Urethral cancer medical therapy
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
Medical therapy
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. 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.
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. 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.
For squamous cell cancers, agents that have been used in penile cancer or anal carcinoma include:
- Cisplatin
- 5-Fluorouracil
- Bleomycin
- Methotrexate
- Irinotecan
- Gemcitabine
- Paclitaxel
- Docetaxel
- Mitomycin-C
Chemotherapy for transitional cell urethral tumors is extrapolated from experience with transitional cell bladder tumors and, therefore, usually contains the following:
- Methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC).
- Paclitaxel.
- Carboplatin.
- 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.
Distal Urethral Cancer
Female Distal 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 may be 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), brachytherapy or a combination of brachytherapy and external-beam radiation therapy are alternatives to surgical resection of the distal third of the urethra. Patients with T3 distal urethral lesions, or lesions that recur after treatment with local excision or radiation therapy, require anterior exenteration and urinary diversion.
If inguinal nodes are palpable, frozen section confirmation of tumor should be obtained. If positive for malignancy, ipsilateral node dissection is indicated. If no inguinal adenopathy exists, node dissection is not generally performed, and the nodes are followed clinically.
- Standard treatment options:
- Open excision and organ-sparing conservative surgical therapy.
- Ablative techniques, such as transurethral resection, electroresection and fulguration, or laser vaporization-coagulation (Tis, Ta, T1 lesions).
- External-beam radiation therapy, brachytherapy, or a combination of the two (T1, T2 lesions).
- Anterior exenteration with or without preoperative radiation and diversion (T3 lesions or recurrent lesions).
Male Distal Urethral Cancer
If the malignancy is in the pendulous urethra and is superficial, there is potential for long-term disease-free survival. In the rare cases that involve mucosa only (stage 0/Tis, Ta), resection and fulguration may be used. 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. Penile amputation is used for infiltrating lesions. Traditionally, a 2-cm margin proximal to the tumor is used, but the optimal margin has not been well studied. Local recurrences after amputation are rare.
The role of 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 or a combination of chemotherapy and radiation therapy.
If inguinal nodes are palpable, ipsilateral node dissection is indicated after frozen section confirmation of tumor, because cure is still achievable with limited regional nodal metastases. If no inguinal adenopathy exists, node dissection is not generally performed, and the nodes are followed clinically.
- Standard treatment options:
- Open-excision and organ-sparing conservative, surgical therapy.
- Ablative techniques, such as transurethral resection, electroresection and fulguration, or laser vaporization-coagulation (Tis, Ta, T1 lesions).
- Amputation of the penis (T1, T2, T3 lesions).
- Radiation (T1, T2, T3 lesions, if amputation is refused).
- Combined chemotherapy and radiation therapy.