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© 2021 The Authors. Société Internationale d'Urologie Journal, published by the Société Internationale d'Urologie, Canada.

Evaluation of the Guidelines for Penile Cancer 
Treatment: Overview and Assessment
Abdulmajeed Aydh,1,2 Shahrokh F. Shariat,1,3,4,5,6,7,8,9 Reza Sari Motlagh,1 Ekaterina Laukhtina,1,9  
Fahad Quhal,1,10 Keiichiro Mori,1,11 Hadi Mostafaei,1,12 Andrea Necchi,13 Benjamin Pradere1,14

1 Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria 2 Department of Urology, King Faisal Medical City,  
Abha, Saudi Arabia 3 Department of Urology, Weill Cornell Medical College, New York, United States 4 Department of Urology, University of Texas Southwestern, Dallas, 
United States 5 Department of Urology, Second Faculty of Medicine, Charles University, Prague, Czech Republic 6 European Association of Urology Research Foundation, 
Arnhem, Netherlands 7 Karl Landsteiner Institute, Vienna, Austria 8Division of Urology, Department of Special Surgery, Jordan University Hospital, The University of 
Jordan, Amman, Jordan 9 Institute for Urology and Reproductive Health, Sechenov University, Moscow, Russia 10 Department of Urology, King Fahad Specialist Hospital, 
Dammam, Saudi Arabia 11 Department of Urology, Jikei University School of Medicine, Tokyo, Japan 12 Research Center for Evidence Based Medicine, Tabriz University of 
Medical Sciences, Tabriz, Iran 13 Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy 14 Department of Urology, University Hospital of Tours, Tours, France

Abstract

Introduction Medical organizations have provided evidence-based guidelines for penile cancer treatment. This 
current review aims to compare and appraise guidelines on penile cancer treatment to provide a useful summary for 
clinicians.  

Materials and Methods We searched in PubMed and Medline for guidelines published between January 1, 
2010, and February 1, 2020. The search query terms were “penile cancer,” “penile tumor,” “guidelines,” and “penile 
malignancy.” In the final analysis, we include the most recent versions of relevant guidelines published in English. 
The Appraisal of Guidelines for Research and Evaluation II (AGREE II) instrument was used to appraise the quality 
of each guideline.

Results In the final analysis, we included guidelines from the National Comprehensive Cancer Network (updated 
in 2020), The European Association of Urology (updated in 2018), and The European Society for Medical Oncology 
(published in 2013). The overall agreement among reviewers was excellent. The range of scores for each domain was 
as follows: scope and purpose (46% to 61%); stakeholder involvement (33% to 60%); rigor of development (34% to 
69%); clarity and presentation (61% to 81%); applicability (33% to 59%) and editorial independence (52% to 78%). The 
European Association of Urology and National Comprehensive Cancer Network clinical practice guidelines received 
better scores according to the AGREE II evaluation.

Conclusion Despite the effort made by the guidelines groups to make a practical guideline regarding penile cancer 
treatment, the actual available evidence is weak. However, we believe our recommendations offer clear guidance. 

Introduction

Penile cancer is an aggressive disease that represents less than 1% of all malignancies in the United States and 
Europe[1,2]. Penile cancer is common in the elderly, with a peak incidence in the seventh decade of life[3]. The most 
com¬mon histological subtype for penile cancer is squamous cell carcinoma[4]. Given the complex nature of penile 
cancer, different therapeutic options are available. Furthermore, there is growing interest in molecularly targeted 

Key Words Competing Interests Article Information

Guidelines, penile cancer, penile malignancy, 
penile tumor

None declared. Received on December 22, 2020 
Accepted on March 1, 2021

Soc Int Urol J.2021;2(3):171–186

DOI: https://doi:10.48083/TKFP8406

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https://doi:10.48083/TKFP8406
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therapy, and tyrosine kinase inhibitors are showing 
promising results[5]. However, because of its rarity, most 
of the recommendations mainly rely on retrospective 
studies[6,7].

In the last decade, several scientific organizations 
have provided evidence-based guidelines to improve 
patients' selection of each treatment modality. The 
European Association of Urology (EAU) guidelines on 
Penile Cancer were first published in 2000 and were last 
updated in 2018. The National Comprehensive Cancer 

Network (NCCN) penile cancer guidelines were last 
updated in 2020, while the last European Society for 
Medical Oncology (ESMO) clinical practice guidelines 
was released in 2013. 

This study aims to conduct a review, comparison, and 
appraisal of the guidelines on the treatment of penile 
cancer to provide universal and practical guidance 
for physicians in their clinical decision-making. We 
aimed to provide authoritative guidance with clear 
recommendations from the best guidelines.

Materials and Methods
We searched PubMed and Medline for guidelines 
published between January 1, 2010, and February 1, 
2020. The search terms were “penile cancer,” “penile 
tumor,” “guidelines,” and “penile malignancy.” Also, we 
searched through the websites of international urology 
and oncology societies for the most recent guidelines 
on penile cancer. In the final analysis, we included 
the most recent English version of each guideline. 
Non-English national guidelines were excluded. The 
Appraisal of Guidelines for Research and Evaluation 

Abbreviations 
AGREE II Appraisal of Guidelines for Research and Evaluation II
NCCN National Comprehensive Cancer Network
EAU European Association of Urology
ESMO European Society for Medical Oncology
EBRT external beam radiation therapy
PLND pelvic lymph node dissection
LOE level of evidence
GOR grade of recommendation

TABLE 1. 
Guidelines for the management penile cancer according to T stage

Treatment

EAU Guidelines NCCN Guidelines ESMO Guidelines

Recommendation
Grade of 

recommendation
Level of 

evidence
Recommendation

Grade of 
recommendation

Level of 
evidence

Recommendation
Grade of 

recommendation
Level of 

evidence

STAGE Tis

Topical treatment with  
5-fluorouracil (5-FU) or imiquimod

5-FU is an effective first-line treatment 
Strong 

recommendation

Tis, Ta, and T1 penile cancer 
lesions may be amenable to 

conservative penile organ-sparing 
approaches, including topical 

therapy

Considered
appropriate

2A

Penile-preserving techniques, 
including topical therapy  

(5% 5-fluorouracil and  
5% imiquimod cream)

C IV

Laser ablation
(Nd:YAG) or Carbon dioxide (CO2) laser is an 

effective treatment option
Strong 

recommendation

The use of therapeutic lasers 
to treat selected primary penile 
tumors has been reported with 

acceptable outcomes

Considered
appropriate

2B
Laser therapy using CO2 or 

Nd: YAG laser
C III

Glans resurfacing
Glans resurfacing, total or partial, can be a 
primary treatment for PeIN or a secondary

Strong 
recommendation

Glansectomy, removal of the glans 
penis, may be considered for
patients with distal tumors

Considered
appropriate 2B Partial/total glans resurfacing C III

Wide local excision with circumcision
Glans resurfacing, total or partial, can be a 
primary treatment for PeIN or a secondary

Penile tumors of the shaft may be 
treated with wide local excision, 

with or without circumcision 

Considered
appropriate 2A

Wide local excision and 
circumcision

C IV

Mohs surgery Historical technique
Mohs surgery is an alternative to 
wide local excision in select cases

2B

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II (AGREE II) instrument was used to appraise the 
quality of guidelines[8]. This instrument permits the 
evaluation of the scope and purpose of the guidelines, 
stakeholder involvement, rigor of development, clarity of 
presentation, applicability, and editorial independence. 
The overall assessment is the final mean of all domains, 
which gives an overview of each guideline score. The 
AGREE II recommends 2 or more appraisers. Therefore, 
each guideline was evaluated by 5 appraisers (BP, EL, 
FQ, HM, and KM) to enhance the authenticity of the 
assessment. The appraisal was performed after the 
completion of an online training module on AGREE II 
website[9]. The 5 reviewers were experienced in urologic 
oncology and were mentored by 2 oncologic urologists 
(SFS, BP) experienced in guidelines writing and grade of 
recommendation rating.

Results
Guidelines from 3 international organizations were 
included in the final analysis: the 2020 update of the 
NCCN guideline[10], the 2018 update of the EAU 
guidelines[11], and the 2013 update of the ESMO 
guidelines[12].

Level of evidence assessment and grading of 
recommendations
Two guidelines (EAU and NCCN) provided a detailed 
and strict methodology for searching and acquisition 
of evidence from the literature. The ESMO guideline 
is an expert consensus statement so did not include 
a systematic literature search. All 3 guidelines (EAU, 
NCCN, and ESMO) provided a description of the systems 
used for grading the level of evidence. In the EAU 
guidelines, a modified Grading of Recommendations 
Assessment, Development, and Evaluation (GRADE) 
was used[13,14]. For each recommendation within the 
guidelines, there was also an accompanying online 
strength rating form, which addresses several elements. 
The NCCN guidelines used the Categories of Evidence 
and Consensus to grade the recommendations; they 
also provide Categories of Preference to help users chose 
the optimal recommendation based on efficacy, safety, 
evidence, or affordability.

The ESMO guidelines adapted the Infectious Diseases 
Society of America-United States Public Health Service 
Grading System[15].

continued on page 174

TABLE 1. 
Guidelines for the management penile cancer according to T stage

Treatment

EAU Guidelines NCCN Guidelines ESMO Guidelines

Recommendation
Grade of 

recommendation
Level of 

evidence
Recommendation

Grade of 
recommendation

Level of 
evidence

Recommendation
Grade of 

recommendation
Level of 

evidence

STAGE Tis

Topical treatment with  
5-fluorouracil (5-FU) or imiquimod

5-FU is an effective first-line treatment 
Strong 

recommendation

Tis, Ta, and T1 penile cancer 
lesions may be amenable to 

conservative penile organ-sparing 
approaches, including topical 

therapy

Considered
appropriate

2A

Penile-preserving techniques, 
including topical therapy  

(5% 5-fluorouracil and  
5% imiquimod cream)

C IV

Laser ablation
(Nd:YAG) or Carbon dioxide (CO2) laser is an 

effective treatment option
Strong 

recommendation

The use of therapeutic lasers 
to treat selected primary penile 
tumors has been reported with 

acceptable outcomes

Considered
appropriate

2B
Laser therapy using CO2 or 

Nd: YAG laser
C III

Glans resurfacing
Glans resurfacing, total or partial, can be a 
primary treatment for PeIN or a secondary

Strong 
recommendation

Glansectomy, removal of the glans 
penis, may be considered for
patients with distal tumors

Considered
appropriate 2B Partial/total glans resurfacing C III

Wide local excision with circumcision
Glans resurfacing, total or partial, can be a 
primary treatment for PeIN or a secondary

Penile tumors of the shaft may be 
treated with wide local excision, 

with or without circumcision 

Considered
appropriate 2A

Wide local excision and 
circumcision

C IV

Mohs surgery Historical technique
Mohs surgery is an alternative to 
wide local excision in select cases

2B

173SIUJ.ORG SIUJ  •  Volume 2, Number 3  •  May 2021

Evaluation of the Guidelines for Penile Cancer Treatment: Overview and Assessment

http://siuj.org


TABLE 1. 
Guidelines for the management penile cancer according to T stage, Cont'd

Treatment
EAU Guidelines NCCN Guidelines ESMO Guidelines

Recommendation
Grade of 

recommendation
Level of 

evidence
Recommendation

Grade of 
recommendation

Level of 
evidence

Recommendation
Grade of 

recommendation
Level of 

evidence

STAGE Ta, T1a (G1, G2) 

Wide local excision with circumcision
Partial glansectomy or total glansectomy  
with reconstruction are surgical options

Strong 
recommendation

Penile tumors of the shaft may be 
treated with wide local excision, 

with or without circumcision 

Considered
appropriate

2A
Penile-preserving techniques, 

including wide local excision plus 
reconstructive surgery

C III

Glans resurfacing
Partial glansectomy or total glansectomy  
with reconstruction are surgical options

Strong 
recommendation

Glansectomy may be considered 
for select patients with distal 

tumors

Considered
appropriate

2B

Glansectomy with reconstruction
Partial glansectomy or total glansectomy  
with reconstruction are surgical options

Strong 
recommendation

Glansectomy is not recommended 
unless required to ensure 

complete tumor eradication with 
negative margins

Considered
appropriate

2A

Radiotherapy
External beam radiotherapy  

or brachytherapy is radiotherapeutic  
options

Strong 
recommendation

2B
Consider <4 cm: Brachytherapy or  

EBRT >4 cm: EBRT with 
chemotherapy

Considered
appropriate

2B
Radiotherapy delivered as EBRT 
or brachytherapy with interstitial 

implant
C IV

Laser ablation
Small lesions can also be  
treated by laser therapy

Strong 
recommendation

The use of therapeutic lasers 
to treat selected primary penile 
tumors has been reported with 

acceptable outcomes

Considered
appropriate

2B
Laser therapy C IV

Partial penectomy
Strong 

recommendation

Partial or total penectomy 
when invasion into the corpora 

cavernosum is necessary to 
achieve a negative margin

Considered
appropriate

2A

Mohs surgery
Strong 

recommendation

Mohs surgery is an alternative 
to wide local excision in select 

cases.

Considered
appropriate

2B

STAGE T1B (G3) AND T2

Wide local excision plus reconstruction
Local excision, partial glansectomy or  

total glansectomy with reconstruction are  
surgical options

Strong 
recommendation

Penile tumors of the shaft may be 
treated with wide local excision

Considered
appropriate

2A
If tumor <50% of the glans and no 
invasion of the corpora cavernosa

B III

Glansectomy with circumcision  
and reconstruction

Local excision, partial glansectomy or  
total glansectomy with reconstruction are  

surgical options

Strong 
recommendation

Glansectomy may be considered 
for select patients with distal 

tumors

Considered
appropriate

2A
If tumor <50% of the glans and no 
invasion of the corpora cavernosa

B III

Radiotherapy
External beam radiotherapy or  

brachytherapy  
is radiotherapeutic options

Strong 
recommendation

Consider <4 cm: Brachytherapy or  
EBRT >4 cm: EBRT with 

chemotherapy

Considered
appropriate

2B
<4 cm: Brachytherapy or EBRT
>4 cm: EBRT with chemotherapy

III

Total penectomy OR Partial
Total glansectomy, with or without resurfacing  

of the corporeal heads, is recommended
Strong 

recommendation

Partial or total penectomy 
when invasion into the corpora 

cavernosum is necessary to 
achieve a negative margin

Considered
appropriate

2A
Tumors with invasion into corpora 
cavernosa

B III

174 SIUJ  •  Volume 2, Number 3  •  May 2021 SIUJ.ORG

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TABLE 1. 
Guidelines for the management penile cancer according to T stage, Cont'd

Treatment
EAU Guidelines NCCN Guidelines ESMO Guidelines

Recommendation
Grade of 

recommendation
Level of 

evidence
Recommendation

Grade of 
recommendation

Level of 
evidence

Recommendation
Grade of 

recommendation
Level of 

evidence

STAGE Ta, T1a (G1, G2) 

Wide local excision with circumcision
Partial glansectomy or total glansectomy  
with reconstruction are surgical options

Strong 
recommendation

Penile tumors of the shaft may be 
treated with wide local excision, 

with or without circumcision 

Considered
appropriate

2A
Penile-preserving techniques, 

including wide local excision plus 
reconstructive surgery

C III

Glans resurfacing
Partial glansectomy or total glansectomy  
with reconstruction are surgical options

Strong 
recommendation

Glansectomy may be considered 
for select patients with distal 

tumors

Considered
appropriate

2B

Glansectomy with reconstruction
Partial glansectomy or total glansectomy  
with reconstruction are surgical options

Strong 
recommendation

Glansectomy is not recommended 
unless required to ensure 

complete tumor eradication with 
negative margins

Considered
appropriate

2A

Radiotherapy
External beam radiotherapy  

or brachytherapy is radiotherapeutic  
options

Strong 
recommendation

2B
Consider <4 cm: Brachytherapy or  

EBRT >4 cm: EBRT with 
chemotherapy

Considered
appropriate

2B
Radiotherapy delivered as EBRT 
or brachytherapy with interstitial 

implant
C IV

Laser ablation
Small lesions can also be  
treated by laser therapy

Strong 
recommendation

The use of therapeutic lasers 
to treat selected primary penile 
tumors has been reported with 

acceptable outcomes

Considered
appropriate

2B
Laser therapy C IV

Partial penectomy
Strong 

recommendation

Partial or total penectomy 
when invasion into the corpora 

cavernosum is necessary to 
achieve a negative margin

Considered
appropriate

2A

Mohs surgery
Strong 

recommendation

Mohs surgery is an alternative 
to wide local excision in select 

cases.

Considered
appropriate

2B

STAGE T1B (G3) AND T2

Wide local excision plus reconstruction
Local excision, partial glansectomy or  

total glansectomy with reconstruction are  
surgical options

Strong 
recommendation

Penile tumors of the shaft may be 
treated with wide local excision

Considered
appropriate

2A
If tumor <50% of the glans and no 
invasion of the corpora cavernosa

B III

Glansectomy with circumcision  
and reconstruction

Local excision, partial glansectomy or  
total glansectomy with reconstruction are  

surgical options

Strong 
recommendation

Glansectomy may be considered 
for select patients with distal 

tumors

Considered
appropriate

2A
If tumor <50% of the glans and no 
invasion of the corpora cavernosa

B III

Radiotherapy
External beam radiotherapy or  

brachytherapy  
is radiotherapeutic options

Strong 
recommendation

Consider <4 cm: Brachytherapy or  
EBRT >4 cm: EBRT with 

chemotherapy

Considered
appropriate

2B
<4 cm: Brachytherapy or EBRT
>4 cm: EBRT with chemotherapy

III

Total penectomy OR Partial
Total glansectomy, with or without resurfacing  

of the corporeal heads, is recommended
Strong 

recommendation

Partial or total penectomy 
when invasion into the corpora 

cavernosum is necessary to 
achieve a negative margin

Considered
appropriate

2A
Tumors with invasion into corpora 
cavernosa

B III

continued on page 176

175SIUJ.ORG SIUJ  •  Volume 2, Number 3  •  May 2021

Evaluation of the Guidelines for Penile Cancer Treatment: Overview and Assessment

http://siuj.org


TABLE 1. 
Guidelines for the management penile cancer according to T stage, Cont'd

Treatment
EAU Guidelines NCCN Guidelines ESMO Guidelines

Recommendation
Grade of 

recommendation
Level of 

evidence
Recommendation

Grade of 
recommendation

Level of 
evidence

Recommendation
Grade of 

recommendation
Level of 

evidence

STAGE T2

Total glansectomy
Total glansectomy, with or without resurfacing 

of the corporeal heads, is recommended
Strong 

recommendation
3 C III

Radiotherapy Radiation therapy is an option
Strong 

recommendation

Consider
<4 cm: Brachytherapy or EBRT

>4 cm: EBRT with chemotherapy

Considered
appropriate

2B
<4 cm: Brachytherapy or EBRT

>4 cm: EBRT with chemotherapy
D

Total penectomy OR Partial
Partial amputation should be considered in 

patients unfit for reconstructive surgery
Strong 

recommendation

Partial or total penectomy 
when invasion into the corpora 

cavernosum is necessary to 
achieve a negative margin

Considered
appropriate

2A
Tumors with invasion into corpora 

cavernosa
B III

STAGE T3

Partial amputation with reconstruction or  
total penectomy

Glansectomy with distal corporectomy and 
reconstruction or partial amputation with 

reconstruction are standard 

Strong 
recommendation

Partial or total penectomy 
when invasion into the corpora 

cavernosum is necessary to 
achieve a negative margin

Considered
appropriate

2A
T3-4 or N+: circumcision followed 

by EBRT with chemotherapy
D

Radiotherapy Radiation therapy is an option
Strong 

recommendation
EBRT with chemotherapy are 

treatment options

Considered
appropriate 3

STAGE T3 WITH INVASION OF THE URETHRA

Partial penectomy or total penectomy
Glansectomy with distal corporectomy and 
reconstruction or partial amputation with 

reconstruction are standard

Strong 
recommendation

Partial or total penectomy 
when invasion into the corpora 

cavernosum is necessary to 
achieve a negative margin

Considered
appropriate

2A
T3-4 or N+: circumcision followed 

by EBRT with chemotherapy
D

Radiotherapy Radiation therapy is an option
Strong 

recommendation
EBRT with chemotherapy are 

treatment options
Considered
appropriate

2B

STAGE T4

Partial penectomy or total penectomy
Extensive partial amputation or total 

penectomy with perineal urethrostomy is the 
standard advisable treatment

Weak 
recommendation

Partial or total penectomy 
when invasion into the corpora 

cavernosum is necessary to 
achieve a negative margin

Considered
appropriate

2A
T3-4 or N+: circumcision followed 

by EBRT with chemotherapy
D

Radiotherapy Palliative radiotherapy is an option
EBRT with chemotherapy are 

treatment options
Considered
appropriate

3

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TABLE 1. 
Guidelines for the management penile cancer according to T stage, Cont'd

Treatment
EAU Guidelines NCCN Guidelines ESMO Guidelines

Recommendation
Grade of 

recommendation
Level of 

evidence
Recommendation

Grade of 
recommendation

Level of 
evidence

Recommendation
Grade of 

recommendation
Level of 

evidence

STAGE T2

Total glansectomy
Total glansectomy, with or without resurfacing 

of the corporeal heads, is recommended
Strong 

recommendation
3 C III

Radiotherapy Radiation therapy is an option
Strong 

recommendation

Consider
<4 cm: Brachytherapy or EBRT

>4 cm: EBRT with chemotherapy

Considered
appropriate

2B
<4 cm: Brachytherapy or EBRT

>4 cm: EBRT with chemotherapy
D

Total penectomy OR Partial
Partial amputation should be considered in 

patients unfit for reconstructive surgery
Strong 

recommendation

Partial or total penectomy 
when invasion into the corpora 

cavernosum is necessary to 
achieve a negative margin

Considered
appropriate

2A
Tumors with invasion into corpora 

cavernosa
B III

STAGE T3

Partial amputation with reconstruction or  
total penectomy

Glansectomy with distal corporectomy and 
reconstruction or partial amputation with 

reconstruction are standard 

Strong 
recommendation

Partial or total penectomy 
when invasion into the corpora 

cavernosum is necessary to 
achieve a negative margin

Considered
appropriate

2A
T3-4 or N+: circumcision followed 

by EBRT with chemotherapy
D

Radiotherapy Radiation therapy is an option
Strong 

recommendation
EBRT with chemotherapy are 

treatment options

Considered
appropriate 3

STAGE T3 WITH INVASION OF THE URETHRA

Partial penectomy or total penectomy
Glansectomy with distal corporectomy and 
reconstruction or partial amputation with 

reconstruction are standard

Strong 
recommendation

Partial or total penectomy 
when invasion into the corpora 

cavernosum is necessary to 
achieve a negative margin

Considered
appropriate

2A
T3-4 or N+: circumcision followed 

by EBRT with chemotherapy
D

Radiotherapy Radiation therapy is an option
Strong 

recommendation
EBRT with chemotherapy are 

treatment options
Considered
appropriate

2B

STAGE T4

Partial penectomy or total penectomy
Extensive partial amputation or total 

penectomy with perineal urethrostomy is the 
standard advisable treatment

Weak 
recommendation

Partial or total penectomy 
when invasion into the corpora 

cavernosum is necessary to 
achieve a negative margin

Considered
appropriate

2A
T3-4 or N+: circumcision followed 

by EBRT with chemotherapy
D

Radiotherapy Palliative radiotherapy is an option
EBRT with chemotherapy are 

treatment options
Considered
appropriate

3

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Evaluation of the Guidelines for Penile Cancer Treatment: Overview and Assessment

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Treatment strategy according to stage
Organ-sparing treatment in Tis, Ta, and T1a tumors 

All 3 guidelines (EAU, NCCN, and ESMO), advise 
organ-sparing approaches in patients diagnosed with 
Tis, Ta, and T1 penile cancer lesions. However, the 
EAU guidelines highlight the absence of randomized 
cont rol led t r ia ls or compa rat ive obser vat iona l 
studies for treatment options for localized penile 

cancer. Nevertheless, from a cosmetic and functional 
standpoint, balanced with the risk of recurrence 
and progression of these stages, penile preservation 
is considered superior to partial or total penectomy 
and should be performed for localized penile cancer 
(staged ≤ T1)[16].

Topical agents are the least invasive and easiest 
treatment options for superficial and localized lesions. 

TABLE 2. 

Author recommendations for penile cancer guidelines

Topical Laser Surgery Radiotherapy

Tis

5-fluorouracil (5FU) 
or imiquimod 5% 
for superficial lesions  
± photo dynamic control 

Tis  T2 glans 
Laser ablation 
with CO2 or
Nd:YAG laser 

• Glans resurfacing (Removal 
of glans epithelium) for lesions 
confined to glans

• Glansectomy (Leaving corpora 
intact 
compared to partial penectomy) 

• Circumcision for lesions 
confined  
to prepuce 

• Wide local excision  
+ reconstruction ± skin grafting 

Ta, T1 & T2
confined to  
the glans 

X

Ta  T2
Radiotherapy by 
• External beam 
• (EBRT) or as 
• Brachytherapy 

T2  Corpora 
cavernosa (CC) 

X X
• Partial penectomy + 

reconstruction

T3 (Three) 
invasion of  

 Urethra
X X

• Partial penectomy
• Total penectomy with perineal 

urethrostomy 

T4  Adjacent 
structures 

X X
• Neoadjuvant chemo + surgery 

in responders or Palliative EBRT

Nodal metastases

No palpable inguinal nodes Palpable (cN1/cN2) Fixed (cN3) Pelvic lymphadenopathy

Tis, Ta G1, 
T1G1

> T1G2

Radical inguinal 
lymphadenectomy

Neoadjuvant chemotherapy
± followed in responders by
Radical inguinal 
lymphadenectomy

Ipsilateral pelvic  
lymphadenectomy if
(pN2) ≥ 2 inguinal nodes are
involved on one side and if
(pN3) Extracapsular nodal
metastasis

Surveillance

Staging by
Dynamic 
sentinel node 
biopsy

Chemotherapy

• Neoadj.: T4, fixed N3 
• Adjuvant: pN2/pN3

Adjuvant chemo in pN2/pN3 patients after radical lymphadenectomy 
3–4 cycles of TPF: paclitaxel, cisplatin, 5-fluorouracil (5FU)

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Before their use, the EAU guidelines recommend 
performing a circumcision. The EAU and NCCN 
guidelines make clear that there is a requirement for 
long-term surveillance. Another option is laser therapy, 
which could be performed as day-case surgery. When 
laser therapy is performed, the EAU guidelines mandate 
a second biopsy before treatment is initiated. A partial or 
total glans resurfacing can be an alternative in the first-
line treatment for penile intraepithelial lesions (PeIN) or 
could be proposed after topical or laser therapy failure. 
In the case of wide local excision, Mohs surgery can be 
proposed in selected cases according to the EAU and 
NCCN guidelines (Table 1).

Summary of treatment recommendations: For 
patients w it h penile Tis or Ta, we recommend 
topical therapy[17,18] and excisional organ-sparing 
technique[19], a topical agent such as imiquimod (5%) 
or 5-fluorouracil (5FU) cream, circumcision and wide 
local excision, laser therapy, or complete glansectomy 
(Table 2).
Invasive disease treatment confined  
to the glans T1/T2
For T1 and T2 tumors localized to the glans, the 3 
guidelines proposed different strategies, including 
surgery with laser therapy, local excision, partial 
glansectomy, or total glansectomy, and radiotherapy 
or brachytherapy. For the treatment of invasive disease 
confined to the glans, the EAU and the ESMO guidelines 
agree on conservative approaches, such as wide local 
excision or glansectomy, while the NCCN guidelines 
recommended it only in T1 high grade (G3–4). 

For radiotherapy, the NCCN and the EAU guidelines 
recommended brachy t herapy or ex terna l bea m 
radiation therapy  (EBRT) for tumors less than 4 cm. 
A circumcision is mandated by the NCCN guidelines 
before radiot herapy (RT) to prevent radiation-
related complications. For tumors larger than 4 cm, a 
multimodal treatment combining radiotherapy and 
chemotherapy is recommended (Table 1).

Summary of treatment recommendations: Our 
recommendation for the treatment of invasive 
disease confined to the glans is a glansectomy with 
or without resurfacing with a partial thickness 
skin graft of the corporeal heads[20]. A partial 
amputation for patients who are not candidates for 
reconstructive surgery should be performed[21]. 
Radiotherapy may also be an option[22] (Table 2).

Treatment of invasive disease T3/T4
For tumors with invasion of the corpora cavernosum, 
a partial or total penectomy is mandatory to achieve a 
total resection with negative margin according to the 
NCCN and the EAU guidelines. EBRT with concurrent 

chemotherapy is also an option in the NCCN guidelines, 
while it is the primar y treatment in the ESMO 
guidelines. The EAU guidelines consider radiation 
as a treatment option only for T3 and as a palliative 
treatment in T4 disease (Table 1).

Summary of treatment recommendations: For 
the treatment of cT3, we recommend glansectomy 
with corporectomy and reconstruction or partial 
penectomy with reconstruction as a standard 
of care[23,24]. Total penectomy with perineal 
urethrostomy is considered in selected cases. For 
cT4 disease, the recommended treatment remains 
a total penectomy with perineal urethrostomy[24]. 
Neoadjuvant chemotherapy for the locally advanced 
disease should be systematically considered and 
proposed[25,26] (Table 2).

Guidelines for treatment strategies for nodal 
metastases: cN0 
The ESMO, NCCN, and EAU guidelines all recommend 
surveillance for Tis, Ta G1, and T1G1 stages. Invasive 
lymph node staging either by bilateral modified inguinal 
lymphadenectomy or by dynamic sentinel node biopsy 
is recommended for ≥ T1G2 (Table 3). There is currently 
no role for prophylactic radiation to the inguinal lymph 
nodes instead of lymph node dissection or biopsy[27].

Summary of treatment recommendations: There 
are considerable discussions among researchers 
in the management of cN0 disease. Nonetheless, 
we believe that it is justif ied to  recommend 
surveillance for Tis, Ta G1, and T1G1 if the patient 
is compliant[28]. In contrast, at least a dynamic 
sentinel node biopsy should be recommended 
to improve the outcome for ≥ T1G2 disease[29]  
(Table 2).

Guidelines for treatment strategies for nodal 
metastases: cN1/cN2
A ll 3 guidelines recommend a radica l inguina l 
lymphadenectomy for clinically positive lymph nodes. 
The confirmation of clinically positive lymph nodes 
should be made by surgical resection and frozen section 
according to the EAU guidelines, while, according to the 
NCCN, the confirmation can be made by percutaneous 
biopsy, or by fine-needle aspiration (FNA) in the ESMO 
guidelines (Table 3).

Summa r y of treatment recommendations: 
Radi cal inguinal lymphadenectomy seems to 
improve survival and should be recommended for 
every patient with cN1/N2[30] (Table 2).

Guidelines for treatment strategies for nodal 
metastases: cN3
F o r  f i x e d  i n g u i n a l  n o d a l  m a s s  o r  p e l v i c 
lymphadenopathy (cN3), neoadjuvant chemotherapy 

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continued on page 182

TABLE 3. 
Guidelines for the management of nodal metastasis and adjuvant therapy for penile cancer

EAU Guidelines NCCN Guidelines ESMO Guidelines

Recommendation
Grade of 

recommendation
Level of 

evidence
Recommendation

Grade of 
recommendation

Level of 
evidence

Recommendation
Grade of 

recommendation
Level of 

evidence

STAGE CN0

Surveillance is only 
recommended in patients  

with pTis/pTa tumors

Strong 
recommendation

Most low-risk patients are 
followed with a surveillance

as the probability of occult micro 
metastases in ILNs is low

Considered
appropriate 2A

Low- risk (Tis, Ta, T1G1) and 
intermediate-risk (T1G2) are 
followed with surveillance

B

> T1G2: invasive lymph node 
staging is recommended by 

either bilateral modified inguinal 
lymphadenectomy or dynamic 

sentinel node biopsy

Strong 
recommendation

2B
For high-risk standard or modified 

ILND or DSNB is strongly 
recommended in high-risk

Considered
appropriate

2A

DSNB is recommended in 
patients with non-palpable 
inguinal lymph nodes T1G2  

or greater

B

STAGE CN1/CN2

A radical inguinal 
lymphadenectomy  

should be performed

Strong 
recommendation

2B

Percutaneous lymph node biopsy 
is considered standard

Positive findings warrant an 
immediate ILND

2A

Fine-needle aspiration (FNA) 
of the LN is standard for these 

patients (omitting the procedure 
for high-risk tumors to avoid 

delay of ILND)

STAGE CN3

Multimodal treatment with 
neoadjuvant chemotherapy

followed by radical 
lymphadenectomy in  

responders is recommended

Weak 
recommendation

Should receive neoadjuvant 
Chemotherapy followed by 
radical inguinal and PLND 

lymphadenectomy in responders

Considered
appropriate

2A
Patients with fixed nodes should 
be considered for neoadjuvant 

chemoradiotherapy
C III

Consider postoperative 
radiotherapy or 

chemoradiotherapy
2B

Responders receive 
consolidation surgery (bilateral 
and deep ILND and ipsilateral 

PLND if possible)

STAGE PELVIC LYMPH NOD

Patients with 2 or more inguinal 
lymph node metastases on 

one side and/or extracapsular 
lymph node extension need 
to undergo ipsilateral pelvic 

lymphadenectomy

Strong 
recommendation

2B

PLND should be considered at the 
time or following ILND in patients 

with ≥ three positive inguinal 
nodes on the ipsilateral ILND site

Considered
appropriate

2A
Patients with fixed nodes should 
be considered for neoadjuvant 

chemoradiotherapy
C III

Bilateral PLND should be 
considered either at the time or 
following ILND in patients with 

≥4 positive inguinal nodes

Considered
appropriate

2A

Responders receive 
consolidation surgery (bilateral 
and deep ILND and ipsilateral 

PLND if possible)

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followed by a radical lymphadenectomy is supported by 
both NCCN and EAU guidelines. The ESMO guidelines 
recommend a multimodal treatment including chemo-
radiot herapy fol lowed by consolidation surger y 
(inguinal lymph node dissection [ILND] and ipsilateral 
pelvic lymph node dissection [PLND]). This treatment 
regimen is one of the options in the NCCN guidelines 
but is considered only as a palliative treatment in the 
EAU guidelines (Table 3).

Summary of treatment recommendations: For 
cN3, we recommend a radical lymphadenectomy 
after neoadjuvant chemotherapy for every responder 
to improve disease-free survival[25] (Table 2).

Enlarged pelvic lymph nodes
For surgically resectable lesions, all 3 guidelines 
recommend neoadjuvant systemic chemotherapy, 
followed by unilateral/bilateral PLND in case of 
treatment response. The EAU guidelines recommend 
lymphadenectomy for ipsilateral PLND if 2 or more 
inguinal lymph nodes are affected on one side or if 
extracapsular nodal metastasis is reported, followed 
by adjuvant chemotherapy. For enlarged pelvic lymph 
nodes where surgery is not possible, the NCCN and 
the ESMO guidelines recommend chemo-radiotherapy 
(Table 3).

Summary of treatment recommendations: PLND 
is recommended for patients with 2 or more 
inguinal lymph nodes affected on one side or if 
extra-nodal extension is found[31] (Table 2). 

Guidelines for chemotherapy
Both the EAU and ESMO guidelines state that 
neoadjuvant chemotherapy followed by radical surgery 
is advisable in unresectable lymph node metastases. 
The NCCN g uidelines recommend neoadjuvant 
chemotherapy in patients with ≥ 4 cm inguinal 
lymph nodes (fixed or mobile). The EAU and ESMO 
guidelines recommend adjuvant chemotherapy after 
lymphadenectomy in patients with pN2/pN3 disease. In 
contrast, the NCCN guidelines recommended adjuvant 
chemotherapy only if it was not given preoperatively, and 
if the pathology shows high-risk features (Tables 3,4).

Su m ma r y of t re at ment recom mend at ions:  
A neoadjuvant chemotherapy should be proposed 
systematically for patients with cN3 inguinal lymph 
nodes and discussed for all clinical lymph nodes ≥ 
4cm. An adjuvant chemotherapy should be offered 
to patients with pN2/pN3 disease without previous 
systemic treatment. Three to 4 cycles of paclitaxel, 
cisplatin, 5-fluorouracil (5FU) are the recommended 
regimen[32–34] (Table 2). 

continued on page 182

TABLE 3. 
Guidelines for the management of nodal metastasis and adjuvant therapy for penile cancer

EAU Guidelines NCCN Guidelines ESMO Guidelines

Recommendation
Grade of 

recommendation
Level of 

evidence
Recommendation

Grade of 
recommendation

Level of 
evidence

Recommendation
Grade of 

recommendation
Level of 

evidence

STAGE CN0

Surveillance is only 
recommended in patients  

with pTis/pTa tumors

Strong 
recommendation

Most low-risk patients are 
followed with a surveillance

as the probability of occult micro 
metastases in ILNs is low

Considered
appropriate 2A

Low- risk (Tis, Ta, T1G1) and 
intermediate-risk (T1G2) are 
followed with surveillance

B

> T1G2: invasive lymph node 
staging is recommended by 

either bilateral modified inguinal 
lymphadenectomy or dynamic 

sentinel node biopsy

Strong 
recommendation

2B
For high-risk standard or modified 

ILND or DSNB is strongly 
recommended in high-risk

Considered
appropriate

2A

DSNB is recommended in 
patients with non-palpable 
inguinal lymph nodes T1G2  

or greater

B

STAGE CN1/CN2

A radical inguinal 
lymphadenectomy  

should be performed

Strong 
recommendation

2B

Percutaneous lymph node biopsy 
is considered standard

Positive findings warrant an 
immediate ILND

2A

Fine-needle aspiration (FNA) 
of the LN is standard for these 

patients (omitting the procedure 
for high-risk tumors to avoid 

delay of ILND)

STAGE CN3

Multimodal treatment with 
neoadjuvant chemotherapy

followed by radical 
lymphadenectomy in  

responders is recommended

Weak 
recommendation

Should receive neoadjuvant 
Chemotherapy followed by 
radical inguinal and PLND 

lymphadenectomy in responders

Considered
appropriate

2A
Patients with fixed nodes should 
be considered for neoadjuvant 

chemoradiotherapy
C III

Consider postoperative 
radiotherapy or 

chemoradiotherapy
2B

Responders receive 
consolidation surgery (bilateral 
and deep ILND and ipsilateral 

PLND if possible)

STAGE PELVIC LYMPH NOD

Patients with 2 or more inguinal 
lymph node metastases on 

one side and/or extracapsular 
lymph node extension need 
to undergo ipsilateral pelvic 

lymphadenectomy

Strong 
recommendation

2B

PLND should be considered at the 
time or following ILND in patients 

with ≥ three positive inguinal 
nodes on the ipsilateral ILND site

Considered
appropriate

2A
Patients with fixed nodes should 
be considered for neoadjuvant 

chemoradiotherapy
C III

Bilateral PLND should be 
considered either at the time or 
following ILND in patients with 

≥4 positive inguinal nodes

Considered
appropriate

2A

Responders receive 
consolidation surgery (bilateral 
and deep ILND and ipsilateral 

PLND if possible)

181SIUJ.ORG SIUJ  •  Volume 2, Number 3  •  May 2021

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TABLE 3. 
Guidelines for the management of nodal metastasis and adjuvant therapy for penile cancer, Cont'd

EAU Guidelines NCCN Guidelines ESMO Guidelines

Recommendation
Grade of 

recommendation
Level of 

evidence
Recommendation

Grade of 
recommendation

Level of 
evidence

Recommendation
Grade of 

recommendation
Level of 

evidence

STAGE CHEMOTHERAPY

Neoadjuvant chemotherapy 
using cisplatin- and the taxane-
based triple combination should 
be used in patients with fixed, 
unresectable, nodal disease

Strong 
recommendation

2A

Neoadjuvant chemotherapy with 
TIP (paclitaxel, ifosfamide, and 

cisplatin) is preferred  
(prior to ILND) in patients with  

≥4 cm inguinal lymphnodes  
(fixed or mobile)

Considered
appropriate

2A

Neoadjuvant chemotherapy 
followed by radical surgery is 
advisable in unresectable or 

recurrent LN metastases

C

Strong 
recommendation

2B

Adjuvant chemotherapy it is 
reasonable to give four courses  
of TIP in the adjuvant setting if 
it was not given preoperatively 

and the pathology shows 
high-risk features

2A
Adjuvant chemotherapy is 

recommended in pN2-3
patients

C

STAGE RADIOTHERAPY

Not recommended for nodal 
disease except as a palliative

option

Strong 
recommendation

Adjuvant EBRT or 
chemoradiotherapy can also  

be considered for patients with 
high-risk features

Considered
appropriate

2B
The role of adjuvant

postoperative radiation  
is controversial

TABLE 4. 

Guidelines of chemotherapy regimen for penile cancer

EAU Guidelines NCCN Guidelines ESMO Guidelines

Treatment
Grade of 

recommendation
Level of 

evidence
Treatment

Grade of 
recommendation

Level of evidence Treatment
Grade of 

recommendation
Level of 

evidence

NEOADJUVANT CHEMOTHERAPY

(4 cycles)

cisplatin- and taxane-
based regimen

Weak 2A
(4 courses)

TIP (paclitaxel, ifosfamide, 
and cisplatin)

2A
Considered
appropriate

(4 courses)

TIP (paclitaxel, ifosfamide, 
and cisplatin)

C III

ADJUVANT CHEMOTHERAPY

(3 to 4 cycles)

cisplatin, a taxane and 
5-fluorouracil or ifosfamide

Strong 2B

(4 courses)
Preferred regimen is  

TIP (paclitaxel, ifosfamide, 
and cisplatin)

Other recommended 
regimen is 5- fluorouracil + 

cisplatin

2A
Considered
appropriate

No clear recommendation

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Guidelines for Adjuvant Radiotherapy
NCCN guidelines indicate that adjuvant EBRT or 

chemo-radiotherapy can be considered for patients 
with high-risk features, but the EAU guidelines do 
not recommend it except for palliative treatment. 
According to the ESMO guidelines, the role of adjuvant 
radiotherapy in the management of penile cancer 
remains controversial (Tables 3,4).

Summa r y of treatment recommendations: 
Adjuvant radiotherapy is recommended after PLND 
for patients with positive results in ILND[35,36].

Assessment of the quality of the guidelines 
with the AGREE II instrument

The AGREE Instrument is a 23-item tool comprising 
6 quality and 2 overall assessment domains. A unique 
dimension of guideline quality is captured in each 
domain. Table 3 shows the results of the guidelines 
appraisal by the 5 reviewers. For the Domain 1 scope 
and purpose, which is related to the specific health 
questions, the overall aim of the guideline, and the 
target population, EAU and NCCN both scored 
61%, while ESMO scored only 46%. Concerning the 
stakeholder involvement focuses on the extent to which 
the guidelines were developed by the appropriate 
stakeholders, the lowest score was 33% for ESMO, 
while EAU and NCCN reached approximately the 
same score with 59% and 60%, respectively. Regarding 
rigor of development concerned with the approaches 
to formulate the recommendations and the process 
used to gather and make the evidence and to update 
them, the appraiser gave the best score to the EAU and 
NCCN guidelines with 69% and 61%, respectively; 
while the ESMO, with a score of 34% did not reach the 
expected standard. With respect to structure, language, 
format, and clarity of presentation, the NCCN had a 
score of 81%, followed by the EAU, with 77%, and the 
ESMO with 61%. Resource implications of applying the 
guideline, strategies to improve uptake, and applicability 
pertaining to the likely barriers to and facilitators of 
implementation were scored at 33%, 53%, and 59% for 
the ESMO, NCCN, and EAU guidelines, respectively. 
For editorial independence, which concerns there being 
no competing interests that might bias the formulation 
of recommendations, the scores were 78% for the EAU 
guidelines, 57% for the ESMO guidelines, and 52% for 
the NCCN guidelines. Overall assessment includes 
rating the recommendation of guidelines for practice 
use and the overall quality of the guidelines. The highest 
score was reached by the EAU guidelines with a total rate 
of 77%, and the lowest score by the ESMO guidelines 
with a rate of 40%, while the NCCN guidelines also 
reached a high rate with 73% (Table 5).

TABLE 3. 
Guidelines for the management of nodal metastasis and adjuvant therapy for penile cancer, Cont'd

EAU Guidelines NCCN Guidelines ESMO Guidelines

Recommendation
Grade of 

recommendation
Level of 

evidence
Recommendation

Grade of 
recommendation

Level of 
evidence

Recommendation
Grade of 

recommendation
Level of 

evidence

STAGE CHEMOTHERAPY

Neoadjuvant chemotherapy 
using cisplatin- and the taxane-
based triple combination should 
be used in patients with fixed, 
unresectable, nodal disease

Strong 
recommendation

2A

Neoadjuvant chemotherapy with 
TIP (paclitaxel, ifosfamide, and 

cisplatin) is preferred  
(prior to ILND) in patients with  

≥4 cm inguinal lymphnodes  
(fixed or mobile)

Considered
appropriate

2A

Neoadjuvant chemotherapy 
followed by radical surgery is 
advisable in unresectable or 

recurrent LN metastases

C

Strong 
recommendation

2B

Adjuvant chemotherapy it is 
reasonable to give four courses  
of TIP in the adjuvant setting if 
it was not given preoperatively 

and the pathology shows 
high-risk features

2A
Adjuvant chemotherapy is 

recommended in pN2-3
patients

C

STAGE RADIOTHERAPY

Not recommended for nodal 
disease except as a palliative

option

Strong 
recommendation

Adjuvant EBRT or 
chemoradiotherapy can also  

be considered for patients with 
high-risk features

Considered
appropriate

2B
The role of adjuvant

postoperative radiation  
is controversial

TABLE 4. 

Guidelines of chemotherapy regimen for penile cancer

EAU Guidelines NCCN Guidelines ESMO Guidelines

Treatment
Grade of 

recommendation
Level of 

evidence
Treatment

Grade of 
recommendation

Level of evidence Treatment
Grade of 

recommendation
Level of 

evidence

NEOADJUVANT CHEMOTHERAPY

(4 cycles)

cisplatin- and taxane-
based regimen

Weak 2A
(4 courses)

TIP (paclitaxel, ifosfamide, 
and cisplatin)

2A
Considered
appropriate

(4 courses)

TIP (paclitaxel, ifosfamide, 
and cisplatin)

C III

ADJUVANT CHEMOTHERAPY

(3 to 4 cycles)

cisplatin, a taxane and 
5-fluorouracil or ifosfamide

Strong 2B

(4 courses)
Preferred regimen is  

TIP (paclitaxel, ifosfamide, 
and cisplatin)

Other recommended 
regimen is 5- fluorouracil + 

cisplatin

2A
Considered
appropriate

No clear recommendation

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Evaluation of the Guidelines for Penile Cancer Treatment: Overview and Assessment

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Discussion
Clinical guidelines help physicians to choose the 

best treatment available for individual patients. Fewer 
guidelines are available in the case of rare diseases, and 
only 3 guidelines in English have been published on the 
management of penile cancer. The recommendations 
made in these guidelines are not always in agreement. 
Therefore, to help urologists in their decision-making 
process regarding therapy, we evaluated and compared 
the guidelines of the NCCN, EAU, and ESMO on the 
management of penile cancer. Using the AGREE II tool, 
we assessed the quality of the guidelines. We discuss 
the differences in terms of LOE and GOR that arise as a 
result of different methods of evaluation used. The EAU 
and NCCN guidelines incorporate more recent literature 
than the ESMO guidelines, which have not been updated 
for 7 years.

The EAU guidelines use a modif ied Grading 
of Recommendations Assessment, Development, 
and Evaluation (GR ADE) methodolog y. For each 
recommendation within the guidelines, there is 
an accompanying online strength rating form that 
addresses several elements. The ESMO adapted the 
Infectious Diseases Society of America-United States 
Public Health Service Grading System. The level of 
evidence assessment and grading of recommendations in 
NCCN guidelines are based on randomized controlled 
trials, clinical trials, guidelines, systematic reviews, 
meta-analysis, and validation studies. Evaluation of 
LOE and GOR are more specified clearly in the NCCN 

guidelines than in the other 2 guidelines. Although these 
3 guidelines developed in different ways, it is reassuring 
that they have considerable similarities, albeit some 
small but potentially significant differences between 
them. The evidence available is weak in penile cancer, 
and a consequence of the scarcity in evidence is that way, 
some recommendations are based on the panel’s review 
of the low-level evidence and expert opinion.

One of the contentious points is the advantage of both 
neoadjuvant and adjuvant radiotherapy in the treatment 
of penile cancer patients with LN metastases. There is 
some evidence for adjuvant nodal radiotherapy in in 
vulvar carcinoma, which shares many characteristics 
with penile cancer[37,38]. However, high-quality 
evidence to suggest a clear benefit to radiotherapy 
in penile cancer is lacking[39,40]. In a retrospective 
study of 2458 patients in the SEER database (National 
Cancer Institute Surveillance, Epidemiology and End 
Results Program), no advantage was observed with the 
use of EBRT for penile cancer patients compared to 
surgery alone on cancer-specific survival[41]. A similar 
conclusion was reached by Franks et al., who reported 
poor long-term survival for patients treated with 
adjuvant radiotherapy[42]. These essential findings are 
consistent with those of other studies, which showed no 
patient benefit[43,44–48]. However, A series of recent 
studies have indicated that  adjuvant radiotherapy 
i mprove d su r v iv a l a nd de c re a s e d re c u r renc e 
rate[35,36,49].

TABLE 5. 

AGREE II evaluation of guidelines for the management of penile cancer

Scope and 
purpose

%

Stakeholder 
involvement

%

Rigor of  
development

%

Clarity of  
presentation

%
Applicability

%

Editorial  
independence

%

Overall 
assessment

%

Final 
recommendations

EAU GUIDELINES 

61 59 69 77 59 78 77
Yes–3, Yes with 
modifications–2, 

No–0

NCCN GUIDELINES

61 60 61 81 53 52 73
Yes–3, Yes with 
modifications–2, 

No–0

ESMO GUIDELINES

46 33 34 61 33 57 40
Yes–0, Yes with 
modifications–2, 

No–3

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Conclusion
This is the first attempt to review and appraise 

guidelines for penile cancer management systematically. 
Although all guidelines strive to be evidence-based, 
some recommendations differ between the guidelines 
because the underlying evidence is poor. Also, these 
guidelines are produced in the United States and Europe, 

so that their applicability in other regions with a high 
incidence of penile cancer is uncertain. This point may 
encourage organizations in other areas to produce their 
own guidelines. The best way to improve the guidelines 
is to conduct more prospective trials to strengthen the 
data underlying the recommendations.

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