The importance of extranodal extension in penile cancer: a meta-analysis.
BACKGROUND
The role of extranodal extension (ENE) in penile cancer is controversial and has not been well studied. The aim of this study was to investigate the importance of ENE in predicting prognosis and presence of pelvic lymph node metastasis (PLNM) in penile cancer patients.


METHODS
We searched related studies in Medline, Embase, Cochrane Library, and Scopus database. Hazard ratio (HR) and odds ratio (OR) were directly extracted or indirectly estimated from the included studies.


RESULTS
A total of ten studies with 1,142 patients were included in this meta-analysis. Patients with ENE showed a worse cancer-specific survival (CSS) (HR = 1.90, 95 % confidence interval [CI] = 1.35-2.67, P = 0.0002) and overall survival (HR = 4.04, 95 % CI = 1.02-16.1, P = 0.05) than those without ENE. Further subgroup analysis revealed that the predictive value of ENE for CSS in penile cancer patients was significant regardless of the study's country of origin, but not in the subgroup with shorter follow-up time (<36 months, P = 0.38). Patients with ENE also showed a higher incidence of presenting with PLNM (OR = 4.95, 95 % CI = 2.58-9.49, P < 0.001). A stratified analysis demonstrated that the predictive role of ENE for PLNM was only detected in studies with a larger sample size (> 100 cases). No significant publication bias was observed, as suggested by Begg's and Egger's tests.


CONCLUSIONS
ENE is associated with worse prognosis and high risk of PLNM in penile cancer patients. Due to the limited number of studies included in this meta-analysis, a large-scale, well-designed study will be required to verify our results.
Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, P. R. China. zhangzhl@sysucc.org.cn.|State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, 510060, P. R. China. zhangzhl@sysucc.org.cn.
Zhi-Ling
ZL
Zhang
Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, P. R. China. 13632350652@139.com.|State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, 510060, P. R. China. 13632350652@139.com.|Department of Nephrology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, 510080, P. R. China. 13632350652@139.com.
Chun-Ping
CP
Yu
Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, P. R. China. liuzhw@sysucc.org.cn.|State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, 510060, P. R. China. liuzhw@sysucc.org.cn.
Zhuo-Wei
ZW
Liu
Northeast Ohio Medical University, Rootstown, OH, 44272, USA. lvelet@neomed.edu.
Liliya
L
Velet
Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, P. R. China. liyongh@sysucc.org.cn.|State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, 510060, P. R. China. liyongh@sysucc.org.cn.
Yong-Hong
YH
Li
Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, P. R. China. jianglij@sysucc.org.cn.|State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, 510060, P. R. China. jianglij@sysucc.org.cn.
Li-Juan
LJ
Jiang
Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, P. R. China. zhoufj@sysucc.org.cn.|State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, 510060, P. R. China. zhoufj@sysucc.org.cn.
Fang-Jian
FJ
Zhou
D006801:Humans; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D016017:Odds Ratio; D010412:Penile Neoplasms / Q000175:diagnosis / Q000401:mortality* / Q000473:pathology*; D011379:Prognosis; D016016:Proportional Hazards Models; D017594:Publication Bias