Combining tumor deposits with the number of lymph node metastases to improve the prognostic accuracy in stage III colon cancer: a post hoc analysis of the CALGB/SWOG 80702 phase III study (Alliance)
In colon cancer, tumor deposits (TD) are considered in assigning prognosis and staging only in the absence of lymph node metastasis (i.e. stage III pN1c tumors). We aimed to evaluate the prognostic value of the presence and the number of TD in patients with stage III, node-positive colon cancer. All...
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| Veröffentlicht in: | Annals of oncology 2021-10, Vol.32 (10), p.1267-1275 |
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| creator | Cohen, R. Shi, Q. Meyers, J. Jin, Z. Svrcek, M. Fuchs, C. Couture, F. Kuebler, P. Ciombor, K.K. Bendell, J. De Jesus-Acosta, A. Kumar, P. Lewis, D. Tan, B. Bertagnolli, M.M. Philip, P. Blanke, C. O'Reilly, E.M. Shields, A. Meyerhardt, J.A. |
| description | In colon cancer, tumor deposits (TD) are considered in assigning prognosis and staging only in the absence of lymph node metastasis (i.e. stage III pN1c tumors). We aimed to evaluate the prognostic value of the presence and the number of TD in patients with stage III, node-positive colon cancer.
All participants from the CALGB/SWOG 80702 phase III trial were included in this post hoc analysis. Pathology reports were reviewed for the presence and the number of TD, lymphovascular and perineural invasion. Associations with disease-free survival (DFS) and overall survival (OS) were evaluated by multivariable Cox models adjusting for sex, treatment arm, T-stage, N-stage, lymphovascular invasion, perineural invasion and lymph node ratio.
Overall, 2028 patients were included with 524 (26%) TD-positive and 1504 (74%) TD-negative tumors. Of the TD-positive patients, 80 (15.4%) were node negative (i.e. pN1c), 239 (46.1%) were pN1a/b ( |
| doi_str_mv | 10.1016/j.annonc.2021.07.009 |
| format | Article |
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All participants from the CALGB/SWOG 80702 phase III trial were included in this post hoc analysis. Pathology reports were reviewed for the presence and the number of TD, lymphovascular and perineural invasion. Associations with disease-free survival (DFS) and overall survival (OS) were evaluated by multivariable Cox models adjusting for sex, treatment arm, T-stage, N-stage, lymphovascular invasion, perineural invasion and lymph node ratio.
Overall, 2028 patients were included with 524 (26%) TD-positive and 1504 (74%) TD-negative tumors. Of the TD-positive patients, 80 (15.4%) were node negative (i.e. pN1c), 239 (46.1%) were pN1a/b (<4 positive lymph nodes) and 200 (38.5%) were pN2 (≥4 positive lymph nodes). The presence of TD was associated with poorer DFS [adjusted hazard ratio (aHR) = 1.63, 95% CI 1.33-1.98] and OS (aHR = 1.59, 95% CI 1.24-2.04). The negative effect of TD was observed for both pN1a/b and pN2 groups. Among TD-positive patients, the number of TD had a linear negative effect on DFS and OS. Combining TD and the number of lymph node metastases, 104 of 1470 (7.1%) pN1 patients were re-staged as pN2, with worse outcomes than patients confirmed as pN1 (3-year DFS rate: 65.4% versus 80.5%, P = 0.0003; 5-year OS rate: 87.9% versus 69.1%, P = <0.0001). DFS was not different between patients re-staged as pN2 and those initially staged as pN2 (3-year DFS rate: 65.4% versus 62.3%, P = 0.4895).
Combining the number of TD and the number of lymph node metastases improved the prognostication accuracy of tumor-node-metastasis (TNM) staging.
•TD are observed in one-quarter of stage III colon cancers.•TD are associated with worse prognosis in stage III colon cancer, regardless of the lymph node substage.•TD should be considered as a quantitative parameter since their number has a prognostic impact.•Adding the number of TD to the count of lymph node metastases improves the prognostication accuracy.</description><identifier>ISSN: 0923-7534</identifier><identifier>EISSN: 1569-8041</identifier><identifier>DOI: 10.1016/j.annonc.2021.07.009</identifier><identifier>PMID: 34293461</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>adjuvant ; Cancer ; Colonic Neoplasms - pathology ; colorectal cancer ; Extranodal Extension ; Human health and pathology ; Humans ; Hépatology and Gastroenterology ; Life Sciences ; Lymph Nodes - pathology ; Lymphatic Metastasis ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; stage III ; tumor deposit</subject><ispartof>Annals of oncology, 2021-10, Vol.32 (10), p.1267-1275</ispartof><rights>2021 European Society for Medical Oncology</rights><rights>Copyright © 2021 European Society for Medical Oncology. Published by Elsevier Ltd. All rights reserved.</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c497t-fba3ddbe1b2e772dfc70aa0655093b153250d276574b70408dd8027daa86fd3b3</citedby><cites>FETCH-LOGICAL-c497t-fba3ddbe1b2e772dfc70aa0655093b153250d276574b70408dd8027daa86fd3b3</cites><orcidid>0000-0001-9602-5162 ; 0000-0001-6835-4751 ; 0000-0002-8454-7497</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34293461$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.sorbonne-universite.fr/hal-03334446$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Cohen, R.</creatorcontrib><creatorcontrib>Shi, Q.</creatorcontrib><creatorcontrib>Meyers, J.</creatorcontrib><creatorcontrib>Jin, Z.</creatorcontrib><creatorcontrib>Svrcek, M.</creatorcontrib><creatorcontrib>Fuchs, C.</creatorcontrib><creatorcontrib>Couture, F.</creatorcontrib><creatorcontrib>Kuebler, P.</creatorcontrib><creatorcontrib>Ciombor, K.K.</creatorcontrib><creatorcontrib>Bendell, J.</creatorcontrib><creatorcontrib>De Jesus-Acosta, A.</creatorcontrib><creatorcontrib>Kumar, P.</creatorcontrib><creatorcontrib>Lewis, D.</creatorcontrib><creatorcontrib>Tan, B.</creatorcontrib><creatorcontrib>Bertagnolli, M.M.</creatorcontrib><creatorcontrib>Philip, P.</creatorcontrib><creatorcontrib>Blanke, C.</creatorcontrib><creatorcontrib>O'Reilly, E.M.</creatorcontrib><creatorcontrib>Shields, A.</creatorcontrib><creatorcontrib>Meyerhardt, J.A.</creatorcontrib><title>Combining tumor deposits with the number of lymph node metastases to improve the prognostic accuracy in stage III colon cancer: a post hoc analysis of the CALGB/SWOG 80702 phase III study (Alliance)</title><title>Annals of oncology</title><addtitle>Ann Oncol</addtitle><description>In colon cancer, tumor deposits (TD) are considered in assigning prognosis and staging only in the absence of lymph node metastasis (i.e. stage III pN1c tumors). We aimed to evaluate the prognostic value of the presence and the number of TD in patients with stage III, node-positive colon cancer.
All participants from the CALGB/SWOG 80702 phase III trial were included in this post hoc analysis. Pathology reports were reviewed for the presence and the number of TD, lymphovascular and perineural invasion. Associations with disease-free survival (DFS) and overall survival (OS) were evaluated by multivariable Cox models adjusting for sex, treatment arm, T-stage, N-stage, lymphovascular invasion, perineural invasion and lymph node ratio.
Overall, 2028 patients were included with 524 (26%) TD-positive and 1504 (74%) TD-negative tumors. Of the TD-positive patients, 80 (15.4%) were node negative (i.e. pN1c), 239 (46.1%) were pN1a/b (<4 positive lymph nodes) and 200 (38.5%) were pN2 (≥4 positive lymph nodes). The presence of TD was associated with poorer DFS [adjusted hazard ratio (aHR) = 1.63, 95% CI 1.33-1.98] and OS (aHR = 1.59, 95% CI 1.24-2.04). The negative effect of TD was observed for both pN1a/b and pN2 groups. Among TD-positive patients, the number of TD had a linear negative effect on DFS and OS. Combining TD and the number of lymph node metastases, 104 of 1470 (7.1%) pN1 patients were re-staged as pN2, with worse outcomes than patients confirmed as pN1 (3-year DFS rate: 65.4% versus 80.5%, P = 0.0003; 5-year OS rate: 87.9% versus 69.1%, P = <0.0001). DFS was not different between patients re-staged as pN2 and those initially staged as pN2 (3-year DFS rate: 65.4% versus 62.3%, P = 0.4895).
Combining the number of TD and the number of lymph node metastases improved the prognostication accuracy of tumor-node-metastasis (TNM) staging.
•TD are observed in one-quarter of stage III colon cancers.•TD are associated with worse prognosis in stage III colon cancer, regardless of the lymph node substage.•TD should be considered as a quantitative parameter since their number has a prognostic impact.•Adding the number of TD to the count of lymph node metastases improves the prognostication accuracy.</description><subject>adjuvant</subject><subject>Cancer</subject><subject>Colonic Neoplasms - pathology</subject><subject>colorectal cancer</subject><subject>Extranodal Extension</subject><subject>Human health and pathology</subject><subject>Humans</subject><subject>Hépatology and Gastroenterology</subject><subject>Life Sciences</subject><subject>Lymph Nodes - pathology</subject><subject>Lymphatic Metastasis</subject><subject>Neoplasm Staging</subject><subject>Prognosis</subject><subject>Retrospective Studies</subject><subject>stage III</subject><subject>tumor deposit</subject><issn>0923-7534</issn><issn>1569-8041</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9ks2O0zAUhSMEYsrAGyDk5cyinevYiRMWSKWCTqVKswDE0nJsp3GV2MV2ivqCPBfOdBh-FkiWbF2f-x3dq5NlrzEsMODyZr8Q1jorFznkeAFsAVA_yWa4KOt5BRQ_zWZQ52TOCkIvshch7AGgrPP6eXZBaF4TWuJZ9mPlhsZYY3cojoPzSOmDCyYG9N3EDsVOIzsOjfbItag_DYcOWac0GnQUIR0dUHTIDAfvjvpenl4760I0EgkpRy_kCRmLknin0WazQdL1ziIprNT-LRIo-UXUuSS3oj8FEyaribRabtfvbz59vVujChjk6NAlw3tGiKM6oatl35uJc_0ye9aKPuhXD_dl9uXjh8-r2_n2br1JnLmkNYvzthFEqUbjJteM5aqVDISAsiigJg0uSF6AyllZMNowoFApVUHOlBBV2SrSkMvs3Zl7GJtBK6lt9KLnB28G4U_cCcP__rGm4zt35BXDNSU0Aa7PgO6fttvllk81IIRQSssjTtqrBzPvvo06RD6YIHXfC6vdGHheFAXGhGFIUnqWSu9C8Lp9ZGPgU1z4np_jwqe4cGA8xSW1vflznMemX_n4Pa9OSz0a7XmQRqeNK-O1jFw583-Hn9aw1KQ</recordid><startdate>20211001</startdate><enddate>20211001</enddate><creator>Cohen, R.</creator><creator>Shi, Q.</creator><creator>Meyers, J.</creator><creator>Jin, Z.</creator><creator>Svrcek, M.</creator><creator>Fuchs, C.</creator><creator>Couture, F.</creator><creator>Kuebler, P.</creator><creator>Ciombor, K.K.</creator><creator>Bendell, J.</creator><creator>De Jesus-Acosta, A.</creator><creator>Kumar, P.</creator><creator>Lewis, D.</creator><creator>Tan, B.</creator><creator>Bertagnolli, M.M.</creator><creator>Philip, P.</creator><creator>Blanke, C.</creator><creator>O'Reilly, E.M.</creator><creator>Shields, A.</creator><creator>Meyerhardt, J.A.</creator><general>Elsevier Ltd</general><general>Elsevier</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>1XC</scope><scope>VOOES</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-9602-5162</orcidid><orcidid>https://orcid.org/0000-0001-6835-4751</orcidid><orcidid>https://orcid.org/0000-0002-8454-7497</orcidid></search><sort><creationdate>20211001</creationdate><title>Combining tumor deposits with the number of lymph node metastases to improve the prognostic accuracy in stage III colon cancer: a post hoc analysis of the CALGB/SWOG 80702 phase III study (Alliance)</title><author>Cohen, R. ; Shi, Q. ; Meyers, J. ; Jin, Z. ; Svrcek, M. ; Fuchs, C. ; Couture, F. ; Kuebler, P. ; Ciombor, K.K. ; Bendell, J. ; De Jesus-Acosta, A. ; Kumar, P. ; Lewis, D. ; Tan, B. ; Bertagnolli, M.M. ; Philip, P. ; Blanke, C. ; O'Reilly, E.M. ; Shields, A. ; Meyerhardt, J.A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c497t-fba3ddbe1b2e772dfc70aa0655093b153250d276574b70408dd8027daa86fd3b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>adjuvant</topic><topic>Cancer</topic><topic>Colonic Neoplasms - pathology</topic><topic>colorectal cancer</topic><topic>Extranodal Extension</topic><topic>Human health and pathology</topic><topic>Humans</topic><topic>Hépatology and Gastroenterology</topic><topic>Life Sciences</topic><topic>Lymph Nodes - pathology</topic><topic>Lymphatic Metastasis</topic><topic>Neoplasm Staging</topic><topic>Prognosis</topic><topic>Retrospective Studies</topic><topic>stage III</topic><topic>tumor deposit</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cohen, R.</creatorcontrib><creatorcontrib>Shi, Q.</creatorcontrib><creatorcontrib>Meyers, J.</creatorcontrib><creatorcontrib>Jin, Z.</creatorcontrib><creatorcontrib>Svrcek, M.</creatorcontrib><creatorcontrib>Fuchs, C.</creatorcontrib><creatorcontrib>Couture, F.</creatorcontrib><creatorcontrib>Kuebler, P.</creatorcontrib><creatorcontrib>Ciombor, K.K.</creatorcontrib><creatorcontrib>Bendell, J.</creatorcontrib><creatorcontrib>De Jesus-Acosta, A.</creatorcontrib><creatorcontrib>Kumar, P.</creatorcontrib><creatorcontrib>Lewis, D.</creatorcontrib><creatorcontrib>Tan, B.</creatorcontrib><creatorcontrib>Bertagnolli, M.M.</creatorcontrib><creatorcontrib>Philip, P.</creatorcontrib><creatorcontrib>Blanke, C.</creatorcontrib><creatorcontrib>O'Reilly, E.M.</creatorcontrib><creatorcontrib>Shields, A.</creatorcontrib><creatorcontrib>Meyerhardt, J.A.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Hyper Article en Ligne (HAL)</collection><collection>Hyper Article en Ligne (HAL) (Open Access)</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Annals of oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cohen, R.</au><au>Shi, Q.</au><au>Meyers, J.</au><au>Jin, Z.</au><au>Svrcek, M.</au><au>Fuchs, C.</au><au>Couture, F.</au><au>Kuebler, P.</au><au>Ciombor, K.K.</au><au>Bendell, J.</au><au>De Jesus-Acosta, A.</au><au>Kumar, P.</au><au>Lewis, D.</au><au>Tan, B.</au><au>Bertagnolli, M.M.</au><au>Philip, P.</au><au>Blanke, C.</au><au>O'Reilly, E.M.</au><au>Shields, A.</au><au>Meyerhardt, J.A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Combining tumor deposits with the number of lymph node metastases to improve the prognostic accuracy in stage III colon cancer: a post hoc analysis of the CALGB/SWOG 80702 phase III study (Alliance)</atitle><jtitle>Annals of oncology</jtitle><addtitle>Ann Oncol</addtitle><date>2021-10-01</date><risdate>2021</risdate><volume>32</volume><issue>10</issue><spage>1267</spage><epage>1275</epage><pages>1267-1275</pages><issn>0923-7534</issn><eissn>1569-8041</eissn><abstract>In colon cancer, tumor deposits (TD) are considered in assigning prognosis and staging only in the absence of lymph node metastasis (i.e. stage III pN1c tumors). We aimed to evaluate the prognostic value of the presence and the number of TD in patients with stage III, node-positive colon cancer.
All participants from the CALGB/SWOG 80702 phase III trial were included in this post hoc analysis. Pathology reports were reviewed for the presence and the number of TD, lymphovascular and perineural invasion. Associations with disease-free survival (DFS) and overall survival (OS) were evaluated by multivariable Cox models adjusting for sex, treatment arm, T-stage, N-stage, lymphovascular invasion, perineural invasion and lymph node ratio.
Overall, 2028 patients were included with 524 (26%) TD-positive and 1504 (74%) TD-negative tumors. Of the TD-positive patients, 80 (15.4%) were node negative (i.e. pN1c), 239 (46.1%) were pN1a/b (<4 positive lymph nodes) and 200 (38.5%) were pN2 (≥4 positive lymph nodes). The presence of TD was associated with poorer DFS [adjusted hazard ratio (aHR) = 1.63, 95% CI 1.33-1.98] and OS (aHR = 1.59, 95% CI 1.24-2.04). The negative effect of TD was observed for both pN1a/b and pN2 groups. Among TD-positive patients, the number of TD had a linear negative effect on DFS and OS. Combining TD and the number of lymph node metastases, 104 of 1470 (7.1%) pN1 patients were re-staged as pN2, with worse outcomes than patients confirmed as pN1 (3-year DFS rate: 65.4% versus 80.5%, P = 0.0003; 5-year OS rate: 87.9% versus 69.1%, P = <0.0001). DFS was not different between patients re-staged as pN2 and those initially staged as pN2 (3-year DFS rate: 65.4% versus 62.3%, P = 0.4895).
Combining the number of TD and the number of lymph node metastases improved the prognostication accuracy of tumor-node-metastasis (TNM) staging.
•TD are observed in one-quarter of stage III colon cancers.•TD are associated with worse prognosis in stage III colon cancer, regardless of the lymph node substage.•TD should be considered as a quantitative parameter since their number has a prognostic impact.•Adding the number of TD to the count of lymph node metastases improves the prognostication accuracy.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>34293461</pmid><doi>10.1016/j.annonc.2021.07.009</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0001-9602-5162</orcidid><orcidid>https://orcid.org/0000-0001-6835-4751</orcidid><orcidid>https://orcid.org/0000-0002-8454-7497</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | adjuvant Cancer Colonic Neoplasms - pathology colorectal cancer Extranodal Extension Human health and pathology Humans Hépatology and Gastroenterology Life Sciences Lymph Nodes - pathology Lymphatic Metastasis Neoplasm Staging Prognosis Retrospective Studies stage III tumor deposit |
| title | Combining tumor deposits with the number of lymph node metastases to improve the prognostic accuracy in stage III colon cancer: a post hoc analysis of the CALGB/SWOG 80702 phase III study (Alliance) |
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