Cancer of unknown primary: recent advancements in the diagnosis and treatment

Ting ZHAO; Xiaowei ZHANG; Xin LIU; Qifeng WANG; Xichun HU; Zhiguo LUO

doi:10.19401/j.cnki.1007-3639.2024.12.008

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Cancer of unknown primary: recent advancements in the diagnosis and treatment

Review | 更新时间：2025-12-31

- Cancer of unknown primary: recent advancements in the diagnosis and treatment
- China Oncology Vol. 34, Issue 12, Pages: 1134-1143(2024)
- 作者机构：
  
  1. 复旦大学附属肿瘤医院肿瘤内科，复旦大学上海医学院肿瘤学系，上海 200032
  2. 复旦大学附属肿瘤医院病理科，复旦大学上海医学院肿瘤学系，上海 200032
- 作者简介：
  
  LUO Zhiguo
- 基金信息：
- DOI：10.19401/j.cnki.1007-3639.2024.12.008
  CLC：
- Received：18 September 2024，
  
  Published：30 December 2024
- 稿件说明：
移动端阅览
Ting ZHAO, Xiaowei ZHANG, Xin LIU, et al. Cancer of unknown primary: recent advancements in the diagnosis and treatment[J]. China Oncology, 2024, 34(12): 1134-1143.
DOI：

Ting ZHAO, Xiaowei ZHANG, Xin LIU, et al. Cancer of unknown primary: recent advancements in the diagnosis and treatment[J]. China Oncology, 2024, 34(12): 1134-1143. DOI： 10.19401/j.cnki.1007-3639.2024.12.008.

摘要

原发灶不明肿瘤（cancer of unknown primary，CUP）是一类经组织病理学确认为转移，但经系统性检查仍然无法明确原发灶的转移性肿瘤的统称，约占全球所有癌症新发病例的3%~5%，其总生存期（overall survival，OS）仅2.7~16.0个月。CUP因原发灶的隐匿性及异质性导致其诊断成为长期困扰临床医师的关键问题，也是CUP精准治疗最大的阻碍。在诊断方面，在免疫组织化学时代，两轮标志物的诊断可以让大约70%的CUP明确原发灶，然而，免疫组织化学对于原发不明未分化癌的诊断价值极其有限，且结果易受实验因素及人为因素干扰。近年来，随着肿瘤诊断进入分子检测时代，基于细胞学、组织学、基因表达谱（gene expression profiling，GEP）、基因组及表观基因组分析等技术已经能够准确地检出90%的原发灶。目前，国内可帮基因公司研发的90基因肿瘤组织起源检测已被证实诊断CUP原发灶的准确率高达94.4%，为CUP的精准治疗奠定了基础。在治疗方面，CUP既往的治疗是采用铂类药物和紫杉类药物的经验性化疗方案，患者的生存及预后并没有得到显著改善。自2008年以来，全球范围内陆续开展了分子检测指导的CUP器官特异性治疗的临床研究，但因研究设计缺陷以及结果争议等问题，尚未在国际范围内达成共识。器官特异性治疗相较于经验性化疗可改善患者的无进展生存期（progression-free survival，PFS）和OS。有鉴于此，2017年，复旦大学附属肿瘤医院多原发与不明原发肿瘤诊治中心开展了全球首个Ⅲ期临床研究，结果证实，90基因检测指导的器官特异性治疗可显著地改善患者的PFS，且OS有获益的趋势，两组患者在不良反应方面的差异无统计学意义，由此奠定了器官特异性治疗在CUP一线治疗中的地位。本文综述CUP的流行病学、发病机制、临床特征及CUP诊断从免疫组织化学时代到分子检测时代的进步，也将介绍CUP治疗从经验性化疗到分子检测指导的器官特异性治疗的进展。此外，本文详述二线治疗方案的探索以及临床分层管理模式的建立是未来CUP研究领域的两个重要方向。本综述旨在总结CUP诊断与治疗的进展，进一步明确CUP的研究方向，以最大程度地改善CUP患者的生存及预后。

Abstract

Cancer of unknown primary (CUP) refers to a group of histopathologically confirmed malignancies that cannot be identified in terms of their primary origin despite thorough investigations. CUP accounts for approximately 3%-5% of all newly diagnosed cancers worldwide

with an overall survival (OS) ranging from 2.7 to 16.0 months. CUP has long been a significant scientific challenge due to the elusive nature and heterogeneity of the primary sites. In the era of immunohistochemistry (IHC)

IHC has been applied to identify the primary site in approximately 70% of CUP cases. However

IHC also has limitations for undifferentiated cancers of unknown primary

and results can be influenced by experimental and human factors. In recent years

with the development of molecular tumor profiling (MTP)

techniques such as cytology

histology

gene expression profiling (GEP)

genomics and epigenomics have been able to accurately detect the primary site in 90% of cases. Currently

the 90-gene tumor tissue origin test has been proven to have an accuracy rate of 94.4% in diagnosing the primary site of CUP

laying the foundation for precision treatment. In the past

platinum and taxane-based empirical chemotherapy was commonly used for treating CUP. However

these treatments did not yield significant improvements in patient survival and prognosis. Since 2008

there has been a global emergence of clinical studies on MTP-guided first-line therapy for CUP. However

due to study design flaws and result controversies

there is no international consensus on the superiority of organ-specific treatment over empirical chemotherapy in terms of improving progression-free survival (PFS) and OS for CUP. Based on this

our center conducted the world's first phase Ⅲ clinical trial in 2017

and demonstrated improved PFS and favorable OS by GEP-guided site-specific therapy of CUP

which established the primacy of site-specific first-line therapy for CUP. In this review

we detailed the epidemiology

pathogenesis

clinical characteristics and the progression of CUP diagnosis from the era of IHC to MTP. Furthermore

we reviewed the advancements in CUP treatment from empirical chemotherapy to MTP-guided organ-specific treatment. Additionally

this review delved into the exploration of second-line treatment options and the establishment of a clinical stratified management model

which are two topics in future research of CUP. This review aimed to summarize the progress in the diagnosis and treatment of CUP

further explore future research directions for CUP

and improve the survival and prognosis of patients with CUP.

关键词

Keywords

references

MOON I , LOPICCOLO J , BACA S C , et al . Machine learning for genetics-based classification and treatment response prediction in cancer of unknown primary [J ] . Nat Med , 2023 , 29 ( 8 ): 2057 - 2067 . DOI: 10.1038/s41591-023-02482-6 http://doi.org/10.1038/s41591-023-02482-6

LEE M S , SANOFF H K . Cancer of unknown primary [J ] . BMJ , 2020 , 371 : m4050 .

RASSY E , PAVLIDIS N . Progress in refining the clinical management of cancer of unknown primary in the molecular era [J ] . Nat Rev Clin Oncol , 2020 , 17 ( 9 ): 541 - 554 . DOI: 10.1038/s41571-020-0359-1 http://doi.org/10.1038/s41571-020-0359-1

DUM D , MENZ A , VÖLKEL C , et al . Cytokeratin 7 and cytokeratin 20 expression in cancer: a tissue microarray study on 15 424 cancers [J ] . Exp Mol Pathol , 2022 , 126 : 104762 .

GRECO F A , LENNINGTON W J , SPIGEL D R , et al . Molecular profiling diagnosis in unknown primary cancer: accuracy and ability to complement standard pathology [J ] . J Natl Cancer Inst , 2013 , 105 ( 11 ): 782 - 790 . DOI: 10.1093/jnci/djt099 http://doi.org/10.1093/jnci/djt099

HANDORF C R , KULKARNI A , GRENERT J P , et al . A multicenter study directly comparing the diagnostic accuracy of gene expression profiling and immunohistochemistry for primary site identification in metastatic tumors [J ] . Am J Surg Pathol , 2013 , 37 ( 7 ): 1067 - 1075 . DOI: 10.1097/PAS.0b013e31828309c4 http://doi.org/10.1097/PAS.0b013e31828309c4

YE Q , WANG Q F , QI P , et al . Development and clinical validation of a 90-gene expression assay for identifying tumor tissue origin [J ] . J Mol Diagn , 2020 , 22 ( 9 ): 1139 - 1150 . DOI: S1525-1578(20)30368-8 http://doi.org/S1525-1578(20)30368-8

LU M Y , CHEN T Y , WILLIAMSON D F K , et al . AI-based pathology predicts origins for cancers of unknown primary [J ] . Nature , 2021 , 594 ( 7861 ): 106 - 110 .

NGUYEN L , VAN HOECK A , CUPPEN E . Machine learning-based tissue of origin classification for cancer of unknown primary diagnostics using genome-wide mutation features [J ] . Nat Commun , 2022 , 13 ( 1 ): 4013 . DOI: 10.1038/s41467-022-31666-w http://doi.org/10.1038/s41467-022-31666-w

TIAN F , LIU D , WEI N , et al . Prediction of tumor origin in cancers of unknown primary origin with cytology-based deep learning [J ] . Nat Med , 2024 , 30 ( 5 ): 1309 - 1319 . DOI: 10.1038/s41591-024-02915-w http://doi.org/10.1038/s41591-024-02915-w

ZHANG S R , HE S T , ZHU X , et al . DNA methylation profiling to determine the primary sites of metastatic cancers using formalin-fixed paraffin-embedded tissues [J ] . Nat Commun , 2023 , 14 ( 1 ): 5686 . DOI: 10.1038/s41467-023-41015-0 http://doi.org/10.1038/s41467-023-41015-0

HAINSWORTH J D , RUBIN M S , SPIGEL D 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 ] . J Clin Oncol , 2013 , 31 ( 2 ): 217 - 223 . DOI: 10.1200/JCO.2012.43.3755 http://doi.org/10.1200/JCO.2012.43.3755

HAYASHI H , KURATA T , TAKIGUCHI Y , 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 ] . J Clin Oncol , 2019 , 37 ( 7 ): 570 - 579 .

HAYASHI H , TAKIGUCHI Y , MINAMI H , et al . Site-specific and targeted therapy based on molecular profiling by next-generation sequencing for cancer of unknown primary site: a nonrandomized phase 2 clinical trial [J ] . JAMA Oncol , 2020 , 6 ( 12 ): 1931 - 1938 . DOI: 10.1001/jamaoncol.2020.4643 http://doi.org/10.1001/jamaoncol.2020.4643

FUSCO M J , KNEPPER T C , BALLIU J , et al . Evaluation of targeted next-generation sequencing for the management of patients diagnosed with a cancer of unknown primary [J ] . Oncologist , 2022 , 27 ( 1 ): e9 - e17 . DOI: 10.1093/oncolo/oyab014 http://doi.org/10.1093/oncolo/oyab014

LIU X , ZHANG X W , JIANG S Y , et al . Site-specific therapy guided by a 90-gene expression assay versus empirical chemotherapy in patients with cancer of unknown primary (Fudan CUP-001): a randomised controlled trial [J ] . Lancet Oncol , 2024 , 25 ( 8 ): 1092 - 1102 .

URBAN D , RAO A , BRESSEL M , et al . Cancer of unknown primary: a population-based analysis of temporal change and socioeconomic disparities [J ] . Br J Cancer , 2013 , 109 ( 5 ): 1318 - 1324 .

BREWSTER D H , LANG J , BHATTI L A , et al . Descriptive epidemiology of cancer of unknown primary site in Scotland, 1961-2010 [J ] . Cancer Epidemiol , 2014 , 38 ( 3 ): 227 - 234 . DOI: 10.1016/j.canep.2014.03.010 http://doi.org/10.1016/j.canep.2014.03.010

RANDÉN M , RUTQVIST L E , JOHANSSON H . Cancer patients without a known primary: incidence and survival trends in Sweden 1960-2007 [J ] . Acta Oncol , 2009 , 48 ( 6 ): 915 - 920 . DOI: 10.1080/02841860902862503 http://doi.org/10.1080/02841860902862503

BINDER C , MATTHES K L , KOROL D , et al . Cancer of unknown primary-epidemiological trends and relevance of comprehensive genomic profiling [J ] . Cancer Med , 2018 , 7 ( 9 ): 4814 - 4824 .

MNATSAKANYAN E , TUNG W C , CAINE B , et al . Cancer of unknown primary: time trends in incidence, United States [J ] . Cancer Causes Control , 2014 , 25 ( 6 ): 747 - 757 .

QI P , SUN Y F , LIU X , et al . Clinicopathological, molecular and prognostic characteristics of cancer of unknown primary in China: an analysis of 1 420 cases [J ] . Cancer Med , 2023 , 12 ( 2 ): 1177 - 1188 .

RASSY E , PAVLIDIS N . The currently declining incidence of cancer of unknown primary [J ] . Cancer Epidemiol , 2019 , 61 : 139 - 141 . DOI: S1877-7821(19)30056-6 http://doi.org/S1877-7821(19)30056-6

LÓPEZ-LÁZARO M . The migration ability of stem cells can explain the existence of cancer of unknown primary site. Rethinking metastasis [J ] . Oncoscience , 2015 , 2 ( 5 ): 467 - 475 .

OLIVIER T , FERNANDEZ E , LABIDI-GALY I , et al . Redefining cancer of unknown primary: is precision medicine really shifting the paradigm? [J ] . Cancer Treat Rev , 2021 , 97 : 102204 .

RASSY E , ASSI T , PAVLIDIS N . Exploring the biological hallmarks of cancer of unknown primary: where do we stand today? [J ] . Br J Cancer , 2020 , 122 ( 8 ): 1124 - 1132 .

JOOSSE S A , PANTEL K . Genetic traits for hematogeneous tumor cell dissemination in cancer patients [J ] . Cancer Metastasis Rev , 2016 , 35 ( 1 ): 41 - 48 .

KOLLING S , VENTRE F , GEUNA E , et al . “Metastatic cancer of unknown primary” or “primary metastatic cancer”? [J ] . Front Oncol , 2019 , 9 : 1546 .

SUN W , WU W , WANG Q F , et al . Clinical validation of a 90-gene expression test for tumor tissue of origin diagnosis: a large-scale multicenter study of 1 417 patients [J ] . J Transl Med , 2022 , 20 ( 1 ): 114 .

LAPROVITERA N , RIEFOLO M , AMBROSINI E , et al . Cancer of unknown primary: challenges and progress in clinical management [J ] . Cancers , 2021 , 13 ( 3 ): 451 .

HEMMINKI K , BEVIER M , HEMMINKI A , et al . Survival in cancer of unknown primary site: population-based analysis by site and histology [J ] . Ann Oncol , 2012 , 23 ( 7 ): 1854 - 1863 . DOI: 10.1093/annonc/mdr536 http://doi.org/10.1093/annonc/mdr536

ROSS J S , WANG K , GAY L , et al . Comprehensive genomic profiling of carcinoma of unknown primary site: new routes to targeted therapies [J ] . JAMA Oncol , 2015 , 1 ( 1 ): 40 - 49 . DOI: 10.1001/jamaoncol.2014.216 http://doi.org/10.1001/jamaoncol.2014.216

ROSS J S , SOKOL E S , MOCH H , et al . Comprehensive genomic profiling of carcinoma of unknown primary origin: retrospective molecular classification considering the CUPISCO study design [J ] . Oncologist , 2021 , 26 ( 3 ): e394 - e402 . DOI: 10.1002/onco.13597 http://doi.org/10.1002/onco.13597

VARGHESE A M , ARORA A , CAPANU M , et al . Clinical and molecular characterization of patients with cancer of unknown primary in the modern era [J ] . Ann Oncol , 2017 , 28 ( 12 ): 3015 - 3021 . DOI: 10.1093/annonc/mdx545 http://doi.org/10.1093/annonc/mdx545

MÖHRMANN L , WERNER M , OLEŚ M , et al . Comprehensive genomic and epigenomic analysis in cancer of unknown primary guides molecularly-informed therapies despite heterogeneity [J ] . Nat Commun , 2022 , 13 ( 1 ): 4485 . DOI: 10.1038/s41467-022-31866-4 http://doi.org/10.1038/s41467-022-31866-4

KIM H M , KOO J S . Programmed death-ligand 1 expression in carcinoma of unknown primary [J ] . BMC Cancer , 2024 , 24 ( 1 ): 689 . DOI: 10.1186/s12885-024-12437-w http://doi.org/10.1186/s12885-024-12437-w

POSNER A , SIVAKUMARAN T , PATTISON A , et al . Immune and genomic biomarkers of immunotherapy response in cancer of unknown primary [J ] . J Immunother Cancer , 2023 , 11 ( 1 ): e005809 .

MORAN S , MARTÍNEZ-CARDÚS A , SAYOLS S , et al . Epigenetic profiling to classify cancer of unknown primary: a multicentre, retrospective analysis [J ] . Lancet Oncol , 2016 , 17 ( 10 ): 1386 - 1395 . DOI: S1470-2045(16)30297-2 http://doi.org/S1470-2045(16)30297-2

BRIASOULIS E , TSOKOS M , FOUNTZILAS G , et al . Bcl2 and p53 protein expression in metastatic carcinoma of unknown primary origin: biological and clinical implications. A Hellenic Co-operative Oncology Group study [J ] . Anticancer Res , 1998 , 18 ( 3B ): 1907 - 1914 .

GALLOWAY T J , RIDGE J A . Management of squamous cancer metastatic to cervical nodes with an unknown primary site [J ] . J Clin Oncol , 2015 , 33 ( 29 ): 3328 - 3337 . DOI: 10.1200/JCO.2015.61.0063 http://doi.org/10.1200/JCO.2015.61.0063

SHAO Y L , LIU X , HU S L , et al . Sentinel node theory helps tracking of primary lesions of cancers of unknown primary [J ] . BMC Cancer , 2020 , 20 ( 1 ): 639 . DOI: 10.1186/s12885-020-07042-6 http://doi.org/10.1186/s12885-020-07042-6

CLAPS G , FAOUZI S , QUIDVILLE V , et al . The multiple roles of LDH in cancer [J ] . Nat Rev Clin Oncol , 2022 , 19 ( 12 ): 749 - 762 . DOI: 10.1038/s41571-022-00686-2 http://doi.org/10.1038/s41571-022-00686-2

NIKOLOVA P N , HADZHIYSKA V H , MLADENOV K B , et al . The impact of 18 F-FDG PET/CT in the clinical management of patients with lymph node metastasis of unknown primary origin [J ] . Neoplasma , 2021 , 68 ( 1 ): 180 - 189 .

ZAUN G , WEBER M , METZENMACHER M , et al . SUVmax above 20 in 18 F-FDG PET/CT at initial diagnostic workup associates with favorable survival in patients with cancer of unknown primary [J ] . J Nucl Med , 2023 , 64 ( 8 ): 1191 - 1194 .

RUSTHOVEN K E , KOSHY M , PAULINO A C . The role of fluorodeoxyglucose positron emission tomography in cervical lymph node metastases from an unknown primary tumor [J ] . Cancer , 2004 , 101 ( 11 ): 2641 - 2649 . DOI: 10.1002/cncr.20687 http://doi.org/10.1002/cncr.20687

EILSBERGER F , NOLTENIUS F E , LIBRIZZI D , et al . Real-life performance of F-18-FDG PET/CT in patients with cervical lymph node metastasis of unknown primary tumor [J ] . Biomedicines , 2022 , 10 ( 9 ): 2095 .

GU B X , XU X P , ZHANG J , et al . The added value of 68 Ga-FAPI PET/CT in patients with head and neck cancer of unknown primary with 18 F-FDG-negative findings [J ] . J Nucl Med , 2022 , 63 ( 6 ): 875 - 881 .

ROSSI G , NANNINI N , COSTANTINI M . Morphology and more specific immunohistochemical stains are fundamental prerequisites in detection of unknown primary cancer [J ] . J Clin Oncol , 2009 , 27 ( 4 ): 649 - 650 . DOI: 10.1200/JCO.2008.20.3604 http://doi.org/10.1200/JCO.2008.20.3604

DERMAWAN J K , RUBIN B P . The role of molecular profiling in the diagnosis and management of metastatic undifferentiated cancer of unknown primary molecular profiling of metastatic cancer of unknown primary [J ] . Semin Diagn Pathol , 2021 , 38 ( 6 ): 193 - 198 .

VARADHACHARY G R , TALANTOV D , RABER M N , et al . Molecular profiling of carcinoma of unknown primary and correlation with clinical evaluation [J ] . J Clin Oncol , 2008 , 26 ( 27 ): 4442 - 4448 . DOI: 10.1200/JCO.2007.14.4378 http://doi.org/10.1200/JCO.2007.14.4378

VAN LAAR R K , MA X J , DE JONG D , et al . Implementation of a novel microarray-based diagnostic test for cancer of unknown primary [J ] . Int J Cancer , 2009 , 125 ( 6 ): 1390 - 1397 . DOI: 10.1002/ijc.24504 http://doi.org/10.1002/ijc.24504

PILLAI R , DEETER R , RIGL C T , et al . Validation and reproducibility of a microarray-based gene expression test for tumor identification in formalin-fixed, paraffin-embedded specimens [J ] . J Mol Diagn , 2011 , 13 ( 1 ): 48 - 56 . DOI: 10.1016/j.jmoldx.2010.11.001 http://doi.org/10.1016/j.jmoldx.2010.11.001

MONZON F A , MEDEIROS F , LYONS-WEILER M , et al . Identification of tissue of origin in carcinoma of unknown primary with a microarray-based gene expression test [J ] . Diagn Pathol , 2010 , 5 : 3 . DOI: 10.1186/1746-1596-5-3 http://doi.org/10.1186/1746-1596-5-3

HAINSWORTH J D , SCHNABEL C A , ERLANDER M G , et al . A retrospective study of treatment outcomes in patients with carcinoma of unknown primary site and a colorectal cancer molecular profile [J ] . Clin Colorectal Cancer , 2012 , 11 ( 2 ): 112 - 118 .

FERRACIN M , PEDRIALI M , VERONESE A , et al . MicroRNA profiling for the identification of cancers with unknown primary tissue-of-origin [J ] . J Pathol , 2011 , 225 ( 1 ): 43 - 53 .

VARADHACHARY G R , SPECTOR Y , ABBRUZZESE J L , et al . Prospective gene signature study using microRNA to identify the tissue of origin in patients with carcinoma of unknown primary [J ] . Clin Cancer Res , 2011 , 17 ( 12 ): 4063 - 4070 . DOI: 10.1158/1078-0432.CCR-10-2599 http://doi.org/10.1158/1078-0432.CCR-10-2599

LAPROVITERA N , RIEFOLO M , PORCELLINI E , et al . MicroRNA expression profiling with a droplet digital PCR assay enables molecular diagnosis and prognosis of cancers of unknown primary [J ] . Mol Oncol , 2021 , 15 ( 10 ): 2732 - 2751 .

SANDEN M O , WASSMAN R , ASHKENAZI K , et al . Observational study of real world clinical performance of microrna molecular profiling for cancer of unknown primary (CUP) [J ] . J Clin Oncol , 2013 , 31 ( 15_suppl ): e22173 .

POSNER A , PRALL O W , SIVAKUMARAN T , et al . A comparison of DNA sequencing and gene expression profiling to assist tissue of origin diagnosis in cancer of unknown primary [J ] . J Pathol , 2023 , 259 ( 1 ): 81 - 92 .

STACKPOLE M L , ZENG W H , LI S , et al . Cost-effective methylome sequencing of cell-free DNA for accurately detecting and locating cancer [J ] . Nat Commun , 2022 , 13 ( 1 ): 5566 . DOI: 10.1038/s41467-022-32995-6 http://doi.org/10.1038/s41467-022-32995-6

ZHAO Y , PAN Z W , NAMBURI S , et al . CUP-AI-Dx: a tool for inferring cancer tissue of origin and molecular subtype using RNA gene-expression data and artificial intelligence [J ] . EBioMedicine , 2020 , 61 : 103030 .

SHEN Y F , CHU Q J , YIN X X , et al . TOD-CUP: a gene expression rank-based majority vote algorithm for tissue origin diagnosis of cancers of unknown primary [J ] . Brief Bioinform , 2021 , 22 ( 2 ): 2106 - 2118 . DOI: 10.1093/bib/bbaa031 http://doi.org/10.1093/bib/bbaa031

CONWAY A M , PEARCE S P , CLIPSON A , et al . A cfDNA methylation-based tissue-of-origin classifier for cancers of unknown primary [J ] . Nat Commun , 2024 , 15 ( 1 ): 3292 .

MASSARD C , LORIOT Y , FIZAZI K . Carcinomas of an unknown primary origin: Diagnosis and treatment [J ] . Nat Rev Clin Oncol , 2011 , 8 ( 12 ): 701 - 710 .

MARTIN M , VILLAR A , SOLE-CALVO A , et al . Doxorubicin in combination with fluorouracil and cyclophosphamide (i.v. FAC regimen, day 1, 21) versus methotrexate in combination with fluorouracil and cyclophosphamide (i.v. CMF regimen, day 1, 21) as adjuvant chemotherapy for operable breast cancer: a study by the GEICAM group [J ] . Ann Oncol , 2003 , 14 ( 6 ): 833 - 842 .

SCHUETTE K , FOLPRECHT G , KRETZSCHMAR A , et al . Phase Ⅱ trial of capecitabine and oxaliplatin in patients with adeno- and undifferentiated carcinoma of unknown primary [J ] . Onkologie , 2009 , 32 ( 4 ): 162 - 166 .

HAINSWORTH J D , SPIGEL D R , BURRIS H A 3rd , et al . Oxaliplatin and capecitabine in the treatment of patients with recurrent or refractory carcinoma of unknown primary site: a phase 2 trial of the Sarah Cannon Oncology Research Consortium [J ] . Cancer , 2010 , 116 ( 10 ): 2448 - 2454 . DOI: 10.1002/cncr.25029 http://doi.org/10.1002/cncr.25029

SHIN D Y , CHOI Y H , LEE H R , et al . A phase Ⅱ trial of modified FOLFOX6 as first-line therapy for adenocarcinoma of an unknown primary site [J ] . Cancer Chemother Pharmacol , 2016 , 77 ( 1 ): 163 - 168 .

BRIASOULIS E , KALOFONOS H , BAFALOUKOS D , et al . Carboplatin plus paclitaxel in unknown primary carcinoma: a phase Ⅱ Hellenic Cooperative Oncology Group Study [J ] . J Clin Oncol , 2000 , 18 ( 17 ): 3101 - 3107 .

GRECO F A , ERLAND J B , MORRISSEY L H , et al . Carcinoma of unknown primary site: phase Ⅱ trials with docetaxel plus cisplatin or carboplatin [J ] . Ann Oncol , 2000 , 11 ( 2 ): 211 - 215 .

EL-RAYES B F , SHIELDS A F , ZALUPSKI M , et al . A phase Ⅱ study of carboplatin and paclitaxel in adenocarcinoma of unknown primary [J ] . Am J Clin Oncol , 2005 , 28 ( 2 ): 152 - 156 .

PARK Y H , RYOO B Y , CHOI S J , et al . A phase Ⅱ study of paclitaxel plus cisplatin chemotherapy in an unfavourable group of patients with cancer of unknown primary site [J ] . Jpn J Clin Oncol , 2004 , 34 ( 11 ): 681 - 685 .

HUEBNER G , LINK H , KOHNE C H , et al . Paclitaxel and carboplatin vs gemcitabine and vinorelbine in patients with adeno- or undifferentiated carcinoma of unknown primary: a randomised prospective phase Ⅱ trial [J ] . Br J Cancer , 2009 , 100 ( 1 ): 44 - 49 .

HASEGAWA H , ANDO M , YATABE Y , et al . Site-specific chemotherapy based on predicted primary site by pathological profile for carcinoma of unknown primary site [J ] . Clin Oncol (R Coll Radiol) , 2018 , 30 ( 10 ): 667 - 673 . DOI: S0936-6555(18)30309-1 http://doi.org/S0936-6555(18)30309-1

TANIZAKI J , YONEMORI K , AKIYOSHI K , et al . Open-label phase Ⅱ study of the efficacy of nivolumab for cancer of unknown primary [J ] . Ann Oncol , 2022 , 33 ( 2 ): 216 - 226 .

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Society of Cancer of Multiple and Unknown Primary of China Anti-Cancer Association Yuguang

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Department of Medical Oncology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University

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