Primary urethral tumors are rare. The Surveillance, Epidemiology, and End Results study has reported that the annual age-adjusted incidence rates of primary urethral tumors are 4.3/million in men and 1.5/million in women in the United States.3 Histologically, transitional cell carcinoma is the most common type (55%), followed by SCC (21.5%) and adenocarcinoma (16.4%). In addition, urethral metastatic tumors are rare.4 There are only few reports of urethral metastatic tumors of urological and colorectal carcinomas.
In contrary, locally advanced cervical cancer often involves the vagina. However, cutaneous metastasis, including the vulva arising from cervical cancer, is also rare.5, 6 Only a few cases of vulvar skin metastasis of cervical cancer have been reported in the Korean literature.7–10 In these cases, vulvar skin metastasis is observed as a recurrence after the initial treatment. The interval between the diagnosis of cervical cancer and that of cutaneous metastasis was 8–131 months. The main clinical manifestations were erythematous papules, nodules, and vesicles in the vulva.
In addition, we found only six case reports of clitoral metastasis of cervical cancer.11–16 The main manifestations of clitoral metastasis are clitoral pain and enlargement. However, in our case, no metastatic lesions were observed in the vulva or clitoris. To the best of our knowledge, the present case is the first report of external urethral orifice metastasis in primary cervical cancer. The external urethral orifice can easily be overlooked on physical examination of patients with cervical cancer not only by gynecologists but also by radiation oncologists. Moreover, in the present case, there were no urological symptoms (urination pain, hematuria, dysuria). Therefore, this rare case report suggested that gynecologists and radiation oncologists should keep in mind to examine not only the cervix and vagina but also the external urethral orifice for patients with primary cervical cancer.
Considering tumor involvement, we performed EBRT followed by intraluminal urethral BT using the Lumencath applicator to treat the entire urethra. Recently, guidelines on primary urethral carcinoma published by the European Association of Urology have described the role of radiotherapy.17 Milosevic et al. have reported 34 women with primary urethral carcinoma treated with radiotherapy.18 Twenty patients (59%) received BT with or without EBRT. The 7-year actuarial overall and cause-specific survival rates were 41% and 45%, respectively. Large primary tumor bulk and treatment with EBRT alone (no BT) were independent poor prognostic factors for local tumor recurrence. In their study, BT reduced the risk of local recurrence by a factor of 4.2.
The largest retrospective study of treating primary carcinoma of the female urethra with radiotherapy was published by the University of Texas M.D. Anderson Cancer Center.19 Eighty-six patients received radiotherapy alone: 35 were treated with a combination of EBRT and interstitial BT, 21 received EBRT only, and 30 received interstitial BT only. The cumulative doses ranged from 40 to 106 Gy (median, 65 Gy). The 1-, 2-, and 5-year local control rates in 84 evaluable patients were 72%, 65%, and 64%, respectively. Of note, pelvic toxicity in patients achieving local control was considerable (49%), including urethral stenosis (n = 11), fistula or necrosis (n = 10), and cystitis and/or hemorrhage (n = 6), with 30% of the reported complications graded as severe. Higher doses correlated with a greater incidence of complications but not with improved local control.
Dose constraints for the female urethra in high-dose-rate BT (HDR-BT) are unknown. Therefore, we used urethra dose constraints in the HDR-BT of prostate cancer as a reference. The American Brachytherapy Society HDR prostate BT guidelines provide guidance on organs-at-risk dose constraints.20 The Radiation Therapy Oncology Group 0321 study (EBRT 45 Gy followed by HDR-BT 19 Gy/2 fractions for prostate cancer) has demonstrated a higher urethral dose associated with greater acute/late genitourinary toxicities.21 Based on these available data, we aimed to prescribe a 100% dose (6 Gy per fraction) in the BT session at the CTVurethra, 2 mm from a 16-French Foley catheter, which is nearly equal to the urethral mucosa. As a result, the averages of CTVurethra D90, urethra D0.1 cc, and D1 cc were 5.6 Gy, 18.1 Gy, and 9.0 Gy, respectively. However, in only short-term follow-up, there were no grade ≥ 3 acute and late toxicities, and we achieved excellent local control for both primary tumor and external urethral orifice metastasis of cervical cancer. Intraluminal urethral BT using the Lumencath applicator is a good treatment option for cervical cancer with urethral involvement. Further follow-up is needed to determine the late toxicities of this treatment.