Carcinoma of the penis: Epidemiology, risk factors, staging, and prognosis

Author
Curtis A Pettaway, MD
Section Editor
Jerome P Richie, MD, FACS
Deputy Editor
Michael E Ross, MD
Disclosures: Curtis A Pettaway, MD Nothing to disclose. Jerome P Richie, MD, FACS Employment: Metamark
Genetics. Michael E Ross, MD Nothing to disclose.
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed
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All topics are updated as new evidence becomes available and our peer review process is
complete.
Literature review current through: Jun 2015. | This topic last updated: Jan 15, 2015.
INTRODUCTION Carcinoma of the penis is a rare malignancy that typically presents as a
painless lump or ulcer on the penis. The vast majority consist of primary epithelial squamous cell
carcinoma. The diagnosis is made based upon biopsy of the lesion.
The epidemiology and risk factors for penile cancer, staging, and prognosis are reviewed here. The
clinical presentation, pathologic features, diagnosis, and treatment of penile cancer are covered
separately. (See "Carcinoma of the penis: Clinical presentation and diagnosis" and "Carcinoma of
the penis: Surgical and medical treatment".)
EPIDEMIOLOGY Cancers of the penis are rare in the United States, Europe, and other
industrialized countries, but are more common in less developed areas of the world, such as parts
of Africa, Asia, and South America. In the United States, penile carcinoma accounts for less than 1
percent of cancers in men, with less than 2000 new cases and 300 deaths annually [1]. However, in
parts of Africa, Asia, and South America, penile cancer accounts for approximately 10 to 20 percent
of all malignancies in men [2].
Penile cancer is typically a disease of older men and rates increase steadily with age [3]. The mean
age at diagnosis is 60 years, though penile cancer is seen in men less than 40 years [4,5].
The prevalence of penile cancer varies by race [3,6]. In a study profiling invasive squamous cell
carcinoma of the penis, 4967 men diagnosed between 1998 and 2003 were identified through the
Surveillance, Epidemiology, and End Results (SEER) program with the following findings [3]:
The incidence rate (per 100,000 men) of squamous cell carcinoma of the penis is
comparable between white and black men (0.81 versus 0.82, respectively; rate ratio [RR] 1.01,
95% CI 0.90-1.13).
Compared with white men, Asian/Pacific Islander men had a 55 percent lower incidence rate
of penile carcinoma (0.37; RR 0.45, 95% CI 0.35-0.58).
There is a higher incidence rate among Hispanic men compared with non-Hispanic men (RR
1.72, 95% CI 1.56-1.88).

RISK FACTORS A number of factors affect the risk of developing penile cancer or a precursor
lesion. In one series, 137 men with penile cancer and 606 men without cancer were interviewed to
ascertain risk factors for in situ and invasive penile cancer [7]. Men who developed penile cancer
were more often single, never married (odds ratio [OR] 2.5, 95% CI 1.1-5.6), and were circumcised
at an older age (mean age, 38 versus 20 years).
Additional risk factors for penile carcinoma include medical conditions affecting the penis, phimosis,
infection with human papillomavirus (HPV), and HIV infection. These and other factors are
discussed below.
Medical conditions of the penis The following medical conditions involving the penis are
associated with an increased risk of penile cancer [7,8]:
Prior history of genital warts (OR 7.6, 95% CI 4.3-13.5).
Prior history of urinary tract infection (OR 1.7, 95% CI 1.1-2.7).
Penile tear (OR 5.2, 95% CI 3.1-8.7). Among men circumcised in childhood the risk was
twofold greater (OR 2.1, 95% CI 1.0-4.7); among men never circumcised, however, it was over
12-fold higher (OR 12.5, 95% CI 5.0-30.5).
History of a chronic penile rash lasting one month or longer (OR 3.2, 95% CI 1.5-6.8).
Prior penile injury (OR 3.5, 95% CI 2.5-8.5).
Known urethral stricture (OR 2.0, 95% CI 1.1-3.9).
Phimosis Phimosis is a circumferential fibrosis of preputial tissue that leads to narrowing and an
inability to retract the penile foreskin over the glans penis. The presence of phimosis is associated
with a 7 to 10-fold higher risk of penile cancer [7,9].
Although men not circumcised in childhood are at an increased risk of penile cancer, at least one
study suggests that this risk is mediated by the presence of phimosis [7]. In a study of 127 men with
penile cancer and 671 men without penile cancer (serving as the control group), major findings
were:
A lack of circumcision was associated with a twofold increased risk of penile cancer (odds
ratio [OR] 2.3, 95% CI 1.3-4.1).
Among uncircumcised men, a history of phimosis increased the risk of penile cancer (OR
11.4, 95% CI 5.0-25.9).
The risk of penile cancer was not elevated among uncircumcised men who did not report a
history of phimosis (OR 0.5, 95% CI 0.1-2.5), though the study was underpowered to evaluate
this association.
Human papillomavirus infection The presence of human papillomavirus (HPV) DNA can be
identified in 30 to 50 percent of all penile carcinomas [10-13]. In a systematic review that included
1466 men with penile carcinomas, 47 percent of cases were associated with HPV, with the majority
associated with HPV-16 (60 percent) or HPV-18 (13 percent) [12]. In contrast, the rate of HPV
infection in the foreskins of otherwise healthy men without penile cancer ranges from 0 to 6 percent
[14,15]. The impact of HPV on prognosis is discussed below. (See 'Prognosis' below
and "Carcinoma of the penis: Clinical presentation and diagnosis", section on 'Molecular
alterations' and "Virology of human papillomavirus infections and the link to cancer", section on
'HPV Genotypes and risk of cancer'.)

HIV infection The incidence of penile cancer is approximately eightfold higher in HIV-infected
men compared with that in non-HIV-infected men. However, penile carcinoma is not considered an
AIDS-defining malignancy [16]. (See "HIV infection and malignancy: Management considerations".)
The mechanism underlying this observation is unclear. Although HIV may be directly responsible,
the increased incidence of penile cancer in this population may be mediated by HPV. HIV infection
is associated with an increased incidence of HPV infection, which may be due to lifestyle risk
factors for acquiring both viruses or may be caused by the host responses to these viruses.
(See "HIV infection and malignancy: Management considerations", section on 'Genitourinary
malignancies'.)
Smegma Smegma is a cheese-like substance produced by glands located within the inner
surface of the foreskin [17]. Smegma begins to form in the first few days of life as the result of
desquamation of epithelial cells in the preputial sac. In addition, secretions from preputial glands
also contribute to smegma formation. Although smegma has been shown to be carcinogenic in
animal models, it is not clear whether it is a carcinogen in humans or an independent risk factor for
penile cancer [18].
Other factors Other factors associated with penile cancer include:
Tobacco exposure Tobacco exposure (ie, smoking or chewing tobacco) is associated with
an increased risk of penile cancer in a dose-dependent fashion [7,8,19,20]. In populationbased case control studies, smokers were 3 to 4.5 times more likely to have penile cancer
compared with nonsmokers [7,8]. The association between smoking and penile cancer is
independent of known confounding factors (such as sexual history) [19].
Cigarette smoke may increase the likelihood of penile cancer by inhibiting the function of
antigen-presenting Langerhans cells, with a subsequent detrimental effect on immune system
surveillance [21]. Alternatively, HPV infection, chronic penile irritation, or phimosis may act
synergistically with cigarette smoking to promote malignant transformation [8].
Psoralen and ultraviolet A photochemotherapy (PUVA) Patients treated with PUVA have an
increased incidence of penile cancer [19,22]. In a prospective study of 892 men treated with
PUVA, 14 patients (2 percent) developed squamous cell carcinoma of the penis or scrotum
[22]. This was approximately 60 times higher than the expected incidence in the general
population. Furthermore, the risk was increased in those exposed to higher levels of PUVA.
Zoophilia In one study from South America, 118 men with penile cancer were compared
with 374 men without penile cancer seen in the same clinics [9]. In multivariate analysis, sex
with animals was associated with a twofold higher risk for penile cancer (OR 2.07, 95% CI
1.21-3.52).
There is no association between sexual orientation and risk of penile cancer [7].
STAGING OF PENILE CANCER The Tumor Node Metastasis (TNM) staging system is used for
staging carcinoma of the penis (table 1). This system was revised in 2010, and is supported by both
the American Joint Committee on Cancer (AJCC) and the International Union for Cancer Control
(UICC) [23].
All men with penile cancer require careful examination of the penis and palpation of the inguinal
lymph nodes. The need for surgical staging of the inguinal nodes is subsequently determined based

upon characteristics of the penile tumor (ie, grade, stage, lymphovascular invasion) and the
presence of palpable inguinal lymph nodes. Computed tomography (CT) is usually not indicated for
newly diagnosed patients without palpable inguinal adenopathy. (See 'Assessment for distant
metastatic (M) disease' below.)
Tumor (T) assessment Clinical examination (by visual inspection and palpation) is required to
evaluate the primary lesion. When the depth or extent of tumor infiltration cannot be determined by
clinical exam, magnetic resonance imaging (MRI) may help identify invasion into the corpora
cavernosum or spongiosum [24].
Information about the primary tumor is used in treatment planning, especially when organpreserving strategies are being considered [25].
Regional node (N) assessment Penile cancer initially spreads through the lymphatics, with the
initial site of involvement being the inguinal nodes, followed sequentially by the pelvic and then
retroperitoneal nodes. Therefore, the accurate assessment of the regional lymph nodes is essential
for both prognosis and the proper management of patients, since resection of small-volume
pathologically involved regional lymph nodes can be curative [26]. (See 'Prognosis' below.)
Unfortunately, a false negative clinical examination of the inguinal region can occur in 9 to 60
percent of patients, depending on primary tumor pathologic features [27,28].
For men presenting with clinical adenopathy, men with large body mass index, and men who have
had prior inguinal procedures, we perform imaging because of the limited usefulness of the physical
exam in these settings [29]. Imaging studies used in this setting include CT, MRI, or CT images
fused with positron emission tomography (CT/PET) [30].
Staging techniques The staging of the inguinal region among men with invasive penile primary
tumors and no palpable adenopathy may be done by ultrasound-guided fine needle aspiration
(FNA), dynamic sentinel node biopsy (DSNB), or superficial or modified inguinal node dissection.
Both of the latter invasive procedures require intraoperative frozen sections of lymph nodes to aid in
treatment planning. A decision on the appropriate approach takes into account the clinical exam and
whether tumor-defined risk factors for regional node involvement are present. The information
obtained at staging is required to formulate an appropriate treatment plan for men with penile
cancer. (See "Carcinoma of the penis: Surgical and medical treatment", section on 'Approach to the
regional nodes'.)
Fine needle aspiration (FNA) FNA is a minimally invasive method to evaluate for malignancy in
men who present with palpable adenopathy. It is performed without local anesthesia using a 23 to
27 gauge needle. The sensitivity and specificity of FNA among men with clinically palpable nodes
are over 90 percent [31]. Among men with no palpable adenopathy, the sensitivity of ultrasoundguided FNA was 39 percent (9 of 23 groins containing metastases), with a specificity of 100 percent
in a series from the Netherlands [32].
Dynamic sentinel node biopsy (DSNB) Lymphatic mapping is based upon the concept that
penile cancers have specific patterns of lymphatic spread and that one or more nodes (ie, sentinel
nodes) are the first to be involved with metastatic disease within a given lymph node basin. This is
demonstrated by injecting the penile tumor with vital blue dye and radioactive tracer followed by
examination of the draining inguinal lymph nodes. If the sentinel lymph nodes are not involved, the

entire basin should be free of tumor. Lymphatic mapping and DSNB have been shown to reliably
predict the presence of regional nodal involvement in other malignancies, such as melanoma and
breast cancer.
A 2012 meta-analysis of 17 studies reported on the detection rate and sensitivity of sentinel node
biopsy in penile cancer [33]:
The pooled sensitivity was 88 percent (95% CI, 83 to 92 percent).
When studies that included patients with palpable nodes were excluded, the pooled
sensitivity increased to 90 percent (95% CI, 85 to 94 percent).
Incorporation of inguinal ultrasound increased the pooled sensitivity of sentinel node
biopsy to 93 percent.
Because of the risk of a false negative result, this approach should be performed only at centers
staffed by experienced surgeons and nuclear medicine specialists. The importance of experience
was demonstrated in a 2010 study that included 342 patients assessed with a modied DSNB
protocol from two high-volume centers [34]. In this experience, the false-negative rate was two
percent (six patients with groin metastases after a negative DSNB).
Superficial inguinal lymph node dissection (SILND) A superficial inguinal lymph node
dissection (SILND) provides more information than biopsy of a single node or group of nodes. In
addition, the possibility of not identifying the sentinel node is limited by removal of all potential
sentinel nodes, and the dissection is readily performed by any surgeon experienced in inguinal
surgery without the need for specialized equipment.
SILND can identify microscopic metastases in patients with a clinically normal inguinal examination,
without the need for a pelvic dissection. This was demonstrated in a retrospective study of 31 men,
most of whom had nonpalpable inguinal nodes at presentation [35]. There were no recurrences
among men who underwent a SILND [35]. However, SILND was associated with a higher overall
complication rate compared with DSNB (12 to 35 versus 5 to 7 percent, respectively).
Modified inguinal lymph node dissection Modified inguinal lymph node dissection was
originally described by Catalona and subsequently updated in two other small series [36-38]. It is
similar to a superficial dissection in creating thick skin flaps, sparing the saphenous vein, and
reducing the borders of dissection. It differs from a superficial dissection in that nodes within the
fossa ovalis are also removed by skeletonizing the femoral vessels. In one series that included nine
patients, there were no inguinal recurrences among patients with negative nodes post-dissection
with 67 months follow-up. The most common complications were lymphoceles and mild extremity
edema.
Staging approach Given the morbidity associated with inguinal lymph node dissection, we tailor
our approach based on tumor-associated risk factors. This enables us to select patients at high risk
for nodal involvement who would be most likely to benefit from surgical staging.
Clinically negative inguinal exam For men with a clinically negative inguinal exam, staging of
the regional nodes is based upon risk estimates for occult nodal metastases.
Both the European Association of Urology (EAU) and the International Consultation on Urologic
Diseases (ICUD) have convened expert panels to provide evidence-based evaluation and
management of the inguinal region. Risk groupings are based upon reported estimates of the

incidence of inguinal lymph node metastases, given the presence of specific prognostic factors.
However, the accuracy of these models has not been established, and there is no consensus on a
preferred model.
EAU system The EAU system stratified the risk of nodal metastases on the basis of tumor
stage and grade among men with no palpable nodes [39]:
Low risk Men with pTis, pTa, and pT1 grade 1 tumor. The risk of nodal involvement
was less than 17 percent.
Intermediate risk Men with pT1 grade 2 tumors. The risk for nodal involvement varied
widely between 9 to 44 percent in two series [40,41].
High risk Men with pT1 grade 3 or pT2 to pT3 tumors. The risk for nodal involvement
was 68 to 73 percent [39].
The ICUD group utilized a risk-based nomogram that takes into account eight
clinicopathologic factors to define risk [42,43]: tumor thickness, microscopic growth pattern,
Broders grade, presence of vascular or lymphatic embolization, infiltration of the corpora
cavernosa, corpus spongiosum or urethra, and the clinical stage of groin lymph nodes.
Compared with EAU systems, the nomogram had better predictive accuracy, though they have
yet to be externally validated and have not been widely adopted [42].
Low risk (nomogram probability of less than 10 percent) pTis, pTa, PT1, no
lymphovascular invasion (LVI)
Intermediate risk (nomogram probability of 10 to 50 percent) T1 grade 2, pT2 grade 1,
no LVI
High risk (nomogram probability of >50 percent) pT2 to 4, grade 2 to 3, or LVI
We apply the following guidelines for staging of men with newly diagnosed penile cancer based on
similarities between the updated EAU and National Comprehensive Cancer Center Guidelines
recommendations [44,45]:
Low risk For men with pTis, Ta, or T1 grade 1 tumors with no LVI (TMN, pT1a) (table 1), we
suggest surveillance rather than either nodal assessment by dynamic sentinel node biopsy or
superficial or modified inguinal node dissection. The complications of nodal evaluation
outweigh the diagnostic and therapeutic benefits of the procedure. (See "Carcinoma of the
penis: Surgical and medical treatment", section on 'Treatment of low-risk disease'.)
Intermediate risk For men with pT1 grade 2 tumors with no LVI (pT1a), we suggest
dynamic sentinel node biopsy, if the expertise is available locally. Superficial or modified
inguinal dissection is an alternative procedure. Active surveillance is a reasonable alternative
to surgery, provided men are informed about the risk of nodal metastases and are compliant
with follow-up. (See 'Dynamic sentinel node biopsy (DSNB)' above and 'Superficial inguinal
lymph node dissection (SILND)' above and 'Modified inguinal lymph node dissection' above.)
High risk For men with grade 3 tumors, clinically negative lymph nodes, and the presence
of LVI (ie, pT1b), we suggest superficial or modified inguinal node dissection or dynamic
sentinel node biopsy to stage the inguinal region.
Clinically suspicious inguinal exam For men with evidence of palpable adenopathy on clinical
exam, we and others suggest a fine needle aspiration (FNA) for pathologic assessment rather than
observation or an initial course of antibiotic therapy. The FNA is sensitive and reliable enough for
diagnostic purposes and will aide in further treatment planning.

For men with low-risk disease (pTis, pTa, pT1 grade 1) with clinically suspicious adenopathy
but a negative FNA, we suggest an excisional biopsy for definitive diagnosis.
For men with high-risk disease with clinically suspicious adenopathy but a negative FNA, we
suggest a superficial or modified inguinal node dissection.
For men with a positive FNA, we proceed with definitive surgical treatment. (See "Carcinoma
of the penis: Surgical and medical treatment".)
For patients with proven metastases by FNA or node biopsy, additional imaging studies such as CT
and CT/PET may be of value in predicting adverse nodal features such as 3 positive nodes,
extranodal extension, or pelvic metastases [30,46].
Men who present with bulky (node size 4 cm) or unresectable lymphadenopathy should proceed
with medical treatment, usually in the form of neoadjuvant chemotherapy or RT. (See "Carcinoma of
the penis: Surgical and medical treatment", section on 'Approach to locally advanced or
unresectable disease'.)
Assessment for distant metastatic (M) disease Hematogenous spread is rare until late in the
disease course, and as such, penile cancer rarely presents with distant metastases. In one series of
681 patients, only 24 (4 percent) developed distant metastatic disease, and in all cases it was late
in the course following locoregional treatment [47]. Therefore, we do not perform routine diagnostic
imaging to assess for distant metastatic disease unless the patient exhibits bulky regional nodal
metastases.
For patients with bulky regional nodal metastases and those presenting with signs and symptoms of
metastatic disease (eg, cachexia, pain, hepatomegaly), computed tomography of the chest,
abdomen, and pelvis should be performed. PET/CT is also a sensitive imaging option [30,46]. In
addition, routine laboratory studies should include serum calcium to evaluate for tumor-induced
hypercalcemia because prompt treatment can rapidly reverse altered mental status [48]. Brain
metastasis from penile carcinoma is exceedingly rare and MRI among asymptomatic patients is not
required.
PROGNOSIS The presence of nodal involvement is the single most important prognostic factor
for men with penile cancer. Accumulating evidence suggests that human papillomavirus (HPV)
infection may play a prognostic role as well.
Nodal involvement The single most important prognostic factor for survival among patients with
penile cancer is the presence and extent of nodal metastases (table 1). The five-year cancerspecific survival (CSS) stratified by nodal involvement was as follows in a published review article
[49] (table 1):
pN0 (no inguinal metastases) 85 to 100 percent
pN1 (single metastasis) 79 to 89 percent
pN2 (bilateral or multiple inguinal metastases) 17 to 60 percent
pN3 (pelvic metastases) 0 to 17 percent
Given the poor prognosis associated with extranodal extension, it has been incorporated in the pN3
category (along with pelvic nodal metastases) in the 2009 American Joint Commission on Cancer
(AJCC) staging system [23].

The prognostic significance of both of these factors was shown in one series of 102 patients with
node-positive disease. Of 21 patients with pelvic node involvement, all had succumbed to disease
within three years of diagnosis [50]. In the same series, extranodal extension was seen in the
inguinal region in 54 men. These patients had a significantly lower rate of five year survival
compared with those without evidence of extranodal extension (9 versus 90 percent) [50].
Impact of HPV-infection The presence of high-risk HPV DNA may be associated with improved
disease-free survival in penile cancer. High-risk HPV DNA expression does not appear to be
strongly correlated with lymph node metastasis, but in some studies it is associated with a survival
benefit [10,11,51-54].
In a study of 82 men with penile cancer, HPV DNA was detected in 30 percent [10]. Although
HPV positive tumors were less likely to be associated with lymphatic tumor embolization, there
was no difference in either the presence of lymph node metastases or in the 10-year survival
rate (68 versus 69 percent in HPV-negative and HPV-positive patients).
A separate study of 171 patients reported the presence of high-risk HPV in 29 percent of
tumors [11]. The presence of high-risk HPV DNA in penile carcinoma was associated with
significantly improved disease-specific survival at five years (hazard ratio for mortality 0.14,
95% CI 0.03-0.63; 93 versus 78 percent in HPV-negative patients). In a subsequent study
from the same institution that included 212 additional patients, the incidence of high-risk HPV
DNA was 25 percent and did not correlate with the presence of lymph node metastasis.
However, the five-year disease-specific survival rates among the HPV-negative and positive
cohorts were 82 and 96 percent (p = 0.02), respectively. The prognostic value of HPV
presence remained after adjusting for stage, grade, lymphovascular invasion (LVI), and age
[51].
The expression of the cell cycle regulatory protein p16ink4a (P16) is highly correlated with
HPV infection, with a sensitivity and specificity of 67 to 88 percent and 89 to 91 percent,
respectively [52,53]. P16 immunohistochemistry is relatively simple to perform when compared
with polymerase chain reaction assays for HPV genotyping. In a study from Germany,
prognosis was assessed based upon p16 expression in a cohort of 92 penile cancer patients.
The two-year cancer-specific survival rate was higher in those who were p16 positive (95
versus 73 percent), and the difference persisted at five years (85 versus 57 percent) [54].
Collectively, emerging data suggest that high-risk HPV DNA expression in tumors may be a positive
prognostic factor for survival and that measuring p16 expression in tumors via
immunohistochemistry provides similar information. P16 expression along with viral koilocytic
changes, tumor stage, and grade were independent prognosticators of cause-specific survival.
SUMMARY AND RECOMMENDATIONS
Cancers of the penis are rare in the United States, Europe, and other industrialized
countries, but occur at a higher frequency in developing countries. (See'Epidemiology' above.)
Penile cancer is typically a disease of older men and rates increase steadily with age,
although men of any age may be affected. (See 'Epidemiology' above.)
A number of risk factors are associated with an increased risk of penile cancer, including
medical conditions of the penis, phimosis, human papillomavirus (HPV) infection, and HIV
infection. (See 'Risk factors' above.)

The Tumor Node Metastasis (TNM) staging system is used for staging carcinoma of the
penis. (See 'Staging of penile cancer' above.)
All men with penile cancer require examination of the penis and inguinal region. Radiologic
exam by computed tomography or MRI is suggested for patients presenting with clinical
adenopathy or those with large body mass index because of the limited usefulness of the
physical exam in that setting. (See 'Tumor (T) assessment' above.)
Surgical assessment of nodes in men with penile cancer is based on primary tumor factors at
diagnosis that place them at varying risk for inguinal lymph node metastases as defined by the
tumor stage, grade, LVI, and the presence of palpable adenopathy. (See 'Regional node (N)
assessment' above.)
For men with no palpable adenopathy on clinical exam (see 'Clinically negative inguinal
exam' above):
We suggest surveillance for men with low-risk disease (eg, pTa, pTis, or pT1 grade 1, no
poorly differentiated cancer, no LVI [ie, AJCC stage pT1a]), rather than nodal
assessment by dynamic sentinel node biopsy (DSNB) or superficial inguinal node
dissection (SILND) (Grade 2C). The complications of nodal evaluation outweigh the
diagnostic and therapeutic benefits of the procedure. (See "Carcinoma of the penis:
Surgical and medical treatment", section on 'Treatment of low-risk disease'.)
Among patients with intermediate-risk disease (eg, pT1 grade 2, American Joint
Committee on Cancer [AJCC] T1a) (No LVI), either a DSNB or a modified or superficial
ILND can be performed, with the choice based on local expertise. However, for wellinformed and compliant patients, close observation at three-month intervals may be a
reasonable alternative.
We recommend an initial staging superficial or modified ILND or DSNB for men with
high-risk disease (AJCC stage pT1b [grade 3 or LVI]), depending on local expertise.
These men are not appropriate candidates for surveillance.
For men with palpable adenopathy on clinical exam, we and others suggest a fine needle
aspiration (FNA) for pathologic assessment rather than observation or an initial course of
antibiotic therapy. (See 'Clinically suspicious inguinal exam' above.)
For men with low-risk disease with clinically suspicious adenopathy but a negative FNA,
we perform an excisional biopsy for definitive diagnosis.
For men with high-risk disease with clinically suspicious adenopathy but a negative
FNA, we suggest a superficial or modified inguinal node dissection. (See"Carcinoma of
the penis: Surgical and medical treatment", section on 'Clinically suspicious
examination'.)
For men with a positive FNA, we suggest a therapeutic inguinal node dissection after
the appropriate imaging studies are performed. (See "Carcinoma of the penis: Surgical
and medical treatment", section on 'Clinically suspicious examination'.)
For men who present with bulky (node 4 cm) or unresectable lymphadenopathy, we suggest
neoadjuvant chemotherapy rather than surgery (Grade 2B). Prior to treatment, these men
should undergo a further staging work-up to define the extent of disease. (See "Carcinoma of
the penis: Surgical and medical treatment", section on 'Approach to locally advanced or
unresectable disease'.)

The presence and extent of inguinal lymph node metastases is the strongest predictor of
cancer-specific survival. (See 'Prognosis' above.)
High-risk HPV DNA expression along with p16 measured in primary tumors may represent
emerging prognostic markers in penile cancer.
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