08 Primary Urethral Carcinoma LR 1

Guidelines on
Primary Urethral
Carcinoma
G. Gakis, J.A. Witjes, E. Compérat, N.C. Cowan, M. De Santis,
T. Lebret, M.J. Ribal, A. Sherif
© European Association of Urology 2014

TABLE OF CONTENTS PAGE
1. INTRODUCTION 3
2. METHODOLOGY 3
3. LEVEL OF EVIDENCE AND GRADE OF RECOMMENDATION 3
4. EPIDEMIOLOGY 4
5. AETIOLOGY AND RISK FACTORS 4
6. HISTOPATHOLOGY 5
7. CLASSIFICATION 5
7.1 TNM staging system 5
7.2 Tumour grade 6
8. SURVIVAL 6
8.1 Long-term survival after primary urethral carcinoma 6
8.2 Predictors of survival in primary urethral carcinoma 6
9. DIAGNOSIS AND STAGING 7

9.1 History 7
9.2 Clinical examination 7
9.3 Urinary cytology 7
9.4 Diagnostic urethrocystoscopy and biopsy 7
9.5 Radiological imaging 7
9.6 Regional lymph nodes 7
10. TREATMENT OF LOCALISED PRIMARY URETHRAL CARCINOMA 8

10.1 Treatment of localised primary urethral carcinoma in males 8
10.2 Treatment of localised urethral carcinoma in females 8
10.2.1 Urethrectomy and urethra-sparing surgery 8
10.2.2 Radiotherapy 8
11. MULTIMODAL TREATMENT IN ADVANCED URETHRAL CARCINOMA 9

11.1 Preoperative cisplatinum-based chemotherapy 9
11.2 Preoperative chemoradiotherapy in locally advanced squamous cell carcinoma of
the urethra 9
12. TREATMENT OF UROTHELIAL CARCIMONA OF THE PROSTATE 10
13. FOLLOW-UP 10
14. REFERENCES 10
15. ABBREVIATIONS USED IN THE TEXT 15
2 PRIMARY URETHRAL CARCINOMA - MARCH 2013

1. INTRODUCTION
The European Association of Urology (EAU) Guidelines Group on Muscle-invasive and Metastatic Bladder
Cancer has prepared these guidelines to deliver current evidence-based information on the diagnosis and
treatment of patients with primary urethral carcinoma (UC). When the first carcinoma in the urinary tract is
detected in the urethra, this is defined as primary UC, in contrast to secondary UC, which presents as recurrent
carcinoma in the urethra after prior diagnosis and treatment of carcinoma elsewhere in the urinary tract. Most
often, secondary UC is reported after radical cystectomy for bladder cancer (1) (see Chapter 14 of the EAU
Guidelines on Muscle-invasive and Metastatic Bladder Cancer [2]).
2. METHODOLOGY
A systematic literature search was performed to identify studies reporting urethral malignancies. Medline was
searched using the controlled vocabulary of the Medical Subject Headings (MeSH) database, along with a free-
text protocol, using one or several combinations of the following terms: adenocarcinoma, adjuvant treatment,
anterior, chemotherapy, distal urethral carcinoma, lower, neoadjuvant, partial, penectomy, penile-preserving
surgery, posterior, primary, proximal urethral carcinoma, radiotherapy, recurrence, risk factors, squamous
cell carcinoma, survival, transitional cell carcinoma, urethra, urethrectomy, urethral cancer, urinary tract, and
urothelial carcinoma. No randomised controlled trials (RCTs) were identified and articles were selected based
on study design, treatment modality and long-term outcomes. Older studies (> 10 years) were considered if
they contained historically relevant data or in the absence of newer data.
3. LEVEL OF EVIDENCE AND GRADE OF

RECOMMENDATION
References in the text have been assessed according to their level of scientific evidence (LE), and guideline
recommendations have been graded according to the listings in Tables 1 and 2, based on the Oxford Centre for
Evidence-based Medicine Levels of Evidence (3). Grading aims to provide transparency between the underlying
evidence and the recommendation given (3). Due to the fact that primary UC belongs to the family of rare
cancers, most studies are retrospective, and recommendations given in these guidelines are mainly based on
level 3 evidence.
Table 1: Level of evidence*
Level Type of evidence

1a Evidence obtained from meta-analysis of randomised trials.
1b Evidence obtained from at least one randomised trial.
2a Evidence obtained from one well-designed controlled study without randomisation.
2b Evidence obtained from at least one other type of well-designed quasi-experimental study.
3 Evidence obtained from well-designed non-experimental studies, such as comparative studies,
correlation studies and case reports.
4 Evidence obtained from expert committee reports or opinions or clinical experience of respected
authorities.
*Modified from Sackett et al. (3).
It should be noted that when recommendations are graded, the link between the LE and grade of
recommendation (GR) is not directly linear. Availability of RCTs may not necessarily translate into a grade A
recommendation when there are methodological limitations or disparity in published results.
Alternatively, the absence of a high level of evidence does not preclude a grade A recommendation,
if there is overwhelming clinical experience and consensus. There may be exceptional situations where
corroborating studies cannot be performed - perhaps for ethical or other reasons - and in this case,
unequivocal recommendations are considered helpful. Whenever this occurs, it is indicated in the text as
“upgraded based on panel consensus”. The quality of the underlying scientific evidence - although a very
PRIMARY URETHRAL CARCINOMA - MARCH 2013 3

important factor - has to be balanced against benefits and burdens, values and preferences, and costs when a
grade is assigned (4-6).
The EAU Guidelines Office does not perform structured cost assessments, nor can they address local/
national preferences in a systematic fashion. However, whenever these data are available, the Expert Panel will
include the information.
Table 2: Grade of recommendation*
Grade Nature of recommendations

A Based on clinical studies of good quality and consistency that addressed specific recommendations,
including at least one randomised trial.
B Based on well-conducted clinical studies, but without randomised clinical trials.
C Made despite the absence of directly applicable clinical studies of good quality.
*Modified from Sackett et al. (3).
Publication history
This 2013 guidelines document on Primary Urethral Carcinoma is the first publication on this topic by the EAU.
This is the current authorised edition of this guideline.
This document was subjected to blinded peer review prior to publication.
Potential conflict of interest statement

The expert panel have submitted potential conflict of interest statements that can be viewed on the EAU
website: http://www.uroweb.org/guidelines/online-guidelines/.
4. EPIDEMIOLOGY
Primary UC is considered a rare cancer, accounting for < 1% of all malignancies (7) (ICD-O3 topography code:
C68.0 [8]).
The RARECARE project, which has been set up to describe the epidemiology of rare urogenital
cancers in 64 European population-based cancer registries (covering 32% of the population of the 27
Member States of the European Union (EU), has reported recently on 1,059 new cases of epithelial urethral
tumours detected between 1995 and 2002 (9). In early 2008, the prevalence of UC in the 27 EU countries was
4,292 cases with an estimated annual incidence of 655 new cases. The age-standardised ratio was 1.1 per
million inhabitants (1.6/million in men and 0.6/million in women; a male to female ratio of 2.9) (9). There were
differences between European regions; potentially caused by registration or classification (9). Likewise, in an
analysis of the Surveillance, Epidemiology and End Results (SEER) database, the incidence of primary UC
peaked in the > 75 years age group (7.6/1,000,000). The age-standardised rate was 4.3/million in men and 1.5/
million in women, and was almost negligible in those aged < 55 years (0.2/million) (10).
5. AETIOLOGY AND RISK FACTORS

For male primary UC, various predisposing factors have been reported, including urethral strictures (11,12),
chronic irritation after intermittent catheterisation/urethroplasty (13-15), external beam irradiation therapy (16),
radioactive seed implantation (17), and chronic urethral inflammation/urethritis following sexually transmitted
diseases (i.e. condylomata associated with human papilloma virus 16) (18,19). In female UC, urethral diverticula
(20-22) and recurrent urinary tract infections (23) have been associated with primary carcinoma. Clear cell
adenocarcinoma may also have a congenital origin (24).

6. HISTOPATHOLOGY
Both the RARECARE project and SEER database have reported that urothelial carcinoma of the urethra is the
predominant histological type of primary urethral cancer (54-65%), followed by squamous cell carcinoma (SCC;
16-22%) and adenocarcinoma (AC; 10-16%) (9,10). A recent SEER analysis of 2,065 men with primary urethral
cancer (mean age: 73 years) found that urothelial carcinoma (78%) was most common, and SCC (12%) and
AC (5%) were significantly less frequent (25). In women, a recent report of the National Cancer Registry of the
Netherlands on primary urethral cancer reported that urothelial carcinoma occurred in 45% of cases, followed
by AC in 29%, SCC in 19%, and other histological entities in 6% (26). Several other rare histological types of
urethral malignancies have been also described in these studies.
7. CLASSIFICATION
7.1 TNM staging system
In men and women, UC is classified according to the 7th edition of the TNM classification (8) (Table 3). It should
be noted that there is a separate TNM staging system for prostatic UC (8). Of note, for cancers occurring in
urethral diverticulum stage T2 is not applicable as urethral diverticula are lacking periurethral muscle (27).
NM classification (7th edition) for UC (8). Primary tumour stage is separated into UC and UC of
Table 3: T
the prostate
T - Primary tumour (men and women)

Tx Primary tumour cannot be assessed
Tis Carcinoma in situ
T0 No evidence of primary tumour
Ta Non-invasive papillary carcinoma
T1 Tumour invades subepithelial connective tissue
T2 Tumour invades any of the following structures: corpus spongiosum, prostate, peri-urethral muscle
T3 Tumour invades any of the following structures: corpus cavernosum, invasion beyond prostatic
capsule, anterior vaginal wall, bladder neck
T4 Tumour invades other adjacent organs
Primary tumour in prostatic urethra
Tx Primary tumour cannot be assessed
Tis pu Carcinoma in situ in the prostatic urethra
Tis pd Carcinoma in situ in the prostatic ducts
T0 No evidence of primary tumour
T1 Tumour invades subepithelial connective tissue (only in case of concomitant prostatic urethral
involvement)
T2 Tumour invades any of the following structures: corpus spongiosum, prostatic stroma, periurethral
muscle
T3 Tumour invades any of the following structures: corpus cavernosum, beyond prostatic capsule,
bladder neck
T4 Tumour invades other adjacent organs
N - Regional lymph nodes
Nx Regional lymph nodes cannot be assessed
N0 No regional lymph node metastases
N1 Metastasis in a single lymph node < 2 cm in greatest dimension
N2 Metastasis in a single lymph node > 2 cm in greatest dimension or in multiple nodes
M - Distant metastasis
Mx Distant metastasis cannot be assessed
M0 No distant metastasis
M1 Distant metastasis

7.2 Tumour grade
The former WHO grading system of 1973 which differentiated urothelial carcinomas into three different grades
(G1-G3) has been replaced by the grading system of 2004 that differentiates urothelial UC into PUNLMP, low
grade and high grade. Non-urothelial UC is graded by a trinomial system that differentiates between well-
differentiated (G1), moderately differentiated (G2), and poorly differentiated tumours (G3). Table 4 lists the
different grading systems according to the WHO 1973 and 2004 systems (28).
Table 4: Histopathological grading of urothelial and non-urothelial primary UC (28)
PUNLMP Papillary urothelial neoplasm of low malignant

potential
Low grade Well differentiated
High grade Poorly differentiated
Non-urothelial UC
Gx Tumour grade not assessable
G1 Well differentiated
G2 Moderately differentiated
G3 Poorly differentiated
Recommendation LE GR
Pathological staging and grading of primary UC should follow the 2009 TNM classification und 3 B
WHO 2004 grading system.
8. SURVIVAL
8.1 Long-term survival after primary urethral carcinoma
According to the RARECARE project, the mean 1- and 5-year overall survival in patients with UC in Europe is
71% and 54%, respectively (9). With longer follow-up, a SEER analysis of 1,615 cases reported median 5- and
10-year overall survival rates of 46% and 29%, respectively. Cancer-specific survival at 5 and 10 years was
68% and 60%, respectively (10).
8.2 Predictors of survival in primary urethral carcinoma

In Europe, mean 5-year overall survival does not substantially differ between the sexes (9). Predictors of
decreased survival in patients with primary UC are:
• Advanced age and race (> 65 years) (9,29)
• Stage, grade, nodal involvement and metastasis (25)
• Tumour size and proximal tumour location (25)
• Extent of surgical treatment and treatment modality (25, 29)
• Underlying histology (9,26,29)
Some limitations have to be taken into account in the interpretation of these results. In the Dutch study, the
numbers were low (n = 91) (26). In the large SEER database (n = 2,046), therapy is not well specified in relation
to survival (25). Finally, in contrast to the RARECARE project (9), the opposite findings were reported in the
SEER database in relation to the role of histology on survival in male patients (29).
Conclusion LE
Risk factors for survival in primary UC are: age, tumour stage and grade, nodal stage, presence of 3
distant metastasis, histological type, tumour size, tumour location, and type and modality of treatment.

9. DIAGNOSIS AND STAGING
9.1 History
When becoming clinically apparent, most patients (45-57%) with primary UC present with symptoms
associated with locally advanced disease (T3/T4) (26,30). At initial presentation visible haematuria or bloody
urethral discharge is reported in up to 62% of the cases. Further symptoms of locally advanced disease include
an extraurethral mass (52%), bladder outlet obstruction (48%), pelvic pain (33%), urethrocutaneous fistula
(10%), abscess formation (5%) or dyspareunia (30).
9.2 Clinical examination

In men, physical examination should comprise palpation of the extern genitalia for suspicious indurations or
masses and digital rectal examination (31). In women, further pelvic examination with careful inspection and
palpation of the urethra should be performed, especially in those with primary onset of irritative or obstructive
voiding. In addition, bimanual examination, when necessary under general anaesthesia, should be performed
for local clinical staging and to exclude the presence of colorectal or gynaecological malignancies.
Bilateral inguinal palpation should be conducted to assess the presence of enlarged lymph nodes,
describing location, size and mobility (32).
9.3 Urinary cytology

The role of urinary cytology in primary UC is limited, and its sensitivity ranges between 55 and 59% (33).
Detection rate depends on the underlying histological entity. In male patients, the sensitivity for urothelial
carcinoma and SCC was reported to be 80% and 50%, respectively, whereas in female patients sensitivity was
found to be 77% for SCC and 50% for urothelial carcinoma.
9.4 Diagnostic urethrocystoscopy and biopsy

Diagnostic urethrocystoscopy and biopsy enables primary assessment of a urethral tumour in terms of
tumour extent, location and underlying histology (31). To enable accurate pathological assessment of surgical
margins, biopsy sites (proximal/distal end) should be marked and sent together with clinical information to the
pathologist. Careful cystoscopic examination is necessary to exclude the presence of concomitant bladder
tumours (2). A cold-cup biopsy enables accurate tissue retrieval for histological analysis and avoids artificial
tissue damage. In patients with larger lesions, transurethral resection (optionally in men under penile blood
arrest using a tourniquet) can be performed for histological diagnosis. In patients with suspected urothelial
carcinoma of the prostatic urethra or ducts, resectoscope loop biopsy of the prostatic urethra (at 5 and 7
o’clock positions from the bladder neck and distally around the area of the verumontanum) can contribute to an
improved detection rate (34).
9.5 Radiological imaging

Radiological imaging of urethral cancer aims to assess local tumour extent and to detect lymphatic and
distant metastatic spread. For local staging, there is increasing evidence that magnetic resonance imaging
(MRI) is superior to computed tomography (CT) in terms of staging accuracy. Imaging for regional lymph node
metastases should concentrate on inguinal and pelvic lymph nodes, using either MRI or CT. Distant staging
should concentrate on chest and liver, with CT of the thorax and abdomen in all patients with invasive disease
(> cT1N0M0 (35-39). If imaging of the remainder of the urothelium is required, then CT should include CT
urography with an excretory phase (40).
9.6 Regional lymph nodes

In contrast to penile cancer, in which clinically enlarged lymph nodes at initial diagnosis are not uncommon due
to inflammatory conditions (41), enlarged lymph nodes in urethral cancer often represent metastatic disease
(42). In men, lymphatics from the anterior urethra drain into the superficial and deep inguinal lymph nodes and
subsequently to the pelvic (external, obturator and internal iliac) lymph nodes. Conversely, lymphatic vessels
of the posterior urethra drain into the pelvic lymph nodes. In women, the lymph of the proximal third drains into
the pelvic lymph node chains, whereas the distal two-thirds initially drains into the superficial and deep inguinal
nodes (43,44).
Nodal control in urethral cancer can be achieved either by regional lymph node dissection (31),
radiotherapy (45) or chemotherapy (42). Currently, there is no clear evidence to support prophylactic bilateral
inguinal and/or pelvic lymphadenectomy in all patients with urethral cancer. However, in patients with clinically
enlarged inguinal/pelvic lymph nodes or invasive tumours, regional lymphadenectomy should be considered for
initial treatment because cure might still be achievable with limited disease (31).

Conclusion LE
Patients with clinically enlarged inguinal or pelvic lymph nodes often exhibit pathological lymph node 3
metastasis.
Recommendations LE GR
Diagnosis includes urethrocystoscopy with biopsy and urinary cytology. 3 B
CT of the thorax and abdomen should be used to assess distant metastases. 3 B
Pelvic MRI is the preferred method to assess local extent of urethral tumour. 3 B
10. TREATMENT OF LOCALISED PRIMARY

URETHRAL CARCINOMA
10.1 Treatment of localised primary urethral carcinoma in males
Previously, treatment of male anterior urethral cancer has followed the procedure for penile cancer, with
aggressive surgical excision of the primary lesion with a wide safety margin (31). Distal urethral tumours exhibit
significantly improved survival rates compared with proximal tumours (46). Therefore, optimising treatment
of distal urethral cancer has become the focus of clinicians to improve functional outcome and quality of life,
while preserving oncological safety. A retrospective series found no evidence of local recurrence, even with
< 5-mm resection margins (median follow-up: 17-37 months), in men with pT1-3N0-2 anterior UC treated with
well-defined penis-preserving surgery and additional iliac/inguinal lymphadenectomy for clinically suspected
lymph node disease (47). This suggests that prognosis is mainly determined by nodal stage. Similar results for
the feasibility of penile-preserving surgery have been reported in other retrospective series (30,48).
Recommendation LE GR
In localised anterior urethral tumours, penile-preserving surgery is an alternative to primary 3 B
urethrectomy, if negative surgical margins can be achieved.
10.2 Treatment of localised urethral carcinoma in females

10.2.1 Urethrectomy and urethra-sparing surgery
In women with localised urethral cancer, to provide the highest chance of local cure, primary radical
urethrectomy should remove all the periurethral tissue from the bulbocavernosus muscle bilaterally and distally,
with a cylinder of all adjacent soft tissue up to the pubic symphysis and bladder neck. Bladder neck closure
and proximal diversion through appendico-vesicostomy for primary anterior urethral lesions has been shown to
provide satisfactory functional results in women (31).
Many recent series have reported outcomes in women with mainly anterior urethral cancer undergoing
primary treatment with urethra-sparing surgery or radiotherapy, compared to primary urethrectomy, with the aim
of maintaining integrity and function of the lower urinary tract (49,50). In long-term series with median follow-up
of 153-175 months, local recurrence rates in women undergoing partial urethrectomy with intraoperative frozen
section analysis were 22-60%, and distal sleeve resection of > 2 cm resulted in secondary urinary incontinence
in 42% of patients who required additional reconstructive surgery (49,50). Ablative surgical techniques, that is,
transurethral resection (TUR) or laser, used for small distal urethral cancer, have also resulted in a considerable
local failure rate of 16%, with a cancer-specific survival rate of 50%. This emphasises the critical role of local
tumour control in women with distal urethral cancer to prevent local and systemic progression (49).
10.2.2 Radiotherapy
In women, radiotherapy was investigated in several older long-term series with a medium follow-up of 91-105
months (45,47). With a median cumulative dose of 65 Gy (range: 40-106 Gy), the 5-year local control rate
was 64% and 7-year cancer-specific survival was 49% (45). Most local failures (95%) occurred within the
first 2 years after primary treatment (47). The extent of urethral tumour involvement was found to be the only
parameter independently associated with local tumour control but the type of radiotherapy (external beam
vs. interstitial brachytherapy) was not (45). In one study, the addition of brachytherapy to external beam
radiotherapy reduced the risk of local recurrence by a factor of 4.2 (51). Of note, pelvic toxicity in those
achieving local control was considerable (49%), including urethral stenosis, fistula, necrosis, and haemorrhagic
cystitis, with 30% of the reported complications graded as severe (45).

In women with anterior urethral tumours, urethra-sparing surgery is an alternative to primary 3 B
urethrectomy if negative surgical margins can be achieved intraoperatively.
In women, local radiotherapy is an alternative to urethral surgery for localised urethral tumours. 3 C
11. MULTIMODAL TREATMENT IN ADVANCED

URETHRAL CARCINOMA
11.1 Preoperative cisplatinum-based chemotherapy
Recent retrospective studies have reported that modern cisplatinum-based polychemotherapeutic regimens
are effective in advanced primary urethral cancer, providing prolonged survival even in lymph-node-positive
disease. Moreover, they have emphasised the critical role of surgery after chemotherapy for achieving long-
term survival in patients with locally advanced urethral cancer. The largest retrospective series reported
outcomes in 44 patients with advanced primary urethral cancer. Patients were subjected to specific
cisplatinum-based polychemotherapeutic regimens according to the underlying histology. The overall response
rate for the various regimens was 72%. The median overall survival of the entire cohort was 32 months. Of
note, patients who underwent surgery after chemotherapy had significantly improved overall survival compared
with those who were managed with chemotherapy alone (42).
11.2 Preoperative chemoradiotherapy in locally advanced squamous cell carcinoma of the

urethra
The clinical feasibility of preoperative local radiotherapy with concurrent radiosensitising chemotherapy prior to
surgery in locally advanced SCC has been reported in several case series (52-57). The largest and most recent
series reported outcomes in 18 patients with primary locally advanced urethral cancer. A complete response
to primary chemoradiotherapy was observed in 83% of the patients. The 5-year overall and disease-specific
survival was 60% and 83%, respectively. Patients undergoing salvage surgery after chemoradiotherapy
experienced a higher 5-year disease-free survival than those without salvage surgery (72% vs. 54%) (57).
Conclusions LE
In locally advanced UC, cisplatinum-based chemotherapy with curative intent prior to surgery 4
improves survival compared to surgery alone.
In locally advanced SCC of the urethra, combination of curative radiotherapy with radiosensitising 4
chemotherapy with curative intent prior to surgery improves survival compared to surgery alone.
Patients with locally advanced UC should be discussed within a multidisciplinary team of 4 A
urologists, radio-oncologists and oncologists.
Chemotherapeutic regimens with curative intent should be cisplatinum based. 4 C
In locally advanced SCC of the urethra, chemoradiotherapy with curative intent prior to surgery 4 C
is an option.

12. TREATMENT OF UROTHELIAL CARCIMONA OF
THE PROSTATE
Local conservative treatment with extensive TUR and subsequent Bacille-Calmette-Guérin (BCG) instillation
is effective in patients with Ta or Tis prostatic UC (58,59). Likewise, patients undergoing TUR of the prostate
prior to BCG experience improved complete response rates compared with those who do not (95% vs. 66%)
(60). Risk of understaging local extension of prostatic urethral cancer at TUR is increased, especially in patients
with ductal or stromal involvement (61). In smaller series, response rates to BCG in patients with prostatic
duct involvement have been reported to vary between 57 and 75% (58,62). Some former series have reported
superior oncological results for the initial use of radical cystoprostatectomy as a primary treatment option in
patients with ductal involvement (63,64). In 24 patients with prostatic stromal invasion treated with radical
cystoprostatectomy, a lymph node mapping study found that 12 patients had positive lymph nodes, with an
increased proportion located above the iliac bifurcation (65).
Patients with non-invasive UC or carcinoma in situ of the prostatic urethra and prostatic ducts 3 C
can be treated with a urethra-sparing approach with TUR and BCG.
In patients with non-invasive UC or carcinoma in situ, prior TUR of the prostate should be 3 C
performed to improve response to BCG.
Cystoprostatectomy with extended pelvic lymphadenectomy should be reserved for patients 3 C
not responding to BCG or as primary treatment option in patients with extensive ductal or
stromal involvement.
13. FOLLOW-UP
COMMENTARY: Given the low incidence of primary urethral cancer, defined follow-up has not been
investigated systematically so far. Therefore, it seems reasonable to tailor surveillance regimens according
to the patients’ individual risk factors (Chapter 8.2). In patients undergoing urethra-sparing surgery, it seems
prudent to advocate a more extensive follow-up with urinary cytology, urethrocytoscopy and cross-sectional
imaging despite the lack of specific data.
14. REFERENCES
1. Boorjian SA, Kim SP, Weight CJ, et al. Risk factors and outcomes of urethral recurrence following
radical cystectomy. Eur Urol 2011 Dec;60(6):1266-72.
http://www.ncbi.nlm.nih.gov/pubmed/21871713
2. Witjes JA, Compérat E, Cowan NC, et al; members of the EAU Guidelines Panel on Muscle-invasive
and Metastatic Bladder Cancer. EAU Guidelines on Muscle-invasive and Metastatic Bladder Cancer.
Edn. presented at the EAU Annual Congress Stockholm 2014. ISBN 978-90-79754-65-6. Arnhem, The
Netherlands.
http://www.uroweb.org/guidelines/online-guidelines/
3. Oxford Centre for Evidence-based Medicine Levels of Evidence (May 2009). Produced by Bob
Phillips, Chris Ball, Dave Sackett, Doug Badenoch, Sharon Straus, Brian Haynes, Martin Dawes since
November 1998. Updated by Jeremy Howick March 2009.
http://www.cebm.net/index.aspx?o=1025 (Access date December 2013)
4. Atkins D, Best D, Briss PA, et al; GRADE Working Group. Grading quality of evidence and strength of
recommendations. BMJ 2004 Jun 19;328(7454):1490.
5. Guyatt GH, Oxman AD, Vist GE, et al. GRADE: an emerging consensus on rating quality of evidence
and strength of recommendations. BMJ 2008;336(7650):924-6.

6. Guyatt GH, Oxman AD, Kunz R, et al; GRADE Working Group. Going from evidence to
recommendations. BMJ 2008 May 10;336(7652):1049-51.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2376019/?tool=pubmed
7. Gatta G, van der Zwan JM, Casali PG, et al; The RARECARE working group. Rare cancers are not so
rare: The rare cancer burden in Europe. Eur J Cancer 2011; Nov;47(17):2493-511.
8. Sobin LH, Gospodariwicz M, Wittekind C (eds). TNM classification of malignant tumors. UICC
International Union Against Cancer. 7th edn. Wiley-Blackwell, 2009 Dec; pp. 266-9.
http://www.uicc.org/tnm/
9. Visser O, Adolfsson J, Rossi S, et al; The RARECARE working group. Incidence and survival of rare
urogenital cancers in Europe. Eur J Cancer 2012 Mar;48(4):456-64;
10. Swartz MA, Porter PM, Lin DW, et al. Incidence of primary urethral carcinoma in the United States.
Urology 2006 Dec;68(6):1164-8.
11. Medina Pérez M, Valero Puerta J, Sánchez González M, et al. (Squamous carcinoma of the male
urethra, its presentation as a scrotal abscess.) Arch Esp Urol 1999 Sep;52(7):792-4. [Article in Spanish]
12. Van de Voorde W, Meertens B, Baert L, et al. Urethral squamous cell carcinoma associated with
urethral stricture and urethroplasty. Eur J Surg Oncol 1994 Aug;20(4):478-83.
13. Colapinto V, Evans DH. Primary carcinoma of the male urethra developing after urethroplasty for
stricture. J Urol 1977 Oct;118:581-4.
14. Mohanty NK, Jolly BB, Saxena S, et al. Squamous cell carcinoma of perineal urethrostomy. Urol Int
1995;55(2):118-9.
15. Sawczuk I, Acosta R, Grant D,et al. Post urethroplasty squamous cell carcinoma. N Y State J Med
1986 May;86(5):261-3. [No abstract available]
16. Mohan H, Bal A, Punia RP, et al. Squamous cell carcinoma of the prostate. Int J Urol 2003 Feb;
10:114-6.
17. Arva NC, Das K. Diagnostic dilemmas of squamous differentiation in prostate carcinoma case report
and review of the literature. Diagn Pathol 2011 May 31;6:46
18. Cupp MR, Malek RS, Goellner JR, et al. Detection of human papillomavirus DNA in primary squamous
cell carcinoma of the male urethra. Urology 1996 Oct;48(4):551-5.
19. Wiener JS, Liu ET, Walther PJ. Oncogenic human papillomavirus type 16 is associated with squamous
cell cancer of the male urethra. Cancer Res 1992 Sep;52(18):5018-23.
20. Ahmed K, Dasgupta R, Vats A, et al. Urethral diverticular carcinoma: an overview of current trends in
diagnosis and management. Int Urol Nephrol 2010 Jun;42(2):331-41.
21. Chung DE, Purohit RS, Girshman J, Urethral diverticula in women: discrepancies between magnetic
resonance imaging and surgical findings. J Urol 2010 Jun;183(6):2265-9.
22. Thomas AA, Rackley RR, Lee U, et al. Urethral diverticula in 90 female patients: a study with emphasis
on neoplastic alterations. J Urol 2008 Dec;180(6):2463-7.
23. Libby B, Chao D, Schneider BF. Non-surgical treatment of primary female urethral cancer. Rare Tumors
2010 Sep 30;2(3):e55.
24. Gandhi JS, Khurana A, Tewari A, et al. Clear cell adenocarcinoma of the male urethral tract. Indian J
Pathol Microbiol 2012 Apr-Jun;55(2):245-7.

25. Rabbani F. Prognostic factors in male urethral cancer. Cancer 2011 June 117(1):2426-34.
26. Derksen JW, Visser O, de la Rivière GB, et al. Primary urethral carcinoma in females: an epidemiologic
study on demographical factors, histological types, tumour stage and survival. World J Urol 2012 May.
Epub ahead of print.
27. Golijanin D, Yossepowitch O, Beck SD, et al. Carcinoma in a bladder diverticulum: presentation and
treatment outcome. J Urol 2003 Nov;170(5):1761-4.
28. WHO Classification of Tumours: Pathology and Genetics of Tumours of the Urinary System and Male
Genital Organs (IARC WHO Classification of Tumours) ed. E.J. Eble J, Sesterhenn I, Sauter G. 2004,
Lyon: IARC Press.
http://www.iarc.fr/en/publications/pdfs-online/pat-gen/bb7/BB7.pdf
29. Champ CE, Hegarty SE, Shen X, et al. Prognostic factors and outcomes after definitive treatment of
female urethral cancer: a population-based analysis. Urology 2012 Aug;80(2):374-81.
30. Gheiler EL, Tefilli MV, Tiguert R, et al. Management of primary urethral cancer. Urology 1998
Sep;52(3):487-93.
31. Karnes RJ, Breau RH, Lightner DJ. Surgery for urethral cancer. Urol Clin North Am 2010
Aug;37(3):445-57.
32. Blaivas JG, Flisser AJ, Bleustein CB, et al. Periurethral masses: etiology and diagnosis in a large series
of women. Obstet Gynecol 2004 May;103(5 Pt 1):842-7.
33. Touijer AK, Dalbagni G. Role of voided urine cytology in diagnosing primary urethral carcinoma.
Urology 2004 Jan;63(1):33-5.
34. Donat SM, Wei DC, McGuire MS, et al. The efficacy of transurethral biopsy for predicting the long-term
clinical impact of prostatic invasive bladder cancer. J Urol 2001 May;165(5):1580-4.
35. Kim B, Kawashima A, LeRoy AJ. Imaging of the male urethra. Semin Ultrasound CT MR 2007
Aug;28(4):258-73.
36. Neitlich JD, Foster HE Jr, Glickman MG, et al. Detection of urethral diverticula in women: comparison
of a high resolution fast spin echo technique with double balloon urethrography. J Urol 1998
Feb;159(2):408-10.
37. Ryu J, Kim B. MR imaging of the male and female urethra. Radiographics 2001 Sep-Oct;21(5):
1169-85.
38. Stewart SB, Leder RA, Inman BA. Imaging tumors of the penis and urethra. Urol Clin North Am 2010
Aug;37(3):353-67.
39. Gourtsoyianni S, Hudolin T, Sala E, et al. MRI at the completion of chemoradiotherapy can accurately
evaluate the extent of disease in women with advanced urethral carcinoma undergoing anterior pelvic
exenteration. Clin Radiol 2011 Nov;66(11):1072-8.
40. Picozzi S, Ricci C, Gaeta M, et al. Upper urinary tract recurrence following radical cystectomy for
bladder cancer: a meta-analysis on 13,185 patients. J Urol 2012 Dec;188(6):2046-54.
41. Heyns CF, Fleshner N, Sangar V, et al. Management of the lymph nodes in penile cancer. Urology 2010
Aug;76(2 Suppl 1):S43-57.
42. Dayyani F, Pettaway CA, Kamat AM, et al. Retrospective analysis of survival outcomes and the role of
cisplatin-based chemotherapy in patients with urethral carcinomas referred to medical oncologists.
Urol Oncol 2013 Oct;31(7):1171-7. [Epub ahead of print]

43. Campbell SC WP, Surgery of penile and urethral carcinoma, in Urology, K.L. Wein AJ, Novick AC,
Partin AW, Peters CA, Editors. 2007, Saunders Elsevier: Philadelphia. p. 993-1022.
44. Carroll PR, Dixon CM. Surgical anatomy of the male and female urethra. Urol Clin North Am 1992
May;19(2):339-46.
45. Garden AS, Zagars GK, Delclos L. Primary carcinoma of the female urethra. Results of radiation
therapy. Cancer 1993 May 15;71(10):3102-8.
46. Dalbagni G, Zhang ZF, Lacombe L, et al. Male urethral carcinoma: analysis of treatment outcome.
Urology 1999 Jun;53(6):1126-32.
47. Smith Y, Hadway P, Ahmed S, et al. Penile-preserving surgery for male distal urethral carcinoma.
BJU Int 2007 Jul;100(1):82-7.
48. Hakenberg OW, Franke HJ, Froehner M, et al. The treatment of primary urethral carcinoma--the
dilemmas of a rare condition: experience with partial urethrectomy and adjuvant chemotherapy.
Onkologie 2001 Feb;24(1):48-52.
49. DiMarco DS, Dimarco CS, Zincke H, et al. Surgical treatment for local control of female urethral
carcinoma. Urol Oncol 2004 Sep-Oct;22(5):404-9.
50. DiMarco DS, DiMarco CS, Zincke H, et al. Outcome of surgical treatment for primary malignant
melanoma of the female urethra. J Urol 2004 Feb;171(2 Pt 1):765-7.
51. Milosevic MF, Warde PR, Banerjee D, et al. Urethral carcinoma in women: results of treatment with
primary radiotherapy. Radiother Oncol 2000 Jul;56(1):29-35.
52. Lutz ST, Huang DT. Combined chemoradiotherapy for locally advanced squamous cell carcinoma of
the bulbomembranous urethra: a case report. J Urol 1995 May;153(5):1616-8.
53. Tran LN, Krieg RM, Szabo RJ. Combination chemotherapy and radiotherapy for a locally advanced
squamous cell carcinoma of the urethra: a case report. J Urol 1995 Feb;153(2):422-3.
54. Licht MR, Klein EA, Bukowski R, et al. Combination radiation and chemotherapy for the treatment of
squamous cell carcinoma of the male and female urethra. J Urol 1995 Jun;153(6):1918-20.
55. Hara I, Hikosaka S, Eto H, et al. Successful treatment for squamous cell carcinoma of the female
urethra with combined radio- and chemotherapy. Int J Urol 2004 Aug;11(8):678-82.
56. Johnson DW, Kessler JF, Ferrigni RG, et al. Low dose combined chemotherapy/radiotherapy in the
management of locally advanced urethral squamous cell carcinoma. J Urol 1989 Mar;141(3):615-6.
57. Cohen MS, Triaca V, Billmeyer B, et al. Coordinated chemoradiation therapy with genital preservation
for the treatment of primary invasive carcinoma of the male urethra. J Urol 2008 Feb;179(2):536-41;
discussion 541.
58. Palou Redorta J, Schatteman P, Huguet Pérez J, et al. Intravesical instillations with bacillus calmette-
guérin for the treatment of carcinoma in situ involving prostatic ducts. Eur Urol 2006 May;49(5):834-8;
discussion 838.
59. Taylor JH, Davis J, Schellhammer P. Long-term follow-up of intravesical bacillus Calmette-Guérin
treatment for superficial transitional-cell carcinoma of the bladder involving the prostatic urethra. Clin
Genitourin Cancer 2007 Sep;5(6):386-9.
60. Gofrit ON, Pode D, Pizov G, et al. Prostatic urothelial carcinoma: is transurethral prostatectomy
necessary before bacillus Calmette-Guérin immunotherapy? BJU Int 2009 Apr;103(7):905-8.
61. Njinou Ngninkeu B, Lorge F, Moulin P, et al. Transitional cell carcinoma involving the prostate: a
clinicopathological retrospective study of 76 cases. J Urol 2003 Jan;169(1):149-52.

62. Palou J, Baniel J, Klotz L, et al. Urothelial carcinoma of the prostate. Urology 2007 Jan;69(1 Suppl):
50-61.
63. Hillyard RW Jr, Ladaga L, Schellhammer PF. Superficial transitional cell carcinoma of the bladder
associated with mucosal involvement of the prostatic urethra: results of treatment with intravesical
bacillus Calmette-Guerin. J Urol 1988 Feb;139(2):290-3.
64. Solsona E, Iborra I, Ricós JV, et al. The prostate involvement as prognostic factor in patients with
superficial bladder tumors. J Urol 1995 Nov;154(5):1710-3.
65. Vazina A, Dugi D, Shariat SF, et al. Stage specific lymph node metastasis mapping in radical
cystectomy specimens. J Urol 2004 May;171(5):1830-4.

15. ABBREVIATIONS USED IN THE TEXT
This list is not comprehensive for the most common abbreviations
AC Adenocarcinoma
AJCC American Joint Committee on Cancer
BCG Bacille-Calmette-Guérin
BT Brachytherapy
CT Computed tomography
MRI Magnetic resonance imaging
MVAC Methotrexate, Vinblastin, Doxorubicin, Cisplatin
PUNLMP Papillary urothelial neoplasm of low malignant potential
RC Radical cystectomy
RCT Randomized Controlled Trial
SCC Squamous cell carcinoma
SEER Surveillance, Epidemiology and End Results
TNM Tumour-Node-Metastasis
TUR Transurethral Resection
UC Urothelial carcinoma
WHO World Health Organization
Conflict of interest
All members of the Muscle-invasive and Metastatic Bladder Cancer guidelines working group have provided
disclosure statements of all relationships that they have that might be perceived as a potential source of a
conflict of interest. This information is publically accessible through the European Association of Urology
website. This guidelines document was developed with the financial support of the European Association of
Urology. No external sources of funding and support have been involved. The EAU is a non-profit organisation
and funding is limited to administrative assistance and travel and meeting expenses. No honoraria or other
reimbursements have been provided.


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Guidelines on

© European Association of Urology 2014

3. LEVEL OF EVIDENCE AND GRADE OF RECOMMENDATION 3

5. AETIOLOGY AND RISK FACTORS 4

9. DIAGNOSIS AND STAGING 7

10. TREATMENT OF LOCALISED PRIMARY URETHRAL CARCINOMA 8

11. MULTIMODAL TREATMENT IN ADVANCED URETHRAL CARCINOMA 9

12. TREATMENT OF UROTHELIAL CARCIMONA OF THE PROSTATE 10

15. ABBREVIATIONS USED IN THE TEXT 15

2 PRIMARY URETHRAL CARCINOMA - MARCH 2013

3. LEVEL OF EVIDENCE AND GRADE OF

Table 1: Level of evidence*

Level Type of evidence

PRIMARY URETHRAL CARCINOMA - MARCH 2013 3

Table 2: Grade of recommendation*

Grade Nature of recommendations

This document was subjected to blinded peer review prior to publication.

Potential conflict of interest statement

5. AETIOLOGY AND RISK FACTORS

4 PRIMARY URETHRAL CARCINOMA - MARCH 2013

T - Primary tumour (men and women)

PRIMARY URETHRAL CARCINOMA - MARCH 2013 5

Table 4: Histopathological grading of urothelial and non-urothelial primary UC (28)

PUNLMP Papillary urothelial neoplasm of low malignant

8.2 Predictors of survival in primary urethral carcinoma

6 PRIMARY URETHRAL CARCINOMA - MARCH 2013

9.2 Clinical examination

9.3 Urinary cytology

9.4 Diagnostic urethrocystoscopy and biopsy

9.5 Radiological imaging

9.6 Regional lymph nodes

PRIMARY URETHRAL CARCINOMA - MARCH 2013 7

10. TREATMENT OF LOCALISED PRIMARY

10.2 Treatment of localised urethral carcinoma in females

8 PRIMARY URETHRAL CARCINOMA - MARCH 2013

11. MULTIMODAL TREATMENT IN ADVANCED

11.2 Preoperative chemoradiotherapy in locally advanced squamous cell carcinoma of the

PRIMARY URETHRAL CARCINOMA - MARCH 2013 9

10 PRIMARY URETHRAL CARCINOMA - MARCH 2013

PRIMARY URETHRAL CARCINOMA - MARCH 2013 11

12 PRIMARY URETHRAL CARCINOMA - MARCH 2013

PRIMARY URETHRAL CARCINOMA - MARCH 2013 13

14 PRIMARY URETHRAL CARCINOMA - MARCH 2013

PRIMARY URETHRAL CARCINOMA - MARCH 2013 15

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11.2 Preoperative chemoradiotherapy in locally advanced squamous cell carcinoma of the