Treatment Option Overview
Information about the treatment of urethral cancer and the outcomes of therapy is derived from retrospective, single-center case series and represents a very low level of evidence of 3iiiDiv. The majority of this information comes from the small numbers of cases accumulated over many decades at major academic centers. Therefore, the treatment in these reports is usually not standardized and the treatment also spans eras of shifting supportive care practices. Because of the rarity of urethral cancer, its treatment may also reflect extrapolation from the management of other urothelial malignancies, such as bladder cancer in the case of transitional cancers, and anal cancer in the case of squamous cell carcinomas.
Role of Surgery
Surgery is the mainstay of therapy for urethral cancers in both women and men.[Level of evidence: 3iiiDiv] The surgical approach depends on tumor stage and anatomic location, and tumor grade plays a less important role in treatment decisions.[1,2] Although the traditional recommendation has been to achieve a 2-cm tumor-free margin, the optimal surgical margin has not been rigorously studied and is not well defined. The role of lymph node dissection is not clear in the absence of clinical involvement, and the role of prophylactic dissection is controversial. Radiation therapy and/or chemotherapy may be added in some cases in patients with extensive disease or in an attempt at organ preservation; but there are no clear guidelines for patient selection, and the low level of evidence precludes confident conclusions about their incremental benefit.[2,3]
Ablative techniques, such as transurethral resection, electroresection and fulguration, or laser vaporization-coagulation, are used to preserve organ function in cases of superficial anterior tumors, although the supporting literature is scant.
Role of Radiation Therapy
Radiation therapy with external beam, brachytherapy, or a combination is sometimes used for the primary therapy of early-stage proximal urethral cancers, particularly in women.[Level of evidence: 3iiiDiv] Brachytherapy may be delivered with low-dose-rate iridium-192 sources using a template or urethral catheter. Definitive radiation is also sometimes used for advanced-stage tumors, but because monotherapy of large tumors has shown poor tumor control, it is more frequently incorporated into combined modality therapy after surgery or with chemotherapy. There are no head-to-head comparisons of these various approaches, and patient selection may explain differences in outcomes among the regimens.[Level of evidence: 3iiiDiv]
The most commonly used tumor doses are in the range of 60 Gy to 70 Gy. Severe complication rates for definitive radiation are about 16% to 20% and include fistula development, especially for large tumors invading the vagina, bladder, or rectum. Urethral strictures also occur in the setting of urethral-sparing treatment. Toxicity rates increase at doses greater than 65 Gy to 70 Gy. Intensity-modulated radiation therapy has come into more common use in an attempt to decrease local morbidity of the radiation.
Role of Chemotherapy
The literature on chemotherapy for urethral carcinoma is anecdotal in nature and restricted to retrospective, single-center case series or case reports.[Level of evidence: 3iiiDiv] A wide variety of agents used alone or in combination have been reported over the years, and their use has largely been extrapolated from experience with other urinary tract tumors.
- Methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC).
- Ifosfamide, with occasional complete responses.
Chemotherapy has been used alone for metastatic disease or in combination with radiation therapy and/or surgery for locally advanced urethral cancer. It may be used in the neoadjuvant setting with radiation therapy in an attempt to increase the resectability rate or in an attempt at organ preservation. However, the impact of any of these regimens on survival is not known for any stage or setting.
- Trabulsi DJ, Gomella LG: Cancer of the urethra and penis. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2011, pp 1272-79.
- Karnes RJ, Breau RH, Lightner DJ: Surgery for urethral cancer. Urol Clin North Am 37 (3): 445-57, 2010. [PUBMED Abstract]
- Cohen MS, Triaca V, Billmeyer B, et al.: Coordinated chemoradiation therapy with genital preservation for the treatment of primary invasive carcinoma of the male urethra. J Urol 179 (2): 536-41; discussion 541, 2008. [PUBMED Abstract]
- Koontz BF, Lee WR: Carcinoma of the urethra: radiation oncology. Urol Clin North Am 37 (3): 459-66, 2010. [PUBMED Abstract]
- Trabulsi EJ, Hoffman-Censits J: Chemotherapy for penile and urethral carcinoma. Urol Clin North Am 37 (3): 467-74, 2010. [PUBMED Abstract]
- VanderMolen LA, Sheehy PF, Dillman RO: Successful treatment of transitional cell carcinoma of the urethra with chemotherapy. Cancer Invest 20 (2): 206-7, 2002. [PUBMED Abstract]
- Lin CC, Hsu CH, Huang CY, et al.: Phase II trial of weekly paclitaxel, cisplatin plus infusional high dose 5-fluorouracil and leucovorin for metastatic urothelial carcinoma. J Urol 177 (1): 84-9; discussion 89, 2007. [PUBMED Abstract]