Editing Urethral Tumours

== Benign Urethral Tumours ==

* '''Rare'''; only a few small series and case reports in the literature
* '''Most frequently reported:'''
*# '''Leiomyoma'''
*# '''Hemangioma'''
*# '''Fibroepithelial polyp'''

=== Leiomyoma ===

* '''Epidemiology'''
** '''Occur primarily in women'''
** Most present in the 3rd or 4th decade of life
* Diagnosis and evaluation
** Most common clinical presentations include:
*** Palpable anterior vaginal mass
*** Storage LUTS
**** Voiding LUTS occur less frequently
*** UTI
*** Hematuria
** May be discovered incidentally during routine pelvic examination or an unrelated surgical procedure
* Management
** Tumor recurrence is rare; all reported urethral leiomyomas to date have followed a benign course

=== Hemangioma ===

* '''Epidemiology'''
** '''More common in males'''
** Most present in the 2nd or 3rd decade of life
* Diagnosis and evaluation
** Most common clinical presentations include:
*** Intermittent hematuria
*** Bloody urethral discharge
*** Hematospermia
** '''Diagnosis and Evaluation'''
*** '''Cystoscopy may underestimate the overall extent of the hemangioma'''
*** '''MRI may be helpful in select cases to better delineate the extent of the lesion'''
* '''Management'''
** '''Smaller hemangiomas are generally treated with TUR fulguration or laser'''
*** '''Recurrent bleeding as a result of inadequate ablation may occur.''' In this setting, or when the hemangioma is more extensive, '''open excision''' with one- or two-stage urethral reconstruction '''may be required'''

=== Fibroepithelial polyp ===

* Epidemiology
** Rare
** '''Usually diagnosed in males''' in the 1st decade of life
* Pathology
** Benign tumors of mesodermal origin that can occur in the upper or lower urinary tract
* Diagnosis and evaluation
** Most common clinical presentations include:
*** Restriction of the urinary stream
*** Frequency
*** Dysuria
* Management
** TUR is usually curative
** Pathologic examination is required to rule out a more aggressive lesion such as urothelial papilloma or inverted papilloma

== '''Urethral cancer''' ==

=== '''TNM Staging (AJCC 8th edition§)''' ===

* '''Primary tumour (T) (male and female)'''
** TX: Primary tumor cannot be assessed
** T0: No evidence of primary tumor
** '''Ta: Non-invasive papillary, polypoid, or verrucous carcinoma'''
** '''Tis: Carcinoma in situ'''
** '''T1: invades subepithelial connective tissue'''
** '''T2: invades'''
**# '''Corpus spongiosum OR'''
**# '''Periurethral muscle'''
** '''T3: invades'''
**# '''Corpus cavernosum''' '''OR'''
**# '''Anterior vagina'''
** '''T4: invades other adjacent organs (e.g. invasion of bladder wall)'''
* '''Urothelial carcinoma of the prostate'''
** '''pTis: carcinoma in situ of the prostatic urethra, periurethra or ducts'''
*** '''Tis pu: Carcinoma in situ, involvement of prostatic urethra'''
*** '''Tis pd: Carcinoma in situ, involvement of prostatic ducts'''
** '''pT1: invasion of prostatic urethral subepithelial connective tissue'''
** '''pT2: invasion of prostatic stroma'''
*** '''In the bladder cancer TNM staging system, only patients with prostatic stromal invasion, either direct or indirect, are considered to have T4a-staged bladder cancer disease'''
*** '''Extension of the tumor into the prostatic urethra without stromal invasion is currently classified under the prostatic urethral section, not bladder'''
** '''pT3''': invasion of periprostatic fat or bladder neck (extraprostatic extension)
** '''pT4''': invasion of adjacent organs (example: bladder wall, rectal wall)
* '''Regional lymph nodes (N) (similar to bladder)'''
** Nx: lymph nodes cannot be assessed
** N0: no lymph node metastasis
** N1: single regional lymph node in the true pelvis
*** True pelvis lymph nodes (5)
***# Perivesical
***# Obturator
***# Internal iliac (hypogastric)
***# External iliac
***# Presacral lymph nodes
** N2: multiple regional lymph node metastases in the true pelvic
** N3: lymph node metastasis to the common iliac lymph nodes
* Distant metastasis (M)
** MX: Presence of distant metastasis cannot be assessed
** M0: No distant metastasis
** M1: Distant metastasis

=== '''Male urethral cancer''' ===

==== Epidemiology ====

* Rare
* Usually presents in the 5th decade of life

==== '''Pathogenesis''' ====

* '''Risk factors for male urethral cancer (3):'''

# '''Chronic inflammation''' resulting from a history of frequent sexually transmitted diseases, urethritis
# '''Urethral stricture'''
# '''HPV subtype 16 for squamous cell carcinoma of the urethra'''

==== Natural history ====

* Can spread by
** Direct extension to adjacent structures
*** Usually involving the vascular spaces of the corpus spongiosum and the periurethral tissues
** Lymphatic dissemination to regional lymph nodes
** Hematogenous dissemination
*** Uncommon except in advanced disease

==== '''Lymphatic drainage of male urethra''' ====

* '''Anterior urethra drains into the (3):'''
*# '''Superficial inguinal lymph nodes'''
*# '''Deep inguinal lymph nodes'''
*# '''External iliac lymph nodes (occasionally)'''
* '''Posterior urethra'''
** '''Drains into the (1):'''
*** '''Pelvic lymph nodes'''
***# Perivesical
***# Obturator
***# Internal iliac (hypogastric)
***# External iliac
***# Presacral lymph nodes

==== '''Tumour Location''' ====

# '''Bulbomembranous urethra (most commonly involved, 60%)'''
# '''Penile urethra (30%)'''
# '''Prostatic urethra (10%)'''
#* See Urothelial Carcinoma of the Prostate Chapter Notes

==== '''Pathology''' ====

* '''Most common (≈80%) histology overall is urothelial carcinoma'''
** '''Squamous cell carcinoma in ≈10%'''
** '''Adenocarcinoma in 5%'''
** '''Other histologies in 5%'''
* '''The histologic subtype of urethral cancer varies by anatomic location''' (related to cell lining of that part of the urethra):
** '''Bulbomembranous urethra: 80% squamous''', 10% urothelial, 10% adenocarcinoma or undifferentiated
** '''Penile urethra: 90% squamous''', 10% urothelial
** '''Prostatic urethra: 90% urothelial''', 10% squamous

==== '''Diagnosis and Evaluation''' ====

* '''UrologySchool.com Summary'''
** '''H+P'''
** '''Imaging'''
*** '''Primary: MRI'''
*** '''Metastases:'''
**** '''Regional: CT abdomen/pelvis'''
**** '''Distant: CT chest'''
** '''Other'''
*** '''Cystoscopy with biopsy'''
* '''History and Physical Exam'''
** '''History'''
*** '''Usually delayed presentation; 96% are symptomatic at presentation'''
*** '''Most common presenting symptoms: urethral bleeding, palpable urethral mass, and voiding LUTS'''
** '''Physical Exam'''
*** '''Bimanual palpation of the external genitalia examination under anesthesia, urethra, rectum, and perineum, aids in evaluating the extent of local involvement by tumor'''
**** If rectal involvement is suspected on bimanual examination or by the patient’s symptoms, an evaluation of the lower colon by barium enema study and flexible sigmoidoscopy is recommended to assist with surgical planning
*** '''Palpable inguinal lymph nodes occur in ≈20-30% of cases and almost always represent metastatic disease, in contrast to penile cancer, in which a large percentage of palpable nodes may be inflammatory'''
* '''Laboratory'''
** '''Voided urine cytology is not reliable for diagnosis of primary urethral carcinoma'''
* '''Imaging'''
** '''CT scan of the chest, abdomen, and pelvis (or in some cases by MRI) to evaluate local soft tissue involvement, lymph node involvement, bone extension, and the presence of distant metastatic disease'''
*** '''MRI is the most sensitive staging modality for the assessment of local tumor extent;''' may be particularly helpful for detecting invasion of the corpora cavernosa
* '''Other'''
** '''Cystoscopy and transurethral or needle biopsy of the lesion is performed'''

==== Management ====

* '''Surgical excision is the primary form of treatment'''
* '''Depends on the tumour location and clinical stage'''
* '''Anterior urethra'''
** '''In general, more amenable to surgical control and better prognosis than posterior urethral carcinoma, which is often associated with extensive local invasion and distant metastasis'''
** '''Carcinoma of the Penile Urethra'''
*** '''Superficial, papillary, or low-grade tumors'''
**** '''Options (3):'''
****# '''Transurethral resection'''
****# '''Local excision'''
****# '''Distal urethrectomy and perineal urethrostomy'''
*** '''In patients with invasive disease'''
**** '''Localized to the distal half of the penis, partial penectomy with a 2-cm negative margin remains the traditional treatment for pT2 tumors (infiltrating the corpus spongiosum)'''
***** Excellent local control after this procedure has been documented
***** '''For patients with invasive anterior urethral cancer with the intent of genital preservation, chemoradiation has been reported as an option'''
**** '''Extending to or involving the proximal penile urethra, total penectomy is required to obtain an adequate margin of excision'''
*** '''Inguinal lymphadenectomy in penile urethral carcinoma'''
**** '''Non-palpable (cN0): not recommended'''
***** '''Unlike penile cancer with high-risk features, survival benefit from prophylactic inguinal lymph node dissection in patients without palpable inguinal nodes has not been demonstrated with urethral cancer'''
**** '''Palpable (cN+ [, resectable]): recommended'''
***** Cases of cure with limited nodal disease have been reported and therefore inguinal lymphadenectomy should be considered in the presence of palpable inguinal lymph nodes.
** '''Carcinoma of the Bulbomembranous Urethra'''
*** '''Radical cystoprostatectomy, pelvic lymphadenectomy, and total penectomy are often required'''
**** '''Poor survival''' has been recorded for all forms of treatment, but radical excision continues to be an important component of treatment in some patients.
*** Summary of steps:
**** Position: low lithotomy to allow perineal access.
**** [Further details in Campbell’s]
*** '''Because of the relatively poor outcomes after surgery alone for advanced tumors of the posterior urethra, multimodal therapy in this setting is increasing'''
**** '''Squamous cell cancers respond poorly to the M-VAC regimen''' [SASP]
* '''Posterior Urethra'''
** '''Carcinoma of the Prostatic Urethra'''
*** See Urothelial Carcinoma of the Prostate Chapter Notes
** '''Management of the urethra after cystectomy'''
*** '''Timing of urethral recurrence post-cystectomy'''
**** ≈40% of urethral recurrences are diagnosed within 1 year after cystoprostatectomy, with a median time to diagnosis of 18 months
**** Late urethral recurrence have been reported, indicating the need for prolonged surveillance in these patients
*** '''Diagnosis and Evaluation'''
**** '''After non-orthotopic diversion, urethral wash cytology has traditionally been recommended and leads to earlier diagnosis of urethral recurrence than when evaluation is delayed until symptoms occur'''
**** '''After orthotopic, diversion, voided urine cytology is part of standard surveillance'''
**** '''Patients with positive results for urine or urethral wash cytology or symptoms of urethral bleeding, discharge, or palpable mass are evaluated with cystoscopy and biopsy.'''
***** '''Pelvic CT or MRI may be necessary to aid in assessment of the local extent of larger invasive tumors and to assess for metastatic disease'''.
**** '''Management'''
***** '''Patients who develop urethral carcinoma in situ after orthotopic diversion may respond to urethral perfusion with BCG, but this treatment is ineffective for those with papillary or invasive disease and these patients may require urethrectomy'''
***** '''When a delayed urethrectomy is performed in a male patient after radical cystectomy, it is important to remove the fossa navicularis and urethral meatus''' because of the high incidence of involvement of the squamous epithelium
***** '''Total urethrectomy after cutaneous diversion'''
****** Technique: The high or exaggerated lithotomy position provides optimal exposure for total urethrectomy, with the hips and knees gently flexed and the lower limbs abducted in boot-type stirrups. [Further detail’s in Campbell’s]
***** '''Total urethrectomy after orthotopic diversion'''
****** Technique: Total urethrectomy after orthotopic urinary diversion is performed through an abdominoperineal approach [Further detail’s in Campbell’s]
****** In most situations, urinary diversion is accomplished with an ileal conduit

== Female urethral cancer ==

=== Epidemiology ===

* Rare
* Most diagnosed in the 5th and 6th decade

=== Pathogenesis ===

* '''Risk factors for female urethral cancer (7):'''

# '''Leukoplakia'''
# '''Chronic irritation'''
# '''Proliferative lesions e.g. caruncles'''
# '''Polyps'''
# '''Parturition'''
# '''Urethral diverticulum'''
# '''HPV (particularly HPV 6) or other viral infections'''

* Childhood UTIs is not a risk factor

=== Anatomy ===

* '''The female urethra has been divided into an anterior segment (distal 1/3rd) and a posterior segment (proximal 2/3rd)'''
** '''Anterior segment'''
*** '''Lined by stratified squamous epithelium''' '''Posterior segment'''
*** '''May be excised while urinary continence is maintained'''
*** '''Lined by typical urothelium'''
* '''Lymphatic drainage:'''
** '''Anterior urethra and labia'''
*** '''Drain into'''
**** '''Superficial inguinal nodes and then to the deep inguinal nodes''' '''Posterior urethra'''
*** '''Drains into'''
**** '''External iliac nodes (primarily)'''
**** '''Internal iliac/hypogastric and obturator lymph node (secondarily)'''
** Crossover and communications are possible

=== Pathology ===

* '''Squamous cell carcinoma'''
** '''Most common (30-70%) histologic type overall'''
*** '''Recall in men, overall ≈80% are urothelial'''
* '''Urothelial (10%)'''
* '''Adenocarcinomas (25%)'''
** '''Most common malignant pathology in female urethral diverticulum is adenocarcinoma'''
* '''No difference in survival based on histologic subtype'''

=== Diagnosis and evaluation ===

* '''History and Physical exam'''
** A thorough pelvic examination, evaluating for a palpable anterior vaginal mass
*** '''Differential diagnosis of a palpable anterior vaginal mass:'''
***# '''Urethral diverticulum'''
***# '''Urethral cancer'''
***# '''Urethral polyp'''
***# '''Other benign neoplasm, such as urethral caruncle, leiomyoma'''
***#* '''Most common urethral mass in a female: urethral caruncle'''
** Speculum examination should visualize the urethral meatus directly and evaluate for potential involvement of the vaginal wall and vulva
* '''Imaging'''
** '''Primary'''
*** '''MRI'''
**** Soft tissue contrast is superior to that with CT and MRI gives the best anatomic detail in this area.
**** MRI can assess local extension and lymph node involvement.
** '''Metastasis'''
*** Additional staging studies with chest radiograph or chest CT are appropriate.
*** Bone scan may be performed if clinical suspicion exists of bone involvement due to symptoms or laboratory abnormalities such as elevated alkaline phosphatase or serum calcium
* '''Other'''
** '''Cystourethroscopy and examination under anesthesia'''

=== Management ===

* '''Depends primarily on tumor location and clinical stage'''
* '''Options:'''
*# '''Surgery'''
*# '''Radiation therapy'''
*# '''Chemotherapy'''
*# '''Combination therapy'''
*** '''Treatment has trended toward a multimodality approach'''
* '''Distal 1/3rd urethra'''
** '''Distal lesions are associated with improved survival compared with proximal urethral cancers'''
*** Tumors in the distal (anterior) urethra tend to be low stage
** '''Small, exophytic, superficial tumors arising from the urethral meatus or distal third of the urethra'''
*** '''Options:'''
***# '''Circumferential excision of the distal urethra and inclusion of a portion of the anterior vaginal wall via a transvaginal approach'''
***#* ,Cure rates of 70-90% have been achieved with local excision alone
***# '''Radiation'''
***** '''Effective for low-stage distal urethral carcinomas; an alternative in women when surgical resection would negatively affect functional outcomes'''
** '''Indications for groin dissection (2):'''
**# '''Patients without distant metastasis who present with inguinal or pelvic lymphadenopathy'''
**#* '''Clinically palpable inguinal nodes are found in up to 20-30% of patients overall, and these are confirmed to be malignant in ≈90% of cases'''
**# '''Patients who develop regional adenopathy during surveillance'''
* '''Proximal 2/3rd urethra'''
** '''More likely to be high stage and may extend into the bladder and vagina'''
** '''Anterior exenteration (cystourethrectomy), pelvic lymph node dissection, and wide vaginal or complete vaginal excision are often required to obtain negative surgical margins'''
** '''Radiotherapy alone for proximal invasive urethral carcinoma has yielded poor local control'''
** '''A combination of chemotherapy, radiation therapy, and surgery has been recommended for optimal local and distant disease control in advanced female urethral cancer'''
* '''Urethral Recurrence after Cystectomy for bladder cancer in Women'''
** Incidence ranges from 1-13%
** '''No definitive treatment recommendations for women with urethral cancer recurrence after orthotopic diversion due to limited literature'''.
*** Urethrectomy and surgical resection of the area of the urethra-pouch anastomosis with conversion to a continent cutaneous urinary diversion seem feasible and reasonable in the absence of metastatic disease

== Questions ==

# List benign tumours of the urethra
# Describe the pT staging of urethral cancer
# What are risk factors for male urethral cancer?
# What is the most common histology in male urethral cancer?
# What is the most common site of involvement in male urethral cancer?
# What is the lymphatic drainage pattern of the male urethra?
# What is the recommended margin for partial penectomy in male urethral cancer?
# What is the lymphatic drainage pattern of the female urethra?
# What is the most common histology of female urethral carcinoma? Female urethral carcinoma in a diverticulum?
# What is the differential diagnosis of a palpable anterior vaginal mass?
# What is the management of female urethral cancer?

== Answers ==

# List benign tumours of the urethra
## Leiomyoma
## Hemangioma
## Fibroepithelial polyp
# Describe the pT staging of urethral cancer
#* TX: Primary tumor cannot be assessed
#* T0: No evidence of primary tumor
#* Ta: Non-invasive papillary, polypoid, or verrucous carcinoma
#* Tis: Carcinoma in situ
#* T1: invades subepithelial connective tissue
#* T2: invades corpus spongiosum, prostate, or periurethral muscle
#* T3: invades corpus cavernosum, beyond prostatic capsule, anterior vagina, or bladder neck
#* T4: invades other adjacent organs
# What are risk factors for male urethral cancer?
## Chronic inflammation
## Urethral stricture
## HPV 16 for SCC of urethra
# What is the most common histology in male urethral cancer?
#* Urothelial
# What is the most common site of involvement in male urethral cancer?
#* Bulbomembranous urethra
# What is the lymphatic drainage pattern of the male urethra?
#* Anterior urethra drains into the superficial and deep inguinal lymph nodes and occasionally into the external iliac lymph nodes
#* Posterior urethra drains into the pelvic lymph nodes [external iliac, internal iliac, common iliac, obturator]
# What is the recommended margin for partial penectomy in male urethral cancer?
#* 2cm
# What is the lymphatic drainage pattern of the female urethra?
#* Posterior urethra: primarily external iliac nodes and secondarily to the internal iliac/hypogastric and obturator lymph node chains
#* Anterior urethra and labia: superficial and then deep inguinal nodes
# What is the most common histology of female urethral carcinoma? Female urethral carcinoma in a diverticulum?
#* Squamous cell carcinoma
#* Adenocarcinoma
# What is the differential diagnosis of a palpable anterior vaginal mass?
## Urethral diverticulum
## Urethral cancer
## Urethral polyp
## Other benign neoplasm, such as a leiomyoma
# What is the management of female urethral cancer?
#* Distal 1/3 urethra
#** Superficial, exophytic, low-grade: surgical excision or radiation
#* Proximal 2/3 urethra
#** Anterior exenteration (cystourethrectomy), pelvic lymph node dissection, and wide vaginal or complete vaginal excision

== References ==

* Wein AJ, Kavoussi LR, Partin AW, Peters CA (eds): CAMPBELL-WALSH UROLOGY, ed 11. Philadelphia, Elsevier, 2015, vol 1, chap 38
* Filippou P, Smith AB. 2019 AUA Update on Management of the Malignant Urethral Mass in Females