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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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Urinary System Cancers

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    MeSH term: Urethral Neoplasms
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Latest Research Publications

This list of publications is regularly updated (Source: PubMed).

Hansen MF, Abel I, Clasen-Linde E
Primary malignant melanoma of the urethra in a patient with rheumatoid arthritis treated with methotrexate.
BMJ Case Rep. 2019; 12(4) [PubMed] Related Publications
We report a case of a 79-year-old woman with urinary incontinence who presented at a urogynaecology appointment. Her medical history included rheumatoid arthritis (RA) treated with methotrexate (MXT) for 22 years. A polypoidal lesion was protruding from the meatus urethrae. The histoimmunocytology confirmed a primary superficial spreading malignant melanoma. The tumour was extensively excised, but 8 months later, due to a lymphatic nodal swelling, a positron emission tomography/CT was performed showing a process suspicious of malignant melanoma and multiple distant metastasis. The subsequent treatment was palliative and 1 year later, the patient died. The aetiology of malignant melanomas in the urethra is poorly understood. There is consistent evidence that RA is associated with a number of cancers, but it remains controversial whether this risk is increased with MXT. This case emphasises the importance of gynaecological examination even in patients with only weak symptoms from the pelvic region, especially in patients undergoing immunosuppressive treatment.

Palmisano F, Lorusso V, Spinelli MG, et al.
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
Primary urethral lymphoma is a rare entity without a standardized treatment protocol. We report a case of an elderly woman presenting with a caruncle associated with vaginal spotting and intermittent dysuria. She underwent surgical excision of the lesion. Histological analysis revealed a blastoid variant of mantle cell lymphoma, a previously unreported subtype. The patient received chlorambucil assisting a rapid local disease progression. She died of disseminated disease 6 months after diagnosis. A review of the lymphomas of the urethra is included.

Raison N, McGovern U, Hines J, Volanis D
Mixed adenoneuroendocrine carcinoma of the urethra.
BMJ Case Rep. 2019; 12(3) [PubMed] Related Publications
Mixed adenoneuroendocrine carcinoma (MANEC) is a rare tumour found predominantly in the gastrointestinal tract. Comprising adenocarcinomatous and neuroendocrine components, MANEC have been reported in the bladder. We report the first case to our knowledge of a MANEC arising in the urethra. A 62-year-old woman presented with a suburethral mass. Initial excision of the mass revealed it to be a MANEC. Immunohistochemistry staining was positive for CK20 and synaptophysin associated with neuroendocrine tumours. Cross-sectional imaging ruled out metastases and the patient underwent radical urethrectomy, vaginal reconstruction and Mitrofanoff urinary diversion. The patient declined adjuvant chemotherapy and remained under regular surveillance. MANECs are uncommon tumours and treatment was therefore guided by expert opinion. A multidisciplinary approach is essential with the early involvement of surgeons, oncologists, histopathologist, radiologist and neuroendocrine specialists.

Roth B, Furrer MA, Giannakis I, et al.
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
PURPOSE: We investigated the influence of positive pre-cystectomy biopsies of the prostatic urethra in males and the bladder neck in females on urethral recurrence, cancer specific and overall survival, and functional outcomes after orthotopic bladder substitution.
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.

Davuluri M, Long B, Semple S, et al.
Primary Urethral Melanoma: A Case Report and Literature Review.
Urology. 2019; 126:1-4 [PubMed] Related Publications
Patients with localized urethral melanoma have a high risk of recurrence and poor disease-specific survival. Multi-disciplinary approach including surgery, radiation therapy, and chemotherapy/immunotherapy is needed to maximize survival. Current research efforts include investigation of novel tyrosine kinases as well as the combination of targeted therapies with immunotherapies in this population. Combinations may provide a synergistic effect to overcome various obstacles to disease response.

Antwerpen I, Gstrein L, Moskovszky L, et al.
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
This case report describes a unique manifestation of a primary urethral squamous cell carcinoma (SCC) as the underlying pathology in an 80-year-old male patient who underwent partial penectomy due to an enlarging penile mass. Persistent pain in the right knee was discovered to be a pathologic fracture using magnetic resonance imaging. Computed tomography-guided biopsy confirmed metastatic SCC. Whole-body positron emission tomography revealed systemic dissemination to multiple sites. Orthopedic knee replacement was performed in combination with local radiotherapy. Palliative chemotherapy was rejected due to poor performance status. Primary urethral SCC is rare and an uncommon cause of advanced penile cancer. These findings could be of great interest to clinicians for two reasons. First, a tumor's appearance can be misleading. Consequently, histological work-up in accordance with clinical guidelines is necessary for accurate diagnosis. Second, a more comprehensive investigation is required when clinical symptoms persist despite the use of conventional treatment. Our case is an instance in which persistent pain masked the presence of downstream metastasis. We believe that these aforementioned points are of significant clinical importance and present a salient learning opportunity.

Werntz RP, Riedinger CB, Fantus RJ, et al.
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
INTRODUCTION: Urethral squamous cell cancer is a rare disease with limited clinical recommendations regarding management of the inguinal lymph nodes. Despite the similarities to penile cancer in terms of squamous cell carcinoma (SCC) histology and lymphatic drainage, there is not enough evidence to recommend for or against a prophylactic inguinal lymph node dissection (ILND) in patients with clinically negative groins and a primary tumor stage of T1b or higher. The objective of the study was to identify the rate of prophylactic inguinal lymph node dissection, node positive rate, and overall survival in patients with clinical T1 to T4 stage. The patients were separated into clinical N stage and the rates of node positivity were compared. We hypothesize that the node positivity rate would be similar to that observed in penile cancer of similar clinical T and N stage and provide evidence for prophylactic inguinal lymph node dissection in urethral squamous cancer. We also sought to determine the value of ILND in clinically node positive (cN+) and clinically node negative (cN-) patients.
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.

Yang N, Lu J, Lu Y, et al.
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
The incidence of primary malignant melanoma (MM) of female urethra is extremely low, leading to paucity of recommendations on management. The objectives of our study were to gain more insight into the clinical features, diagnosis, treatment, and prognosis of this rare type of tumor. We carried out a retrospective analysis of all four cases who underwent an operation in our hospital since 1980. Moreover, other 32 cases of MM that have been reported in Chinese papers were also included for further review. The age of the patients ranged from 38 to 81 years. A mass in the urethral meatus and hematuria are common presentations. The final diagnosis depends on histopathological examination. After surgery alone or combined with chemotherapy/radiotherapy/immunotherapy, all cases were followed for 1-151 months, whereas only one lived for more than 4 years after receiving the diagnosis. A timely and accurate diagnosis of MM is critical, especially for hypomelanotic and amelanotic cases. Immunohistochemical staining and electron microscopy are necessary for a precise diagnosis in some cases. Extensive resection, early chemotherapy, and immunotherapy may help to improve survival.

Sharifiaghdas F, Mahmoudnejad N, Rostaminezhad N, Parvin M
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
Genitourinary hemangiomas are very rare. To our knowledge few cases of female urethral hemangiomas have been reported and presenting cases are the first reports in Iran.They should be considered as differential diagnosis of any female patient with microscopic or gross hematuria or bloody urethral discharge, especially when other parts of urinary system are radiologically intact. Thorough physical examination of genital area is highly recommended in order not to miss any urethral lesions. Herein we report two cases of female urethral cavernous hemangioma, their management and a review of literature.

Zhou X, Ji H, Zhang H, et al.
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
Objectives To report on the treatment of urethral recurrence after orthotopic urinary diversion at our institution. Methods We retrospectively reviewed clinical information of urethral recurrence in patients who underwent radical cystectomy and orthotopic urinary diversion between January 1998 and January 2013. Results Of 341 patients, 282 presented for follow-up (median follow-up: 56 months; range: 1-174 months). Eight patients developed local recurrence of urothelial cancer after radical cystectomy. The rate of urethral recurrence (1.4%) in female patients who underwent orthotopic urinary diversion was lower than in male patients (3.3%). The median (range) time to recurrence was 33 (6-120) months after radical cystectomy and orthotopic urinary diversion. Recurrences were treated by transurethral resection of tumour, urethrectomy, neobladder resection, revision of urinary diversion, adjuvant chemotherapy, or radiation therapy, based on individual circumstances. Survival analysis showed that 5-year cancer-specific survival was significantly higher in patients with urethral recurrence alone (83.3%), compared with patients with other recurrences, including pelvic/abdomen recurrence and distant metastasis (26.8%). Conclusions En bloc urethrectomy and revision of urinary diversion remain the principle surgical choices. Selection of transurethral tumour resection was based on tumour stage and was used in carefully chosen patients. Cancer-specific survival might depend on multidisciplinary therapy.

Guo H, Peng X, Jin C, et al.
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
To evaluate the characteristics of lichen sclerosus (LS) accompanied by urethral squamous cell carcinoma (USCC) and to raise urologists' awareness about the early management of LS, a retrospective analysis was performed on the clinical features, diagnosis, treatment, and prognosis of 18 male genital LS accompanied by USCC patients who were referred to Shanghai Sixth People's Hospital between June 2000 and August 2014. All of the patients had a long-term history of LS, urethral strictures, and urethral dilatation. Seven patients are with distal (glanular or penile) USCC, 10 patients with proximal USCC, and one with entire USCC. The most common presentation, except for LS and urethral strictures, was periurethral abscess, followed by extraurethral mass, pelvic pain, urethrocutaneous fistula, hematuria, and bloody urethral discharge. All had primary surgical excision that was adapted to tumor location and extension. All of the USCC were positive for P53 and Ki-67. P16 was positive in four cases of human papillomavirus (HPV)-associated USCC and negative in 14 cases of HPV-independent USCC. Patients with distal USCC had a significant longer survival time than proximal USCC ( p < .05). LS should be treated early to prevent the disease progression. LS probably has some associations with USCC. Distal USCC has a relatively better prognosis than proximal USCC.

Son CH, Liauw SL, Hasan Y, Solanki AA
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
PURPOSE: Urethral cancer is rare, with limited data guiding treatment. A national hospital-based registry was used to evaluate the role of local therapy in these patients.
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.

Itesako T, Eura R, Okamoto Y, et al.
Oral Propranolol in a Child With Infantile Hemangioma of the Urethra.
Urology. 2018; 122:165-168 [PubMed] Related Publications
Infantile hemangiomas (IH) are the most common in the head and neck region.

Peyton CC, Azizi M, Chipollini J, et al.
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
BACKGROUND: Primary urethral carcinoma (PUC) is rare, and standard treatment recommendations are lacking. We examined the variation in treatments and survival outcomes of female PUC at a single, tertiary referral cancer center.
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.

Ballard DH, Rove KO, Coplen DE, et al.
Fibroepithelial polyp causing urethral obstruction: Diagnosis by cystourethrogram.
Clin Imaging. 2018 Sep - Oct; 51:164-167 [PubMed] Free Access to Full Article Related Publications
Fibroepithelial polyps of the urethra are rare benign tumors that predominantly affect males in childhood or adolescence. In this report, we present a case of a 3-year-old boy in acute urinary retention with a urethral fibroepithelial polyp manifesting as a large filling defect on voiding cystourethrogram and successfully managed endoscopically with transurethral resection.

Nadimi AE, Hendi A
Penile squamous cell carcinoma with urethral extension treated with Mohs micrographic surgery.
Cutis. 2018; 101(4):E15-E18 [PubMed] Related Publications
Penile squamous cell carcinoma (SCC) with considerable urethral extension is uncommon and difficult to manage. It often is resistant to less invasive and nonsurgical treatments and frequently results in partial or total penectomy, which can lead to cosmetic disfigurement, functional issues, and psychological distress. We report a case of penile SCC in situ with considerable urethral extension with a focus of cells suspicious for moderately well-differentiated and invasive SCC that was treated with Mohs micrographic surgery (MMS). A review of the literature on penile tumors treated with MMS also is provided.

Inoue S, Ide H, Mizushima T, et al.
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
We investigated the role of NF-κB in the development and progression of urothelial cancer as well as cross-talk between NF-κB and androgen receptor (AR) signals in urothelial cells. Immunohistochemistry in surgical specimens showed that the expression levels of NF-κB/p65 (

Gangadhar P, Pai MR, Sandhya I
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
Female urethral carcinoma is extremely rare and accounts for 0.02% of all women's cancers and <1% of cancers in the female genitourinary tract. Adenocarcinoma accounts for only 10% of urethral carcinomas in females. Due to their location, presentation is usually late and tumors are often missed on physical examination. As in this case, nonspecific symptoms in the early stages may delay the diagnosis in most patients. Herein, we present an extremely rare case of the columnar type of primary female urethral adenocarcinoma exhibiting colonic adenocarcinoma features which to the authors' best knowledge has not been reported to date. The present study emphasizes the importance of a careful clinical examination and also highlights the role of imaging studies, and biopsy in making an accurate preoperative diagnosis of this rare disease. The disease may have devastating sequelae due to local and metastatic involvement if not recognized and treated earlier.

Tzou DT, Cadwell C, Simko JP, et al.
Management of Inverted Papilloma During Holmium Laser Enucleation of the Prostate.
Urology. 2018; 116:e5-e6 [PubMed] Related Publications
Inverted papilloma of the prostatic urethra is an especially rare finding. A 75-year-old man with urinary retention wished to proceed with a holmium laser enucleation of the prostate (HoLEP) and was found to have a mass arising from his prostate vs bladder on preoperative imaging. Cystourethroscopy revealed the mass arising from the median lobe of the prostate. After transurethral resection and frozen analysis confirmed the benign pathology of an inverted papilloma, the patient subsequently underwent a successful HoLEP during the same surgical setting. Images of this rare prostatic mass are presented to increase urologist recognition and to assist management during HoLEP.

Mallya V, Mallya A, Gayathri J
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
Urethral cancer is a rare malignancy with urothelial subtype being the most common followed by adenocarcinoma. In women, the usual presentation is urinary retention and hematuria. Clear cell variety of adenocarcinoma is a rarer entity which usually has a better prognosis than other variants. Lymph node metastasis is seen in about 30% of urethral cancers. Histopathological differential diagnosis includes Skene gland carcinoma and nephrogenic adenoma. Herein, we present a 58-year-old female patient who presented for evaluation of lymph node mass in the inguinal region. The detailed evaluation revealed clear cell adenocarcinoma of the urethra as the primary with lymph node metastasis.

Tsutsumi S, Kawahara T, Hattori Y, et al.
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
BACKGROUND: Female urethral carcinoma is a very rare disease that accounts for 0.02% of malignant diseases in female patients.
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.

Kang DH, Lee JY, Jung DC, et al.
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
OBJECTIVE: To review the tertiary referral hospital experiences of men presenting with painless postcoital gross hematuria (PCGH) and suggest a management algorithm.
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.

Hsu FS, Su CH, Huang KH
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
Few effective treatment options are available for patients with advanced or metastatic urothelial carcinoma (UC) after unsuccessful first-line platinum-based chemotherapy. To date, immune checkpoint inhibitors are novel therapeutic agents for UC treatment. From May 2016 to May 2017, five anti-PD-1/PD-L1 monoclonal antibodies received accelerated or regular approval from the US Food and Drug Administration (FDA) for the treatment of patients with locally advanced or metastatic UC. The present comprehensive review presents the background information of these five US FDA-approved anticancer agents to provide a basic but concise understanding of these agents for advanced studies. We summarize their immune checkpoint mechanisms, clinical efficacy, recommended usage protocols, adverse events, and the limitations of the PD-L1 biomarker assays.

Miyake M, Tatsumi Y, Matsumoto H, et al.
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
OBJECTIVES: To describe the clinicopathological characteristics and prognosis of subsequent non-muscle-invasive bladder cancer (NMIBC) after radical nephroureterectomy (RNU) for upper urinary tract urothelial carcinoma (UTUC), and particularly its response to intravesical Bacillus Calmette-Guérin (BCG).
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.

Mendiratta P, Rini BI, Tendulkar RD
Organ Preservation for Recurrent Urethral Adenocarcinoma With Concurrent Chemotherapy and Radiation.
Urology. 2018; 113:e1-e2 [PubMed] Related Publications
Urethral adenocarcinoma of males is a rare disease with limited prospective data to define optimal treatment. Surgical excision remains the primary treatment for early-stage disease. Multimodality therapy with a combination of chemotherapy, radiation, or surgery has been explored in patients with locally advanced disease. We present the case of a 45-year-old-man with a locally recurrent urethral adenocarcinoma after initial surgical resection managed successfully with combined weekly cisplatinum and radiation therapy.

Dell'Atti L, Galosi AB
Female Urethra Adenocarcinoma.
Clin Genitourin Cancer. 2018; 16(2):e263-e267 [PubMed] Related Publications
Female urethra adenocarcinoma (FUA) is a rare aggressive tumor that occurs in Skene ducts and glands. It is associated with a relatively poor prognosis. The aim of this review was to evaluate FUA in terms of epidemiology, risk factors, diagnosis, natural history of disease, modalities of treatment, and outcomes. These tumors are usually large masses, which typically spread through the lymphatic system. Patients present with vague symptoms similar to urinary tract infections. Cystourethroscopy permits visualization of the urethral tumor and allows biopsies to be performed to remove samples for histologic examination. Magnetic resonance imaging is recommended for tumor staging. Local, superficial, and distal urethral tumors may be treated by partial resection with preservation of the urethra. Radical urethrectomy with wide, comprehensive resection of the paraurethral tissues and anterior vaginal wall may offer superior local control for this disease. Advanced FUA and lymph node positivity are associated with poor prognosis for all survival outcomes (recurrence-free, cancer-specific, and overall survival). Multimodal therapy including surgery, chemotherapy, and radiotherapy is required in the modern management of FUA, although the specific role and combination of each treatment is less clearly determined. Wide resection after chemotherapy and/or radiotherapy is associated with the best local control, but it reduces quality of life.

Gakis G, Schubert T, Morgan TM, et al.
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
BACKGROUND: To evaluate the impact of salvage therapy (ST) on overall survival (OS) in recurrent primary urethral cancer (PUC).
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.

Agrawal S, Lacy JM, Bagga H, et al.
Secondary Urethral Malignancies Following Prostate Brachytherapy.
Urology. 2017; 110:172-176 [PubMed] Related Publications
OBJECTIVE: To understand urethral secondary malignancies among patients treated with brachytherapy (BRT) for primary prostate cancer.
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.

Muto M, Inamura K, Ozawa N, et al.
Skene's gland adenocarcinoma with intestinal differentiation: A case report and literature review.
Pathol Int. 2017; 67(11):575-579 [PubMed] Related Publications
Adenocarcinoma of Skene's gland (the female homolog to the male prostate) is extremely rare, with only a few cases reported. We present a case of Skene's gland adenocarcinoma with intestinal differentiation. The patient was a 69-year-old Japanese woman who was operated on for a recurrent tumor of the external ostium of the urethra. Histopathologically, the tumor showed glandular and cribriform patterns with a signet-ring cell component in a mucus lake. Immunohistochemically, the tumor cells were positive for prostate specific acid phosphatase (PSAP), and AMACR, and negative for Nkx3.1 or prostate specific antigen (PSA). Although in situ lesion could not be discovered, positive immunostainings for Nkx3.1, PSAP, and androgen receptor in the remaining paraurethral glands around the tumor indirectly but strongly suggest that the tumor had originated from Skene's gland. This tumor also showed intestinal differentiation as suggested histologically and by positive immunostainings for CDX2, MUC2, and CK20, along with negative immunostaining for CK7. It is often very difficult to identify the origin of a female urethral carcinoma. In such cases, immunohistochemical features can be an essential clue to the origin. We therefore present this instructive case with a literature review.

Zhang M, Adeniran AJ, Vikram R, et al.
Carcinoma of the urethra.
Hum Pathol. 2018; 72:35-44 [PubMed] Free Access to Full Article Related Publications
Primary carcinomas of the urethra are rare and poorly understood lesions; hence, their clinical and pathologic spectrum is not completely defined. We analyzed a series of 130 primary urethral tumors and classified 106 of them as primary urethral carcinomas. The age at diagnosis of patients with primary urethral carcinomas ranged from 42 to 97 years (mean, 69.4 years; median, 70 years). There were 73 male and 33 female patients with a ratio of 2.2:1. In male patients, the tumors most frequently developed in the bulbous-membranous segment of the urethra. In female patients, the entire length of the urethra was typically involved. Microscopically, they were poorly differentiated carcinomas with hybrid squamous and urothelial features and developed from precursor intraepithelial conditions such as dysplasia and carcinoma in situ, which were frequently present in the adjacent urethral mucosa. High-risk human papilloma virus infection could be documented in 31.6% of these tumors. Follow-up information was available for 95 patients. Twenty-three patients died of the disease with a mean and median survival of 39 and 21 months, respectively. Urethral carcinomas are aggressive tumors with a high propensity for regional and distant metastases with mean and median survival of 39 and 21 months, respectively. Our observations have important implications for the management of patients with primary carcinoma of the urethra by defining them as a unique entity linked to human papilloma virus infection.

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