Urethral Cancer Flashcards
What percentage of urethral cancers are urothelial in origin?
A recent SEER (2004 to 2016) analysis demonstrated that
52.9% of primary urethral carcinomas are of urothelial origin
SCC (23.9% of cases)
Adenocarcinoma (14.6%)
Other histologies (8.7%)
Risk factors for urethral cancer
History of urothelial cancer, with recurrence rate in urethra of 4.9%
Sexually transmitted disease
Urethritis
Urethral stricture disease
Human papilloma virus (particularly subtypes 16 & 18)
Smoking
Symptoms of Urethral Cancer
Urethral cancer is frequently symptomatic at presentation in both men and women (~95%)
Common symptoms:
Irritative or obstructive voiding
Hematuria
Primary urethral bleeding
Additionally, especially in women, masses may be palpable and cause pain. The rare presentations of urethral carcinoma within urethral diverticula typically present with dyspareunia, dysuria, dribbling (the 3 D’s of urethral diverticulum). Solid components within a diverticulum can raise suspicion of concomitant malignancy and prompt biopsy.
T stage
Tis
Female urethra or male anterior urethra
Male posterior urethra
-Carcinoma in situ
-Prostatic urethra or periurethral or prostatic ducts without stromal invasion
Ta - Non-invasive papillary or verrucous carcinoma
T1 - Invades lamina propria (subepithelial connective tissue)
T2
Female urethra or male anterior urethra
Male posterior urethra
-invades corpus spongiosum, or periurethral muscle
-invades prostatic stroma (either by ducts or direct extension)
T3
Female urethra or male anterior urethra
Male posterior urethra
-invades corpus cavernosum or anterior vagina
-invades periprostatic fat
T4 - Invades adjacent organs (bladder, rectum, uterus)
N stage
N0 - Negative nodes
N1 - Single Node
N2 - Multiple Nodes
M stage
M0 - No metastases
M1 - Distant metastases
What can you tell about the T stage from a physical exam?
On physical examination of the male, the penis and perineum should be carefully palpated.
-Presence of a palpable mass usually indicates an invasive tumor (≥T2) and occasionally clear invasion of the corpora cavernosa is palpable (T3).
-DRE should be performed to evaluate for palpable prostatic invasion.
In women, a bimanual examination and careful speculum examination are required.
-A urethral diverticulum may be palpable and vaginal invasion is usually easily detectable (T3).
In both men and women, palpation of the inguinal nodes should be performed to rule out nodal involvement.
-Lymphedema of the lower extremities may point to inguinal or pelvic nodal involvement.
What workup should you do for urethral cancer?
Cystoscopy with look into a urethral diverticulum
Consider transvaginal needle biopsy
RUG in men
Ultrasound of the penis (MRI is preferred)
Abdominal-pelvic-inguinal imaging (CT, MRI, PET) - Contrast-enhanced MRI provides the best resolution images of the urethra and is favored over CT in most circumstances. Pelvic MRI (including the inguinal region/mid-upper thigh) is the preferred imaging modality to assess the local extent of the urethral tumor and regional lymph node involvement.
What percentage of men with urethral cancer have associated urethral strictures?
50%
Treatment of Squamous Cell Carcinoma of the Urethra
Patients with squamous cell carcinoma can be treated with either chemo-radiation or neoadjuvant chemotherapy followed by surgical consolidation.
Triple therapy (chemoradiation therapy followed by surgery) is sometimes used for bulky yet localized urethral cancer with direct extension into the pubis or genitourinary diaphragm
TUR for urethral cancer
TUR is the treatment of choice for all small non-invasive tumors of the distal urethra.
Additionally, TUR is the primary method used to stage and treat prostatic urethral and ductal cancer, obtain tissue for histology, and relieve urethral obstruction.
In patients with a history of NMIBC with normal cystoscopy and positive cytology, a clinician should consider prostatic urethral biopsies since tumor recurrences can involve the prostatic urethra in 24-39% of cases.
Such biopsies are normally done at the 5 and 7 o’clock positions to ensure sampling of the prostatic ducts.
If prostate urethral cancer (non invasive or CIS) is found after TUR …
For cases of non-invasive prostatic urethral carcinoma or carcinoma in situ, mucosal tumors, located in the prostatic urethra,
a TUR of the prostate (including the bladder neck to allow contact of intravesical agents to the posterior urethra/prostatic urethra) is followed by adjuvant intravesical BCG with maintenance therapy
Prostatic duct involvement is often seen with carcinoma in situ of the prostatic urethra (confined to the urothelium of the prostatic duct).
Based on small retrospective series CIS of the prostatic ducts may be treated with TUR followed by intravesical BCG with caution as there is high risk of progression, and patients may benefit from radical therapy.
In patients with urothelial carcinoma of the prostatic urethra with prostate stromal invasion, neoadjuvant cisplatin-based chemotherapy followed by radical cystoprostatectomy is the treatment of choice.
In patients with urothelial carcinoma of the prostatic urethra with prostate stromal invasion
In patients with urothelial carcinoma of the prostatic urethra with prostate stromal invasion, neoadjuvant cisplatin-based chemotherapy followed by radical cystoprostatectomy is the treatment of choice.
Penectomy in Urethral Cancers
If T2 (just spongiosum), can do a segmental urethrectomy.
If T3 (involving cavernosum), perform partial or radical penectomy. If radical penectomy, perineal urethrostomy.
Total Penectomy with Prostatectomy and Bladder Neck Closure
Bulky adenocarcinomas or squamous cell carcinomas of the bulbar and membranous urethra can be very challenging to manage.
Often, after resection, there is not enough urethral length to allow a perineal urethrostomy or there is no remaining urinary sphincter to allow for continence. Additionally, the prostate may be involved and require resection.
In this situation, one can consider bladder neck closure and either an incontinent ileal vesicostomy or Mitrofanoff-type channel.
NB: This is contraindicated in urothelial carcinomas given the risk of local recurrence within bladder and need for ongoing cystoscopic surveillance which is challenging to perform through either an ileal chimney or catheterizable channel.
When to do a cystoprostatectomy in urethral cancer
Invasive urothelial carcinomas of the prostatic/membranous urethra are usually best treated with radical cystoprostatectomy with total urethrectomy.
Neoadjuvant or adjuvant cisplatin-based chemotherapy should be strongly considered.
Radiotherapy in Urethral Cancer
Neoadjuvant radiotherapy can be used to downstage very large urethral tumors, particularly those locally invading the pubic rami.
Adjuvant radiation can be used to treat patients with bulky tumors and positive margins at surgical resection.
Chemoradiation therapy is an acceptable multimodal treatment especially for patients with squamous cell histology.
Treatment of Female Urethral Cancer
The treatment of urethral cancer in woman depends on tumor histology, stage, grade, and location.
For patients with locally advanced tumors, multimodality therapy is preferred based on small retrospective series. Although there are no randomized trials to guide treatment, patients with locally advanced urothelial carcinoma of the urethra are typically treated with Cisplatin-based neoadjuvant chemotherapy followed by surgery with curative intent.
Patients with squamous cell carcinoma can be treated with either chemo-radiation therapy or neoadjuvant chemotherapy followed by surgical consolidation.
Triple therapy (chemoradiation therapy followed by surgery) can be used for bulky yet localized urethral cancer (rare T4N0M0–typically squamous) with direct extension into the pubis or genitourinary diaphragm
Transurethral Resection (TUR) in women with urethral cancer
As with men, TUR is the treatment of choice for all non-invasive tumors in women. It is diagnostic, yielding histology and staging data. Women are at higher risk of post-TUR incontinence and great care is needed to prevent this complication.
Partial Urethrectomy and Diverticulectomy
Partial urethrectomy in the female is often difficult given the short length of the female urethra (~4cm) with risk to the urinary sphincter mechanism.
Nevertheless, resection of the distal urethra is sometimes possible.
Post-resection closure usually requires a vaginal flap.
Patients should be counselled that recurrences are common.
Tumors occurring in urethral diverticula can sometimes be managed with diverticulectomy and local excision of the surrounding tissues and vaginal wall.
Lymphadenectomy in Urethral Cancer
Contrary to the management of the cN0 inguinal nodes in penile cancer, management of the cN0 inguinal lymph nodes in primary anterior urethral cancer is not based on pT status of the primary tumor.
All patients undergoing cystectomy or cystoprostatectomy (posterior/proximalurethral carcinomas) should undergo bilateral pelvic lymphadenectomy since the risk of nodal involvement is high.
Patients with palpable or enlarged inguinal nodes on imaging should undergo percutaneous lymph node biopsy. Despite the limited number of published series, systemic therapy along with consolidative radiation or surgery is recommended.
Unlike in penile cancer, the benefit of prophylactic inguinal lymph node dissection (regardless of pT status) in patients with cN0 squamous cell of the anterior (male) or distal (female) urethra is not supported in the literature. The incidence of pathologic node positivity in the setting of clinical negative inguinal nodes appears to be less than 10%.
All patients at risk for inguinal metastases not undergoing inguinal lymphadenectomy should have their inguinal regions examined and imaged regularly during surveillance visits.
When is chemo indicated for urethral cancer?
Chemotherapy is indicated for patients with locally advanced T3/T4 disease and in those with nodal or systemic metastases.
Survival for urethral cancer
The prognosis for urethral cancer is stage-dependent
5-year survival of 80% for stage I, 50% for stage II, 30% for stage III, and 10% for stage IV
Poor prognostic factors include
(i) tumors of the proximal urethra
(ii) stage T2 or higher
(iii) lymph node involvement
(iv) advanced age.
In both men and woman, a more proximal location and higher stage portend a worse prognosis. Women have inferior survival compared to men.
