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Does Cancer of Unknown Primary (CUP) Truly Exist as a Distinct Cancer Entity?
Cancer of unknown primary (CUP) designates an enigmatic cancer entity with histologic confirmation of malignancy from a metastasis but no identifiable primary tumor in spite of a thorough diagnostic work-up. In this review, we discuss the validity of CUP as a distinct cancer entity as well as diagno...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2019
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6534107/ https://www.ncbi.nlm.nih.gov/pubmed/31165045 http://dx.doi.org/10.3389/fonc.2019.00402 |
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author | Bochtler, Tilmann Krämer, Alwin |
author_facet | Bochtler, Tilmann Krämer, Alwin |
author_sort | Bochtler, Tilmann |
collection | PubMed |
description | Cancer of unknown primary (CUP) designates an enigmatic cancer entity with histologic confirmation of malignancy from a metastasis but no identifiable primary tumor in spite of a thorough diagnostic work-up. In this review, we discuss the validity of CUP as a distinct cancer entity as well as diagnostic pitfalls. As arguments against a distinct entity, the diagnosis of CUP is erroneous in some cases. Diagnostic pitfalls include incomplete diagnostics, uncertainty in classifying a lesion as either primary or metastasis and mistaking a relapse of an antecedent malignancy as CUP due to histologic and immunohistologic disparities. Given the high frequency of prior malignancies in CUP patients, relapse of an antecedent cancer should always be carefully excluded. Gene expression profiling-based classifier assays aim at aligning the molecular profile of CUP patients with established primary cancer patterns for highest congruency in order to identify the putative primary and treat accordingly. However, the spectrum of predicted putative primaries by molecular techniques is somewhat at odds with the primaries identified in autopsy series. Also, a first randomized clinical trial did not show superiority of primary-tailored therapy over unspecific platinum-based chemotherapy. CUP cases share an aggressive clinical course, atypical metastasis pattern, rapid progression of metastases, a generally poor response to chemotherapy and dismal outcome as distinct clinical features. Metastatic spread appears to take place in the early stages of tumor evolution, with CUP metastases subsequently undergoing genetic evolution toward a chromosomally highly complex and instable karyotype independent from the primary tumor. In clinical practice, the diagnosis of CUP is valid when no primary tumor is detectable. Treatment should ideally offer broad spectrum coverage across numerous malignancies and be well-established in CUP as is the case for carboplatin/paclitaxel and cisplatin / gemcitabine in particular, but it should also cover the most likely putative primary. The diligent diagnosis of CUP is warranted for clinical trials, making the eligibility process particularly laborious. In conclusion, we deem CUP a distinct cancer entity and the diagnosis accurate in most patient cases. |
format | Online Article Text |
id | pubmed-6534107 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-65341072019-06-04 Does Cancer of Unknown Primary (CUP) Truly Exist as a Distinct Cancer Entity? Bochtler, Tilmann Krämer, Alwin Front Oncol Oncology Cancer of unknown primary (CUP) designates an enigmatic cancer entity with histologic confirmation of malignancy from a metastasis but no identifiable primary tumor in spite of a thorough diagnostic work-up. In this review, we discuss the validity of CUP as a distinct cancer entity as well as diagnostic pitfalls. As arguments against a distinct entity, the diagnosis of CUP is erroneous in some cases. Diagnostic pitfalls include incomplete diagnostics, uncertainty in classifying a lesion as either primary or metastasis and mistaking a relapse of an antecedent malignancy as CUP due to histologic and immunohistologic disparities. Given the high frequency of prior malignancies in CUP patients, relapse of an antecedent cancer should always be carefully excluded. Gene expression profiling-based classifier assays aim at aligning the molecular profile of CUP patients with established primary cancer patterns for highest congruency in order to identify the putative primary and treat accordingly. However, the spectrum of predicted putative primaries by molecular techniques is somewhat at odds with the primaries identified in autopsy series. Also, a first randomized clinical trial did not show superiority of primary-tailored therapy over unspecific platinum-based chemotherapy. CUP cases share an aggressive clinical course, atypical metastasis pattern, rapid progression of metastases, a generally poor response to chemotherapy and dismal outcome as distinct clinical features. Metastatic spread appears to take place in the early stages of tumor evolution, with CUP metastases subsequently undergoing genetic evolution toward a chromosomally highly complex and instable karyotype independent from the primary tumor. In clinical practice, the diagnosis of CUP is valid when no primary tumor is detectable. Treatment should ideally offer broad spectrum coverage across numerous malignancies and be well-established in CUP as is the case for carboplatin/paclitaxel and cisplatin / gemcitabine in particular, but it should also cover the most likely putative primary. The diligent diagnosis of CUP is warranted for clinical trials, making the eligibility process particularly laborious. In conclusion, we deem CUP a distinct cancer entity and the diagnosis accurate in most patient cases. Frontiers Media S.A. 2019-05-17 /pmc/articles/PMC6534107/ /pubmed/31165045 http://dx.doi.org/10.3389/fonc.2019.00402 Text en Copyright © 2019 Bochtler and Krämer. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Oncology Bochtler, Tilmann Krämer, Alwin Does Cancer of Unknown Primary (CUP) Truly Exist as a Distinct Cancer Entity? |
title | Does Cancer of Unknown Primary (CUP) Truly Exist as a Distinct Cancer Entity? |
title_full | Does Cancer of Unknown Primary (CUP) Truly Exist as a Distinct Cancer Entity? |
title_fullStr | Does Cancer of Unknown Primary (CUP) Truly Exist as a Distinct Cancer Entity? |
title_full_unstemmed | Does Cancer of Unknown Primary (CUP) Truly Exist as a Distinct Cancer Entity? |
title_short | Does Cancer of Unknown Primary (CUP) Truly Exist as a Distinct Cancer Entity? |
title_sort | does cancer of unknown primary (cup) truly exist as a distinct cancer entity? |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6534107/ https://www.ncbi.nlm.nih.gov/pubmed/31165045 http://dx.doi.org/10.3389/fonc.2019.00402 |
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