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BMC Cancer

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Open Access 01-12-2015 | Research article

The importance of extranodal extension in penile cancer: a meta-analysis

Authors: Zhi-Ling Zhang, Chun-Ping Yu, Zhuo-Wei Liu, Liliya Velet, Yong-Hong Li, Li-Juan Jiang, Fang-Jian Zhou

Published in: BMC Cancer | Issue 1/2015

Abstract

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.

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Backes DM, Kurman RJ, Pimenta JM, Smith JS. Systematic review of human papillomavirus prevalence in invasive penile cancer. Cancer Causes Control. 2009;20(4):449–57.CrossRefPubMed

Chaux A, Netto GJ, Rodriguez IM, Barreto JE, Oertell J, Ocampos S, et al. Epidemiologic profile, sexual history, pathologic features, and human papillomavirus status of 103 patients with penile carcinoma. World J Urol. 2013;31(4):861–7.CrossRefPubMed

Parkin DM, Whelan SL, Ferlay J, Teppo L, Thomas DB. Cancer incidence in five continents, vol. VIII. Lyon: IARC Scientific Publications; 2002. p. 236–7.

Misra S, Chaturvedi A, Misra NC. Penile carcinoma: a challenge for the developing world. Lancet Oncol. 2004;5(4):240–7.CrossRefPubMed

Jin F, Devesa SS, Chow WH, Zheng W, Ji BT, Fraumeni Jr JF, et al. Cancer incidence trends in urban shanghai, 1972-1994: an update. Int J Cancer. 1999;83(4):435–40.CrossRefPubMed

Srinivas V, Morse MJ, Herr HW, Sogani PC, Whitmore Jr WF. Penile cancer: relation of extent of nodal metastasis to survival. J Urol. 1987;137(5):880–2.PubMed

Ravi R. Correlation between the extent of nodal involvement and survival following groin dissection for carcinoma of the penis. Br J Urol. 1993;72(5 Pt 2):817–9.CrossRefPubMed

Protzel C, Alcaraz A, Horenblas S, Pizzocaro G, Zlotta A, Hakenberg OW. Lymphadenectomy in the surgical management of penile cancer. Eur Urol. 2009;55(5):1075–88.CrossRefPubMed

Edge S, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A. American Joint Committee on Cancer, American Cancer Society. AJCC Cancer Staging Manual, 7th ed, 2010. New York: Springer; 2010.

10.

Tobias-Machado M, Tavares A, Ornellas AA, Molina Jr WR, Juliano RV, Wroclawski ER. Video endoscopic inguinal lymphadenectomy: a new minimally invasive procedure for radical management of inguinal nodes in patients with penile squamous cell carcinoma. J Urol. 2007;177(3):953–7. discussion 958.CrossRefPubMed

11.

Ficarra V, Akduman B, Bouchot O, Palou J, Tobias-Machado M. Prognostic factors in penile cancer. Urology. 2010;76(2 Suppl 1):S66–73.CrossRefPubMed

12.

Novara G, Galfano A, De Marco V, Artibani W, Ficarra V. Prognostic factors in squamous cell carcinoma of the penis. Nat Clin Pract Urol. 2007;4(3):140–6.CrossRefPubMed

13.

Djajadiningrat RS, Graafland NM, van Werkhoven E, Meinhardt W, Bex A, van der Poel HG, et al. Contemporary management of regional nodes in penile cancer-improvement of survival? J Urol. 2014;191(1):68–73.CrossRefPubMed

14.

Pandey D, Mahajan V, Kannan RR. Prognostic factors in node-positive carcinoma of the penis. J Surg Oncol. 2006;93(2):133–8.CrossRefPubMed

15.

Sun M, Djajadiningrat RS, Alnajjar HM, Trinh QD, Graafland NM, Watkin N, et al. Development and external validation of a prognostic tool for prediction of cancer-specific mortality after complete loco-regional pathological staging for squamous cell carcinoma of the penis. BJU Int. 2015;116(5):734-743.

16.

Liu JY, Li YH, Zhang ZL, Yao K, Ye YL, Xie D, et al. The risk factors for the presence of pelvic lymph node metastasis in penile squamous cell carcinoma patients with inguinal lymph node dissection. World J Urol. 2013;31(6):1519–24.CrossRefPubMed

17.

Svatek RS, Munsell M, Kincaid JM, Hegarty P, Slaton JW, Busby JE, et al. Association between lymph node density and disease specific survival in patients with penile cancer. J Urol. 2009;182(6):2721–7.CrossRefPubMed

18.

Lughezzani G, Catanzaro M, Torelli T, Piva L, Biasoni D, Stagni S, et al. The Relationship Between Lymph Node Ratio and Cancer-Specific Survival in a Contemporary Series of Patients with Penile Cancer and Lymph Node Metastases. BJU Int. 2013. doi:10.1111/bju.12510.

19.

Hakenberg OW, Compérat EM, Minhas S, Necchi A, Protzel C, Watkin N. EAU guidelines on penile cancer: 2014 update. Eur Urol. 2015;67(1):142–50.CrossRefPubMed

20.

Lont AP, Kroon BK, Gallee MP, van Tinteren H, Moonen LM, Horenblas S. Pelvic lymph node dissection for penile carcinoma: extent of inguinal lymph node involvement as an indicator for pelvic lymph node involvement and survival. J Urol. 2007;177(3):947–52. discussion 952.CrossRefPubMed

21.

Zhu Y, Zhang SL, Ye DW, Yao XD, Jiang ZX, Zhou XY. Predicting pelvic lymph node metastases in penile cancer patients: a comparison of computed tomography, Cloquet’s node, and disease burden of inguinal lymph nodes. Onkologie. 2008;31(1-2):37–41.CrossRefPubMed

22.

Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ. 2009;339:b2535.CrossRefPubMedPubMedCentral

23.

Wells GA, Shea B, O’Connell D, Peterson J, Welch V, Losos M, et al. The Newcastle–Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. 2003. Available at: http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp.

24.

Tierney JF, Stewart LA, Ghersi D, Burdett S, Sydes MR. Practical methods for incorporating summary time-to-event data into meta-analysis. Trials. 2007;8:16.CrossRefPubMedPubMedCentral

25.

Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315(7109):629–34.CrossRefPubMedPubMedCentral

26.

Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics. 1994;50(4):1088–101.CrossRefPubMed

27.

Zhu Y, Ye DW, Yao XD, Zhang SL, Dai B, Zhang HL. New N staging system of penile cancer provides a better reflection of prognosis. J Urol. 2011;186(2):518–23.CrossRefPubMed

28.

Lughezzani G, Catanzaro M, Torelli T, Piva L, Biasoni D, Stagni S, et al. The relationship between characteristics of inguinal lymph nodes and pelvic lymph node involvement in penile squamous cell carcinoma: a single institution experience. J Urol. 2014;191(4):977–82.CrossRefPubMed

29.

Graafland NM, van Boven HH, van Werkhoven E, Moonen LM, Horenblas S. Prognostic significance of extranodal extension in patients with pathological node positive penile carcinoma. J Urol. 2010;184(4):1347–53.CrossRefPubMed

30.

Ornellas AA, Kinchin EW, Nobrega BL, Wisnescky A, Koifman N, Quirino R. Surgical treatment of invasive squamous cell carcinoma of the penis: Brazilian National Cancer Institute long-term experience. J Surg Oncol. 2008;97(6):487–95.CrossRefPubMed

31.

Sonpavde G, Pagliaro LC, Buonerba C, Dorff TB, Lee RJ, Di Lorenzo G. Penile cancer: current therapy and future directions. Ann Oncol. 2013;24(5):1179–89.CrossRefPubMedPubMedCentral

32.

Pizzocaro G, Piva L. Adjuvant and neoadjuvant vincristine, bleomycin, and methotrexate for inguinal metastases from squamous cell carcinoma of the penis. Acta Oncol. 1988;27(6b):823–4.CrossRefPubMed

Title: The importance of extranodal extension in penile cancer: a meta-analysis
Authors: Zhi-Ling Zhang
Chun-Ping Yu
Zhuo-Wei Liu
Liliya Velet
Yong-Hong Li
Li-Juan Jiang
Fang-Jian Zhou
Publication date: 01-12-2015
Publisher: BioMed Central
Published in: BMC Cancer / Issue 1/2015
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/s12885-015-1834-4

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Abstract

Background

Methods

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