Urethral cancer: Treatment - Health Professional Information [NCI PDQ]

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of urethral cancer. This summary is reviewed regularly and updated as necessary by the PDQ Adult Treatment Editorial Board.

Information about the following is included in this summary:

• Prognosis.
• Cellular classification.
• Staging.
• Treatment options by different types of tumors.

This summary is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.

Some of the reference citations in the summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Adult Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations. Based on the strength of the available evidence, treatment options are described as either “standard” or “under clinical evaluation.” These classifications should not be used as a basis for reimbursement determinations.

This summary is available in a patient version, written in less technical language, and in Spanish.

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 tumor is of less importance in determining response to therapy and survival.[1]

Anterior Urethral Cancer

These lesions are often superficial.

• Female: Meatal and/or distal urethral cancer (i.e., the lesions of the distal third of the urethra).
• Male: Penile or anterior portion of the urethra, including the meatus and pendulous urethra.

Posterior Urethral Cancer

These lesions are often deeply invasive.

• Female: Entire urethral cancer; lesions not clearly limited to the distal third of the urethra.
• Male: Bulbomembranous and prostatic urethral cancer.

Urethral Cancer Associated with Invasive Bladder Cancer

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 Definitions by Depth of Invasion

• 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.
  • Female: Vagina, labia, muscle
  • Male: Corpus cavernosum, muscle
• Stage D1 (N+): Regional nodes; pelvic and inguinal.
• Stage D2 (N+, M+): Distant nodes; visceral metastases.

References:

1. Grigsby PW, Corn BW: Localized urethral tumors in women: indications for conservative versus exenterative therapies. J Urol 147 (6): 1516-20, 1992.

Female Anterior Urethral Cancer

If the malignancy is at or just within the meatus and superficial parameters (stage 0/Tis, Ta), 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 and stage B, T1 and T2, respectively), interstitial radiation therapy or a combination of interstitial radiation therapy and external-beam radiation therapy 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- to 4-month intervals.[1,2,3]

STANDARD TREATMENT OPTIONS:

1. Open excision or electroresection and fulguration, or laser vaporization-coagulation (Tis, Ta, T1 lesions).
2. External-beam radiation therapy or interstitial radiation therapy or a combination of both (T1, T2 lesions).
3. Anterior exenteration with or without preoperative radiation and diversion (T3 lesions/recurrent lesions).

Male Anterior Urethral Cancer

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/Tis, Ta), 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 cm 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- to 4-month intervals.[6,7,8]

STANDARD TREATMENT OPTIONS:

1. Open excision or electroresection and fulguration, or laser vaporization-coagulation.
2. Amputation of penis (T1, T2, T3 lesions).
3. Radiation (T1, T2, T3 lesions, if amputation is refused).

References:

1. Johnson DE, O'Connell JR, Delclos L: Carcinoma of the urethra. In: Javadpour N, ed.: Principles and Management of Urologic Cancer. 2nd ed. Baltimore, Md: Williams and Wilkins, 1983, pp 598-621.
2. Bracken RB, Johnson DE, Miller LS, et al.: Primary carcinoma of the female urethra. J Urol 116 (2): 188-92, 1976.
3. Sailer SL, Shipley WU, Wang CC: Carcinoma of the female urethra: a review of results with radiation therapy. J Urol 140 (1): 1-5, 1988.
4. Chao KS, Perez CA: Penis and male urethra. In: Perez CA, Brady LW, eds.: Principles and Practice of Radiation Oncology. 3rd ed. Philadelphia, Pa: Lippincott-Raven Publishers, 1998, pp 1717-1732.
5. Donat S, Cozzi P, Herr H: Surgery of penile and urethral carcinoma. In: Walsh PC, Retik AB, Vaughan ED, et al., eds.: Campbell's Urology. 8th ed. Philadelphia: Saunders, 2002, pp 2983-2991.
6. Mullin EM, Anderson EE, Paulson DF: Carcinoma of the male urethra. J Urol 112 (5): 610-3, 1974.
7. Ray B, Canto AR, Whitmore WF Jr: Experience with primary carcinoma of the male urethra. J Urol 117 (5): 591-4, 1977.
8. Webster GD: The urethra. In: Paulson DF, ed.: Genitourinary Surgery. Vol. 2. New York: Churchill Livingston, 1984, pp 399-583.

Female Posterior Urethral Cancer

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, which is administered 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 cm in greatest dimension, radiation alone, nonexenterative surgery alone, or the combination may be sufficient to provide an excellent outcome.[1]

As with male urethral carcinoma, it is reasonable to consider removal of part of the pubic symphysis and the inferior pubic rami to maximize the surgical margin and hopefully to 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 cm in diameter, a 60% 5-year survival can be anticipated; for those greater than 4 cm in diameter, the 5-year survival falls to 13%.[2,3,4,5]

STANDARD TREATMENT OPTIONS:

1. Preoperative radiation followed by anterior exenteration and urinary diversion with bilateral pelvic node dissection with or without inguinal node dissection.
2. For tumors that do not exceed 2 cm in greatest dimension, radiation alone, nonexenterative surgery alone, or the combination may be sufficient to provide an excellent outcome.[1]

Male Posterior Urethral Cancer

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, though 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% to 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.[6,7,8,9,10]

Ipsilateral inguinal node dissection is indicated if palpable ipsilateral inguinal adenopathy is found on physical examination and confirmed to be neoplasm by frozen section.[11]

STANDARD TREATMENT OPTIONS:

• Preoperative radiation followed by cystoprostatectomy, urinary diversion, and penectomy with bilateral pelvic node dissection with or without inguinal node dissection.

References:

1. Grigsby PW, Corn BW: Localized urethral tumors in women: indications for conservative versus exenterative therapies. J Urol 147 (6): 1516-20, 1992.
2. Sullivan J, Grabstald H: Management of carcinoma of the urethra. In: Skinner DG, deKernion JB: Genitourinary Cancer. Philadelphia: WB Saunders Company, 1978, pp 419-429.
3. Bracken RB, Johnson DE, Miller LS, et al.: Primary carcinoma of the female urethra. J Urol 116 (2): 188-92, 1976.
4. Sailer SL, Shipley WU, Wang CC: Carcinoma of the female urethra: a review of results with radiation therapy. J Urol 140 (1): 1-5, 1988.
5. Skinner EC, Skinner DG: Management of carcinoma of the female urethra. In: Skinner DG, Lieskovsky G, eds.: Diagnosis and Management of Genitourinary Cancer. Philadelphia, Pa: WB Saunders, 1988, pp 490-496.
6. Ray B, Canto AR, Whitmore WF Jr: Experience with primary carcinoma of the male urethra. J Urol 117 (5): 591-4, 1977.
7. Bracken RB, Henry R, Ordonez N: Primary carcinoma of the male urethra. South Med J 73 (8): 1003-5, 1980.
8. Klein FA, Whitmore WF Jr, Herr HW, et al.: Inferior pubic rami resection with en bloc radical excision for invasive proximal urethral carcinoma. Cancer 51 (7): 1238-42, 1983.
9. Webster GD: The urethra. In: Paulson DF, ed.: Genitourinary Surgery. Vol. 2. New York: Churchill Livingston, 1984, pp 399-583.
10. Donat S, Cozzi P, Herr H: Surgery of penile and urethral carcinoma. In: Walsh PC, Retik AB, Vaughan ED, et al., eds.: Campbell's Urology. 8th ed. Philadelphia: Saunders, 2002, pp 2983-2991.
11. Chao KS, Perez CA: Penis and male urethra. In: Perez CA, Brady LW, eds.: Principles and Practice of Radiation Oncology. 3rd ed. Philadelphia, Pa: Lippincott-Raven Publishers, 1998, pp 1717-1732.

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% of the patients. 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 the morbidity factors, 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 that present with clinical symptoms at a later date when the likelihood of invasion within the corporal bodies is high. The former lesions are often curable, and the latter are only rarely so. Indications for urethrectomy in continuity with cystoprostatectomy are:

• Visible tumor in the urethra.
• Positive swab cytology of the urethra.
• Positive margins of the membranous urethra on frozen section taken at the time of cystoprostatectomy.
• Multiple in situ bladder tumors that extend onto the bladder neck and proximal prostatic urethra.

If the urethra is not removed at the time of cystectomy, optimal follow-up includes periodic cytologic evaluation of saline urethral washings.[1,2,3,4]

STANDARD TREATMENT OPTIONS:

1. In continuity cystourethrectomy.
2. Monitor urethral cytology and delayed urethrectomy.

References:

1. Schellhammer PF, Whitmore WF Jr: Transitional cell carcinoma of the urethra in men having cystectomy for bladder cancer. J Urol 115 (1): 56-60, 1976.
2. Wolinska WH, Melamed MR, Schellhammer PF, et al.: Urethral cytology following cystectomy for bladder carcinoma. Am J Surg Pathol 1 (3): 225-34, 1977.
3. Gowing NFC: Urethral carcinoma associated with cancer of the bladder. Br J Urol 32(4): 428-438, 1960.
4. Hendry WF, Gowing NF, Wallace DM: Surgical treatment of urethral tumours associated with bladder cancer. Proc R Soc Med 67 (4): 304-7, 1974.

STANDARD TREATMENT OPTIONS FOR FEMALE/MALE RECURRENT URETHRAL CANCER:

1. Locally recurrent urethral cancer after radiation therapy should be treated by surgical excision.
2. Locally recurrent urethral cancer after surgery alone should be considered for combination radiation and wider surgical resection.[1]

TREATMENT OPTIONS UNDER CLINICAL EVALUATION:

• Metastatic urethral cancer should be considered for clinical trials using chemotherapy. Early evidence suggests that transitional cell cancer of the urethra may respond favorably to the same chemotherapy regimens employed for advanced transitional cell cancer of the bladder.

References:

1. Scher HI, Yagoda A, Herr HW, et al.: Neoadjuvant M-VAC (methotrexate, vinblastine, doxorubicin and cisplatin) for extravesical urinary tract tumors. J Urol 139 (3): 475-7, 1988.

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Date Last Modified: 2008-01-09