PDQ® Treatment Health Professionals
The prognosis of urethral cancer depends on its anatomical location and the depth of invasion. Superficial tumors located in the anterior urethra of both the female and male are generally curable; deeply invasive lesions or those lesions located in the posterior urethra, because they are almost always deeply invasive, are rarely curable by any combinations of therapy.
Female urethral cancer is more common than male urethral cancer, but both tumors are quite rare. The majority of information comes from cases accumulated over many decades at major cancer centers. Rarely, melanomas or periurethral sarcomas can occur.
The female urethra is lined by transitional cell mucosa proximally and stratified squamous cells distally. Therefore, transitional cell carcinoma is most common in the proximal urethra and squamous cell carcinoma predominates in the distal urethra. Adenocarcinoma is found in both locations and arises from metaplasia of the numerous periurethral glands.
The male urethra is lined by transitional cells in its prostatic and membranous portion and stratified columnar epithelium to stratified squamous epithelium in the bulbous and penile portions. The submucosa of the urethra contains numerous glands. Therefore, urethral cancer in the male can manifest the histological characteristics of transitional cell carcinoma, squamous cell carcinoma or adenocarcinoma.
Except for the prostatic urethra, where transitional cell carcinoma is most common, squamous cell carcinoma is the predominant histology of urethral neoplasms. Since transitional cell carcinoma of the prostatic urethra is usually associated with transitional cell carcinoma of the bladder and/or transitional cell carcinoma arising in prostatic ducts, it is treated according to the guidelines for treatment of these primaries and should be separated from the more distal carcinomas of the urethra.
Prognosis is determined both by the anatomical location of the neoplasm, the size, and the depth of invasion of the primary tumor. The histology of the primary is of less importance in determining response to therapy and survival.
These lesions are often superficial. Female: meatal and/or distal urethral cancer (distal 1/3 of urethra).
Male: penile or anterior portion of the urethra, including the meatus and
These lesions are often deeply invasive. Female: entire urethral cancer; lesions not clearly limited to the distal
Approximately 10% of patients with cystectomy for bladder cancer can be expected to have or develop urethral cancer distal to the urogenital diaphragm.
The 5-year survival associated with urethral cancer is most often determined by the stage.
Stage 0 (Tis, Ta) - limited to mucosa.
Stage A (T1) - submucosal invasion.
Stage B (T2) - infiltrating periurethral muscle or corpus spongiosum.
Stage C (T3) - infiltration beyond periurethral tissue.
Stage D2 (N+, M+) - distant nodes; visceral metastases.
The designations in PDQ that treatments are "standard" or "under clinical evaluation" are not to be used as a basis for reimbursement determinations.
If the malignancy is at or just within the meatus and superficial (stage 0/Ta, Tis) open excision or electroresection and fulguration is possible. Tumor destruction using Nd-YAG or CO2 laser vaporization-coagulation represents an alternative option. For large lesions and more invasive lesions (stage A, B, T1, T2) interstitial radiation or combination of interstitial radiation and external beam, is an alternative to surgical resection of the distal third of the urethra. Patients with T3 anterior urethral lesions or lesions treated by local excision or radiation therapy which then recur require anterior exenteration and urinary diversion.
If inguinal nodes are palpable, frozen section confirmation of tumor is obtained. If positive for malignancy, ipsilateral node dissection is indicated as cure is still achievable with limited regional nodal metastases. If no inguinal adenopathy exists, node dissection is not recommended, but careful inguinal palpation is mandatory at 3-4 month intervals.[1-3]
2. External beam or interstitial irradiation or combination (T1, T2 lesions).
3. Anterior exenteration with or without preoperative irradiation and diversion (T3 lesions/recurrent lesions).
If the malignancy is in the pendulous urethra and is superficial, the potential for cure is high. In the rare case that involves mucosa only, stage 0/Ta, Tis) resection and fulguration is justified as initial therapy. For infiltrating lesions in the fossa navicularis amputation of the glans penis may be adequate treatment. For lesions involving more proximal portions of the distal urethra, excision of the involved segment of the urethra, preserving the penile corpora, may be feasible for superficial tumors. Infiltrating lesions require penile amputation 2 centimeters proximal to tumor. Local recurrences after amputation are rare. The role for radiation therapy in the treatment of anterior urethral carcinoma in the male is not well defined. Some anterior urethral cancers have been cured with radiation alone.[4,5]
If inguinal nodes are palpable, ipsilateral node dissection is indicated after frozen section confirmation of tumor as cure is still achievable with limited regional nodal metastases. If no inguinal adenopathy exists, node dissection is not recommended, but careful inguinal palpation is mandatory at 3-4 month intervals.[6-8]
2. Amputation of penis (T1, T2, T3 lesions).
3. Radiation (T1, T2, T3 lesions if amputation is refused).
Lesions of the posterior or entire urethra are usually associated with invasion and a high incidence of pelvic nodal metastases. The prospects for cure are limited except in the case of small tumors. The best results have been achieved with exenterative surgery and urinary diversion with 5-year survivals ranging from 10% to 20%. It is reasonable to recommend adjunctive radiation therapy preoperatively in an effort to shrink tumor margins. Pelvic lymphadenectomy is performed concomitantly since an occasional patient with nodal metastases will be cured. Ipsilateral inguinal node dissection is indicated only if biopsy of ipsilateral palpable adenopathy is positive on frozen section. For tumors that do not exceed 2 centimeters in greatest dimension, irradiation alone, nonexenterative surgery alone, or the combination may be sufficient to provide an excellent outcome.
As with male urethral carcinoma, it is not unreasonable to consider removal of part of the pubic symphysis and the inferior pubic rami to maximize the surgical margin and hopefully reduce local recurrence. The perineal closure and vaginal reconstruction can be accomplished with the use of myocutaneous flaps.
The prognosis of female urethral cancer has been related to the size of the lesion at presentation. For lesions less than 2 centimeters in diameter, a 60% 5-year survival can be anticipated; for those greater than 4 centimeters in diameter, the 5-year survival falls to 13%.[2-5]
2. For tumors that do not exceed 2 centimeters in greatest dimension, irradiation alone, nonexenterative surgery alone, or the combination may be sufficient to provide an excellent outcome.
Lesions of the bulbomembranous urethra require radical cystoprostatectomy and en bloc penectomy to achieve adequate margins of resection, minimize local recurrence, and achieve cure. Pelvic lymphadenectomy is also recommended in view of the significant incidence of positive nodes, the limited added morbidity from such dissection, and the potential, although limited, possibility for cure. Despite extensive surgery, local recurrence does occur frequently and this event is invariably associated with eventual death from disease. Five-year survival can be expected in only 15%-20% of patients. In an effort to shrink tumor margins, the use of preoperative adjunctive radiation therapy must be considered. In an effort to increase the surgical margins of dissection, resection of the inferior pubic rami and the lower portion of the pubic symphysis has been used. Urinary diversion is required.[6-10]
Ipsilateral inguinal node dissection is indicated if palpable ipsilateral inguinal adenopathy is found on physical examination and confirmed to be neoplasm by frozen section.
Approximately 10% of patients having cystectomy for bladder cancer can be expected to have or to later develop clinical neoplasm of the urethra distal to the urogenital diaphragm. An autopsy series of patients having had cystectomy for bladder cancer documented histologic evidence of urethral neoplasm in 20%. A review from the Royal Marsden Hospital showed that those patients having cystectomy for multiple and superficial bladder lesions have an especially high incidence (34%) of urethral neoplasia.
The benefits of urethrectomy at the time of cystectomy need to be weighed against its morbidity which include added operating time, hemorrhage, and the potential for perineal hernia. However, tumors found incidentally on pathologic examination are much more likely to be superficial or in situ in contrast to those which present with clinical symptoms at a later date where the likelihood of invasion within the corporal bodies is high. The former lesions are often curable and the latter only rarely. Indications for urethrectomy in continuity with cystoprostatectomy are:
2. Monitor urethral cytology and delayed urethrectomy.
Treatment options for female/male recurrent urethral cancer:
2. Locally recurrent urethral cancer after surgery alone should be considered for combination radiation and wider surgical resection.
Date Last Modified: 02/1999