“Metastatic Cancer of Unknown Primary” or “Primary Metastatic Cancer”?
Cancer of unknown primary (CUP) is an umbrella term used to classify a heterogeneous group of metastatic cancers based on the absence of an identifiable primary tumor. Clinically, CUPs are characterized by a set of distinct features comprising early metastatic dissemination in an atypical pattern, a...
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doaj-b62d7f192cd64462bad37f49f7d0542c2020-11-25T01:30:11ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2020-01-01910.3389/fonc.2019.01546509161“Metastatic Cancer of Unknown Primary” or “Primary Metastatic Cancer”?Stefan Kolling0Ferdinando Ventre1Elena Geuna2Melissa Milan3Alberto Pisacane4Carla Boccaccio5Carla Boccaccio6Anna Sapino7Anna Sapino8Filippo Montemurro9Department of Investigative Clinical Oncology, Candiolo Cancer Institute, FPO-IRCCS, Candiolo, ItalyDepartment of Investigative Clinical Oncology, Candiolo Cancer Institute, FPO-IRCCS, Candiolo, ItalyMultidisciplinary Oncology Outpatient Clinic, Candiolo Cancer Institute, FPO-IRCCS, Candiolo, ItalyLaboratory of Exploratory Research and Molecular Cancer Therapy, Candiolo Cancer Institute, FPO-IRCCS, Candiolo, ItalyUnit of Pathology, Candiolo Cancer Institute, FPO- IRCCS, Candiolo, ItalyLaboratory of Cancer Stem Cell Research, Candiolo Cancer Institute, FPO-IRCCS, Candiolo, ItalyDepartment of Oncology, University of Turin Medical School, Candiolo, ItalyUnit of Pathology, Candiolo Cancer Institute, FPO- IRCCS, Candiolo, ItalyDepartment of Medical Sciences, University of Turin, Turin, ItalyMultidisciplinary Oncology Outpatient Clinic, Candiolo Cancer Institute, FPO-IRCCS, Candiolo, ItalyCancer of unknown primary (CUP) is an umbrella term used to classify a heterogeneous group of metastatic cancers based on the absence of an identifiable primary tumor. Clinically, CUPs are characterized by a set of distinct features comprising early metastatic dissemination in an atypical pattern, an aggressive clinical course, poor response to empiric chemotherapy and, consequently, a short life expectancy. Two opposing strategies to change the dismal prognosis for the better are pursued. On the one hand, following the traditional tissue-gnostic approach, more and more sophisticated tissue-of-origin (TOO) classifier assays are employed to push identification of the putative primary to its limits with the clear intent of allowing tumor-site specific treatment. However, robust evidence supporting its routine clinical use is still lacking, notably with two recent randomized clinical trials failing to show a patient benefit of TOO-prediction based site-specific treatment over empiric chemotherapy in CUP. On the other hand, with regards to a tissue-agnostic strategy, precision medicine approaches targeting actionable genomic alterations have already transformed the treatment for many known tumor types. Yet, an unmet need remains for well-designed clinical trials to scrutinize its potential role in CUP beyond anecdotal case reports. In the absence of practice changing results, we believe that the emphasis on finding the presumed unknown primary tumor at all costs, implicit in the term CUP, has biased recent research in the field. Focusing on the distinct clinical features shared by all CUPs, we advocate adopting the term primary metastatic cancer (PMC) to denominate a distinct cancer entity instead. In our view, PMC should be considered the archetype of metastatic disease and as such, despite accounting for a mere 2–3% of malignancies, unraveling the mechanisms at play goes beyond improving the prognosis of patients with PMC and promises to greatly enhance our understanding of the metastatic process and carcinogenesis across all cancer types.https://www.frontiersin.org/article/10.3389/fonc.2019.01546/fullcancer of unknown primary (CUP)primary metastatic cancermetastasisnext generation sequencingtissue of origintargeted therapy |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Stefan Kolling Ferdinando Ventre Elena Geuna Melissa Milan Alberto Pisacane Carla Boccaccio Carla Boccaccio Anna Sapino Anna Sapino Filippo Montemurro |
spellingShingle |
Stefan Kolling Ferdinando Ventre Elena Geuna Melissa Milan Alberto Pisacane Carla Boccaccio Carla Boccaccio Anna Sapino Anna Sapino Filippo Montemurro “Metastatic Cancer of Unknown Primary” or “Primary Metastatic Cancer”? Frontiers in Oncology cancer of unknown primary (CUP) primary metastatic cancer metastasis next generation sequencing tissue of origin targeted therapy |
author_facet |
Stefan Kolling Ferdinando Ventre Elena Geuna Melissa Milan Alberto Pisacane Carla Boccaccio Carla Boccaccio Anna Sapino Anna Sapino Filippo Montemurro |
author_sort |
Stefan Kolling |
title |
“Metastatic Cancer of Unknown Primary” or “Primary Metastatic Cancer”? |
title_short |
“Metastatic Cancer of Unknown Primary” or “Primary Metastatic Cancer”? |
title_full |
“Metastatic Cancer of Unknown Primary” or “Primary Metastatic Cancer”? |
title_fullStr |
“Metastatic Cancer of Unknown Primary” or “Primary Metastatic Cancer”? |
title_full_unstemmed |
“Metastatic Cancer of Unknown Primary” or “Primary Metastatic Cancer”? |
title_sort |
“metastatic cancer of unknown primary” or “primary metastatic cancer”? |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Oncology |
issn |
2234-943X |
publishDate |
2020-01-01 |
description |
Cancer of unknown primary (CUP) is an umbrella term used to classify a heterogeneous group of metastatic cancers based on the absence of an identifiable primary tumor. Clinically, CUPs are characterized by a set of distinct features comprising early metastatic dissemination in an atypical pattern, an aggressive clinical course, poor response to empiric chemotherapy and, consequently, a short life expectancy. Two opposing strategies to change the dismal prognosis for the better are pursued. On the one hand, following the traditional tissue-gnostic approach, more and more sophisticated tissue-of-origin (TOO) classifier assays are employed to push identification of the putative primary to its limits with the clear intent of allowing tumor-site specific treatment. However, robust evidence supporting its routine clinical use is still lacking, notably with two recent randomized clinical trials failing to show a patient benefit of TOO-prediction based site-specific treatment over empiric chemotherapy in CUP. On the other hand, with regards to a tissue-agnostic strategy, precision medicine approaches targeting actionable genomic alterations have already transformed the treatment for many known tumor types. Yet, an unmet need remains for well-designed clinical trials to scrutinize its potential role in CUP beyond anecdotal case reports. In the absence of practice changing results, we believe that the emphasis on finding the presumed unknown primary tumor at all costs, implicit in the term CUP, has biased recent research in the field. Focusing on the distinct clinical features shared by all CUPs, we advocate adopting the term primary metastatic cancer (PMC) to denominate a distinct cancer entity instead. In our view, PMC should be considered the archetype of metastatic disease and as such, despite accounting for a mere 2–3% of malignancies, unraveling the mechanisms at play goes beyond improving the prognosis of patients with PMC and promises to greatly enhance our understanding of the metastatic process and carcinogenesis across all cancer types. |
topic |
cancer of unknown primary (CUP) primary metastatic cancer metastasis next generation sequencing tissue of origin targeted therapy |
url |
https://www.frontiersin.org/article/10.3389/fonc.2019.01546/full |
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