Abstract
Introduction: Lymph node metastasis is an important prognostic marker in penile cancer. Identification of occult metastasis is by lymphadenectomy based on the histological features of primary tumor; however, this leads to unnecessary surgical morbidity in node negative patients. Methods: A retrospective analysis of all surgically treated penile cancer patients managed at our institute from January 2011 to March 2014 was performed. Patient characteristics, histological factors, and lymph node involvement were identified. Logistic regression analysis was used to compute odds ratio (OR) in univariate and multivariate analysis. Results: Ninety seven patients underwent surgical management at our institute during the abovementioned period. Grade III tumor, presence of lymphovascular invasion, tumor thickness >10 mm, perineural invasion (PNI) and Ki67 >50% were significantly associated with nodal metastasis. On multivariate analysis, only presence of PNI was found to be significant (OR: 6.82) (95% confidence interval: 1.72–27.03) (p = 0.006). Conclusion: PNI is a strong independent predictor of occult lymph node metastasis in penile cancers. Its inclusion in stratification of clinically node negative patients will identify high-risk patients who will benefit from prophylactic lymphadenectomy.
References
1.
Harish
K
, Ravi
R
. The role of tobacco in penile carcinoma
. Br J Urol
. 1995
;75
:375
–7
. .2.
Hakenberg
OW
, Compérat
EM
, Minhas
S
, Necchi
A
, Protzel
C
, Watkin
N
. EAU guidelines on penile cancer: 2014 update
. Eur Urol
. 2015
;67
:142
–50
. .3.
Misra
S
, Chaturvedi
A
, Misra
NC
. Penile carcinoma: a challenge for the developing world
. Lancet Oncol
. 2004
;5
:240
–7
. .4.
Kathiresan
N
, Raja
A
, Ramachandran
KK
, Sundersingh
S
. Role of dynamic sentinel node biopsy in carcinoma penis with or without palpable nodes
. Indian J Urol
. 2016
;32
:57
–60
. .5.
Leijte
JAP
, Kirrander
P
, Antonini
N
, Windahl
T
, Horenblas
S
. Recurrence patterns of squamous cell carcinoma of penis: recommendation for follow-up based on a two-centre analysis of 700 patients
. Eur Urol
. 2008
;54
:161
–8
.6.
Pandey
D
, Mahajan
V
, Kannan
RR
. Prognostic factors in node-positive carcinoma of the penis
. J Surg Oncol
. 2006
;93
:133
–8
. .7.
Horenblas
S
. Lymphadenectomy for squamous cell carcinoma of the penis. Part 1: diagnosis of lymph node metastasis
. BJU Int
. 2001
;88
:467
–72
. .8.
Correa
AF
, Handorf
E
, Joshi
SS
, Geynisman
DM
, Kutikov
A
, Chen
DY
, Differences in survival associated with performance of lymph node dissection in patients with invasive penile cancer: results from the national cancer database
. J Urol
. 2018
;199
:1238
–44
. .9.
Senthil Kumar
MP
, Ananthakrishnan
N
, Prema
V
. Predicting regional lymph node metastasis in carcinoma of the penis: a comparison between fine-needle aspiration cytology, sentinel lymph node biopsy and medial inguinal lymph node biopsy
. Br J Urol
. 1998
;81
:453
–7
. .10.
Ramkumar
A
, Seshadri
RA
, Narayanaswamy
K
, Balasubramanian
S
. Risk factors for lymph node metastasis in clinically node-negative penile cancer patients
. Int J Urol
. 2009
;16
(4
):383
–7
. .11.
Aita
GA
, Zequi
SC
, Costa
WH
, Guimarães
GC
, Soares
FA
, Giuliangelis
TS
. Tumor histologic grade is the most important prognostic factor in patients with penile cancer and clinically negative lymph nodes not submitted to regional lymphadenectomy
. Int Braz J Urol
. 2016
;42
:1136
–43
. .12.
Naumann
CM
, Alkatout
I
, Hamann
MF
, Al-Najar
A
, Hegele
A
, Korda
JB
, Interobserver variation in grading and staging of squamous cell carcinoma of the penis in relation to the clinical outcome
. BJU Int
. 2009
;103
:1660
–5
. .13.
Winters
BR
, Mossanen
M
, Holt
SK
, Lin
DW
, Wright
JL
. Predictors of nodal upstaging in clinical node negative patients with penile carcinoma: a national cancer database analysis
. Urology
. 2016
;96
:29
–34
. .14.
Ficarra
V
, Akduman
B
, Bouchot
O
, Palou
J
, Tobias-Machado
M
. Prognostic factors in penile cancer
. Urology
. 2010
;76
:S66
–73
. .15.
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 Sep–Oct
;47
(5
):943
–56
. .16.
Graafland
NM
, Lam
W
, Leijte
JA
, Yap
T
, Gallee
MP
, Corbishley
C
, 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
–7
. .17.
Piña-Oviedo
S
, Ortiz-Hidalgo
C
. The normal and neoplastic perineurium: a review
. Adv Anat Pathol
. 2008
;15
(3
):147
–64
. .18.
Velazquez
EF
, Ayala
G
, Liu
H
, Chaux
A
, Zanotti
M
, Torres
J
, Histologic grade and perineural invasion are more important than tumor thickness as predictor of nodal metastasis in penile squamous cell carcinoma invading 5 to 10 mm
. Am J Surg Pathol
. 2008
;32
(7
):974
–9
. .19.
Albersen
M
, Parnham
A
, Joniau
S
, Sahdev
V
, Christodoulidou
M
, Castiglione
F
, Predictive factors for local recurrence after glansectomy and neoglans reconstruction for penile squamous cell carcinoma
. Urol Oncol
. 2018
;36
(4
):141
–6
. .20.
Vale
L
, Fernandes
B
, Rodrigues
V
, Dinis
P
, Silva
C
, Antunes-Lopes
T
. Prognostic factors in penile cancer: should we avoid inguinal lymph node staging?
Urol Int
. 2021
;105
(9–10
):799
–803
. .21.
Zhou
X
, Qi
F
, Zhou
R
, Wang
S
, Wang
Y
, Wang
Y
, The role of perineural invasion in penile cancer: a meta-analysis and systematic review
. Biosci Rep
. 2018
;38
(5
):BSR20180333
. .22.
Nascimento
ADMTD
, Pinho
JD
, Júnior
AALT
, Larges
JS
, Soares
FM
, Calixto
JRR
, Angiolymphatic invasion and absence of koilocytosis predict lymph node metastasis in penile cancer patients and might justify prophylactic lymphadenectomy
. Medicine
. 2020
;99
:e19128
. .23.
Paner
GP
, Stadler
WM
, Hansel
DE
, Montironi
R
, Lin
DW
, Amin
MB
. Updates in the eighth edition of the tumor-node-metastasis staging classification for urologic cancers
. Eur Urol
. 2018
;73
(4
):560
–9
. .24.
Emerson
RE
, Ulbright
TM
, Eble
JN
, Geary
WA
, Eckert
GJ
, Cheng
L
. Predicting cancer progression in patients with penile squamous cell carcinoma: the importance of depth of invasion and vascular invasion
. Mod Pathol
. 2001
;14
(10
):963
–8
. .25.
Alkatout
I
, Naumann
CM
, Hedderich
J
, Hegele
A
, Bolenz
C
, Jünemann
KP
, Squamous cell carcinoma of the penis: predicting nodal metastases by histologic grade, pattern of invasion and clinical examination
. Urol Oncol
. 2011
;29
(6
):774
–81
. .26.
Berdjis
N
, Meye
A
, Nippgen
J
, Dittert
D
, Hakenberg
O
, Baretton
GB
, Expression of Ki-67 in squamous cell carcinoma of the penis
. BJU Int
. 2005
;96
(1
):146
–8
. .27.
Zhu
Y
, Zhou
XY
, Yao
XD
, Dai
B
, Ye
DW
. The prognostic significance of p53, Ki-67, epithelial cadherin and matrix metalloproteinase-9 in penile squamous cell carcinoma treated with surgery
. BJU Int
. 2007
;100
(1
):204
–8
. .28.
Hu
J
, Cui
Y
, Liu
P
, Zhou
X
, Ren
W
, Chen
J
, Predictors of inguinal lymph node metastasis in penile cancer patients: a meta-analysis of retrospective studies
. Cancer Manag Res
. 2019
;11
:6425
–41
. .© 2021 S. Karger AG, Basel
2021
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.
