This two-part article by Krieg and Hoffman, published last month and concluded in this issue, explores the current management of penile cancer (part 1) and urethral cancer in both men and women (part 2). My remarks will focus on female and male urethral cancer.
Female Urethral Cancer
As Krieg and Hoffman note, the overall outcome for women with carcinoma of the urethra is poor regardless of the treatment modality used. The small number of cases of this cancer reported and the use of different modalities to treat them preclude a meaningful analysis of clinical outcome. Current treatment modalities are ineffective in improving local control and survival. New treatment strategies are clearly needed.
Rates of survival at 5 and 10 years are better for low-stage urethral cancers in women than for high-stage tumors. However, several investigators have shown the inadequacies of a single modality in the management of advanced female urethral cancer.
Anterior exenteration alone led to a 5-year survival of 10% to 17% and a local recurrence rate of 67%. Using radiation therapy, Garden et al achieved 5- and 10-year actuarial survival rates of 41% and 31%, respectively, with a 5-year local control rate of 64%. Narayan et al reported a 5-year survival rate of 0% to 57% (mean, 34%) in females treated with radiation alone.[1]
Foens et al described their experience with 42 patients, 10 of whom underwent surgery and 32 of whom received radiation.[1] The local control rate was better in the radiation group than in the surgery group (64% vs 40%). However, 5-year survival rates were similar in the two groups. The complication rates with radiation therapy were significant (range, 0% to 42%), with most series reporting rates between 16% and 26%.
The combination of different treatment modalities has shown efficacy in other tumor systems, such as rectal carcinoma and head and neck cancer. This led researchers to test the efficacy of a combined-modality approach in patients with advanced urethral carcinoma. In a compilation of data, Narayan reported a 55% survival rate in patients with advanced urethral carcinoma treated with radiotherapy plus surgery, as compared with a rate of 34% in those who received radiation alone.[1]
Our experience treating 72 females with urethral cancer does not differ significantly from other reports. Primary stage, nodal status, and site of disease are independent predictors of survival.[1] We observe no difference in outcome between patients treated with radiation or surgery for invasive urethral cancer. Neoadjuvant radiation therapy improves local control but not survival.
Male Urethral Cancer
Like female urethral cancer, overall survival is better for men with low-stage urethral tumors than for those with high-stage tumors. Also like female urethral cancer, several investigators have shown the inadequacies of a single modality in the management of advanced male urethral cancer.
The majority of male urethral cancers are high-stage tumors, rendering surgical resection inadequate as the sole modality of treatment. In a series published by Dinney et al, two of five patients with tumors of the anterior urethra and none of four patients with tumors of the bulbomembranous urethra were alive after treatment with surgery alone. In our series, 7 (38%) of 18 patients with tumors of the anterior urethra and 5 (14%) of 28 patients with tumors of the bulbar urethra were free of disease following surgery.[2]
Similarly, radiation therapy alone has yielded dismal results. In our series, patients who received radiation therapy followed by salvage surgery seemed to fare worse than those treated initially with surgery.[2] Furthermore, we found no advantage of radiation alone over surgery with respect to survival, local, control, or distant metastasis-free survival.
Failure after radiation therapy usually occurs in the central portion of the tumors, while failure following surgery results from inadequate margins in areas where vital structures interfere with a wide excision.
As mentioned above, the efficacy of combining treatment modalities in other tumor systems has led to a combined-modality approach in the management of advanced urethral carcinoma, with occasional satisfactory results. Combining both modalities is conceptually appealing and is expected to lead to a better outcome. Indeed, radiation therapy given in a neoadjuvant setting improved local control rates. However, this improvement in local control did not translate into better survival. Micrometastatic disease at the time of primary intervention was responsible for the poor results.
Chemoradiation and surgery should be investigated in carcinoma of the urethra, with the goals of improving local control and simultaneously decreasing distant metastasis. Chemotherapy given concomitantly with radiation acts as a radiosensitizer and interferes with cell repair after a sublethal radiation dose
Summary
The treatment of urethral carcinoma in both women and men has lagged behind that of other cancers due to the paucity of cases and the lack of uniformity in management. I propose that locally advanced urethral cancer should be treated aggressively with chemoradiation and surgery.
