Six-year experience of Australia's first dedicated cancer of unknown primary clinic.
Journal
British journal of cancer
ISSN: 1532-1827
Titre abrégé: Br J Cancer
Pays: England
ID NLM: 0370635
Informations de publication
Date de publication:
08 2023
08 2023
Historique:
received:
17
10
2022
accepted:
21
03
2023
revised:
18
03
2023
medline:
14
7
2023
pubmed:
25
5
2023
entrez:
24
5
2023
Statut:
ppublish
Résumé
Diagnosis and management of cancers of unknown primary (CUP) remain challenging. This study examines the referral patterns, management and outcomes of patients referred to Australia's first dedicated CUP clinic. Retrospective medical record review was conducted for patients seen at the Peter MacCallum Cancer Centre CUP clinic between July 2014 and August 2020. Overall survival (OS) was analysed for patients with a CUP diagnosis where treatment information was available. Of 361 patients referred, fewer than half had completed diagnostic work-up at the time of referral. A diagnosis of CUP was established in 137 (38%), malignancy other than CUP in 177 (49%) and benign pathology in 36 (10%) patients. Genomic testing was successfully completed in 62% of patients with initial provisional CUP and impacted management in 32% by identifying a tissue of origin or actionable genomic alteration. The use of site-specific, targeted therapy or immunotherapy was independently associated with longer OS compared to empirical chemotherapy. Our specialised CUP clinic facilitated diagnostic work-up among patients with suspected malignancy and provided access to genomic testing and clinical trials for patients with a CUP diagnosis, all of which are important to improve outcomes in this patient population.
Sections du résumé
BACKGROUND
Diagnosis and management of cancers of unknown primary (CUP) remain challenging. This study examines the referral patterns, management and outcomes of patients referred to Australia's first dedicated CUP clinic.
METHODS
Retrospective medical record review was conducted for patients seen at the Peter MacCallum Cancer Centre CUP clinic between July 2014 and August 2020. Overall survival (OS) was analysed for patients with a CUP diagnosis where treatment information was available.
RESULTS
Of 361 patients referred, fewer than half had completed diagnostic work-up at the time of referral. A diagnosis of CUP was established in 137 (38%), malignancy other than CUP in 177 (49%) and benign pathology in 36 (10%) patients. Genomic testing was successfully completed in 62% of patients with initial provisional CUP and impacted management in 32% by identifying a tissue of origin or actionable genomic alteration. The use of site-specific, targeted therapy or immunotherapy was independently associated with longer OS compared to empirical chemotherapy.
CONCLUSION
Our specialised CUP clinic facilitated diagnostic work-up among patients with suspected malignancy and provided access to genomic testing and clinical trials for patients with a CUP diagnosis, all of which are important to improve outcomes in this patient population.
Identifiants
pubmed: 37225894
doi: 10.1038/s41416-023-02254-6
pii: 10.1038/s41416-023-02254-6
pmc: PMC10338450
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
301-308Informations de copyright
© 2023. The Author(s).
Références
Rassy E, Pavlidis N. Progress in refining the clinical management of cancer of unknown primary in the molecular era. Nat Rev Clin Oncol. 2020;17:541–54.
doi: 10.1038/s41571-020-0359-1
pubmed: 32350398
Pentheroudakis G, Golfinopoulos V, Pavlidis N. Switching benchmarks in cancer of unknown primary: from autopsy to microarray. Eur J Cancer. 2007;43:2026–36.
doi: 10.1016/j.ejca.2007.06.023
pubmed: 17698346
Australian Institute of Health and Welfare. Cancer in Australia 2019. Cancer series no.119. Cat. no. CAN 123. Canberra: AIHW; 2019.
Kolling S, Ventre F, Geuna E, Milan M, Pisacane A, Boccaccio C, et al. “Metastatic Cancer of Unknown Primary” or “Primary Metastatic Cancer”? Front Oncol. 2019;9:1546.
doi: 10.3389/fonc.2019.01546
pubmed: 32010631
Abbruzzese JL, Abbruzzese MC, Hess KR, Raber MN, Lenzi R, Frost P. Unknown primary carcinoma: natural history and prognostic factors in 657 consecutive patients. J Clin Oncol. 1994;12:1272–80.
doi: 10.1200/JCO.1994.12.6.1272
pubmed: 8201389
Urban D, Rao A, Bressel M, Lawrence YR, Mileshkin L. Cancer of unknown primary: a population-based analysis of temporal change and socioeconomic disparities. Br J Cancer. 2013;109:1318–24.
doi: 10.1038/bjc.2013.386
pubmed: 23860528
pmcid: 3778275
Samadder NJ, Smith KR, Hanson H, Pimentel R, Wong J, Boucher K, et al. Familial risk in patients with carcinoma of unknown primary. JAMA Oncol. 2016;2:340–6.
doi: 10.1001/jamaoncol.2015.4265
pubmed: 26863281
Fizazi K, Greco FA, Pavlidis N, Daugaard G, Oien K, Pentheroudakis G, et al. Cancers of unknown primary site: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2015;26:v133–8.
doi: 10.1093/annonc/mdv305
pubmed: 26314775
National Comprehensive Cancer Network. Occult Primary (Version 1.2022). 2019. https://www.nccn.org/professionals/physician_gls/pdf/occult.pdf .
National Institute for Health and Care Excellence (NICE). Metastatic malignant disease of unknown primary origin in adults: diagnosis and management. 2010. https://www.nice.org.uk/guidance/cg104 .
Walker MS, Weinstein L, Luo R, Marino I. Pretreatment costs of care and time to initial treatment for patients with cancer of unknown primary. J Comp Eff Res. 2018;7:523–33.
doi: 10.2217/cer-2017-0104
pubmed: 29855191
Hyphantis T, Papadimitriou I, Petrakis D, Fountzilas G, Repana D, Assimakopoulos K, et al. Psychiatric manifestations, personality traits and health-related quality of life in cancer of unknown primary site. Psychooncology. 2013;22:2009–15.
doi: 10.1002/pon.3244
pubmed: 23359412
Wagland R, Bracher M, Drosdowsky A, Richardson A, Symons J, Mileshkin L, et al. 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. BMJ Open. 2017;7:e017881.
doi: 10.1136/bmjopen-2017-017881
pubmed: 28963312
pmcid: 5623509
Rassy E, Parent P, Lefort F, Boussios S, Baciarello G, Pavlidis N. New rising entities in cancer of unknown primary: Is there a real therapeutic benefit? Crit Rev Oncol Hematol. 2020;147:102882.
doi: 10.1016/j.critrevonc.2020.102882
pubmed: 32106012
Kramer A, Bochtler T, Pauli C, Baciarello G, Delorme S, Hemminki K, et al. Cancer of unknown primary: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2023;34:228–46.
doi: 10.1016/j.annonc.2022.11.013
pubmed: 36563965
Pavlidis N, Pentheroudakis G. Cancer of unknown primary site. Lancet. 2012;379:1428–35.
doi: 10.1016/S0140-6736(11)61178-1
pubmed: 22414598
Tothill RW, Li J, Mileshkin L, Doig K, Siganakis T, Cowin P, et al. Massively-parallel sequencing assists the diagnosis and guided treatment of cancers of unknown primary. J Pathol. 2013;231:413–23.
doi: 10.1002/path.4251
pubmed: 24037760
Ross JS, Sokol ES, Moch H, Mileshkin L, Baciarello G, Losa F, et al. Comprehensive genomic profiling of carcinoma of unknown primary origin: retrospective molecular classification considering the CUPISCO study design. Oncologist. 2021;26:e394–e402.
doi: 10.1002/onco.13597
pubmed: 33219618
Mileshkin LR, Sivakumaran T, Etemadmoghadam D, Tothill R, Fellowes A, Fox SB, et al. Clinical impact of tissue of origin testing and mutation profiling in the Solving Unknown Primary Cancer (SUPER) national prospective study: experience of the first two years. J Clin Oncol. 2019;37:3072.
doi: 10.1200/JCO.2019.37.15_suppl.3072
Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40:373–83.
doi: 10.1016/0021-9681(87)90171-8
pubmed: 3558716
Cancer Council Australia. Optimal care pathway for people with cancer of unknown primary. 2020. https://www.cancer.org.au/assets/pdf/cancer-of-unknown-primary-january-2020 .
Tan SYS, O’Neill S, Goldstein D, Ward RL, Daniels B, Vajdic CM. Predictors of care for patients with cancer of unknown primary site in three Australian hospitals. Asia Pac J Clin Oncol. 2018;14:e512–e20.
doi: 10.1111/ajco.12815
pubmed: 29105289
Stares M, Purshouse K, Knowles G, Haigh R, Irvine J, Gatenby A, et al. Characterisation and outcomes of patients referred to a regional cancer of unknown primary team: a 10-year analysis. Br J Cancer. 2021;125:1503–10.
doi: 10.1038/s41416-021-01544-1
pubmed: 34489587
pmcid: 8608886
Posner A, Prall OW, Sivakumaran T, Etemadamoghadam D, Thio N, Pattison A, et al. A comparison of DNA sequencing and gene expression profiling to assist tissue of origin diagnosis in cancer of unknown primary. J Pathol. 2023;259:81–92.
doi: 10.1002/path.6022
pubmed: 36287571
Mosele F, Remon J, Mateo J, Westphalen CB, Barlesi F, Lolkema MP, et al. Recommendations for the use of next-generation sequencing (NGS) for patients with metastatic cancers: a report from the ESMO Precision Medicine Working Group. Ann Oncol. 2020;31:1491–505.
doi: 10.1016/j.annonc.2020.07.014
pubmed: 32853681
Hayashi H, Kurata T, Takiguchi Y, Arai M, Takeda K, Akiyoshi K, et al. 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. J Clin Oncol. 2019;37:570–9.
doi: 10.1200/JCO.18.00771
pubmed: 30653423
Fizazi K, Maillard A, Penel N, Baciarello G, Allouache D, Daugaard G, et al. 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 an unknown primary (CUP) site (GEFCAPI 04). Ann Oncol. 2019;30:v851–v934.
doi: 10.1093/annonc/mdz394
Hainsworth JD, Rubin MS, Spigel DR, Boccia RV, Raby S, Quinn R, et al. Molecular gene expression profiling to predict the tissue of origin and direct site-specific therapy in patients with carcinoma of unknown primary site: a prospective trial of the Sarah Cannon research institute. J Clin Oncol. 2013;31:217–23.
doi: 10.1200/JCO.2012.43.3755
pubmed: 23032625
Moran S, Martinez-Cardus A, Sayols S, Musulen E, Balana C, Estival-Gonzalez A, et al. Epigenetic profiling to classify cancer of unknown primary: a multicentre, retrospective analysis. Lancet Oncol. 2016;17:1386–95.
doi: 10.1016/S1470-2045(16)30297-2
pubmed: 27575023
Fusco MJ, Knepper TC, Balliu J, Del Cueto A, Laborde JM, Hooda SM, et al. Evaluation of targeted next-generation sequencing for the management of patients diagnosed with a cancer of unknown primary. Oncologist. 2022;27:e9–e17.
doi: 10.1093/oncolo/oyab014
pubmed: 35305098
pmcid: 8842368
Pauli C, Bochtler T, Mileshkin L, Baciarello G, Losa F, Ross JS, et al. A Challenging Task: Identifying Patients with Cancer of Unknown Primary (CUP) According to ESMO Guidelines: The CUPISCO Trial Experience. Oncologist. 2021;26:e769–e79.
doi: 10.1002/onco.13744
pubmed: 33687747
pmcid: 8100559
Mileshkin L, Bochtler T, Gatta G, Kurzrock R, Beringer A, Muller-Ohldach M, et al. Cancer-of-Unknown-Primary-Origin: A SEER-Medicare Study of Patterns of Care and Outcomes among Elderly Patients in Clinical Practice. Cancers (Basel). 2022;14:2905.
doi: 10.3390/cancers14122905
pubmed: 35740574
Vajdic CM, Er CC, Schaffer A, Dobbins T, Wyld L, Meagher NS, et al. An audit of cancer of unknown primary notifications: a cautionary tale for population health research using cancer registry data. Cancer Epidemiol. 2014;38:460–4.
doi: 10.1016/j.canep.2014.05.004
pubmed: 24929356