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Analysis of risk factors determining prognosis of cutaneous squamous-cell carcinoma: a prospective study

Summary Background Cutaneous squamous-cell carcinomas (SCC) are among the most common cancers capable of metastasis. Current Tumour Node Metastasis (TNM) staging includes horizontal tumour size, involvement of extradermal structures, and degree of differentiation. The aim of this study was to prospe...

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Published in:The lancet oncology 2008-08, Vol.9 (8), p.713-720
Main Authors: Brantsch, Kay D, MD, Meisner, Christoph, PhD, Schönfisch, Birgitt, PhD, Trilling, Birgit, Dipl Inform Med, Wehner-Caroli, Jörg, MD, Röcken, Martin, Prof, Breuninger, Helmut, Prof
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container_title The lancet oncology
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creator Brantsch, Kay D, MD
Meisner, Christoph, PhD
Schönfisch, Birgitt, PhD
Trilling, Birgit, Dipl Inform Med
Wehner-Caroli, Jörg, MD
Röcken, Martin, Prof
Breuninger, Helmut, Prof
description Summary Background Cutaneous squamous-cell carcinomas (SCC) are among the most common cancers capable of metastasis. Current Tumour Node Metastasis (TNM) staging includes horizontal tumour size, involvement of extradermal structures, and degree of differentiation. The aim of this study was to prospectively analyse the key factors predicting metastasis and local recurrence in cutaneous SCC. Methods We assessed prospectively investigated potential risk factors for metastasis or local recurrence of SCC, previously suggested by retrospective studies and small case series, in 615 white patients. Between Jan 1, 1990, and Dec 31, 2001, all patients underwent surgery for cutaneous SCC with complete histological examination of the three-dimensional excision margins (3D-histology) in one centre. Univariate and multivariate analysis included tumour thickness, horizontal size, body site, histological differentiation, desmoplastic growth, history of multiple SCC, and immunosuppression. Primary endpoints were time to metastasis and time to local recurrence, defined as the time from date of diagnosis of the primary tumour to the date of diagnosis of metastasis or local recurrence, respectively. Findings 653 patients were enrolled in the study. 38 patients were lost to follow-up leaving 615 assessable patients (median age 73 years [range 27–98]). During a median follow-up period of 43 months (range 1–165), 26 (4%) of 615 patients developed metastases and 20 patients developed local recurrence (3%). Tumours 2·0 mm or less in thickness did not metastasise. Metastases occurred in 12 (4%) of 318 tumours between 2·1 mm and 6·0 mm in thickness, and in 14 (16%) of 90 tumours with a thickness greater than 6·0 mm. On multivariate analysis, key prognostic factors for metastasis were increased tumour thickness (hazard ratio 4·79 [95% CI 2·22–10·36]; p
doi_str_mv 10.1016/S1470-2045(08)70178-5
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Current Tumour Node Metastasis (TNM) staging includes horizontal tumour size, involvement of extradermal structures, and degree of differentiation. The aim of this study was to prospectively analyse the key factors predicting metastasis and local recurrence in cutaneous SCC. Methods We assessed prospectively investigated potential risk factors for metastasis or local recurrence of SCC, previously suggested by retrospective studies and small case series, in 615 white patients. Between Jan 1, 1990, and Dec 31, 2001, all patients underwent surgery for cutaneous SCC with complete histological examination of the three-dimensional excision margins (3D-histology) in one centre. Univariate and multivariate analysis included tumour thickness, horizontal size, body site, histological differentiation, desmoplastic growth, history of multiple SCC, and immunosuppression. Primary endpoints were time to metastasis and time to local recurrence, defined as the time from date of diagnosis of the primary tumour to the date of diagnosis of metastasis or local recurrence, respectively. Findings 653 patients were enrolled in the study. 38 patients were lost to follow-up leaving 615 assessable patients (median age 73 years [range 27–98]). During a median follow-up period of 43 months (range 1–165), 26 (4%) of 615 patients developed metastases and 20 patients developed local recurrence (3%). Tumours 2·0 mm or less in thickness did not metastasise. Metastases occurred in 12 (4%) of 318 tumours between 2·1 mm and 6·0 mm in thickness, and in 14 (16%) of 90 tumours with a thickness greater than 6·0 mm. On multivariate analysis, key prognostic factors for metastasis were increased tumour thickness (hazard ratio 4·79 [95% CI 2·22–10·36]; p&lt;0·0001), immunosuppression (4·32 [1·62–11·52]; p=0·0035), localisation at the ear (3·61 [1·51–8·67]; p=0·0040), and increased horizontal size (2·22 [1·18–4·15]; p=0·0128). The risk of local recurrence depended on increased tumour thickness (6·03 [2·71–13·43]; p&lt;0·0001) and desmoplasia (16·11 [6·57–39·49]; p&lt;0·0001). Interpretation Only SCC greater than 2·0 mm in thickness are associated with a significant risk of metastasis. Tumours greater than 6·0 mm are associated with a high risk of metastasis and local recurrence. Desmoplastic growth is an independent risk factor for local recurrence. Studies should assess the role of follow-up visits and sentinel-lymph-node biopsy in high-risk patients. Funding This study was supported by the German Research Foundation/Sonderforschungsbereich 685 and Deutsche Krebshilfe (MR), the intramural Angewandte Klinische Forschung fellowship (203-1-0) from the University Medical School, Eberhard Karls University Tuebingen (KDB), and the ‘Südwestdeutsche Tumorzentrum’—Comprehensive Cancer Centre Tübingen (KDB, MR, HB).</description><identifier>ISSN: 1470-2045</identifier><identifier>EISSN: 1474-5488</identifier><identifier>DOI: 10.1016/S1470-2045(08)70178-5</identifier><identifier>PMID: 18617440</identifier><identifier>CODEN: LANCAO</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Adult ; Age Distribution ; Aged ; Aged, 80 and over ; Analysis of Variance ; Biopsy, Needle ; Cancer therapies ; Carcinoma, Squamous Cell - epidemiology ; Carcinoma, Squamous Cell - pathology ; Carcinoma, Squamous Cell - secondary ; Carcinoma, Squamous Cell - surgery ; Confidence Intervals ; Female ; Germany - epidemiology ; Hematology, Oncology and Palliative Medicine ; Histology ; Humans ; Immunohistochemistry ; Incidence ; Kaplan-Meier Estimate ; Lymphatic Metastasis ; Male ; Medical prognosis ; Melanoma ; Metastasis ; Middle Aged ; Multivariate Analysis ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local - epidemiology ; Neoplasm Recurrence, Local - pathology ; Neoplasm Staging ; Patients ; Prognosis ; Proportional Hazards Models ; Prospective Studies ; Risk Factors ; Sex Distribution ; Skin cancer ; Skin Neoplasms - epidemiology ; Skin Neoplasms - pathology ; Skin Neoplasms - surgery ; Surgery ; Survival Analysis ; Tumors</subject><ispartof>The lancet oncology, 2008-08, Vol.9 (8), p.713-720</ispartof><rights>Elsevier Ltd</rights><rights>2008 Elsevier Ltd</rights><rights>Copyright Elsevier Limited Aug 2008</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c563t-43c3d4e221c9bec2f5b762083cf57c54ecc29aa7c7db5b97598e0068d4e3b77a3</citedby><cites>FETCH-LOGICAL-c563t-43c3d4e221c9bec2f5b762083cf57c54ecc29aa7c7db5b97598e0068d4e3b77a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18617440$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Brantsch, Kay D, MD</creatorcontrib><creatorcontrib>Meisner, Christoph, PhD</creatorcontrib><creatorcontrib>Schönfisch, Birgitt, PhD</creatorcontrib><creatorcontrib>Trilling, Birgit, Dipl Inform Med</creatorcontrib><creatorcontrib>Wehner-Caroli, Jörg, MD</creatorcontrib><creatorcontrib>Röcken, Martin, Prof</creatorcontrib><creatorcontrib>Breuninger, Helmut, Prof</creatorcontrib><title>Analysis of risk factors determining prognosis of cutaneous squamous-cell carcinoma: a prospective study</title><title>The lancet oncology</title><addtitle>Lancet Oncol</addtitle><description>Summary Background Cutaneous squamous-cell carcinomas (SCC) are among the most common cancers capable of metastasis. Current Tumour Node Metastasis (TNM) staging includes horizontal tumour size, involvement of extradermal structures, and degree of differentiation. The aim of this study was to prospectively analyse the key factors predicting metastasis and local recurrence in cutaneous SCC. Methods We assessed prospectively investigated potential risk factors for metastasis or local recurrence of SCC, previously suggested by retrospective studies and small case series, in 615 white patients. Between Jan 1, 1990, and Dec 31, 2001, all patients underwent surgery for cutaneous SCC with complete histological examination of the three-dimensional excision margins (3D-histology) in one centre. Univariate and multivariate analysis included tumour thickness, horizontal size, body site, histological differentiation, desmoplastic growth, history of multiple SCC, and immunosuppression. Primary endpoints were time to metastasis and time to local recurrence, defined as the time from date of diagnosis of the primary tumour to the date of diagnosis of metastasis or local recurrence, respectively. Findings 653 patients were enrolled in the study. 38 patients were lost to follow-up leaving 615 assessable patients (median age 73 years [range 27–98]). During a median follow-up period of 43 months (range 1–165), 26 (4%) of 615 patients developed metastases and 20 patients developed local recurrence (3%). Tumours 2·0 mm or less in thickness did not metastasise. Metastases occurred in 12 (4%) of 318 tumours between 2·1 mm and 6·0 mm in thickness, and in 14 (16%) of 90 tumours with a thickness greater than 6·0 mm. On multivariate analysis, key prognostic factors for metastasis were increased tumour thickness (hazard ratio 4·79 [95% CI 2·22–10·36]; p&lt;0·0001), immunosuppression (4·32 [1·62–11·52]; p=0·0035), localisation at the ear (3·61 [1·51–8·67]; p=0·0040), and increased horizontal size (2·22 [1·18–4·15]; p=0·0128). The risk of local recurrence depended on increased tumour thickness (6·03 [2·71–13·43]; p&lt;0·0001) and desmoplasia (16·11 [6·57–39·49]; p&lt;0·0001). Interpretation Only SCC greater than 2·0 mm in thickness are associated with a significant risk of metastasis. Tumours greater than 6·0 mm are associated with a high risk of metastasis and local recurrence. Desmoplastic growth is an independent risk factor for local recurrence. Studies should assess the role of follow-up visits and sentinel-lymph-node biopsy in high-risk patients. Funding This study was supported by the German Research Foundation/Sonderforschungsbereich 685 and Deutsche Krebshilfe (MR), the intramural Angewandte Klinische Forschung fellowship (203-1-0) from the University Medical School, Eberhard Karls University Tuebingen (KDB), and the ‘Südwestdeutsche Tumorzentrum’—Comprehensive Cancer Centre Tübingen (KDB, MR, HB).</description><subject>Adult</subject><subject>Age Distribution</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Analysis of Variance</subject><subject>Biopsy, Needle</subject><subject>Cancer therapies</subject><subject>Carcinoma, Squamous Cell - epidemiology</subject><subject>Carcinoma, Squamous Cell - pathology</subject><subject>Carcinoma, Squamous Cell - secondary</subject><subject>Carcinoma, Squamous Cell - surgery</subject><subject>Confidence Intervals</subject><subject>Female</subject><subject>Germany - epidemiology</subject><subject>Hematology, Oncology and Palliative Medicine</subject><subject>Histology</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Incidence</subject><subject>Kaplan-Meier Estimate</subject><subject>Lymphatic Metastasis</subject><subject>Male</subject><subject>Medical prognosis</subject><subject>Melanoma</subject><subject>Metastasis</subject><subject>Middle Aged</subject><subject>Multivariate Analysis</subject><subject>Neoplasm Invasiveness</subject><subject>Neoplasm Recurrence, Local - epidemiology</subject><subject>Neoplasm Recurrence, Local - pathology</subject><subject>Neoplasm Staging</subject><subject>Patients</subject><subject>Prognosis</subject><subject>Proportional Hazards Models</subject><subject>Prospective Studies</subject><subject>Risk Factors</subject><subject>Sex Distribution</subject><subject>Skin cancer</subject><subject>Skin Neoplasms - epidemiology</subject><subject>Skin Neoplasms - pathology</subject><subject>Skin Neoplasms - surgery</subject><subject>Surgery</subject><subject>Survival Analysis</subject><subject>Tumors</subject><issn>1470-2045</issn><issn>1474-5488</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><recordid>eNqFkUtv1TAQhS0EoqXwE0AWCwSLwDixY5sFqKp4SZVYAGvLmUyK2zxu7aTS_fc4N1cgdcPKlvWd45lzGHsu4K0AUb_7IaSGogSpXoN5o0FoU6gH7DQ_y0JJYx4e7htywp6kdA0ZEqAesxNhaqGlhFP2-3z0_T6FxKeOx5BueOdxnmLiLc0UhzCG8Yrv4nQ1TkcKl9mPNC2Jp9vFD_lSIPU9Rx8xjNPg33O_KtKOcA53xNO8tPun7FHn-0TPjucZ-_X508-Lr8Xl9y_fLs4vC1R1NReywqqVVJYCbUNYdqrRdQmmwk5pVJIQS-u9Rt02qrFaWUMAtcmaqtHaV2fs1eabJ7hdKM1uCGmdb5vZ1bYyQlvI4Mt74PW0xJxGciWAtbZUMkNqgzDvkyJ1bhfD4OPeCXBrD-7Qg1tDdmDcoQensu7F0XxpBmr_qY7BZ-DjBlDO4i5QdAkDjUhtiDk2107hv198uOeAfW4LfX9De0p_lxEulQ42k9UDzMFBVX8A7lmuAw</recordid><startdate>20080801</startdate><enddate>20080801</enddate><creator>Brantsch, Kay D, MD</creator><creator>Meisner, Christoph, PhD</creator><creator>Schönfisch, Birgitt, PhD</creator><creator>Trilling, Birgit, Dipl Inform Med</creator><creator>Wehner-Caroli, Jörg, MD</creator><creator>Röcken, Martin, Prof</creator><creator>Breuninger, Helmut, Prof</creator><general>Elsevier Ltd</general><general>Elsevier Limited</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>0TZ</scope><scope>3V.</scope><scope>7RV</scope><scope>7TO</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8C2</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M1P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>20080801</creationdate><title>Analysis of risk factors determining prognosis of cutaneous squamous-cell carcinoma: a prospective study</title><author>Brantsch, Kay D, MD ; Meisner, Christoph, PhD ; Schönfisch, Birgitt, PhD ; Trilling, Birgit, Dipl Inform Med ; Wehner-Caroli, Jörg, MD ; Röcken, Martin, Prof ; Breuninger, Helmut, Prof</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c563t-43c3d4e221c9bec2f5b762083cf57c54ecc29aa7c7db5b97598e0068d4e3b77a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Adult</topic><topic>Age Distribution</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Analysis of Variance</topic><topic>Biopsy, Needle</topic><topic>Cancer therapies</topic><topic>Carcinoma, Squamous Cell - epidemiology</topic><topic>Carcinoma, Squamous Cell - pathology</topic><topic>Carcinoma, Squamous Cell - secondary</topic><topic>Carcinoma, Squamous Cell - surgery</topic><topic>Confidence Intervals</topic><topic>Female</topic><topic>Germany - epidemiology</topic><topic>Hematology, Oncology and Palliative Medicine</topic><topic>Histology</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Incidence</topic><topic>Kaplan-Meier Estimate</topic><topic>Lymphatic Metastasis</topic><topic>Male</topic><topic>Medical prognosis</topic><topic>Melanoma</topic><topic>Metastasis</topic><topic>Middle Aged</topic><topic>Multivariate Analysis</topic><topic>Neoplasm Invasiveness</topic><topic>Neoplasm Recurrence, Local - epidemiology</topic><topic>Neoplasm Recurrence, Local - pathology</topic><topic>Neoplasm Staging</topic><topic>Patients</topic><topic>Prognosis</topic><topic>Proportional Hazards Models</topic><topic>Prospective Studies</topic><topic>Risk Factors</topic><topic>Sex Distribution</topic><topic>Skin cancer</topic><topic>Skin Neoplasms - epidemiology</topic><topic>Skin Neoplasms - pathology</topic><topic>Skin Neoplasms - surgery</topic><topic>Surgery</topic><topic>Survival Analysis</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Brantsch, Kay D, MD</creatorcontrib><creatorcontrib>Meisner, Christoph, PhD</creatorcontrib><creatorcontrib>Schönfisch, Birgitt, PhD</creatorcontrib><creatorcontrib>Trilling, Birgit, Dipl Inform Med</creatorcontrib><creatorcontrib>Wehner-Caroli, Jörg, MD</creatorcontrib><creatorcontrib>Röcken, Martin, Prof</creatorcontrib><creatorcontrib>Breuninger, Helmut, Prof</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Pharma and Biotech Premium PRO</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing &amp; 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Current Tumour Node Metastasis (TNM) staging includes horizontal tumour size, involvement of extradermal structures, and degree of differentiation. The aim of this study was to prospectively analyse the key factors predicting metastasis and local recurrence in cutaneous SCC. Methods We assessed prospectively investigated potential risk factors for metastasis or local recurrence of SCC, previously suggested by retrospective studies and small case series, in 615 white patients. Between Jan 1, 1990, and Dec 31, 2001, all patients underwent surgery for cutaneous SCC with complete histological examination of the three-dimensional excision margins (3D-histology) in one centre. Univariate and multivariate analysis included tumour thickness, horizontal size, body site, histological differentiation, desmoplastic growth, history of multiple SCC, and immunosuppression. Primary endpoints were time to metastasis and time to local recurrence, defined as the time from date of diagnosis of the primary tumour to the date of diagnosis of metastasis or local recurrence, respectively. Findings 653 patients were enrolled in the study. 38 patients were lost to follow-up leaving 615 assessable patients (median age 73 years [range 27–98]). During a median follow-up period of 43 months (range 1–165), 26 (4%) of 615 patients developed metastases and 20 patients developed local recurrence (3%). Tumours 2·0 mm or less in thickness did not metastasise. Metastases occurred in 12 (4%) of 318 tumours between 2·1 mm and 6·0 mm in thickness, and in 14 (16%) of 90 tumours with a thickness greater than 6·0 mm. On multivariate analysis, key prognostic factors for metastasis were increased tumour thickness (hazard ratio 4·79 [95% CI 2·22–10·36]; p&lt;0·0001), immunosuppression (4·32 [1·62–11·52]; p=0·0035), localisation at the ear (3·61 [1·51–8·67]; p=0·0040), and increased horizontal size (2·22 [1·18–4·15]; p=0·0128). The risk of local recurrence depended on increased tumour thickness (6·03 [2·71–13·43]; p&lt;0·0001) and desmoplasia (16·11 [6·57–39·49]; p&lt;0·0001). Interpretation Only SCC greater than 2·0 mm in thickness are associated with a significant risk of metastasis. Tumours greater than 6·0 mm are associated with a high risk of metastasis and local recurrence. Desmoplastic growth is an independent risk factor for local recurrence. Studies should assess the role of follow-up visits and sentinel-lymph-node biopsy in high-risk patients. Funding This study was supported by the German Research Foundation/Sonderforschungsbereich 685 and Deutsche Krebshilfe (MR), the intramural Angewandte Klinische Forschung fellowship (203-1-0) from the University Medical School, Eberhard Karls University Tuebingen (KDB), and the ‘Südwestdeutsche Tumorzentrum’—Comprehensive Cancer Centre Tübingen (KDB, MR, HB).</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>18617440</pmid><doi>10.1016/S1470-2045(08)70178-5</doi><tpages>8</tpages></addata></record>
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ispartof The lancet oncology, 2008-08, Vol.9 (8), p.713-720
issn 1470-2045
1474-5488
language eng
recordid cdi_proquest_miscellaneous_69381790
source Elsevier
subjects Adult
Age Distribution
Aged
Aged, 80 and over
Analysis of Variance
Biopsy, Needle
Cancer therapies
Carcinoma, Squamous Cell - epidemiology
Carcinoma, Squamous Cell - pathology
Carcinoma, Squamous Cell - secondary
Carcinoma, Squamous Cell - surgery
Confidence Intervals
Female
Germany - epidemiology
Hematology, Oncology and Palliative Medicine
Histology
Humans
Immunohistochemistry
Incidence
Kaplan-Meier Estimate
Lymphatic Metastasis
Male
Medical prognosis
Melanoma
Metastasis
Middle Aged
Multivariate Analysis
Neoplasm Invasiveness
Neoplasm Recurrence, Local - epidemiology
Neoplasm Recurrence, Local - pathology
Neoplasm Staging
Patients
Prognosis
Proportional Hazards Models
Prospective Studies
Risk Factors
Sex Distribution
Skin cancer
Skin Neoplasms - epidemiology
Skin Neoplasms - pathology
Skin Neoplasms - surgery
Surgery
Survival Analysis
Tumors
title Analysis of risk factors determining prognosis of cutaneous squamous-cell carcinoma: a prospective study
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