Original Study|Articles in Press

Predictors of Pelvic Lymph Nodal Metastasis in Penile Squamous Cell Carcinoma- Results From a Matched-Pair Analysis

Published:November 17, 2022DOI:



      Pelvic lymph node (PLN) metastasis has a worse prognosis in penile squamous cell carcinoma. This study sought to determine the predictors of PLN metastasis in penile SCC.

      Materials and Methods

      This retrospective study included primary penile resections with inguinal lymph nodes (ILN) and PLN dissections over 10 years (2007-2017). A subset of treatment naïve cases with PLN metastasis was matched for age and tumor size with another subset of cases having metastatic ILN and negative PLN. The variables were correlated with the PLN metastasis using appropriate statistical tests. Internal validation of the multivariate model was conducted by using 2000 bootstraps on the same cohort. The optimum cut-off for the number of positive ILN was obtained by plotting a receiver operating characteristic curve and using the highest Youden’s index as a discriminator.


      A total of 56 cases (28 in each subset) formed the study cohort. On unadjusted analysis the size of the largest ILN (p=0.038), number of positive ILN (p=0.001), percentage of positive ILN (p=0.001), and laterality of ILN involvement (p=0.007) had a significant correlation with PLN metastasis. On adjusted analysis, the number of positive ILN (p=0.011) was the only statistically significant variable. Bootstrapping results indicated that this multivariate model represented the dataset adequately. The maximum Youden’s index was obtained when ≥5 ILN were positive.


      The number of metastatic ILN is the most important predictor of PLN metastasis. A higher threshold of metastatic ILN for addressing PLN dissection can be investigated, particularly in a high disease burden setup.


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        • Lopes A
        • Bezerra AL
        • Serrano SV
        • Hidalgo GS.
        Iliac nodal metastases from carcinoma of the penis treated surgically.
        BJU Int. 2000; 86: 690-693
        • Pandey D
        • Mahajan V
        • Kannan RR.
        Prognostic factors in node-positive carcinoma of the penis.
        J Surg Oncol. 2006; 93: 133-138
        • Ravi R.
        Correlation between the extent of nodal involvement and survival following groin dissection for carcinoma of the penis.
        Br J Urol. 1993; 72: 817-819
        • Lont AP
        • Kroon BK
        • Gallee MPW
        • van Tinteren H
        • Moonen LMF
        • 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: 947-952
        • Zargar-Shoshtari K
        • Djajadiningrat R
        • Sharma P
        • et al.
        Establishing criteria for bilateral pelvic lymph node dissection in the management of penile cancer: Lessons learned from an international multicenter collaboration.
        J Urol. 2015; 194: 696-701
        • Zargar-Shoshtari K
        • Sharma P
        • Djajadiningrat R
        • et al.
        Extent of pelvic lymph node dissection in penile cancer may impact survival.
        World J Urol. 2016; 34: 353-359
        • Lughezzani G
        • Catanzaro M
        • Torelli T
        • 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: 977-982
      1. Flaig T, Spiess PE, Abern A, Agarwal N, Bangs R, Boorjian SA. Penile cancer, version 2.2022, NCCN clinical practice guidelines in oncology. Available at: Accessed January 8, 2022.

      2. Hakenberg OW, Compérat EM, Minhas S, Necchi A, Protzel C, Watkin N. EAU guidelines on penile cancer. Available at: Accessed January 8, 2022.

        • Nelson BA
        • Cookson MS
        • Smith JA
        • Chang SS.
        Complications of inguinal and pelvic lymphadenectomy for squamous cell carcinoma of the penis: a contemporary series.
        J Urol. 2004; 172: 494-497
        • Li Z-S
        • Han H
        • Deng C-Z
        • et al.
        Pelvic lymph node dissection in penile cancer with inguinal lymph node extranodal extension: A multicenter experience.
        Front Surg. 2021; 8644273
        • Liu J-Y
        • Li Y-H
        • Zhang Z-L
        • 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: 1519-1524
        • 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: 37-41
        • Graafland NM
        • Teertstra HJ
        • Besnard APE
        • van Boven HH
        • Horenblas S.
        Identification of high risk pathological node positive penile carcinoma: value of preoperative computerized tomography imaging.
        J Urol. 2011; 185: 881-887
        • Sali AP
        • Menon S
        • Prakash G
        • et al.
        Histopathological risk scoring system as a tool for predicting lymph nodal metastasis in penile squamous cell carcinoma.
        Pathology. 2019; 51: 696-704
        • Carver BS
        • Cronin AM
        • Eggener S
        • et al.
        The total number of retroperitoneal lymph nodes resected impacts clinical outcome after chemotherapy for metastatic testicular cancer.
        Urology. 2010; 75: 1431-1435
        • Box GEP
        • Tidwell PW.
        Transformation of the independent variables.
        Technometrics. 1962; 4: 531-550
        • Fluss R
        • Faraggi D
        • Reiser B.
        Estimation of the Youden Index and its associated cutoff point.
        Biom J. 2005; 47: 458-472
        • Zhang W
        • Gao P
        • Gao J
        • Wu X
        • Liu G
        • Zhang X.
        A clinical nomogram for predicting lymph node metastasis in penile cancer: A SEER-based study.
        Front Oncol. 2021; 11640036
        • Li K
        • Wu G
        • Fan C
        • Yuan H.
        The prognostic significance of primary tumor size in squamous cell carcinoma of the penis.
        Discov Oncol. 2021; 12: 22
        • Hu J
        • Cui Y
        • Liu P
        • et al.
        Predictors of inguinal lymph node metastasis in penile cancer patients: a meta-analysis of retrospective studies.
        Cancer Manag Res. 2019; 11: 6425-6441
        • Zekan DS
        • Dahman A
        • Hajiran AJ
        • Luchey AM
        • Chahoud J
        • Spiess PE.
        Prognostic predictors of lymph node metastasis in penile cancer: a systematic review.
        Int Braz J Urol. 2021; 47: 943-956
        • A Pettaway Curtis
        • John RS
        • Robert KB
        in: Amin MB Edge SB Greene FL AJCC Cancer Staging Manual. American College of Surgeons, Chicago, IL2018: 709-722
        • Leijte JAP
        • Gallee M
        • Antonini N
        • Horenblas S.
        Evaluation of current TNM classification of penile carcinoma.
        J Urol. 2008; 180: 933-938
        • Sun M
        • Djajadiningrat RS
        • Alnajjar HM
        • 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: 734-743
        • Sali AP
        • Menon S
        • Murthy V
        • et al.
        A modified histopathologic staging in penile squamous cell carcinoma predicts nodal metastasis and outcome better than the current AJCC staging.
        Am J Surg Pathol. 2020; 44: 1112-1117
        • Horenblas S
        • van Tinteren H
        • Delemarre JF
        • Moonen LM
        • Lustig V
        • van Waardenburg EW.
        Squamous cell carcinoma of the penis. III. Treatment of regional lymph nodes.
        J Urol. 1993; 149: 492-497
        • Sali AP
        • Prakash G
        • de CássioZequi S
        • et al.
        A comparative study of AJCC and the modified staging system in pT2/pT3 penile squamous cell carcinoma - A validation on an external data set.
        Histopathology. 2022; 80: 566-574