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Rev Mex Urol 2016;76(3):177-182

RGANO OFICIAL DE DIFUSIN DE LA SOCIEDAD MEXICANA DE UROLOGA,


COLEGIO DE PROFESIONISTAS, A.C.

www.elsevier.es/uromx

Clinical case

Partial penectomy as treatment for localized penile cancer at the


Hospital Jurez de Mxico

A.F. Snchez-Bermeo*, G. Martnez-Carrillo, J. Torres-Aguilar and J. Bernal-Hernndez

Urology Service, Hospital Jurez de Mxico, Mexico City, Mexico

Received 23 September 2015; accepted 26 January 2016


Available online 10 March 2016

KEYWORDS Abstract
Cancer of the penis; Background: Cancer of the penis presents in individuals between 50 and 70 years of age,
Partial penectomy; representing only 2-5% of the urogenital tumors in men. However, its incidence varies in some
Papilloma virus; Latin American countries (Paraguay, Brazil) and in Puerto Rico, in which it has been reported to
Phimosis reach 10% of the neoplasias affecting men. Surgery for cancer of the penis is mutilating and
significantly affects the quality of life of these patients. We describe herein our management of
the disease, in accordance with histopathologic stage, proposing less radical management
together with oncologic treatment.
Aim: To present our current management of localized cancer of the penis.
Clinical case: A 42-year-old man presented with a suspicious lesion on the penis plus phimosis.
The lesion was biopsied and the intraoperative histopathologic study was negative for neoplasia.
Lesion excision and circumcision were carried out. The definitive histopathology study was
positive for malignancy and a second surgery (partial penectomy) was performed.
Conclusions: We underline the importance of a correct histopathologic report for aiding the
surgeon in determining the most viable surgery in each case, taking into account the medical,
legal, psychologic, and social aspects of this type of pathology. We also confirm that good
outcome is achieved through adequate surgical management of early-stage disease, as reported
in the medical literature.
2016 Sociedad Mexicana de Urologa. Published by Masson Doyma Mxico S.A. This is an open
access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-
nd/4.0/).

*Corresponding author at: Xola 16 interior 402. Cdigo postal 03400, telephones: 5567051109 cell phone; 55794100 home.
Email: alfredishi@gmail.com, dr.alfredosanchez@hotmail.com (A.F. Snchez-Bermeo).

2007-4085/ 2016 Sociedad Mexicana de Urologa. Publicado por Masson Doyma Mxico S.A. Este es un artculo Open Access bajo la licencia
CC BY-NC-ND (http://creativecommons.org/licenses/by-nc-nd/4.0/).
178 A.F. Snchez-Bermeo et al

PALABRAS CLAVE Penectoma parcial como tratamiento para el cncer de pene localizado, Hospital
Tumor renal; Jurez de Mxico
Voluminoso;
Resumen
Tratamiento;
Antecedentes: El cncer de pene se presenta en hombres entre los 50 y 70 aos de edad,
Nefrectoma radical
representando solamente el 2-5% de los tumores urogenitales masculinos; sin embargo, su
incidencia es variable en algunos pases de Amrica (Paraguay, Brasil, Puerto Rico), en los que
se ha reportado que llega a representar hasta el 10% de las neoplasias masculinas. La ciruga
para el cncer de pene es mutilante y afecta significativamente la calidad de vida de los
pacientes. Mostramos nuestra conducta de acuerdo al estadio histopatolgico y proponemos el
manejo menos radical, simultneamente con el oncolgico.
Objetivo: Presentar el manejo actual de cncer de pene localizado.
Caso clnico: Paciente masculino de 42 aos de edad con lesin sospechosa en pene ms fimosis.
Se realiza biopsia de la misma en primer instan cia con reporte histopatolgico transquirrgico
negativo para neoplasia; se realiza exresis de lesin ms circuncisin. El reporte
histopatolgico definitivo fue positivo para malignidad y se decide llevar a cabo un segundo
tiempo quirrgico (penectoma parcial).
Conclusiones: Destacamos la importancia de un reporte histopatolgico correcto que ayude al
cirujano a normar una conducta quirrgica viable para cada caso, teniendo en cuenta aspectos
mdico-legales, psicolgicos y sociales que implican este tipo de dolencias. Adems confirmamos
que los estadios tempranos con manejo quirrgico adecuado tienen buen pronstico, acorde con
resultados descritos en la literatura.
2016 Sociedad Mexicana de Urologa. Publicado por Masson Doyma Mxico S.A. Este es un
artculo Open Access bajo la licencia CC BY-NC-ND (http://creativecommons.org/licenses/by-
nc-nd/4.0/).

Introduction them were case-control studies. There was a strong


protector effect by circumcision in infancy/adolescence
Penile cancer (PC) presents in men between the ages of 50 against invasive penile cancer (OR = 0.33, 95% CI: 0.13-0.83;
and 70 years, representing only 2-5% of the genitourinary 3 studies). In 2 studies, this same protector effect was not
tumors in men. However, its incidence is variable apparent when the analysis was limited to children with no
in Paraguay, Brazil, and Puerto Rico, where it has been history of phimosis. In contrast, some analyses found that
reported to reach up to 10% of the neoplasias in men. 1 circumcision in adults was associated with a greater risk for
Penile cancer is a rare disease and the poor knowledge invasive penile cancer (OR= 2.71, 95% CI: 0.93-7.94; 3
about the condition among both the public and physicians studies). There was little evidence of an association of
often causes delays in its diagnosis and treatment, making intraepithelial neoplasia of the penis or carcinoma in situ of
them deficient, and can result in the development of the penis with circumcision performed at any age. The
advanced disease requiring extensive surgery. Shabbir et al.2 review by these authors concluded that men that had been
reports that in the United Kingdom, the development of
circumcised in infancy/adolescence had a substantially
supraregional penile cancer centers that combine resources
reduced risk for invasive penile cancer and that this effect
and knowledge has given rise in the last decade to
could be mediated in part by an effect on phimosis.
considerable improvement in the understanding and
Expansion of the circumcision services in sub-Sahara Africa
management of this rare pathology. Nevertheless, there are
as an HIV prevention strategy could reduce the risk for
still holes in our knowledge. Various forms of diagnosis and
penile cancer. However, there is no current demonstration
treatment continue to be controversial, ranging from
prevention and treatment strategies for premalignant of actual benefit. Zequi et al. 4 analyzed whether sexual
disease to the evaluation of lymph node involvement relations with animals was associated with penile cancer
and management of advanced disease. PC has been and sexually transmitted diseases. They found that 136
associated with the risk factors of smoking, phimosis, poor persons (38.4%) engaged in sexual relations with animals
hygiene with an accumulation of smegma and chronic and 48 (45.7%) of them were in the penile cancer group and
irritation (balanoposthitis), and lichen sclerosus. Because of 88 (35.3%) were in the control group (p = 0.073). The authors
the latter factor, some years ago, neonatal circumcision was concluded that sexual relations with animals as a risk factor
proposed as having a protective effect against PC. This for penile cancer merits further study.
was based on a systematic review by Larke et al. 3 of The current medical bibliography accepts the fact that
evidence of an association between circumcision and penile multiple sexual partners is the most important predisposing
cancer. Eight studies were identified that evaluated factor, due to its association with sexually transmitted
the association of circumcision and penile cancer, and 7 of infections, especially the human papillomavirus (HPV).
Partial penectomy as treatment for localized penile cancer at the Hospital Jurez de Mxico 179

Figure 1 Initial lesion, phimosis plus verrucous condyloma acuminata in the glans penis.

There are studies showing that a high percentage of PC is


associated with HPV infection, specifically serotypes 16 and
18, in 80% of primary tumors and 50% of lymph nodes.5-6
Nevertheless, this is incongruous if we consider that the
frequency of this cancer is much lower, compared with the
incidence of cervical cancer, which is also associated with
HPV infection. In addition, a high number of men infected
with HPV are asymptomatic.
Penile cancer is a devastating disease with delayed
diagnosis and causes alterations in body image and self-
esteem, affecting sexual and urinary functions and
compromising quality of life. There has recently been a
growing interest in penile-preserving surgeries for penile
cancer for the purpose of preventing these complications in
the patients.

Case presentation
A 42-year-old man from Mexico City had poor general
hygiene and his past history included: chronic intense
weekly alcoholism reaching drunkenness (since 12 years of
age), smoking (6 cigarettes a day since the age of 9 and to
the present), smoking marijuana for 30 years and up to the
Figure 2 Circumcision plus intraoperative biopsy.
present, and cocaine use for 6 years, but presently
suspended. His sexual activity began at 11 years of age and
he stated having had more than 10 heterosexual partners, was well-differentiated condylomatous squamous cell
never using protection, engaging in risky sexual practices carcinoma of the penis with no perineural or lymphovascular
(with sex workers), and in the past year having only one invasion. According to the report and extension studies
sexual partner. done, the classification was T1N0M0 PC. Partial penectomy
He came to consultation at our service for a lesion at the was then performed. The histopathologic report did not
level of the penis of one-year progression plus phimosis, vary from the previous one and the corpora cavernosa and
with no palpable inguinal lymph nodes (fig. 1). Because of urethra were negative for neoplasia (fig. 3).
the lesion characteristics and the risk factors present, the The patient was released on the second day of hospitaliza-
decision was made to perform circumcision, taking an tion with a transurethral Foley catheter that was removed
intraoperative biopsy (fig. 2). The initial report was negative on the fifth postoperative day (fig. 4). The patient is cu-
for neoplasia (condyloma acuminatum with chronic lichenoid rrently under active surveillance and is asymptomatic with
inflammation). The definitive histopathologic report adequate micturition and nonpainful morning erections.
180 A.F. Snchez-Bermeo et al

Figure 3 Partial penectomy. The urethra is dissected for later urethral meatus creation. The corpora cavernosa and urethra
have no macroscopic alterations.

rational analysis for the therapeutic value of lymph node


dissection. Lymphadenectomy has shown survival benefits,
but it has been suggested that 20% of men with squamous cell
penile cancer have nodal metastases that are not clinically
apparent at the time of initial presentation.
The guidelines for selecting candidates for inguinal
lymph node dissection in patients with clinically negative
inguinal lymph nodes are mainly based on PC histology,
stage, lymphovascular invasion, and primary tumor grade.
However, a recent prospective study stated that these
criteria are still insufficient and that many patients (82%)
have undergone unnecessary lymphadenectomy with this
method of selection. These limitations are the basis for
penile cancer identification through the more reliable
biomarkers. Today there are biomarkers for squamous cell
carcinoma of the penis: associated proliferation markers,
markers related to HPV, P53, cytogenetic markers, and
Figura 4 Postoperative progression. The Foley catheter is squamous cell carcinoma antigen (SCCAg).9 Laniado et al.10
removed (fifth day) and there is adequate micturition and found that the SCCAg was augmented in patients with
nonpainful morning erections. micrometastases to the lymph nodes and showed that an
elevated SCCAg level had a 57% sensitivity and 100%
specificity for predicting lymph node metastasis at a
reference interval of 1.50 g/L.
Discussion In a large case series including 54 patients, Hungerhuber
et al.11 reported a correlation between tumor burden and
Squamous cell carcinoma is the most common histologic SCCAg that increased with extensive lymph node
strain in penile cancer, representing 95% of the cases, as in involvement and metastatic disease. They also stated that
ours, and the remaining 5% correspon d to papillary SCCAg had far-reaching effects on supervision, treatment
carcinoma. Of squamous cell PC, 96% are of the epithelial control, and early recurrence detection after treatment.
strain and 4% are basal cell neoplasias, melanomas, Kaposi The prospective case series by Zhu et al.,12 based on the
sarcomas (pathology whose incidence has increased due to data from 63 patients with penile cancer, showed that
its association with AIDS) and tumors secondary to leukemia despite the confirmation that SCCAg is significantly associated
or lymphoma, as well as anecdotal reports of metastases with lymph node status, it cannot accurately predict the
arising from the kidney and prostate.7-8 presence of occult inguinal lymph node metastasis (LNM).
The biology of squamous cell PC exhibits a prolonged These researchers demonstrated that SCCAg was more an
locoregional phase before distant dissemination, providing a independent prognostic factor in node positive cases and
Partial penectomy as treatment for localized penile cancer at the Hospital Jurez de Mxico 181

was an important predictor of progression-free survival in adhered to deep planes and that are ulcerated and
patients with penile cancer. Despite these promising results, suppurant. They can be accompanied by lymphedema of the
there is still not enough data for including the use of SCCAg pelvic members and genitals. In advanced stages of PC,
in the management guidelines for patients with penile symptoms associated with distant metastasis are
cancer, especially because of the low number of patients common.18-19 The initial dissemination route is through the
involved in these studies. SCCAg appears to be correlated lymphatic vessels of the prepuce to the superficial and
with tumor burden and is useful for following the course of deep inguinal lymph nodes, given that the glans penis
the disease and precocious recurrence. The data on the and urethra drain into the deep external lymph nodes.
capacity of this biomarker to predict the presence of occult Metastases to solid organs via the bloodstream present in
LNM are controversial. A larger prospective study is required less than 10% of patients and the most frequent sites of
to determine the clinical usefulness of this biomarker. metastasis are the lung, liver, and bone. There are several
Saito and Kihara 13 recently suggested that C-reactive clinical stage classifications and the TNM classification is the
protein (CRP) can be a useful biomarker for many types of most widely used in the medical literature. Diagnostic
urologic cancers and that the analysis of the dynamic suspicion is clinical, through appearance and the
changes in CRP concentrations with time could predict abovementioned factors. Diagnosis is established at
tumor aggressiveness and the potential efficacy the time of radical or partial penectomy, depending on the
of treatment. Two studies evaluated CRP blood levels as a clinical stage. Given that there is no consensus on
prognostic marker in penile cancer. In a retrospective study, systematically performing lymphadenectomy in patients
Steffens et al.14 evaluated 79 patients with penile cancer with PC because of the procedures elevated morbidity
and found that an elevated level of preoperative CRP was (cutaneous necrosis, lymphatic fistula, and lymphedema),
significantly associated with lower cancer-specific survival, an effort has been made to improve the staging methods.
but they could not define CRP as an independent prognostic Thus lymphoscintigraphy or dye detection are used to
factor. These preliminary data based on retrospective studies search for the sentinel lymph node, the first node most
suggest that CRP may be an interesting noninvasive prognostic likely to contain metastatic neoplastic cells.20-22
marker and could help identify patients with penile cancer Initial treatment is complete resection of the primary
that could benefit from inguinal lymph node dissection. This tumor through penectomy. The goal is total extirpation of
finding must be confirmed by other studies. the tumor, which is verified through the microscopic study
Biologic markers of associated proliferation, such as Ki- of the surgical margins. Broad-spectrum antibiotics are
67, have been studied as biomarkers in penile cancer. recommended for 4-6 weeks prior to lymphadenectomy or
Stankiewicz et al.15 found a similar association between Ki- sentinel lymph node resection to resolve the regional
67 and tumor grade, but they could not find an association infectious component, thus facilitating the dissection and
with LNM or survival. Likewise, the largest multicenter possibly limiting the complications inherent in
study with 153 patients with squamous cell penile cancer16 lymphadenectomy. The European Association of Urology
found that even though Ki-67 reflected more aggressive proposes that therapeutic success is related to treatment of
behavior and had a positive correlation with the histologic the primary tumor through partial or radical penectomy,
tumor grade, it was not an independent prognostic factor radiotherapy, brachytherapy, or Mohs microsurgery
for cancer-specific survival. According to these results, Ki- accompanied by unilateral or bilateral radical
67 appears to have a positive correlation with tumor grade, lymphadenectomy according to the clinical staging of the
but its prognostic value in relation to LNM or survival is still lymph nodes.23-24 The modifications that have been reported
elusive. in the literature for performing partial lymph node
Zhu et al.17 found that p53 positivity was an independent dissection attempt to reduce the morbidity associated
prognostic factor for survival, even in patients with positive with dissection extension and the devascularization of the
lymph node disease and LNM. In a subgroup analysis it was skin that causes cutaneous necrosis, infection, lymphedema,
found to have a predictive role for T1 patients, helping to and deformity (30-50%).25-26
distinguish those patients at risk for LNM. If partial penectomy is the chosen option, histology should
Currently available methods for predicting results are be carried out by freezing the intraoperative surgical
suboptimal and there is a need for the development of new margins in order to ensure negative margins and
noninvasive markers for penile cancer. Several promising lymphadenectomy without metasasis. 27 The review by
biomarkers for penile cancer have been studied, but none Pompeo et al. 28 proposed various organ-sparing surgical
can be included in current management, mainly due to options, the same ones that have been popularized in
the lack of influence of these studies, given the relatively selected cases (Ta-1, Tis, and some T2), such as wide local
low incidence of this tumor. excision, circumcision, partial penectomy, total or partial
PC presents as a small, visible, verrucous or ulcerative glansectomy with or without glans penis rejuvenation
lesion at the level of the glans penis or the prepuce. It procedures, as well as new glans penis reconstructions using
sometimes bleeds and frequently is associated with spatulated urethral advances or free skin grafts. In general
bacterial infection that produces a fetid odor and has a these options achieve good local control with adequate
purulent secretion. It is not generally painful and due to functional results and satisfactory esthetic appearance.
a lack of medical education together with social and cultural However, there is slight local recurrence compared with
taboos, many patients do not initially seek medical amputations. Contemporary techniques, such as laser or
attention. Early disease progression, as well as secondary cryotherapy, can be carried out in selected cases. In regard
infection, frequently cause unilateral or bilateral inguinal to the primary lesion, the local disease recurrence rate with
adenopathies that can produce large, fixed masses that are total or partial penectomy is between 0-7% and increases to
182 A.F. Snchez-Bermeo et al

50% with conservative treatments such as radiotherapy or 10. Laniado ME, Lowdell C, Mitchell H, et al. Squamous cell carci-
chemotherapy. Follow-up should be carried out every 4 noma antigen: A role in the early identification of nodal metas-
months for the first 2 years, then every 6 months for 2 years, tases in men with squamous cell carcinoma of the penis. BJU
and finally once a year for 4 to 5 years.29 Int. 2003;92:248-50.
11. Hungerhuber E, Schlenker B, Schneede P, et al. Squamous cell
carcinoma antigen correlates with tumor burden but lacks
Ethical responsibilities prognostic potential for occult lymph node metastases in penile
cancer. Urology. 2007;70:975-9.
Protection of persons and animals. The authors declare 12. Zhu Y, Ye DW, Yao XD, et al. The value of squamous cell carci-
that no experiments were performed on humans or animals noma antigen in the prognostic evaluation, treatment monitor-
for this study. ing and follow-up of patients with penile cancer. J Urol.
2008;180:2019-23.
Data confidentiality. The authors declare that they have 13. Saito K, Kihara K. C-reactive protein as a biomarker for urologi-
followed the protocols of their work center in relation to cal cancers. Nat Rev Urol. 2011;8:659-66.
the publication of patient data. 14. Steffens S, al Ghazal A, Steinestel J, et al. High CRP values pre-
dict poor survival in patients with penile cancer. BMC Cancer.
Right to privacy and informed consent. The authors
2013;13:223.
declare that no patient data appear in this article. 15. Stankiewicz E, Ng M, Cuzick J, et al. The prognostic value of
Ki- 67 expression in penile squamous cell carcinoma. J Clin
Financial disclosure Pathol. 2012;65:534-7.
16. May M, Burger M, Otto W, et al. Ki-67, mini-chromosome main-
No financial support was received in relation to this article. tenance 2 protein (MCM2) and geminin have no independent
prognostic relevance for cancer-specific survival in surgically
treated squamous cell carcinoma of the penis. BJU Int.
Conflict of interest 2013;112:E383-90.
17. Zhu Y, Ye DW, Yao XD, et al. The value of squamous cell carci-
The authors declare that there is no conflict of interest. noma antigen in the prognostic evaluation, treatment monitor-
ing and followup of patients with penile cancer. J Urol.
2008;180:2019-23.
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