Penile Cancer| Volume 96, P29-34, October 2016

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Predictors of Nodal Upstaging in Clinical Node Negative Patients With Penile Carcinoma: A National Cancer Database Analysis


      To examine the risk factors associated with upstaging at inguinal lymph node dissection (ILND) in men with penile cancer and clinically negative lymph nodes (cN0) using a large US cancer database.


      The National Cancer Data Base was queried from 1998 to 2012 to identify men with penile cancer who underwent ILND and had complete clinical or pathologic node status available. Lymphovascular invasion (LVI) was available after 2010. Multivariate logistic regression evaluated factors (cT stage, grade, LVI) associated with pathologic nodal upstaging in those with cN0 disease. Correlations between clinical and pathologic node status were also calculated with weighted kappa statistics.


      Complete clinical and pathologic LN status was available for 875 patients. Of these, 461 (53%) were cN0. Upstaging occurred in 111 (24%). When stratified by low, intermediate, and high-risk groups, the proportion with pathologically positive LNs was 16%, 20%, and 27%, respectively (P = .12). On multivariate analysis, limited to men with LVI data available (N = 206), LVI (odds ratio 3.10, 95% confidence interval 1.39-6.92), but not increasing stage (univariate only) or grade (univariate only), was significantly associated with upstaging at ILND.


      In this analysis, of 461 patients with node-negative penile cancer undergoing ILND, upstaging was observed in 24%. LVI was the strongest independent predictor of occult lymph node disease. These findings corroborate the presence of LVI as the significant risk factor for occult micrometastases and suggest a possible improvement in existing risk stratification groupings, with the presence of LVI, regardless of stage or grade, to be considered high-risk disease.
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        • Bouchot O.
        • Rigaud J.
        • Maillet F.
        • Hetet J.F.
        • Karam G.
        Morbidity of inguinal lymphadenectomy for invasive penile carcinoma.
        Eur Urol. 2004; 45 (discussion 765-766): 761-765
        • Protzel C.
        • Alcaraz A.
        • Horenblas S.
        • Pizzocaro G.
        • Zlotta A.
        • Hakenberg O.W.
        Lymphadenectomy in the surgical management of penile cancer.
        Eur Urol. 2009; 55: 1075-1088
        • National Cancer Data Base
        Penile Cancer.
        (Available at:) (Accessed February 1, 2016)
        • Hakenberg O.W.
        • Compérat E.
        • Minhas S.
        • Necchi A.
        • Protzel C.
        • Watkin N.
        European Association Urology (EAU) guidelines on penile cancer.
        (Available at:)
        • Slaton J.W.
        • Morgenstern N.
        • Levy D.A.
        • et al.
        Tumor stage, vascular invasion and the percentage of poorly differentiated cancer: independent prognosticators for inguinal lymph node metastasis in penile squamous cancer.
        J Urol. 2001; 165: 1138-1142
        • Graafland N.M.
        • Lam W.
        • Leijte J.A.
        • et al.
        Prognostic factors for occult inguinal lymph node involvement in penile carcinoma and assessment of the high-risk EAU subgroup: a two-institution analysis of 342 clinically node-negative patients.
        Eur Urol. 2010; 58: 742-747
        • Naumann C.M.
        • Alkatout I.
        • Al-Najar A.
        • et al.
        Lymph-node metastases in intermediate-risk squamous cell carcinoma of the penis.
        BJU Int. 2008; 102: 1102-1106
        • Leijte J.A.
        • Kroon B.K.
        • Valdes Olmos R.A.
        • Nieweg O.E.
        • Horenblas S.
        Reliability and safety of current dynamic sentinel node biopsy for penile carcinoma.
        Eur Urol. 2007; 52: 170-177
        • Schlenker B.
        • Tilki D.
        • Gratzke C.
        • et al.
        Intermediate-differentiated invasive (pT1 G2) penile cancer–oncological outcome and follow-up.
        Urol Oncol. 2011; 29: 782-787
        • Solsona E.
        • Iborra I.
        • Rubio J.
        • Casanova J.L.
        • Ricos J.V.
        • Calabuig C.
        Prospective validation of the association of local tumor stage and grade as a predictive factor for occult lymph node micrometastasis in patients with penile carcinoma and clinically negative inguinal lymph nodes.
        J Urol. 2001; 165: 1506-1509
        • Theodorescu D.
        • Russo P.
        • Zhang Z.F.
        • Morash C.
        • Fair W.R.
        Outcomes of initial surveillance of invasive squamous cell carcinoma of the penis and negative nodes.
        J Urol. 1996; 155: 1626-1631
        • NCCN
        Clinical Practice Guidelines in Oncology: Penile Cancer.
        (Available at:) (1.2016)
        • Ficarra V.
        • Akduman B.
        • Bouchot O.
        • Palou J.
        • Tobias-Machado M.
        Prognostic factors in penile cancer.
        Urology. 2010; 76: S66-S73
        • Heyns C.F.
        • Fleshner N.
        • Sangar V.
        • Schlenker B.
        • Yuvaraja T.B.
        • van Poppel H.
        Management of the lymph nodes in penile cancer.
        Urology. 2010; 76: S43-S57
        • Kroon B.K.
        • Horenblas S.
        • Lont A.P.
        • Tanis P.J.
        • Gallee M.P.
        • Nieweg O.E.
        Patients with penile carcinoma benefit from immediate resection of clinically occult lymph node metastases.
        J Urol. 2005; 173: 816-819
        • Zhu Y.
        • Zhang H.L.
        • Yao X.D.
        • et al.
        Development and evaluation of a nomogram to predict inguinal lymph node metastasis in patients with penile cancer and clinically negative lymph nodes.
        J Urol. 2010; 184: 539-545
        • Hegarty P.K.
        • Kayes O.
        • Freeman A.
        • Christopher N.
        • Ralph D.J.
        • Minhas S.
        A prospective study of 100 cases of penile cancer managed according to European Association of Urology guidelines.
        BJU Int. 2006; 98: 526-531
        • Ficarra V.
        • Zattoni F.
        • Artibani W.
        • et al.
        Nomogram predictive of pathological inguinal lymph node involvement in patients with squamous cell carcinoma of the penis.
        J Urol. 2006; 175 (discussion 1704-1705): 1700-1704
        • Bilimoria K.Y.
        • Stewart A.K.
        • Winchester D.P.
        • Ko C.Y.
        The National Cancer Data Base: a powerful initiative to improve cancer care in the United States.
        Ann Surg Oncol. 2008; 15: 683-690
        • Sharma P.
        • Ashouri K.
        • Zargar-Shoshtari K.
        • Luchey A.M.
        • Spiess P.E.
        Racial and economic disparities in the treatment of penile squamous cell carcinoma: results from the National Cancer Database.
        Urol Oncol. 2015; 34: 122.e9-122.e15
      1. Edge S.B. Byrd D.R. Compton C.C. Fritz A.G. Greene F.L. Trotti A. AJCC Cancer Staging Manual. 7th ed. Springer, France2010 (Available at)
        • Landis J.R.
        • Koch G.G.
        The measurement of observer agreement for categorical data.
        Biometrics. 1977; 33: 159-174
        • Ficarra V.
        • Zattoni F.
        • Cunico S.C.
        • et al.
        Lymphatic and vascular embolizations are independent predictive variables of inguinal lymph node involvement in patients with squamous cell carcinoma of the penis: Gruppo Uro-Oncologico del Nord Est (Northeast Uro-Oncological Group) Penile Cancer data base data.
        Cancer. 2005; 103: 2507-2516
        • Leijte J.A.
        • Hughes B.
        • Graafland N.M.
        • et al.
        Two-center evaluation of dynamic sentinel node biopsy for squamous cell carcinoma of the penis.
        J Clin Oncol. 2009; 27: 3325-3329

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