedgehog pathway activation markers in cancer of
unknown primary. Eur J Clin Invest. 2015 Nov;45(11):1145-52 . Abstract

2015. Economopoulou P, et al.  Cancer of Unknown Primary origin in the genomic era: Elucidating the dark box of cancer. Cancer Treat Rev. May. Abstract.

2016.  A case of S-100 negative melanoma: a diagnostic pitfall in the workup of a poorly differentiated metastatic tumor of unknown origin. Biernacka, A. et al.  Cytojournal 13, 21 (2016).

2016. Gene expression profiling identifies responsive patients with cancer of unknown primary treated with carboplatin, paclitaxel, and everolimus: NCCTG N0871 (alliance).

2016. Pre-referral GP consultations in patients subsequently diagnosed with rarer cancers: a study of patient-reported data.  Mendonca, Silvia C,   Abel, Gary A,   Lyratzopoulos, Georgios. British Journal of General Practice. 1 Mar 2016

2016. Yoon HH, et al. Gene expression profiling identifies responsive patients with cancer of unknown primary treated with carboplatin, paclitaxel, and everolimus. Ann Oncol. 2016;27(2):339. Epub 2015.

2016.  Comparison of responses to closed questions from patients with a known primary versus unknown primary in the 2013 Cancer Patient Experience Survey (England). Schofield, P, Drosdowsky, A, Wagland, R, Symons, J, Mileshkin, L, Richardson, A, Ratchford, D, Bowtell, D, Gough, K.  Australian Government. Cancer Australia.

2016. Pan-cancer transcriptome analysis reveals a gene expression signature for the identification of tumor tissue origin. Qinghua Xu et al. Modern Pathology Modern Pathology (2016) 29, 546–556

2016. Epigenetic profiling to classify cancer of unknown primary: a multicentre, retrospective analysis. Moran, Sebestain et al. Lancet Oncology. Volume 17, No. 10, p1386–1395, October 2016.

2016. Integration of genomics and histology revises diagnosis and enables effective therapy of refractory cancer of unknown primary with PDL1 amplification. Stefan Gröschel et al. Cold Spring Harb Mol Case. Published in Advance August 24, 2016.

2015.  Experiences of Care of Patients with Cancer of Unknown Primary (CUP): Analysis of the 2010, 2011-12 & 2013 Cancer Patient Experience Survey. Wagland R, Bracher M, Ibanez Esqueda A, Schofield P, Richardson A. Southampton University, Health SciencesExecutive summary  and Full report

2015. Cancer of Unknown Primary During Pregnancy: an ExceptionaΙly Rare Coexistence. Nicholas Pavlidis, Fedro Peccatori, Fiona Lofts and Anthony F Greco.   Anticancer Research 35: 575-580.

2015. Comprehensive Genomic Profiling of Carcinoma of Unknown Primary Site – New Routes to Targeted Therapies. Jeffrey S. Ross,  Kai Wang,  Laurie Gay et al. JAMA Oncol. 2015;1(1):40-49

2015. Poorly Differentiated Neoplasms of Unknown Primary Site: Diagnostic Usefulness of a Molecular Cancer Classifier Assay. F. Anthony Greco, Wayne J. Lennington, David R. Spigel, John D. Hainsworth. Molecular Diagnosis & Therapy. Vol 19. Switzerland: Springer International Publishing.

2014. Cancer of unknown primary site: still an entity, a biological mystery and a metastatic model.
Greco FA. Nat Rev Cancer.

2014. Cancer of Unknown Primary Site. F Anthony Greco & John D Hainsworth in Cancer: Principles & Practice of Oncology 10th edition. Chapter 113, page 1720 et seq. Vincent T. DeVita Jr., Theodore S. Lawrence, Steven A. Rosenberg.  USA: Wolters Kluwer. (Full Greco & Hainsworth bibliography).

2014. Cancer of Unknown Primary Site.  Gauri R. Varadhachary and Martin N. Raber. The New England Journal of Medicine NEJM 371;8. Aug.

2014.  Gene expression profiling in patients with carcinoma of unknown primary site: from translational research to standard of care. Hainsworth JD, Greco FA. Virchows Arch. 2014 Apr;464(4);393-402.

2014. Cancer of Unknown Primary (CUP). Richard Osborne’s chapter in Problem Solving in Acute Oncology. Young A, Clark PI, Selby P, editors. 1st ed. Oxford: Clinical Publishing.

2013. Development and implementation of a service for patients with cancer of unknown primary. Knowles, Gillian.
Cancer Nursing Practice . November 2013  Volume 12  Number 9

2013. Uncertainty and anxiety in the cancer of unknown primary patient journey: a multiperspective qualitative study. A Richardson, R Wagland, R Foster, J Symons, C Davis, L Boyland,C Foster, J Addington-Hall in BMJ_Support_Palliat_Care-2013 (November)

2013. Massively-parallel sequencing assists the diagnosis and guided treatment of cancers of unknown primary by Tothill, Bowtell et al in J Pathol. Sep.

2013. Observational study of real world clinical performance of micro RNA molecular profiling for cancer of unknown primary (CUP).  ASCO abstracts

2013.  Novel microRNA-based assay demonstrates 92% agreement with diagnosis based on clinicopathologic and management data in a cohort of patients with carcinoma of unknown primary. Pentheroudakis et al. Molecular Cancer 2013, 12:57

2013. Cancer of Unknown Primary or Unrecognized Adnexal Skin Primary Carcinoma? Limitations of Gene Expression Profiling Diagnosis. F Anthony Greco letter . Journal of Clinical Oncology

2013. Molecular Profiling Diagnosis in Unknown Primary Cancer: Accuracy and Ability to Complement Standard Pathology. F. Anthony Greco, Wayne J. Lennington, David R. Spigel, John D. Hainsworth. JNCI (See also editorial re this article by Schwartz).

2013. Molecular Profiling for Druggable Genetic Abnormalities in CUP . Daniel S.-W. Tan et al.  Journal of Clinical Oncology. May.

2013. National Cancer Patient Experience Survey   (2011/12) – synopsis related to CUP patients

2012.  Southampton University and CUP Foundation patient experience research -Executive Summary

2012. Cancer of Unknown Primary: Progress in the Search for Improved and Rapid Diagnosis Leading Toward Superior Patient Outcomes.  Annals of Oncology.    Greco FA, Oien K, Erlander M, Osborne R, Varadhachary G, Bridgewater J, Cohen D, Wasan H. Feb;23(2):298-304.

2012. Patient’s Preferences Matter – Stop the silent misdiagnosis. Al Mulley, Chris Trimble, Glyn Elwyn. The King’s Fund.

2012. Removing the Unknown From the Carcinoma of Unknown Primary. Adil I. Daud. Journal of clinical oncology.

2012. On the right track.  James & Symons. Cancer Nursing Practice. April

2012. Report of a Collaborative Study Exploring how the Language and Metaphors of Cancer influences Adjustment and Well being following a Course of Cancer Treatment. L. Appleton & M. Flynn. Clatterbridge Centre for Oncology & Liverpool University. April 2012.

2012. A phase II study to evaluate the efficacy and toxicity of oxaliplatin in combination with gemcitabine in carcinoma of unknown primary. Carlson H, Lenzi R, Raber MN, Varadhachary GR. Int J Clin Oncol. 2012 Jan 5.

2012. Molecular Profiling for CUP cancers : Are we there yet? Varadhachary GR. Editorial. Onkologie 2012

2011. Global Cancer Statistics. Ahmedin Jemal et al.  CA CANCER J CLIN 2011;61:69–90

2011.  Carcinoma of unknown primary: key radiological issues from the recent National Institute for Health and Clinical Excellence guidelines.  Taylor, Ben and Bromham, NR. The British Journal of Radiology

2011. Cancer of Unknown Primary site Greco & Hainsworth chapter  in Practice of Oncology

2011. CUP – Where Do We Go Now? Richard Osborne  Oncology News

2011. Evaluating the development of a pathway for patients presenting with metastatic cancer of unidentified primary origin. End of study report for Macmillan Cancer Support. Philippa Hughes, Peter Bath, Clare Farrington, David Brooks & Bill Noble.  Sheffield University July 2011)

2011.  Macmillan Cancer Support statement and Guidance for AO and CUP (July)

2011. Understanding CUP – Guidance for patients and their families. Cancer Council NSW, Australia, with supplementary information including videos.

2011. ‘Understanding provision of chemotherapy to patients with end stage cancer: qualitative interview study’.  Hilde M Buiting et al.   BMJ (April)

2011. Rare cancers are not so rare: The rare cancer burden in Europe. Gemma Gatta et al. European Jnl of Cancer.

2011. Carcinoma of unknown primary: A focused evaluation. Varadhachary GR. J Natl Compr Canc Netw (NCCN). Dec 1;9(12):1406-12.

2011. Prospective gene signature study using microRNA to identify the tissue of origin in patients with carcinoma of unknown primary. Varadhachary GR, Spector Y, Abbruzzese JL, Rosenwald S, Wang H, Aharonov R, Carlson HR, Cohen D, Karanth S, Macinskas J, Lenzi R, Chajut A, Edmonston TB, Raber MN. Clin Cancer Res. 2011 Jun 15;17(12):4063-70. Epub 2011 Apr 29.

2010. Chasing the primary.  Nicola James & John Symons  Cancer Nursing Practice 

2009.  Dilemmas in managing patients with CUP. Symons, James & Brooks. Cancer Nursing Practice

2009. Cancer of Unknown Primary. Mackay, Pithers & Symons MIMS_Oncology and Palliative care

2009. Multicentre validation of a 1,550 gene expresion profile for identification of tumour of unknown origin. Monzon et al.   Journal of Clinical Oncology .

2008.  Understanding and managing CUP. John Symons  British Journal of Nursing 

2008. Liver metastases from cancer of unknown primary (CUPL): A retrospective analysis of presentation,
management and prognosis in 49 patients and systematic review of the literature. George Lazaridis  George Pentheroudakis  George Fountzilas Nicholas Pavlidis. cancer treatment reviews

2008.   Supporting patients with CUP. John Symons  Nursing Times

2008. Combined FDG-PET/CT for the detection of unknown primary tumors: systematic review and meta-analysis. Thomas C. Kwee Robert M. Kwee . Eur Radiol. CUPPETCT2008

2008. MicroRNAs accurately identify cancer tissue origin. Nitzan Rosenfeld et al. Nature Biotechnology.

2008. Gene expression profiling may improve diagnosis in patients with carcinoma of unknown primary. J Bridgewater et al. British Journal of Cancer

2008.  Patients’ experiences of carcinoma of unknown primary site: dealing with uncertainty. Boyland, L & Davis, C . Palliative Medicine. Mar.

CUP Epidemiology

2014. Coding Cancer of Unknown Primary: registration and reporting survey of the UK, Ireland and Australia. Oehler C., Vajdic C., Cooper N., Symons, J. Poster. ENCR Scientific Meeting and General Assembly.  12-14 November 2014, Ispra (Varese), Italy.

2014. Descriptive epidemiology of cancer of unknown primary site in Scotland, 1961–2010. David H. Brewster, Jaroslaw Lang, Lesley A. Bhatti, Catherine S. Thomson, Karin A. Oien. Cancer Epidemiology.  Volume 38, Issue 3, Pages 227–234, June 2014. Abstract and NCIN conference 2014 presentation

2014.  An audit of cancer of unknown primary notifications: A cautionary tale for population health research using cancer registry data. Claire M. Vajdic, Chuang Ching, Andrea Schaffer, Timothy Dobbins, Lucy Wyld, Nicola S. Meagher, Jane Barrett, Robyn L. Ward, Sallie-Anne Pearson.  Cancer Epidemiology. May.

2014. The Challenges of Coding Cancer Of Unknown Primary (CUP) – A Survey Of Current Practices in the UK, Ireland and Australia. Claire  Vajdic, Claudia Oehler, Nicola Cooper, John Symons, NCIN Cancer outcomes conference, 9 & 10 June, Birmingham. Abstract and presentation

2014.Cancer of unknown primary: time trends in incidence, United States. Elena Mnatsakanyan, Wei-Chen Tung, Brenna Caine, Julie Smith-Gagen. Cancer Causes Control  25:747–757

2014. Routes to Diagnosis by route and survival NCIN (shows headline data for CUP with other cancers. See routes to diagnosis workbook on the NCIN page here for full report.)

2014. Routes to diagnosis briefing note on CUP. NCIN.

2012. Site-specific survival rates for CUP according to location of metastases . K. Hemminki, M. Riihimäki, K. Sundquist  and A. Hemminki. International Journal of Cancer

2012. The challenge of attributing causality in Cancer of Unknown Primary.  Vajdic, Claire; Wyld, Lucy; Symons, John. Interntational Journal of Cancer.

2012. Letter responding to the above by Hemminki et al

2011. Global Cancer Statistics. Ahmedin Jemal et al.  CA CANCER J CLIN 2011;61:69–90

2010. NCIN data briefing sheet

2008. Unknown Primary Cancer in New South Wales. Elizabeth Tracey et al. Cancer Institute of NSW  Monograph.

2012. CUP – a rare disease?. John Symons. NCIN conference Poster showing an analysis of international CUP occurence

2011. Capturing CUP data – known unknowns, or unknown unknowns. Binysh, Osborne & Symons. NCIN Conference Poster showing the distribution of CUP by regional networks

2011. CUP – a study of data inequality. John Symons.  NCIN conference Poster showing UK CUP statistics over time

Palliative care

2010. Early Palliative Care for Patients with Metastatic Non–Small-Cell Lung Cancer.  Jennifer S. Temel, et al. The New England Journal of Medicine.

2007. Development and evaluation of a Decision Aid for patients considering first-line chemotherapy for metastatic breast cancer.  Kimberly S. Chiew. Health Expectations. 2007

2004. Improving supportive and palliative care for adults with cancer. Cancer service guidance, NICE. March.

Patients’ stories

2013.  Jersey  CUP Article Jersey

2012. UK Daily Express

2010. UK. Guardian

2010. UK. Yours magazine