Urethral Cancer
Urethral cancer is a rare disease where the cells of the urethra become malignant. The urethra is the tube that empties urine from the bladder. In women, the urethra is approximately 4 cm long and opens to the outside of the body above the vagina. In men, the urethra is approximately 20 cm long, going through the prostate gland and then through the penis to the outside of the body.




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MeSH term: Urethral NeoplasmsUS National Library of Medicine
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National Cancer InstitutePDQ summaries are written and frequently updated by editorial boards of experts Further info.
Clinical Trials - Urethral Cancer
National Cancer Institute
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Medscape
Detailed referenced article by Christopher Powell, MD.
Oncolex - Oslo University Hospital (Norway) and MD Andersen (USA)
Detailed reference article covering etiology, histology, staging, metastatic patterns, symptoms, differential diagnoses, prognosis, treatment and follow-up.
Latest Research Publications
This list of publications is regularly updated (Source: PubMed).
Primary malignant melanoma of the urethra in a patient with rheumatoid arthritis treated with methotrexate.
BMJ Case Rep. 2019; 12(4) [PubMed] Related Publications
Blastoid variant of mantle cell lymphoma of the female urethra mimicking a caruncle: A rare but highly aggressive subtype case with literature review.
Arch Ital Urol Androl. 2019; 91(1):49-50 [PubMed] Related Publications
Mixed adenoneuroendocrine carcinoma of the urethra.
BMJ Case Rep. 2019; 12(3) [PubMed] Related Publications
Positive Pre-cystectomy Biopsies of the Prostatic Urethra or Bladder Neck Do Not Necessarily Preclude Orthotopic Bladder Substitution.
J Urol. 2019; 201(5):909-915 [PubMed] Related Publications
MATERIALS AND METHODS: We retrospectively analyzed the records of 803 consecutive patients, including 703 males and 100 females, who underwent orthotopic bladder substitution as well as pre-cystectomy biopsy of the prostatic urethra in males and the bladder neck in females, at our institution between April 1986 and December 2017.
RESULTS: Pre-cystectomy biopsies were negative in 755 of the 803 patients (94%) (group 1) and positive in 48 (6%) (group 2). Biopsies in group 2 revealed carcinoma in situ in 35 of the 48 cases (73%), pTaG1/G2 in 5 (10%) and pTaG3/pT1G3 in 8 (17%). Median followup was 64 months (IQR 21-128). At a median followup of 56 months (IQR 18-127) urethral recurrence developed in 45 of the 803 patients (5.6%), including 30 of the 755 (4%) in group 1 and 15 of the 48 (31.3%) in group 2 (p <0.001). Only 10 of the 45 patients (22%) with urethral recurrence required salvage urethrectomy while locally conservative treatment was successful in 27 (60%). Of the remaining 8 patients 6 of 45 (13%) underwent synchronous palliative chemotherapy and 2 of 45 (4%) refused treatment. Multivariate regression analysis revealed a higher risk of urethral recurrence if patients had positive pre-cystectomy biopsies (group 2 HR 6.49, 95% CI 3.33-12.62, p <0.001) or received neoadjuvant or adjuvant chemotherapy (HR 3.05, 95% CI 1.66-5.59, p <0.001). Cancer specific and overall survival as well as functional outcomes were similar in the 2 groups.
CONCLUSIONS: Positive pre-cystectomy biopsies prior to orthotopic bladder substitution increased the urethral recurrence rate but did not lower cancer specific or overall survival. Most urethral recurrences were managed successfully by local treatment. Orthotopic bladder substitution is an option in highly selected patients with positive, noninvasive pre-cystectomy biopsies, provided that they undergo regular followup including urethral cytology.
Primary Urethral Melanoma: A Case Report and Literature Review.
Urology. 2019; 126:1-4 [PubMed] Related Publications
Primary urethral squamous cell carcinoma: a unique manifestation of a penile tumor.
J Int Med Res. 2019; 47(2):999-1004 [PubMed] Free Access to Full Article Related Publications
The role of inguinal lymph node dissection in men with urethral squamous cell carcinoma.
Urol Oncol. 2018; 36(12):526.e1-526.e6 [PubMed] Related Publications
METHODS: The National Cancer Database was queried for all cases of primary urethral cancer in men from 2004 to 2014. Patients with other cancer diagnoses, metastasis, nonsquamous histology, female patients, and patients with a history of radiation therapy were excluded. Male patients with urethral squamous cell cancer of the anterior urethra with T1 or higher T stage were included in this study. All-cause mortality was compared using multivariable Cox regression controlling for covariates.
RESULTS: The study included 725 men with urethral SCC with T1 or higher clinical T stage. The median age was 63 years (33-83 interquartile range). Of the 725 men, 536 men did not receive an ILND and 189 (26%) underwent ILND. Patients who received LND had significantly higher clinical T and clinical N stage. There was no difference in age, sex, or histology between those with ILND versus no ILND. In patients with T1 to T4 and clinical N0, the ILND rate was 21.8% (89/396). The lymph node positive rate in patients with N0 and T1 to T4 primary tumor was 9%. In patients with clinically node positive disease (N1/N2), the overall ILND rate was 76%. The lymph node positive rate for patients with clinical nodal disease was 84%. On multivariable analysis cox regression, lymph node positivity was associated with worse overall survival when controlling for T stage, clinical N stage, and age (HR 1.56, 95% 1.3-1.9, P = 0.000). On multivariable analysis after controlling for T stage, sex, and age, having an ILND was associated with improved OS in patients with clinical N1 or N2 disease (HR 0.46, 95% 0.28-0.78 P = 0.002).
CONCLUSION: The node positivity rate in patients with T1 to T4 and N0 is 9%, much lower than reported in penile cancer with a high-risk primary tumor but clinically negative groins. This argues against routine prophylactic inguinal ILND in patients with urethral SCC who are clinically N0, perhaps suggesting different biological behavior of urethral SCC compared to penile SCC. Performing a lymph node dissection in patients with clinically N1 or N2 disease is associated with improved OS.
Primary malignant melanotic melanoma and hypomelanotic melanoma of the female urethra: case series and a review of the literature in China.
Melanoma Res. 2019; 29(1):59-64 [PubMed] Related Publications
Female Urethral Cavernous Hemangioma, A Rare Entity: Two Case Reports and Review of The Literature.
Urol J. 2019; 16(1):89-91 [PubMed] Related Publications
Treatment and outcomes of urethral recurrence after orthotopic neobladder replacement in patients with bladder cancer - practice in a single centre.
J Int Med Res. 2018; 46(9):3928-3937 [PubMed] Free Access to Full Article Related Publications
Lichen Sclerosus Accompanied by Urethral Squamous Cell Carcinoma: A Retrospective Study From a Urethral Referral Center.
Am J Mens Health. 2018; 12(5):1692-1699 [PubMed] Free Access to Full Article Related Publications
Optimizing the Role of Surgery and Radiation Therapy in Urethral Cancer Based on Histology and Disease Extent.
Int J Radiat Oncol Biol Phys. 2018; 102(2):304-313 [PubMed] Related Publications
METHODS AND MATERIALS: We performed a retrospective cohort study of patients who, between 2004 and 20013, received a diagnosis of T0-4N0-2 M0 urethral cancer. Local therapy was radiation therapy (RT), surgery (S), or S and RT (S+RT). The Cox proportional hazards model was used to assess the impact of therapy type on overall survival (primary endpoint). Subgroup analysis by extent of disease (early stage [T0-2 N0] vs locally advanced [T3+ or N+]) and histology was performed.
RESULTS: In our study, 2614 patients had a median follow-up of 28 months. Three-year overall survival was 54%. In 501 patients with locally advanced disease, S+RT was associated with improved survival versus S alone (hazard ratio [HR] 0.58; 95% confidence interval [CI], 0.42-0.80). There was no difference for patients with squamous cell carcinoma by treatment type, but patients with adenocarcinoma (RT vs S: HR 0.20; 95% CI, 0.07-0.60) or transitional cell carcinoma (S+RT vs S: HR 0.45, 95% CI, 0.26-0.77) had improved OS with RT as part of treatment. In 1705 early-stage patients, there was no association with survival when comparing S+RT versus S.
CONCLUSIONS: For patients with locally advanced disease and transitional cell carcinoma undergoing S, the addition of RT is associated with improved overall survival and should be considered. An RT-based approach may be preferred for adenocarcinoma, but there was no clear association with survival by therapy type for squamous cell carcinoma. This study is hypothesis generating; prospective trials are necessary.
Oral Propranolol in a Child With Infantile Hemangioma of the Urethra.
Urology. 2018; 122:165-168 [PubMed] Related Publications
Survival Outcomes Associated With Female Primary Urethral Carcinoma: Review of a Single Institutional Experience.
Clin Genitourin Cancer. 2018; 16(5):e1003-e1013 [PubMed] Related Publications
METHODS: Records of women with PUC referred to our multidisciplinary genitourinary oncology service between 2003 and 2017 were reviewed. Clinical, demographic, pathologic, primary and salvage therapy details, and overall (OS) and recurrence-free survival (RFS) were recorded. Survival outcomes were analyzed for the entire cohort, and cases of locally-advanced (≥ T2 tumor), non-metastatic PUC were evaluated according to treatment intensity. Multimodal treatment (cystourethrectomy + concomitant therapy) was compared with non-multimodal therapy. Contingency analyses and Kaplan-Meier estimates were performed.
RESULTS: Thirty-nine women with PUC were identified. In total, median OS was 36 months (95% confidence interval, 10.6-61.4 months). Twenty-four had T3 to T4 disease, 12 were node-positive, and 3 had distant metastases. Histology included 22 adenocarcinomas, 11 urothelial, 5 squamous, and 1 neuroendocrine. Patients with locally advanced, non-metastatic disease (n = 25) had significantly reduced OS (36 vs. 99 months; P = .016) and RFS (46 months vs. unmet; P = .011) compared with patients with locally confined tumors. Approximately one-half of locally advanced cases were managed with multimodal therapy (4 with neoadjuvant therapy + cystourethrectomy, 8 with cystourethrectomy + adjuvant therapy, and 1 with chemoradiation + consolidative cystourethrectomy). Multimodal therapy had nonsignificant longer OS (36 vs. 16 months) and RFS (58 vs. 16 months), P > .05.
CONCLUSIONS: Locally advanced female PUC has relatively poor survival outcomes. Although we observed a nonsignificant interval improvement in survival with multimodality therapy, the treatment paradigm is inconsistent. Because it is a rare disease, collaborative multi-institutional studies are needed.
Fibroepithelial polyp causing urethral obstruction: Diagnosis by cystourethrogram.
Clin Imaging. 2018 Sep - Oct; 51:164-167 [PubMed] Free Access to Full Article Related Publications
Penile squamous cell carcinoma with urethral extension treated with Mohs micrographic surgery.
Cutis. 2018; 101(4):E15-E18 [PubMed] Related Publications
Nuclear Factor-κB Promotes Urothelial Tumorigenesis and Cancer Progression via Cooperation with Androgen Receptor Signaling.
Mol Cancer Ther. 2018; 17(6):1303-1314 [PubMed] Related Publications
A rare case of primary female urethral adenocarcinoma: Columnar type with colonic adenocarcinoma features.
Indian J Pathol Microbiol. 2018 Jan-Mar; 61(1):127-130 [PubMed] Related Publications
Management of Inverted Papilloma During Holmium Laser Enucleation of the Prostate.
Urology. 2018; 116:e5-e6 [PubMed] Related Publications
Clear cell adenocarcinoma of the urethra with inguinal lymph node metastases: A rare case report and review of literature.
J Cancer Res Ther. 2018 Jan-Mar; 14(2):468-470 [PubMed] Related Publications
Skene duct adenocarcinoma in a patient with an elevated serum prostate-specific antigen level: a case report.
J Med Case Rep. 2018; 12(1):32 [PubMed] Free Access to Full Article Related Publications
CASE PRESENTATION: A 70-year-old Asian Japanese woman with a urethral tumor was referred to our hospital to undergo further examination. Biopsy specimens showed urethral adenocarcinoma that was positive for prostate-specific antigen. Her serum prostate-specific antigen level before surgery was 34.4 ng/ml. Urethral tumor resection with pelvic lymph node resection was performed. Her serum prostate-specific antigen level decreased to < 0.01 ng/ml after surgery.
CONCLUSIONS: We report a very rare case of Skene duct adenocarcinoma in a female patient with serum prostate-specific antigen elevation.
Tertiary Referral Hospital Experiences of Men Presenting With Painless Postcoital Gross Hematuria and a Suggestion for the Management Algorithm.
Urology. 2018; 115:112-118 [PubMed] Related Publications
MATERIALS AND METHODS: We reviewed clinical data from 19 male patients who first visited a clinic because of PCGH between 2009 and 2016. The patients were evaluated according to our tentative management algorithm for painless PCGH. First, a general workup for painless gross hematuria (GH) was performed. If the cause of the PCGH was not identified, a vascular workup of the pelvic vasculatures for PCGH was performed, including transrectal and penile ultrasonography with Doppler study. Pelvic angiography and subsequent angioembolization were recommended at the physician's discretion.
RESULTS: The median age of the patients was 47 (range: 30-67) years. The tentative management algorithm led to no abnormal findings in 7 patients and identified urologic malignancies in 2 patients. Urethrocystoscopy revealed urethral hemangioma in 3 patients. Doppler ultrasonography revealed pelvic varicosities in 3 patients, complicated cyst of Cowper glands in 1 patient, and pelvic arteriovenous malformation in 3 patients. Pelvic angiography was recommended for the 3 patients with pelvic arteriovenous malformation, and 2 of those patients were successfully treated by angioembolization.
CONCLUSION: The clinical approach to painless PCGH should be different from that of painless GH. Both the general and the vascular workup for the pelvic vasculatures for painless GH are mandatory for the evaluation of patients with painless PCGH.
A Comprehensive Review of US FDA-Approved Immune Checkpoint Inhibitors in Urothelial Carcinoma.
J Immunol Res. 2017; 2017:6940546 [PubMed] Free Access to Full Article Related Publications
Outcomes of subsequent non-muscle-invasive bladder cancer treated with intravesical Bacillus Calmette-Guérin after radical nephroureterectomy for upper urinary tract urothelial carcinoma.
BJU Int. 2018; 121(5):764-773 [PubMed] Related Publications
PATIENTS AND METHODS: An observational study was conducted in 1463 patients with UTUC who had undergone RNU and in 1555 patients with primary NMIBC. Of the 1463 patients with UTUC, 256 (17%) subsequently developed NMIBC (UTUC-NMIBC group) and were available for the analysis. The clinicopathological background and outcomes, including intravesical recurrence-free survival and bladder progression-free survival, were compared between the patients with UTUC-NMIBC and the patients with primary NMIBC treated with intravesical BCG. Propensity score matching was performed to adjust for the potential differences in the backgrounds of the two groups. To validate the utility of the CUETO scoring model in the UTUC-NMIBC group, risk scores were calculated and compared with the published probabilities for recurrence and progression.
RESULTS: Compared with the unadjusted primary NMIBC group (n = 352), the UTUC-NMIBC group (n = 75) were found to have a worse prognosis for intravesical recurrence and progression, before propensity score matching. After propensity score matching for potential confounding factors, however, a worse prognosis was observed only for intravesical recurrence. The validation test of the CUETO scoring model for the UTUC-NMIBC group showed a significant difference in the rate of intravesical recurrence and progression for the 0-4 and 5-6 score groups between the UTUC-NMIBC group and the CUETO risk table reference data.
CONCLUSION: Compared with the primary NMIBC group, the UTUC-NMIBC group had a worse prognosis after intravesical BCG, especially with regard to intravesical recurrence. This suggests that patients with UTUC-NMIBC are inherently poor responders to BCG exposure. An optimal treatment strategy and risk scoring model to select patients for adjuvant intravesical BCG, chemotherapy or immediate radical cystectomy should be established.
Organ Preservation for Recurrent Urethral Adenocarcinoma With Concurrent Chemotherapy and Radiation.
Urology. 2018; 113:e1-e2 [PubMed] Related Publications
Female Urethra Adenocarcinoma.
Clin Genitourin Cancer. 2018; 16(2):e263-e267 [PubMed] Related Publications
The prognostic effect of salvage surgery and radiotherapy in patients with recurrent primary urethral carcinoma.
Urol Oncol. 2018; 36(1):10.e7-10.e14 [PubMed] Related Publications
PATIENTS: A series of 139 patients (96 men, 43 women; median age = 66, interquartile range: 57-77) were diagnosed with PUC at 10 referral centers between 1993 and 2012. The modality of ST of recurrence (salvage surgery vs. radiotherapy) was recorded. Kaplan-Meier analysis with log-rank was used to estimate the impact of ST on OS (median follow-up = 21, interquartile range: 5-48).
RESULTS: The 3-year OS for patients free of any recurrence (I), with solitary or concomitant urethral recurrence (II), and nonurethral recurrence (III) was 86.5%, 74.5%, and 48.2%, respectively (P = 0.002 for I vs. III and II vs. III; P = 0.55 for I vs. II). In the 80 patients with recurrences, the modality of primary treatment of recurrence was salvage surgery in 30 (37.5%), salvage radiotherapy (RT) in 8 (10.0%), and salvage surgery plus RT in 5 (6.3%) whereas 37 patients did not receive ST for recurrence (46.3%). In patients with recurrences, those who underwent salvage surgery or RT-based ST had similar 3-year OS (84.9%, 71.6%) compared to patients without recurrence (86.7%, P = 0.65), and exhibited superior 3-year OS compared to patients who did not undergo ST (38.0%, P<0.001 compared to surgery, P = 0.045 to RT-based ST, P = 0.29 for surgery vs. RT-based ST).
CONCLUSIONS: In this study, patients who underwent ST for recurrent PUC demonstrated improved OS compared to those who did not receive ST and exhibited similar survival to those who never developed recurrence after primary treatment.
Secondary Urethral Malignancies Following Prostate Brachytherapy.
Urology. 2017; 110:172-176 [PubMed] Related Publications
PATIENTS AND METHODS: Institutional retrospective review identified 13 patients evaluated from 2003 to 2014 with urethral cancer and history of BRT monotherapy for prostate cancer. All patients were biochemically free of their primary disease and radiation-associated secondary malignancies (RASMs) were confirmed pathologically to be histologically distinct from primary tumor. BRT characteristics, patient age, presentation, staging workup, and clinical course were evaluated.
RESULTS: The mean time from BRT to presenting symptoms of hematuria, urinary retention, and/or renal failure was 71 months. Symptom onset to RASM diagnosis interval was 24 months. Mean time from BRT to RASM diagnosis was 95 months. Eighty-five percent of patients had an undetectable prostate-specific antigen level (<0.2 ng/mL) at last follow-up. Types of RASM included sarcomatoid carcinoma (6), small cell carcinoma (2), urothelial carcinoma with squamous differentiation (2), squamous cell carcinoma (1), rhabdomyosarcoma (1), and urothelial carcinoma (1). A majority of patients were diagnosed with advanced disease with either distant metastases (54%) or local progression (23%). Ten patients died during this study period with median time to death after RASM diagnosis of 6 months.
CONCLUSION: RASMs localized to the posterior urethra displayed advanced disease and high mortality rates. Refractory lower urinary tract symptoms, hematuria, and history of prostate BRT should raise suspicion for urethral RASMs. Further studies are warranted to determine patient and disease characteristics that correlate with disease-specific mortality of secondary urethral malignancies.
Skene's gland adenocarcinoma with intestinal differentiation: A case report and literature review.
Pathol Int. 2017; 67(11):575-579 [PubMed] Related Publications
Carcinoma of the urethra.
Hum Pathol. 2018; 72:35-44 [PubMed] Free Access to Full Article Related Publications