Urethral cancer is a rare but aggressive neoplasm. Early-stage distal lesions can be successfully treated with a single modality. Results for definitive radiotherapy using either or both external beam radiation therapy and brachytherapy have shown excellent cure rates in men and women. The primary advantage of radiotherapy is organ preservation. Advanced tumors, however, have poor outcomes with single modality treatment. Results have been improved using a combination of radiotherapy and chemotherapy, chiefly 5-fluorouracil and mitomycin C. Although literature is limited to case reports because of the rarity of the disease, the markedly improved results compared with older results of surgery with or without radiation warrant consideration.
Primary urethral cancer is a rare diagnosis in men and women, presenting most commonly with bleeding or obstruction. The most common histologic finding is squamous cell carcinoma, although adenocarcinoma and transitional cell carcinoma also occur.
Anatomically, the urethra in men can be divided into 3 sections: the penile (or pendulous) urethra, the bulbomembranous urethra, and the prostatic urethra. In women, the distal half of the urethra is considered the anterior urethra and the proximal half is considered the posterior urethra. Lymphatic drainage patterns follow the surrounding organs and are different for the 3 regions of the urethra. Initial drainage patterns for the penile urethra include the superficial and deep inguinal nodes. The bulbomembranous urethra is drained by the internal and external iliac nodes. Sites of drainage for the prostatic urethra include the internal and external iliacs, the obturator, and the presacral nodal beds.
Historically, urethral cancer carries a poor prognosis, and location and stage affect outcome. Distal lesions have a similar outcome as penile cancer of the same stage and are often treated with similar techniques. Early distal lesions have a very good prognosis with primary excision (70%–100% disease-free survival [DFS]). Prostatic lesions behave and are treated in the same way as bladder carcinoma. Bulbomembranous urethral cancers are more often locally advanced and difficult to manage with surgical techniques; this location carries the worst prognosis (25% DFS).
Role of radiation in early-stage urethral cancers
For small early-stage cancers, a single modality treatment may offer a good chance of control and may limit overall morbidity of therapy. Primary management of urethral cancers in men is most often surgical. In women, radiotherapy is more often the primary modality because of the morbidity associated with surgical management. Radiotherapy, using external beam radiotherapy (EBRT), brachytherapy (BT), or a combination of the two, seems to have equivalent results as surgery, given that all results have been reported in case review form ( Table 1 ).
| Gender | Number of Patients | Treatment, (#) Indicates Number of Patients Receiving Treatment | Mean Follow-up (mo) | OS (%) | CSM (%) | DFS (%) | LC (%) | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Neoadjuvant | Primary | Adjuvant | |||||||||
| Eng et al | 2003 | M/F | 10 | Surgery (9); CRT (1) | 189 | 70 a | 0 a | 70 a | 100 a | ||
| Dalbagni et al | 1999 | M | 10 | Surgery | 125 | 83 b | |||||
| Gheiler et al | 1998 | M/F | 9 | CRT (2) | Surgery | RT (1) | 42 | 89 a | |||
| Moinuddin et al | 1988 | F | 3 | 40 Gy (1) | Surgery | 118 | 67 a | 0 a | 33 a | 67 a | |
| Farrer and Lupu | 1984 | M | 2 | 45 Gy (1) | Surgery | 102 | 100 a | 0 a | 100 a | 100 a | |
| Dinney et al | 1994 | M | 6 | Surgery (5); CRT (1) | 55 | 83 a | 83 a | 83 a | 83 a | ||
| Moinuddin et al | 1988 | F | 3 | EBRT+BT | 27 | 67 a | 0 a | 67 a | 100 a | ||
| Johnson and O’Connell | 1983 | F | 5 | BT ± EBRT | 41 | 80 a | 0 a | 60 a | 60 a | ||
| Prempree et al | 1984 | F | 7 | BT ± EBRT | ns | 71 b | 71 b | ||||
A review from MD Anderson Cancer Center, including 5 women with early-stage urethral cancer, reported excellent local control with 4 out of 5 patients without evidence of disease at a median follow-up of 4 years. Treatment included BT in 4 patients (60 Gy using radium or iridium needles) and a combination of EBRT and BT in 1 patient (70 Gy). Moinuddin Ali and colleagues reported on 3 women with early-stage urethral cancers who were treated with EBRT (40–50 Gy) with a BT boost dose of 28 to 30 Gy. All the 3 patients remained disease free at follow-up periods of 20, 30, and 30 months, respectively.
Radiotherapy alone may be the most optimal treatment in early-stage tumors involving only the distal urethra. In a series from the University of Maryland, 3 women with distal urethral cancers had local control at extended follow-up; disease was controlled only half of the time in 4 women with early-stage tumors involving the proximal urethra. Weghaupt and colleagues confirm this finding in an institutional review of 62 women from the University of Vienna. Five-year overall survival was 71% for women with anterior lesions and 50% for women with distal lesions (outcome was not otherwise evaluated by stage, although most patients were node negative).
Dinney and colleagues reported excellent survival and local control for early-stage urethral cancers of men treated in 5 out of 6 cases by partial penectomy or urethrectomy. One more patient with a stage B bulbomembranous lesion refused surgery and was treated with 66 Gy and concurrent chemotherapy; this patient was disease free at 30 months of follow-up. A series of 9 low-stage distal cancers in both genders found that 83% of patients treated with surgery alone (5 of 6) and 100% of those treated with combination therapy (2 with neoadjuvant chemoradiation and 1 with adjuvant radiation) remained disease free with a mean follow-up of 49 months.
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