J Radiat Oncol (2016) 5:143–151
DOI 10.1007/s13566-016-0247-6
REVIEW
Radiation therapy for the management of penile cancer
M. Leann Smith 1 & Juanita Crook 2 & Ozer Algan 1
Received: 18 September 2015 / Accepted: 3 April 2016 / Published online: 29 April 2016
# Springer-Verlag Berlin Heidelberg 2016
Abstract
Objective This article will focus on the use of radiation ther-
apy in the treatment of penile cancer as an alternative to full or
partial penectomy. The use of brachytherapy as well as exter-
nal beam radiation therapy will be covered.
Methods Pertinent literature concerning radiation therapy
techniques in the treatment of penile cancer will be reviewed.
Results Local control and organ preservation rates with inter-
stitial brachytherapy for penile cancer are in the range of 70–
100 and 55–100 %, respectively. The use of external beam
radiation therapy produces local control rates in the range of
50–70 % with penile preservation in the range of 55–66 %.
The cause-specific survival ranges from 66 to 99 %.
Conclusion Penile cancer is an uncommon cancer that has
historically been treated with penectomy. Although
penectomy provides a high local control rate, it is associated
with significant psychosocial side effects. Radiation therapy
in the form of brachytherapy or external beam therapy offers
an organ-preserving treatment option with high rates of local
control and penile preservation.
Keywords Penile cancer . External beam radiation therapy .
Brachytherapy . Organ sparing
* M. Leann Smith
Mary-smith@ouhsc.edu
1
Stephenson Cancer Center, University of Oklahoma Health Sciences
Center, 800 NE 10th Street, Oklahoma City, OK 73104, USA
2
BCCA Center for the Southern Interior, University of British
Columbia, 399 Royal Avenue, Kelowna, BC V1Y 5L3, Canada
Introduction/epidemiology
Carcinoma of the penis is an uncommon tumor that is more
common in uncircumcised men. In the USA, the incidence of
penile cancer is low with an estimated 1820 new cases and
310 deaths occurring from penile and other rare genital can-
cers in 2015 [1]. The incidence of penile cancer is higher in
Brazil, at 2.9–6.8 case per 100,000, and in India, with a rate of
3.3 per 100,000, than that seen in the USA where the rate is
0.2/100/000 cases [2, 3]. Circumcision has proven to be pro-
tective with a threefold reduction in the risk of penile cancer if
performed during infancy [4]; however, several case reports
have been published describing rare cases of penile cancer in
men circumcised at infancy. Saibishkumar et al. report on
three cases of squamous cell carcinoma of the penis in men
who all had a history of condylomata acuminatum [5]
Phimosis may also be a factor in up to 50 % of cases [6].
Over 95 % of penile cancers are squamous cell carcinomas
(SCC), but other types include basal cell carcinoma, melano-
ma, sarcoma, and lymphoma [2, 7, 8]. Forty to 50 % of pa-
tients with penile cancer will have viral DNA for HPV, with
HPV16 and HPV18 being the more common subtypes [9, 10].
Up to 50 % of patients have inguinal lymph node involve-
ment, which commonly is bilateral [2, 11–15]. The majority of
patients, however, present with early-stage, T1 N0 M0, with
grade 1 or 2 disease [16]. The rate of distant metastasis at
diagnosis is low, at 10 %, even in patients (pts) with advanced
disease [6, 17]. For early-stage penile cancer, the gold stan-
dard has been surgical resection. Local control rates in the
range of 80–90 % are seen with total penectomy surgery
[18–20] and around 72 % for penis-preserving surgery [21].
Despite favorable outcomes, penectomy can have a significant
psychosocial impact on patients [22–24]. Because of the qual-
ity of life and psychosocial impact of penectomy, various
organ-preserving treatment options have been developed.
144 J Radiat Oncol (2016) 5:143–151

These include glans-sparing surgery, laser therapy, brachy- Table 2 AJCC/UICC TNM staging system
therapy, or external beam radiation therapy. AJCC/UICC staging, seventh edition [31]

Tis Carcinoma in situ

Methods T0 No evidence of a primary tumor
Ta Noninvasive verrucous carcinoma
The following discussion will detail the management of penile T1a Invasion of subepithelial connective tissue
with no lymphovascular
cancer with organ-sparing radiation therapy.
Invasion and not poorly differentiated
T1b Invasion of subepithelial connective tissue and
Workup lymphovascular
Invasion or IS poorly differentiated
The location, appearance, size, and depth of invasion of the T2 Invasion of corpus spongiosum or cavernosum
lesion should be evaluated and documented, including exami- T3 Invasion of urethra
nation of the inguinal region, as the presence of inguinal lymph- T4 Invasion of adjacent structures
adenopathy has a significant impact on prognosis, choice of N0 No palpable enlarged inguinal lymph nodes
treatment modality, and outcome. A biopsy is required to con- N1 Palpable, mobile, single unilateral inguinal
firm the diagnosis of cancer as well as to assess the depth of lymph node
invasion. Imaging studies including US, CT scan, PET/CT, and N2 Palpable, fixed, inguinal node(s) or pelvic
MRI scans can all be useful in evaluating the extent of disease lymphadenopathy (unilateral or bilateral)
[25–27]. A meta-analysis from 2012 on the use of PET/CT M0 No distant metastases
suggested a pooled sensitivity and specificity of 81 and 92 %, M1 Distant metastases
respectively [26]. MRI may be best suited for evaluating the Staging
primary for depth of invasion [27]. The use of lymphotropic 0 Tis, Ta N0 M0
nanoparticles as a part of the MRI study has been developed, I T1a N0 M0
[28]. Ferumoxtran-10 has shown promise in determining the II T1b–3 N0 M0
presence of regional lymph node metastases with sensitivity, IIIA T1–3 N1 M0
specificity, PPV, and NPV of 100, 97, 81, and 100 %, IIIB T1–3 N2 M0
respectively [29]. IV T4 any N M0
Any T N3 M0
Any T any N M1
Staging and prognostic factors

The two most common staging systems for penile cancer in-
clude the Jackson Staging System (Table 1), based on extent
of invasion and nodal metastasis [30], and the AJCC/UICC
TNM staging system [31] (Table 2).
Important prognostic factors include the size and extent of
the primary lesion, tumor grade, and the presence of inguinal
and pelvic lymphadenopathy. The risk of nodal involvement
increases with tumor size, depth of invasion, and tumor grade
[22, 32–34, 35]. As the inguinal lymph node burden increases
or with the presence of pelvic nodal metastases, outcomes
Table 1 Jackson Staging System based on extent of invasion and nodal
metastasis
Jackson staging system [30]
Stage
I Cancer confined to the glans or prepuce
II Invasion into shaft or corpora
III Operable inguinal lymph node metastasis
IV Invades adjacent structures or inoperable inguinal lymph nodes
worsen significantly [20, 34–39]. From a treatment outcome
perspective, risk grouping is based on various pathologic fac-
tors including tumor grade, depth of invasion, and lymph node
status. Low risk includes patients with Tis to T1-grade 1 (G1)
tumors and negative inguinal lymph nodes. Patients with T1-
grade 2 (G2) tumors are considered intermediate risk, and
evaluation of additional risk factors such as the presence of
perineural and lymphovascular invasion, tumor size, and
depth of invasion is recommended. For any tumor greater than
T1 or G2 or those considered high risk, lymph node evaluation
is recommended. Locally advanced disease includes T3–T4
tumors; multiple, large, or matted inguinal lymph nodes;
extracapsular extension; or extension to pelvic lymph nodes
(LNs). Prognostic factors for those with advanced stage dis-
ease included ECOG PS >1 or visceral metastases at time of
diagnoses as reported by Pond et al. [38].
Treatment with radiation therapy
Penectomy can provide excellent local control but is asso-
ciated with considerable psychological and sexual
J Radiat Oncol (2016) 5:143–151
morbidity [23, 40, 41]. Partial penectomy and lymphade-
nectomy have been associated with difficulties of body im-
age, sexual function, life interference, and urination [41].
Because of this, more and more patients are undergoing
organ-sparing treatment, as reflected in the updated
European Urology Association guidelines [32]. Radiation
therapy provides organ sparing and can achieve similar
treatment outcomes to penectomy while maintaining organ
function and reducing morbidity [42].
For early-stage cancers, radiation treatment is performed
with either brachytherapy or megavoltage treatment ma-
chines. External beam radiation has the advantage of being
more readily available and producing a more homogenous
dose distribution with a larger margin around the tumor.
Brachytherapy has the advantage of greater conformality
and a shorter treatment time. Most of the published reports
on brachytherapy have used either low dose rate (LDR) or
pulsed dose rate (PDR) brachytherapy. The data for chemo-
radiation therapy in the setting of advanced penile cancer is
limited [43], but an international cooperative phase III trial
is being developed through the International Rare Cancers
Initiative. As of July 2015, this trial has not begun to
accrue patients. Adjuvant RT has been utilized in the set-
ting of positive margins or positive lymph nodes, especially
if multiple lymph nodes or extracapsular extensions are
present [18, 19, 44]. Circumcision, performed prior to ex-
ternal beam radiation therapy (EBRT) or brachytherapy, is
recommended to expose the lesion and allow full evalua-
tion as well as to prevent treatment side effects such as
fibrosis, contracture, and phimosis [45, 46].
Treatment of the primary with brachytherapy
Canada, France, India, and Brazil have provided most of the
data for brachytherapy using LDR iridium (Ir-192) wires or
strands, PDR automated afterloading, or fractionated high-
dose-rate treatments. For patients undergoing LDR brachy-
therapy, the 5-year local control rates range from 78–95 %
(Table 3).
The most commonly prescribed dose is 60 Gray (Gy) de-
livered at 0.40–0.60 Gy per hour. Local control is improved
with wider needle spacing, as this provides a larger margin
and greater depth of treatment in accordance with the Paris
system [14, 31, 47, 48, 49–51]. The penile preservation rate
for patients undergoing LDR brachytherapy ranges from 58 to
88 % at 5 years. The most commonly reported side effects
from brachytherapy include soft tissue ulceration and meatal
stenosis. Factors associated with worsening toxicity include
higher brachytherapy dose rate, larger tumor size/volume of
implant, and higher total treatment dose [46, 52, 53].
Published treatment outcomes with brachytherapy are
listed in Table 3. The 5-year cause-specific survival (CSS)
ranges from 66 to 92 % (5–10 years) depending on the tumor
145
stage and risk group. The impact of local recurrence on
cancer-specific survival is not significant due to the high rates
of successful surgical salvage for tumor recurrence. Several
authors have published results of LDR brachytherapy. Petera
reported on ten patients with early penile cancer treated with
high-dose-rate (HDR) brachytherapy using a breast interstitial
template [51]. The prescribed dose was 54 Gy given in 18
fractions using twice-a-day treatment regimen. At a median
FU of 20 months, they reported a 100 % local control rate and
a 100 % penile preservation rate with no incidence of necrosis
or severe stenosis. Sharma described 14 pts treated with HDR
with T1–T2 stage disease treated with two- to four-plane free-
hand implants using plastic catheters utilizing doses of 42–
51 Gy in 14–17 fractions. All pts developed grade III skin
toxicity that healed within 8 weeks. Three-year overall surviv-
al (OS) was 83 % with a penile preservation rate of 93 %. No
pts experienced urethral stenosis or necrosis [54].
Brachytherapy provides excellent local control, in the range
of 80 %, with an associated high organ preservation rate of
65–93 %. For those patients that develop a local recurrence,
surgical salvage is often successful.
Treatment technique for brachytherapy
Brachytherapy delivers a high dose to a limited volume, main-
taining a high likelihood of cure with an acceptable risk of side
effects. The American Brachytherapy Society–Groupe
European de Curietherapie–European Society of Therapeutic
Radiation Oncology (ABS-GEC-ESTRO) published their
consensus statement on the use of brachytherapy for penile
cancer [50]. The majority of studies used afterloading cathe-
ters placed in accordance with the Paris system of dosimetry
(Table 3). For the majority of tumors, a two- or three-plane
implant is appropriate.
The recommended spacing between the needles is 12–
18 mm [14, 50]. For LDR brachytherapy, the prescription
dose is 60 Gy given at a continuous dose rate of 0.40–
0.60 Gy/h. When PDR brachytherapy is used, hourly pulses
of radiation, equivalent to the hourly dose rate of an LDR
implant, are delivered [31, 50]. The recommended needle
spacing for HDR is 10–12 mm [50]. Because HDR treatments
vary the dose at different dwell positions along each catheter,
the exact spacing of needles is less crucial. CT-based planning
with 3D reconstruction of the catheters, target volume, and
surrounding normal tissues, including urethra and skin, is
mandatory. There are no clearly established dose regimens
for HDR brachytherapy. Generally, treatments are delivered
twice daily, with at least 6 h between treatments. Petera pre-
scribed a dose of 54 Gy, given in 3-Gy fractions, twice daily
[51]. The ABS-GEC-ESTRO report also presented unpub-
lished dose regimens including 38.4-Gy total dose given in
3.2-Gy fraction size over 6 days using a twice daily (BID)
regimen [50].
146 J Radiat Oncol (2016) 5:143–151

Table 3 Outcomes with

brachytherapy Author Treatment N LC Penile preservation Dose (Gy) F/U
months

Chaudhary [55] LDR 23 70 % 70 % 40–60 4–117

8 years 8 years
Crook [45] LDR 67 87.3 % 88 % 60 48
5 years 5 years
Daly [51] LDR 22 95 % 86 % 50–60 63
5 years 5 years
Delannes [56] LDR 51 86 % 75 % 50–65 65
5 years 5 years
DeCrevoisier [53] LDR 144 80 % 72 % 65 68
10 years 10 years
Kiltie [50] LDR 31 81 % 75 % 63.5 61.5
5 years 5 years
Mazeron [57] LDR 50 78 % 74 % 60–70 36–96
5 years 5 years
Petera [47] HDR 10 100 % 100 % 3 BID 20
20mos 20mos X18
Rozan [58] LDR 184 85 % 76 % 59 139
5 years 5 years mean
Sharma [48] HDR 14 90 % 93 % 42–51 22
22 months
Soria [38] HDR 102 89 % 68 % 61–70 111
5 years 10 years
Suchaud [52] LDR 53 79 % 58 % <65 >10 years
5 years 5 years
Akimoto [59] HDR 15 80 % 73 % 32–74 84
5 years 5 years
Neave [69] HDR 24 87 % 55 % 55.6 –
MOLD 5 years 10 years
Rodriguez [60] HDR – 72–80 % 70 % 2–5Gy/fx 2–5 years
MOLD 10 years 30–56 TD

Treatment of the primary with EBRT
The local control rates utilizing external beam radiation ther-
apy in the management of primary penile cancer range from
50 to 70 %, and penile preservation varies from 55 to 66 % for
invasive cancers. Factors predicting worse local control in-
clude a total dose less than 60 Gy, daily fraction size less than
2 Gy, and an overall treatment time greater than 45 days [34,
65]. The 5-year OS rates range from 57 to 88 %. In subset
analysis, the overall survival rates for T1 N0 or T2 N0 disease
are as high as 90–100 %, [61, 62]. The cause-specific rate
varies from 66 to 96 %. The necrosis and stenosis rates report-
ed are in the range of 1–12 % for necrosis and 6–29 % for
stenosis [7, 34, 42, 63, 64, 65–69]. In general, patients selected
for external beam radiation therapy tended to have either more
advanced disease or poorer health and are therefore not surgi-
cal candidates. The external beam radiation literature contains
heterogeneous patient populations and treatment techniques
that span several decades, over which time there have been
vast technological improvements in radiation therapy.
Techniques have advanced from kilovolts and cobalt units to
high-energy linear accelerators with CT-based treatment plan-
ning. Planning and delivery of radiation is now performed in a
more conformal three-dimensional fashion, especially with
the use of intensity-modulated radiation therapy (IMRT).
The ability to verify patient setup has improved with the use
of on-board imagers and cone beam CT scans. This will im-
prove treatment outcomes and reduce side effects from exter-
nal beam radiation therapy.
External beam radiation therapy allows treatment of the full
thickness of the penis while preventing irradiation of surround-
ing normal tissues. Various techniques including the use of a
Perspex block, wax mold, water baths, or use of a cup or box of
rice with a central cutout for the penis have been developed to
achieve this goal [34, 42, 53, 67, 70, 71]. The entire length of
the penis is treated (Fig 1; box of rice with central cutout). The
material used to create the block acts as bolus to ensure ade-
quate dosage of the skin surface. As the treatment progress,
edema may necessitate modification to the chamber. Systems
utilizing the water bath technique [71] require treatment of
J Radiat Oncol (2016) 5:143–151 147

Fig. 1 Box of rice with central cutout

patients in the prone position. Patients are laying either on node dissection (ILD) is recommended for higher-grade or ad-
Styrofoam slabs with a cutout in the region of the pelvis or vanced T stage [33]. Clinically positive lymph nodes should
on a special plate with a central cutout that is attached to the undergo node dissection [19, 72]. Pathologically negative nodes
patient couch top. This cylinder can be filled with lukewarm do not require additional prophylactic treatment of the inguinal
water to act as bolus [70]. Generally, two opposed fields are regions [8, 32, 46, 57, 48]. For unresectable nodal disease, neo-
used with various dose fractionation regimens ranging from adjuvant therapy is recommended. This can be in the form of
35 Gy in 10 fractions to 60 Gy in 25 fractions to 74 Gy in 37 chemotherapy [32, 33], radiotherapy [73, 74], or concurrent che-
fractions. The most commonly used doses are in the range of moradiotherapy [13, 75]. For patients with low nodal tumor bur-
60–66 using standard fractionation size of 2 Gy. Because penile den involving only the superficial inguinal lymph nodes, the
cancer originates on the skin, the skin surface must receive the
full dose. Due to the rarity of penile cancer and the lack of large
trials, treatments are often individualized. Published treatment Table 4 Outcomes with EBRT
outcomes with EBRT are listed in Table 4. Author N LC Penile Dose (Gy) F/U
5 years preservation months
Management of lymph nodes
Azrif [61] 41 62 % 62 % 50–52.5 54
5 years 16 fx
The risk of LN involvement is dependent on the tumor size, Gotsadze [66] 155 65 % 65 % 40–60 78
grade, depth of invasion, and the presence of perineural or 5 years
McLean [70] 26 61.5 % 66 % 25/10 f. or 116
lymphovascular invasion [15, 19, 33]. Because of the midline 5 years 60/25 fx
location, lymphatic spread can occur to either side of the inguinal Mistry [7] 62 63 % 66 % 50/20 fx–55/16 fx 62
5 years
region. Treatment of the regional nodes remains controversial. Neave [69] 20 69.7 % – 50–55 36
For clinically negative inguinal lymph nodes, the risk of Ozsahin [41] 33 44 % 52 % 52 62
micrometastases can be as much as 40 % [20]. In patients with 5 years
Ravi [46] 128 65 % 65 % 50–60 83
palpable LNs, approximately 50 % will be metastatic and 50 % 5 years
reactive [13]. For low-risk early-stage penile cancer with clini- Sarin [33] 59 60 % 55 % 40–78.4 62
cally negative inguinal lymph nodes, observation of the groins is 10 years
Zouhair [39] 23 57 % 18 % 45–74 70
recommended. Pathologic staging of the lymph nodes with either 5 years
dynamic sentinel lymph node biopsy or modified inguinal lymph
148
5-year OS can be as high as 80 % [12], but this decreases to
10–20 % for bilateral or pelvic LN involvement and 10 % in the
presence of extracapsular extension [13]. When treating the re-
gional lymph nodes, a dose of 45–50 Gy in 5 weeks with a boost
to known areas of gross disease or extracapsular extension is
recommended. Many reports for nodal treatment involved treat-
ment prior to the advent of CT simulation and 3D treatment and
included AP or AP/PA fields [44]. Volumes should encompass
both the superficial and the deep inguinal nodes. When the pelvic
lymph nodes are included in the target volume, an IMRT treat-
ment technique can cover the inguinal and pelvic lymph nodes
while limiting the dose to the surrounding normal tissues (Figs. 2
and 3, nine-field IMRT, axial and coronal images). Doses in the
range of 45–50.4 Gy are used for treatment of areas with
suspected microscopic disease. A further boost to a total dose
in the range of 60–70 Gy, depending on the extent of disease, is
recommended for areas with gross residual tumor [37].
Concurrent chemoradiotherapy
There is little published data on concurrent chemoradiation for
penile cancer. Considering a similar entity, SCC of the vulva,
there is published GOG trial data demonstrating high clinical
and pathologic response rates of 64 and 50 %, respectively,
with the combination of EBRT and concurrent cisplatin, mak-
ing this the standard for neoadjuvant care for locally advanced
vulvar cancer [68, 76]. Pond retrospectively reviewed the
Fig. 2 Nine-field IMRT, axial image
J Radiat Oncol (2016) 5:143–151
cases of 26 pts with penile cancer with a wide variation in
stage and some with visceral metastases, who received a wide
dose range of 1800–7000 cGy, treated with EBRT and cisplat-
in. They found poor outcomes for locally advanced disease.
When M1 disease was excluded, OS and progression-free
survival (PFS) were 10 and 6 months, respectively [77]. In a
review by the same author of 140 men from 13 institutions,
cisplatin-based regimens were associated with better OS but
not PFS compared with noncisplatin-based regimens [38].
Effects of treatment on normal tissue
For treatment of the primary, severe skin reaction is the most
common acute side effect seen with EBRT or brachytherapy
and can appear at weeks 2–3 after initiation of treatment.
Treatment includes good hygiene, sitz baths, topicals, and
nonstick dressings. Urethritis can also occur in the acute set-
ting and is generally managed symptomatically. Late effects
include soft tissue ulceration and meatal stenosis. For brachy-
therapy, ulceration generally occurs 6–18 months after treat-
ment but can occur later [63]. The risk of ulceration increases
with doses over 60 Gy [48]. Initial conservative management
is recommended, including the use of creams containing anti-
biotic, steroids, and/or vit. E. In severe cases, hyperbaric ox-
ygen can be very beneficial [78]. Urethral/meatal stenosis
tends to occur within the first couple of years after completion
of therapy. For patients receiving brachytherapy, the proximity
J Radiat Oncol (2016) 5:143–151
Fig. 3 Nine-field IMRT, coronal image
of the needles to the urethra is associated with an elevated risk
of stenosis [57]. For external beam radiation therapy, the risk
of urethral stenosis is associated with fraction sizes >2 Gy.
With the use of proper treatment planning, the likelihood of
these late complications is low, especially when compared to
older treatment techniques.
The psychosocial and psychosexual morbidity of treatment
for penile cancer cannot be overlooked. Regarding one report
on treatment outcomes from brachytherapy, 21 % of pts who
experienced fibrosis and/or necrosis ultimately required am-
putation (56). Potency, or the ability to obtain an erection, is a
concern for many patients. Intercourse can be resumed 4–
6 weeks post brachytherapy, and only 2 of 30 men in a report
by Crook et al. reported a loss of potency after implantation
[78] and 17 % of sexually active patients reported mild im-
pairment in the ability to acquire an erection in another study
by Sarin (38). In patient-reported outcomes, cosmesis was
generally reported as good to excellent after brachytherapy
(60). In a detailed assessment of psychosexual morbidity of
treatment for penile cancer conducted by Opjordsmoen et al.,
overall sexual function was normal or only slightly reduced in
10 of 12 men treated with radiotherapy. When evaluating all
treated patients, including those treated with EBRT and those
treated with partial or total penectomy, they also found that
patients who demonstrated mental symptoms at follow-up
were less satisfied and showed less social activity, than those
who had no mental symptoms (26). This would justify psy-
chosocial treatment for those patients who demonstrate diffi-
culty adapting post treatment.
149
Conclusion
For patients with early-stage (T1 N0, T2 N0) penile cancer,
radiation therapy, either in the form of brachytherapy or exter-
nal beam radiation therapy, offers an organ-preserving treat-
ment option with high rates of local control and penile pres-
ervation. When necessary, surgical salvage for local recur-
rence has little impact on CSS. For advanced disease, a com-
bined modality treatment approach is recommended. In pts
with involved lymph nodes or ECE, adjuvant radiation to
the regional lymph nodes is recommended. Due to the rarity
of this disease and absence of large clinical trials, treatment
needs to be individualized.
Compliance with ethical standards
Conflict of interest M. Leann Smith, Juanita Crook, and Ozer Algan
declare that they have no conflict of interest.
Ethical approval This article does not contain any studies with human
participants or animals, performed by any of the authors.
References
1. American Cancer Society Cancer facts and figures, 2015. http://
www.cancer.org/research/cancerfactsfigures/cancerfactsfigures/
cancer-facts-figures-2015; 2015.
2. Burgers JK, Badalament RA, Drago JR (1992) Penile cancer:
clinical presentation, diagnosis, and staging. Urol Clin N Am
19:247–256
150
3. Parkin, D.M., et al., Cancer incidence in five continents. 2002,
International Agency for Research on Cancer: Lyon: International
Agency for Research on Cancer; 2002. Contract No.: 155.
4. Daling JR et al. (2005) Penile cancer: importance of circumcision,
human papilloma virus and smoking in in-situ and invasive disease.
Int J Cancer 116:606–626
5. Saibishkumar EP, Crook J, Sweet J (2008) Neonatal circumcision
and invasive squamous carcinoma of the penis: a report of 3 cases
and review of the literature. Can Urol Assoc J 2(1):39–42
6. Derakhshani P et al. (1999) Results and 10 year follow up in
patients with squamous cell carcinoma of the penis. Urol Int 62:
238–244
7. Mistry T et al. (2007) A 10-year retrospective audit of penile cancer
management in the UK. BJU Int 100(6):1277–1281
8. National Comprehensive Cancer Network. Penile cancer, version
1.2013. 2013 June 4, 2010; Available from: http://www.nccn.org/
professionals/physician_gls/pdf/penile.pdf.
9. Cubilla AL et al. (1998) Basaloid squamous cell carcinoma: a dis-
tinctive human papilloma virus related penile neoplasm: a report of
20 cases. Am J Surg Path 22:755–761
10. Miralles-Guri C et al. (2009) Human papillomavirus prevalence and
type distribution in penile carcinoma. J Clin Path 62:870–878
11. Campos Martin R (1953) Treatment of cancer of the distal end of
penis. Actas Dermo-Sifiliograficas 44(9):720–726
12. Franks KN et al. (2011) Radiotherapy for node positive penile
cancer: experience of the Leeds teaching hospitals. J Urol 186(2):
524–529
13. Pagliaro LC, Crook J (2009) Multimodality therapy in penile can-
cer: when and which treatments? World J Urol 27(2):221–225
14. Pierquin B, Dutrex A, Paine C (1978) The Paris system in intersti-
tial radiation therapy. Acta Radiol Oncol 17:33
15. Slaton JW et al. (2001) Tumor stage, vascular invasion and the
percentage of poorly differentiated cancer: independent prognosti-
cators for inguinal lymph node metastasis in penile squamous cell
cancer. J Urol 165(4):1138–1142
16. Burt L et al. (2014) Stage presentation, care patterns, and treatment
outcomes for squamous cell carcinoma of the penis. Int J Radiat
Oncol 88(1):94–100
17. Ekstrom T, Edsmyr F (1958) Cancer of the penis: a clinical study of
229 cases. Acta Chir Scand 115:25–45
18. Ariupina EA (2010) Current approaches to treatment of invasive
squamous-cell carcinoma of the penis. Vopr Onkol 56(3):354–358
19. Horenblas S (2001) Lymphadenectomy for squamous cell carcino-
ma of the penis. Part 1: diagnosis of lymph node metastasis. Br J
Urol Int 88:467–472
20. Leijte JA, Kirrander P, Antonini N, et al. (2008) Recurrence patterns
of squamous cell carcinoma of the penis: recommendations for
follow-up based on a two-center analysis of 700 patients. Eur
Urol 54:161–168
21. Lopes A et al. (1996) Prognostic factors in carcinoma of the penis:
multivariate analysis of 145 patients treated with amputation and
lymphadenectomy. J Urol 156(5):1637–1642
22. Kieffer JM (2014) Quality of life for patients treated for penile
cancer. J Urol 192:1105–1110
23. Opjordsmoen S et al. (1994) Sexuality in patients treated for penile
cancer: patients’ experience and doctors’ judgement. Br J Urol
73(5):554–560
24. Mueller-Lisse UG et al. (2008) Functional imaging in penile cancer:
PET/computed tomography, MRI, and sentinel lymph node biopsy.
Curr Opin Urol 18(1):105–110
25. Pandey D, Mahajan V, Kannan RR (2006) Prognostic factors in
node-positive carcinoma of the penis. J Surg Oncol 93:133–18.
26. Keyes O et al. (2007) The role of magnetic resonance imaging in
the local staging of penile cancer. Eur Urol 51:1313–1319
J Radiat Oncol (2016) 5:143–151
27. Van Poppel H (2013) Penile cancer: ESMO Clinical Practice
Guidelines for diagnosis, treatment and follow-up. Ann Oncol 00:
1–10
28. Tabatabaei S, Harisinghani M, McDougal WS (2005) Regional
lymph node staging using lymphotropic nanoparticle enhanced
magnetic resonance imaging with ferumox-tran-10 in patients with
penile caner. J Urol 174(3):923–927
29. Jackson SM (1966) The treatment of carcinoma of the penis. Br J
Surg 53:33–35
30. AJCC (American Joint Committee on Cancer) Cancer staging man-
ual. 7th Edition ed, ed. S.B. Edge, D.R. Byrd, and C.C. Compton.
2010, New York, NY: Springer Science.
31. Crook J, Ma C, Grimard L (2009) Radiation therapy in the man-
agement of the primary penile tumor: an update. World J Urol
27(2):189–196
32. Pizzocaro G, Piva L, Nicolai N (1996) Treatment of lymphatic
metastasis of squamous cell carcinoma of the penis: experience at
the National Tumor Institute or Milan. Arch Ital Urol Androl 68(3):
169–172
33. Sarin R et al. (1997) Treatment results and prognostic factors in 101
men treated for squamous carcinoma of the penis. Int J Radiat
Oncol Biol Phys 38(4):713–722
34. Lont AP et al. (2007) Pelvic lymph node dissection for penile car-
cinoma: extent of inguinal lymph node involvement as an indicator
for pelvic lymph node involvement and survival. J Urol 177(3):
947–952
35. Chen MF et al. (2004) Contemporary management of penile cancer
including surgery and adjuvant radiotherapy: an experience in
Taiwan. World J Urol 22(1):60–66
36. Pond GR (2014) Prognostic risk stratification derived from individ-
ual patient level data for men with advanced penile squamous cell
carcinoma receiving first-line systemic therapy. Urol Oncol 32:
501–508
37. Sadeghi R et al. (2012) Accuracy of 18F-FDG PET/CT for diag-
nosing inguinal lymph node involvement in penile squamous cell
carcinoma: systemic review and meta-analysis of the literature. Clin
Nucl Med 35(5):436–444
38. Soria JC et al. (1997) Squamous cell carcinoma of the penis: mul-
tivariate analysis of prognostic factors and natural history in
monocentric study with a conservative policy. Ann Oncol 8(11):
1089–1098
39. Zouhair A et al. (2001) Radiation therapy alone or combined sur-
gery and radiation therapy in squamous-cell carcinoma of the pe-
nis? Eur J Cancer 37(2):198–203
40. Opjordsmoen S, Fossa SD (1994) Quality of life in patients treated
for penile cancer. A follow-up study. Br J Urol 74(5):652–657
41. Ozsahin M et al. (2006) Treatment of penile carcinoma: to cut or not
to cut? Int J Radiat Oncol Biol Phys 66(3):674–679
42. Antunes AA, Dall’Oglio MF, Srougi M (2007) Organ-sparing treat-
ment for penile cancer. Nat Clin Pract Urol 4(11):596–604
43. Kalidas H (1995) Influence of inguinal node anatomy on radiation
therapy techniques. Med Dosim 20(4):295–300
44. Chen CZ et al. (1997) Pulsed brachytherapy as a substitute for
continuous low dose rate: an in vitro study with human carcinoma
cells. Int J Radiat Oncol Biol Phys 37:137–143
45. Crook JM et al. (2013) American Brachytherapy Society-Groupe
Europeen de Curietherapie-European Society of Therapeutic
Radiation Oncology (ABS-GEC-ESTRO) consensus statement for
penile brachytherapy. Brachytherapy 12:191–198
46. Ravi R, Chaturvedi HK, Sastry DV (1994) Role of radiation ther-
apy in the treatment of carcinoma of the penis. Br J Urol 74(5):
646–651
47. Petera J et al. (2004) High-dose-rate interstitial brachytherapy for the
treatment of penile carcinoma. Strahlenther Onkol 180(2):123–125
J Radiat Oncol (2016) 5:143–151
48. Sharma D et al. (2014) High Dose Rate Interstitial Brachytherapy
for T1-T2 stage penile carcinoma: short term results. Brachytherapy
13(5):481–487
49. Pizzocaro G et al. (2010) EAU penile cancer guidelines 2009. Eur
Urol 57(6):1002–1012
50. Kiltie AE et al. (2000) Iridium-192 implantation for node-negative
carcinoma of the penis: the Cookridge Hospital experience. Clin
Oncol (Royal College of Radiologists) 12(1):25–31
51. Daly NJ, Douchez J, Combes PF (1982) Treatment of carcinoma of
the penis by iridium 192 wire implant. Int J Radiat Oncol Biol Phys
8(7):1239–1243
52. Suchaud JP et al. (1989) Brachytherapy of cancer of the penis.
analysis of a series of 53 cases. J Urol 95(1):27–31
53. de Crevoisier R et al. (2009) Long-term results of brachytherapy for
carcinoma of the penis confined to the glans (N- or NX). Int J
Radiat Oncol Biol Phys 74(4):1150–1156
54. Pond GR, Milowsky MI, Kolinsky MP, Eigi BJ, et al. (2014)
Concurrent chemoradiotherapy for men with locally advanced
penile squamous cell carcinoma. Clin Genitourin Cancer 12(6):
440–446
55. Chaudhary AJ et al. (1999) Interstitial brachytherapy in carcinoma
of the penis. Strahlenther Onkol 175(1):17–20
56. Delannes M et al. (1992) Iridium-192 interstitial therapy for squa-
mous cell carcinoma of the penis. Int J Radiat Oncol Biol Phys
24(3):479–483
57. Mazeron JJ et al. (1984) Interstitial radiation therapy for carcinoma
of the penis using iridium 192 wires The Henri Mondor experience
(1970-1979). Int J Radiat Oncol Biol Physics 10(10):1891–1895
58. Rozan R et al. (1995) Interstitial brachytherapy for penile carcino-
ma: a multicentric survey (259 pts). Radiother Oncol 36(2):83–93
59. Akimoto T et al. (1997) Brachytherapy for penile cancer using
silicon mold. Oncology 54(1):23–27
60. Rodriguez MA (2013) Penile cancer brachytherapy. Rep of Pract
Oncol and Radiat 18:S40–S41
61. Azrif M et al. (2006) External beam radiation therapy in T1–2 N0
penile carcinoma. Clin Oncol (Royal Coll Radiol) 18:320–325
62. Sagerman RH et al. (1984) External-beam irradiation of carcinoma
of the penis. Radiology 152(1):183–185
63. Crook J et al. (2002) Interstitial brachytherapy for penile cancer: an
alternative to amputation. J Urol 167(2 Pt 1):506–511
151
64. Petera J et al. (2011) High-dose rate brachytherapy in the treat-
ment of penile carcinoma–first experience. Brachytherapy 10(2):
136–140
65. Franzen L et al. (1987) A technical device for irradiation in carci-
noma of the penis. Acta Oncol 26(1):77–78
66. Gotsadze D (2000) Is conservative organ-sparing treatment of pe-
nile carcinoma justified? Eur Urol 38(3):306–312
67. Gerber M, Zwergel U, Stockel M (2011) Partial and total
penectomy. Aktuelle Urologie 42(6):383–392
68. Lofroth P-O et al. (2004) Penis holder for external radiation treat-
ment. Radiother Oncol 71(1):115–116
69. Neave F et al. (1993) Carcinoma of the penis: a retrospective review
of treatment with iridium mould and external beam irradiation. Clin
Oncol (Royal College of Radiol) 5(4):207–210
70. McLean M et al. (1993) The results of primary radiation therapy in
the management of squamous cell carcinoma of the penis. Int J
Radiat Oncol Biol Phys 25(4):623–628
71. Gerbaulet A, Lambin P (1992) Radiation therapy of cancer of the
penis. Indications, advantages, and pitfalls. Urol Clin N Am 19(2):
325–332
72. Bouchot O, Rigaud J (2004) Penis tumours: techniques and indica-
tions. Ann Urol 38(6):285–297
73. Pedrick T, Wheeler W, Riemenschneider H (1993) Combined mo-
dality therapy for locally advanced penile squamous cell carcinoma.
Am J Clin Oncol 16:501–505
74. Horenblas S et al. (1993) Squamous cell carcinoma of the penis. III.
Treatment of regional lymph nodes. J Urol 149(3):492–497
75. Solsona E et al. (2004) EAU guidelines on penile cancer. Eur Urol
46(1):1–8
76. Moore DH, Ali S, Koh WF, et al. (2012) A phase II trial of radiation
therapy and weekly cisplatin chemotherapy for the treatment of
locally-advanced squamous cell carcinoma of the vulva: a gyneco-
logic oncology group study. Gynecol Oncol 124(3):529–533
77. Gomez-Iturriaga A, Crook J, Evans W et al. The efficacy of hyper-
baric oxygen therapy in the treatment of medically refractory soft
tissue necrosis after penile brachytherapy. Brachytherapy. 2011
Feb 22.{Epub ahead of print] 2011 Nov-Dec;10(6):491–7.
78. Crook J, Jezioranski J, Cygler JE (2010) Penile brachytherapy:
technical aspects and postimplant issues. Brachytherapy 9(2):
151–158