Urethral Cancer Flashcards
The most common histologies of primary urethral cancer in men are ___ carcinoma, followed by squamous cell carcinoma and adenocarcinoma
urothelial
The most important risk factor for urothelial carcinoma of the urethra is a prior history of ____
bladder cancer.
___% of patients will have locally advanced disease at the time of presentation due to nonspecific LUTS
50
The male urethra averages about ___ cm in length and is divided into the distal and proximal urethra.
20
The lymphatic drainage of the urethra
Proximal urethra drains to the ___ nodes Distal urethra to the ___ nodes
Proximal –> pelvic
Distal –> inguinal
The management of locally advanced disease requires ___
multimodal treatment with a combination of chemotherapy, surgery and radiation
Superficial prostatic urethral disease that is limited to the mucosa without acinar or stromal invasion can undergo successful local treatment with ____
transurethral resection and BCG instillation
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.
Urethral carcinoma
TX
Primary tumour can not be assessed
Urethral carcinoma
T0
No evidence of primary tumour
Urethral carcinoma
Ta
Non-invasisve papillary, polypoid, or verrucous carcinoma
Urethral carcinoma
Tis
Carcinoma in situ
Urethral carcinoma
T1
Tumour invades subepithelial connective tissue
Urethral carcinoma
T2
Tumour invades any of the following: corpus spongiosum, prostate, periurethral muscle
Urethral carcinoma
T3
Tumour invades any of the following: corpus cavernosum, beyond prostatic capsule, anterior vagina, bladder neck (extraprostatic extension)
Urethral carcinoma
T4
Tumour invades other adjacent organs (invasion of the bladder)
Urethral carcinoma
Tis pu
Carcinoma in situ, involvement of prostatic urethra
Urethral carcinoma
Tis pd
Carcinoma in situ, involvement of prostatic ducts
Urethral carcinoma
NX
Regional lymph nodes can not be assessed
Urethral carcinoma
N0
No regional lymph node metastasis
Urethral carcinoma
N1
Metastasis in a single lymph node
Urethral carcinoma
N2
Metastasis in multiple lymph nodes
Urethral carcinoma
M0
No distant metastasis
Urethral carcinoma
M1
Distant metastasis
Clinical Vignette: A 52-year-old man presents with dysuria. He is diagnosed with T1 urethral cancer. What is the first-line treatment?
Options:
A. Partial urethrectomy
B. Radical cystectomy
C. Repeat TUR ± intraurethral BCG or chemotherapy
D. Neoadjuvant chemotherapy
Correct Answer:
C. Repeat TUR ± intraurethral BCG or chemotherapy
Explanation for All Choices:
A. Incorrect - Partial urethrectomy is not first-line for Tis, Ta, T1.
B. Incorrect - Radical cystectomy is recommended for female T2.
C. Correct - The guideline states Repeat TUR ± intraurethral BCG or chemotherapy for Tis, Ta, T1.
D. Incorrect - Neoadjuvant chemotherapy is a consideration but not first-line for these stages.
Memory Tool:
“Tea (T) One Repeat” – T1 involves Repeat TUR.
Reference Citation:
Data from Bladder Cancer, NCCN Clinical Practice Guidelines in Oncology, 2018
Rationale:
Understanding the first-line treatment options for various stages is crucial for optimal patient care.
Clinical Vignette: A 65-year-old man is diagnosed with T2 urethral cancer in the pendulous urethra. What is the recommended first-line treatment?
Options:
A. Radical cystectomy
B. Partial urethrectomy ± penectomy
C. Chemoradiotherapy
D. Repeat TUR
Correct Answer:
B. Partial urethrectomy ± penectomy
Explanation for All Choices:
A. Incorrect - Radical cystectomy is not for male T2 pendulous urethra.
B. Correct - Partial urethrectomy ± penectomy is the first-line treatment for male T2 pendulous urethra.
C. Incorrect - Chemoradiotherapy is a potential adjuvant therapy, not first-line.
D. Incorrect - Repeat TUR is for earlier stages (Tis, Ta, T1).
Memory Tool:
“Pendulous Pen-ectomy” – Pendulous urethra cases may include penectomy.
Reference Citation:
Data from Bladder Cancer, NCCN Clinical Practice Guidelines in Oncology, 2018
Rationale:
Knowing specific treatments for sublocations like the pendulous urethra is vital for tailored care.
Clinical Vignette: A patient has a T2 urethral cancer, and postoperative pathology reports indicate a positive margin. What is the adjuvant therapy?
Options:
A. Additional surgery
B. Neoadjuvant chemotherapy
C. Radiotherapy alone
D. All of the above
Correct Answer:
A. Additional surgery
Explanation for All Choices:
A. Correct - If there’s a positive margin, additional surgery is an option.
B. Incorrect - Neoadjuvant chemotherapy is not specifically recommended for positive margins.
C. Incorrect - Radiotherapy alone is not recommended for positive margins.
D. Incorrect - Additional surgery is the only listed adjuvant therapy for positive margins.
Memory Tool:
“Positive Margin? Add Surgery” – Additional surgery is an option for positive margins.
Reference Citation:
Data from Bladder Cancer, NCCN Clinical Practice Guidelines in Oncology, 2018
Rationale:
Recognizing adjuvant therapy options for positive margins aids in comprehensive patient treatment.
Clinical Vignette: A 55-year-old man with a history of smoking is diagnosed with T2 urethral cancer located in the bulbar urethra. What is the first-line treatment?
Options:
A. Radical cystectomy
B. Urethrectomy ± radical cystectomy
C. Chemoradiotherapy
D. Repeat TUR
Correct Answer:
B. Urethrectomy ± radical cystectomy
Explanation for All Choices:
A. Incorrect - Radical cystectomy is indicated for Female T2.
B. Correct - Urethrectomy ± radical cystectomy is the first-line treatment for male T2 in the bulbar urethra.
C. Incorrect - Chemoradiotherapy can be an adjuvant therapy, not first-line.
D. Incorrect - Repeat TUR is indicated for Tis, Ta, T1 stages.
Memory Tool:
“Bulbar = Both” – Bulbar urethra may involve urethrectomy and cystectomy.
Reference Citation:
Data from Bladder Cancer, NCCN Clinical Practice Guidelines in Oncology, 2018
Rationale:
Understanding specialized treatments for different anatomical locations like the bulbar urethra is crucial for patient-specific management.
Clinical Vignette: A 67-year-old female is diagnosed with T2 urethral cancer. What are the treatment options?
Options:
A. Urethrectomy ± radical cystectomy
B. Radical cystectomy OR Chemoradiotherapy
C. Repeat TUR ± intraurethral BCG or chemotherapy
D. Chemoradiotherapy ± consolidative surgery
Correct Answer:
B. Radical cystectomy OR Chemoradiotherapy
Explanation for All Choices:
A. Incorrect - This is indicated for Male T2 Bulbar urethra.
B. Correct - For Female T2, radical cystectomy or chemoradiotherapy is recommended.
C. Incorrect - This is for Tis, Ta, T1 stages.
D. Incorrect - This is for stages ≥ T3, N0 or N+.
Memory Tool:
“Two Ts, Two Choices” – For Female T2, you have two main choices: Radical cystectomy OR Chemoradiotherapy.
Reference Citation:
Data from Bladder Cancer, NCCN Clinical Practice Guidelines in Oncology, 2018
Rationale:
Being aware of gender-specific recommendations aids in individualized patient treatment.
Clinical Vignette: A patient has been diagnosed with pT3 urethral cancer. What is the adjuvant therapy?
Options:
A. Neoadjuvant chemotherapy
B. Chemoradiotherapy OR Chemotherapy
C. Additional surgery
D. Radiotherapy alone
Correct Answer:
B. Chemoradiotherapy OR Chemotherapy
Explanation for All Choices:
A. Incorrect - Neoadjuvant chemotherapy is a consideration, not an adjuvant therapy for ≥ pT3 or N+.
B. Correct - Chemoradiotherapy OR Chemotherapy are listed adjuvant therapies for these stages.
C. Incorrect - Additional surgery is an option for positive margins, not for ≥ pT3 or N+.
D. Incorrect - Radiotherapy alone is not indicated for this stage.
Memory Tool:
“3+ Therapy Choices for pT3” – pT3 can have Chemoradiotherapy OR Chemotherapy as an option.
Reference Citation:
Data from Bladder Cancer, NCCN Clinical Practice Guidelines in Oncology, 2018
Rationale:
Different stages have specific adjuvant therapies, and it’s crucial to know them for effective management.
