Risk factors for cutaneous squamous cell carcinoma recurrence,metastasis, and disease-specific death: A systematic review and meta-analysis

Agnieszka K. Thompson, Benjamin F. Kelley, Larry J. Prokop, Mohammad H Murad, Christian Baum

Research output: Contribution to journalArticle

110 Citations (Scopus)

Abstract

IMPORTANCE To date, the magnitude of association and the quality of evidence for cutaneous squamous cell carcinoma (cSCC) and risk factors for outcomes have not been reviewed and analyzed systematically. OBJECTIVE To systematically analyze all published data on risk factors for recurrence, metastasis, and disease-specific death (DSD) of cSCC. DATA SOURCES Comprehensive search of Ovid MEDLINE In-Process & Other Non-Indexed Citations, MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus, from each database's inception to May 14, 2015. STUDY SELECTION Inclusion criteria were studies of at least 10 patients, comparative data for at least 1 cSCC risk factor, and an outcome of interest. Exclusion criteria were noncutaneous squamous cell carcinoma (SCC), anogenital SCC, inability to extract cSCC data from other malignancy data, SCC in situ, Marjolin ulcer, and genetic disorders predisposing to cSCC. DATA EXTRACTION AND SYNTHESIS Two reviewers independently abstracted the data. Meta-analysis was performed using the random-effects model. Risk of bias was assessed by the Newcastle-Ottawa Scale. MAIN OUTCOMES AND MEASURES A priori outcomeswere recurrence,metastasis, and DSD. RESULTS Thirty-six studies (17 248 patients with 23 421 cSCCs) were included. Significant risk factors for recurrence were the following: Breslow thickness exceeding 2mm(risk ratio [RR], 9.64; 95%CI, 1.30-71.52), invasion beyond subcutaneous fat (RR, 7.61; 95%CI, 4.17-13.88), Breslow thickness exceeding 6mm(RR, 7.13; 95%CI, 3.04-16.72), perineural invasion (RR, 4.30; 95%CI, 2.80-6.60), diameter exceeding 20mm(RR, 3.22; 95%CI, 1.91-5.45), location on the temple (RR, 3.20; 95%CI, 1.12-9.15), and poor differentiation (RR, 2.66; 95%CI, 1.72-4.14). Significant risk factors formetastasis were: invasion beyond subcutaneous fat (RR, 11.21; 95%CI, 3.59-34.97), Breslow thickness exceeding 2mm(RR, 10.76; 95%CI, 2.55-45.31), Breslow thickness exceeding 6mm(RR, 6.93; 95%CI, 4.02-11.94), diameter exceeding 20mm(RR, 6.15; 95%CI, 3.56-10.65), poor differentiation (RR, 4.98; 95%CI, 3.30-7.49), perineural invasion (RR, 2.95; 95%CI, 2.31-3.75), immunosuppression (RR, 1.59; 95%CI, 1.07-2.37), and location on the temple (RR, 2.82; 95%CI, 1.72-4.63), ear (RR, 2.33; 95%CI, 1.67-3.23), or lip (RR, 2.28; 95%CI, 1.54-3.37). Significant risk factors for DSD were: diameter exceeding 20mm(RR, 19.10; 95%CI, 5.80-62.95), poor differentiation (RR, 5.65; 95%CI, 1.76-18.20), location on the ear (RR, 4.67; 95%CI, 1.28-17.12) or lip (RR, 4.55; 95%CI, 1.41-14.69), invasion beyond subcutaneous fat (RR, 4.49; 95%CI, 2.05-9.82), and perineural invasion (RR, 4.06; 95%CI, 3.10-5.32). Evidence quality was considered low to moderate. CONCLUSIONS AND RELEVANCE Tumor depth is associated with the highest RR of local recurrence and metastasis of cSCC, and tumor diameter exceeding 20mmis associated with the highest RR of DSD. Unified, consistent collection and reporting of risk factors in a prospective, multicentered effort are needed to further understand the increasing incidence of cSCC.

Original languageEnglish (US)
Pages (from-to)419-428
Number of pages10
JournalJAMA Dermatology
Volume152
Issue number4
DOIs
StatePublished - Apr 1 2016

Fingerprint

Meta-Analysis
Squamous Cell Carcinoma
Odds Ratio
Neoplasm Metastasis
Recurrence
Skin
Subcutaneous Fat
Lip
MEDLINE
Ear
Databases
Neoplasms
Inborn Genetic Diseases
Carcinoma in Situ

ASJC Scopus subject areas

  • Dermatology

Cite this

Risk factors for cutaneous squamous cell carcinoma recurrence,metastasis, and disease-specific death : A systematic review and meta-analysis. / Thompson, Agnieszka K.; Kelley, Benjamin F.; Prokop, Larry J.; Murad, Mohammad H; Baum, Christian.

In: JAMA Dermatology, Vol. 152, No. 4, 01.04.2016, p. 419-428.

Research output: Contribution to journalArticle

@article{6d3baab0aa30416c9d46f6b835bf9a4c,
title = "Risk factors for cutaneous squamous cell carcinoma recurrence,metastasis, and disease-specific death: A systematic review and meta-analysis",
abstract = "IMPORTANCE To date, the magnitude of association and the quality of evidence for cutaneous squamous cell carcinoma (cSCC) and risk factors for outcomes have not been reviewed and analyzed systematically. OBJECTIVE To systematically analyze all published data on risk factors for recurrence, metastasis, and disease-specific death (DSD) of cSCC. DATA SOURCES Comprehensive search of Ovid MEDLINE In-Process & Other Non-Indexed Citations, MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus, from each database's inception to May 14, 2015. STUDY SELECTION Inclusion criteria were studies of at least 10 patients, comparative data for at least 1 cSCC risk factor, and an outcome of interest. Exclusion criteria were noncutaneous squamous cell carcinoma (SCC), anogenital SCC, inability to extract cSCC data from other malignancy data, SCC in situ, Marjolin ulcer, and genetic disorders predisposing to cSCC. DATA EXTRACTION AND SYNTHESIS Two reviewers independently abstracted the data. Meta-analysis was performed using the random-effects model. Risk of bias was assessed by the Newcastle-Ottawa Scale. MAIN OUTCOMES AND MEASURES A priori outcomeswere recurrence,metastasis, and DSD. RESULTS Thirty-six studies (17 248 patients with 23 421 cSCCs) were included. Significant risk factors for recurrence were the following: Breslow thickness exceeding 2mm(risk ratio [RR], 9.64; 95{\%}CI, 1.30-71.52), invasion beyond subcutaneous fat (RR, 7.61; 95{\%}CI, 4.17-13.88), Breslow thickness exceeding 6mm(RR, 7.13; 95{\%}CI, 3.04-16.72), perineural invasion (RR, 4.30; 95{\%}CI, 2.80-6.60), diameter exceeding 20mm(RR, 3.22; 95{\%}CI, 1.91-5.45), location on the temple (RR, 3.20; 95{\%}CI, 1.12-9.15), and poor differentiation (RR, 2.66; 95{\%}CI, 1.72-4.14). Significant risk factors formetastasis were: invasion beyond subcutaneous fat (RR, 11.21; 95{\%}CI, 3.59-34.97), Breslow thickness exceeding 2mm(RR, 10.76; 95{\%}CI, 2.55-45.31), Breslow thickness exceeding 6mm(RR, 6.93; 95{\%}CI, 4.02-11.94), diameter exceeding 20mm(RR, 6.15; 95{\%}CI, 3.56-10.65), poor differentiation (RR, 4.98; 95{\%}CI, 3.30-7.49), perineural invasion (RR, 2.95; 95{\%}CI, 2.31-3.75), immunosuppression (RR, 1.59; 95{\%}CI, 1.07-2.37), and location on the temple (RR, 2.82; 95{\%}CI, 1.72-4.63), ear (RR, 2.33; 95{\%}CI, 1.67-3.23), or lip (RR, 2.28; 95{\%}CI, 1.54-3.37). Significant risk factors for DSD were: diameter exceeding 20mm(RR, 19.10; 95{\%}CI, 5.80-62.95), poor differentiation (RR, 5.65; 95{\%}CI, 1.76-18.20), location on the ear (RR, 4.67; 95{\%}CI, 1.28-17.12) or lip (RR, 4.55; 95{\%}CI, 1.41-14.69), invasion beyond subcutaneous fat (RR, 4.49; 95{\%}CI, 2.05-9.82), and perineural invasion (RR, 4.06; 95{\%}CI, 3.10-5.32). Evidence quality was considered low to moderate. CONCLUSIONS AND RELEVANCE Tumor depth is associated with the highest RR of local recurrence and metastasis of cSCC, and tumor diameter exceeding 20mmis associated with the highest RR of DSD. Unified, consistent collection and reporting of risk factors in a prospective, multicentered effort are needed to further understand the increasing incidence of cSCC.",
author = "Thompson, {Agnieszka K.} and Kelley, {Benjamin F.} and Prokop, {Larry J.} and Murad, {Mohammad H} and Christian Baum",
year = "2016",
month = "4",
day = "1",
doi = "10.1001/jamadermatol.2015.4994",
language = "English (US)",
volume = "152",
pages = "419--428",
journal = "JAMA Dermatology",
issn = "2168-6068",
publisher = "American Medical Association",
number = "4",

}

TY - JOUR

T1 - Risk factors for cutaneous squamous cell carcinoma recurrence,metastasis, and disease-specific death

T2 - A systematic review and meta-analysis

AU - Thompson, Agnieszka K.

AU - Kelley, Benjamin F.

AU - Prokop, Larry J.

AU - Murad, Mohammad H

AU - Baum, Christian

PY - 2016/4/1

Y1 - 2016/4/1

N2 - IMPORTANCE To date, the magnitude of association and the quality of evidence for cutaneous squamous cell carcinoma (cSCC) and risk factors for outcomes have not been reviewed and analyzed systematically. OBJECTIVE To systematically analyze all published data on risk factors for recurrence, metastasis, and disease-specific death (DSD) of cSCC. DATA SOURCES Comprehensive search of Ovid MEDLINE In-Process & Other Non-Indexed Citations, MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus, from each database's inception to May 14, 2015. STUDY SELECTION Inclusion criteria were studies of at least 10 patients, comparative data for at least 1 cSCC risk factor, and an outcome of interest. Exclusion criteria were noncutaneous squamous cell carcinoma (SCC), anogenital SCC, inability to extract cSCC data from other malignancy data, SCC in situ, Marjolin ulcer, and genetic disorders predisposing to cSCC. DATA EXTRACTION AND SYNTHESIS Two reviewers independently abstracted the data. Meta-analysis was performed using the random-effects model. Risk of bias was assessed by the Newcastle-Ottawa Scale. MAIN OUTCOMES AND MEASURES A priori outcomeswere recurrence,metastasis, and DSD. RESULTS Thirty-six studies (17 248 patients with 23 421 cSCCs) were included. Significant risk factors for recurrence were the following: Breslow thickness exceeding 2mm(risk ratio [RR], 9.64; 95%CI, 1.30-71.52), invasion beyond subcutaneous fat (RR, 7.61; 95%CI, 4.17-13.88), Breslow thickness exceeding 6mm(RR, 7.13; 95%CI, 3.04-16.72), perineural invasion (RR, 4.30; 95%CI, 2.80-6.60), diameter exceeding 20mm(RR, 3.22; 95%CI, 1.91-5.45), location on the temple (RR, 3.20; 95%CI, 1.12-9.15), and poor differentiation (RR, 2.66; 95%CI, 1.72-4.14). Significant risk factors formetastasis were: invasion beyond subcutaneous fat (RR, 11.21; 95%CI, 3.59-34.97), Breslow thickness exceeding 2mm(RR, 10.76; 95%CI, 2.55-45.31), Breslow thickness exceeding 6mm(RR, 6.93; 95%CI, 4.02-11.94), diameter exceeding 20mm(RR, 6.15; 95%CI, 3.56-10.65), poor differentiation (RR, 4.98; 95%CI, 3.30-7.49), perineural invasion (RR, 2.95; 95%CI, 2.31-3.75), immunosuppression (RR, 1.59; 95%CI, 1.07-2.37), and location on the temple (RR, 2.82; 95%CI, 1.72-4.63), ear (RR, 2.33; 95%CI, 1.67-3.23), or lip (RR, 2.28; 95%CI, 1.54-3.37). Significant risk factors for DSD were: diameter exceeding 20mm(RR, 19.10; 95%CI, 5.80-62.95), poor differentiation (RR, 5.65; 95%CI, 1.76-18.20), location on the ear (RR, 4.67; 95%CI, 1.28-17.12) or lip (RR, 4.55; 95%CI, 1.41-14.69), invasion beyond subcutaneous fat (RR, 4.49; 95%CI, 2.05-9.82), and perineural invasion (RR, 4.06; 95%CI, 3.10-5.32). Evidence quality was considered low to moderate. CONCLUSIONS AND RELEVANCE Tumor depth is associated with the highest RR of local recurrence and metastasis of cSCC, and tumor diameter exceeding 20mmis associated with the highest RR of DSD. Unified, consistent collection and reporting of risk factors in a prospective, multicentered effort are needed to further understand the increasing incidence of cSCC.

AB - IMPORTANCE To date, the magnitude of association and the quality of evidence for cutaneous squamous cell carcinoma (cSCC) and risk factors for outcomes have not been reviewed and analyzed systematically. OBJECTIVE To systematically analyze all published data on risk factors for recurrence, metastasis, and disease-specific death (DSD) of cSCC. DATA SOURCES Comprehensive search of Ovid MEDLINE In-Process & Other Non-Indexed Citations, MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus, from each database's inception to May 14, 2015. STUDY SELECTION Inclusion criteria were studies of at least 10 patients, comparative data for at least 1 cSCC risk factor, and an outcome of interest. Exclusion criteria were noncutaneous squamous cell carcinoma (SCC), anogenital SCC, inability to extract cSCC data from other malignancy data, SCC in situ, Marjolin ulcer, and genetic disorders predisposing to cSCC. DATA EXTRACTION AND SYNTHESIS Two reviewers independently abstracted the data. Meta-analysis was performed using the random-effects model. Risk of bias was assessed by the Newcastle-Ottawa Scale. MAIN OUTCOMES AND MEASURES A priori outcomeswere recurrence,metastasis, and DSD. RESULTS Thirty-six studies (17 248 patients with 23 421 cSCCs) were included. Significant risk factors for recurrence were the following: Breslow thickness exceeding 2mm(risk ratio [RR], 9.64; 95%CI, 1.30-71.52), invasion beyond subcutaneous fat (RR, 7.61; 95%CI, 4.17-13.88), Breslow thickness exceeding 6mm(RR, 7.13; 95%CI, 3.04-16.72), perineural invasion (RR, 4.30; 95%CI, 2.80-6.60), diameter exceeding 20mm(RR, 3.22; 95%CI, 1.91-5.45), location on the temple (RR, 3.20; 95%CI, 1.12-9.15), and poor differentiation (RR, 2.66; 95%CI, 1.72-4.14). Significant risk factors formetastasis were: invasion beyond subcutaneous fat (RR, 11.21; 95%CI, 3.59-34.97), Breslow thickness exceeding 2mm(RR, 10.76; 95%CI, 2.55-45.31), Breslow thickness exceeding 6mm(RR, 6.93; 95%CI, 4.02-11.94), diameter exceeding 20mm(RR, 6.15; 95%CI, 3.56-10.65), poor differentiation (RR, 4.98; 95%CI, 3.30-7.49), perineural invasion (RR, 2.95; 95%CI, 2.31-3.75), immunosuppression (RR, 1.59; 95%CI, 1.07-2.37), and location on the temple (RR, 2.82; 95%CI, 1.72-4.63), ear (RR, 2.33; 95%CI, 1.67-3.23), or lip (RR, 2.28; 95%CI, 1.54-3.37). Significant risk factors for DSD were: diameter exceeding 20mm(RR, 19.10; 95%CI, 5.80-62.95), poor differentiation (RR, 5.65; 95%CI, 1.76-18.20), location on the ear (RR, 4.67; 95%CI, 1.28-17.12) or lip (RR, 4.55; 95%CI, 1.41-14.69), invasion beyond subcutaneous fat (RR, 4.49; 95%CI, 2.05-9.82), and perineural invasion (RR, 4.06; 95%CI, 3.10-5.32). Evidence quality was considered low to moderate. CONCLUSIONS AND RELEVANCE Tumor depth is associated with the highest RR of local recurrence and metastasis of cSCC, and tumor diameter exceeding 20mmis associated with the highest RR of DSD. Unified, consistent collection and reporting of risk factors in a prospective, multicentered effort are needed to further understand the increasing incidence of cSCC.

UR - http://www.scopus.com/inward/record.url?scp=84963745390&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84963745390&partnerID=8YFLogxK

U2 - 10.1001/jamadermatol.2015.4994

DO - 10.1001/jamadermatol.2015.4994

M3 - Article

C2 - 26762219

AN - SCOPUS:84963745390

VL - 152

SP - 419

EP - 428

JO - JAMA Dermatology

JF - JAMA Dermatology

SN - 2168-6068

IS - 4

ER -