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Primary urethral carcinoma (PUC) is a rare disease with frequent nodal metastasis at the time of diagnosis. Few risk factors have been established and overall prognosis remains poor. As of now, no clear therapeutic guidelines are established and management of advanced PUC often involves surgery which can have negative functional and psychological outcomes for the patient. Few authors have already reported the use of chemoradiotherapy alone to avoid surgery with some good short-term results. We report the case of a 48-year-old woman with advanced high-grade urothelial carcinoma of distal urethra associated to bilateral inguinal nodal metastasis. She was similarly and successfully treated using chemoradiotherapy exclusively without significant adverse effects. This experience reinforces benefits of a surgery-sparing management, when possible, as recommended in current guidelines.

Primary urethral carcinoma (PUC) is a rare disease with frequent nodal metastasis at the time of diagnosis. Few risk factors have been established and overall prognosis remains poor. As of now, no clear therapeutic guidelines are established and management of advanced PUC often involves surgery which can have negative functional and psychological outcomes for the patient. Few authors have already reported the use of chemoradiotherapy alone to avoid surgery with some good short-term results. We report the case of a 48-year-old woman with advanced high-grade urothelial carcinoma of distal urethra associated to bilateral inguinal nodal metastasis. She was similarly and successfully treated using chemoradiotherapy exclusively without significant adverse effects. This experience reinforces benefits of a surgery-sparing management, when possible, as recommended in current guidelines. [ABSTRACT FROM AUTHOR]

Primary urethral carcinoma (PUC) has rarely been reported, notably with variant histology. The present case reports a 68-year-old male patient with a 3-month history of difficulty voiding urine accompanied by a burning sensation in the urinary tract and hematuria. Urethrography and computed tomography (CT) indicated a mass localized in the urethral bulb. A fine needle biopsy revealed the mass to be a malignant tumor of the urethra. Partial penectomy was eventually performed and postoperative histopathological examination confirmed that the lesion was PUC, with mixed characteristics of urothelial and squamous differentiation. The patient was postoperatively followed up and at 9 months, a repeat CT scan revealed local recurrence and metastases. The patient rejected further treatment and eventually succumbed to the disease three months later. The present case report demonstrates an example in which urothelial and squamous differentiation simultaneously exist in the pathological report. The clinical features, diagnosis and treatment status of PUC were also summarized and analyzed to improve the clinical understanding of this unique disease. [ABSTRACT FROM AUTHOR]

Abstract Background Primary urethral carcinoma (PUC) is a rare genitourinary malignancy with a relatively poor prognosis. The aim of this study was to examine the impact of surgery on survival of patients diagnosed with PUC. Methods A total of 1544 PUC patients diagnosed between 2004 and 2016 were identified based on the SEER database. The Kaplan-Meier estimate and the Fine and Gray competing risks analysis were performed to assess overall survival (OS) and cancer-specific mortality (CSM). The multivariate Cox regression model and competing risks regression model were used to identify independent risk factors of OS and cancer-specific survival (CSS). Results The 5-yr OS was significantly better in patients who received either local therapy (39.8%) or radical surgery (44.7%) compared to patients receiving no surgery of the primary site (21.5%) (p

Primary urethral carcinoma (PUC) is exceedingly uncommon and accounts for 0.02 % of all female cancers and <1 % of female genitourinary tract malignancy. PUC in female usually presents late with a higher disease stage and, hence, has higher cancer-specific mortality. Due to its rarity, the current recommendation for the management of PUC is still unclear. This study reports two rare cases of 59-year-old and 65-year-old women with PUC, presenting with chief complaint of hematuria. Urethrocystoscopy and biopsy were performed. Pathology results revealed mucinous adenocarcinoma (AC) and urothelial carcinoma (UC) of the urethra, respectively. Radiological imaging was conducted for staging. Both were diagnosed with cT4N2M0. The first patient underwent anterior pelvic exenteration with bilateral ureterocutaneoustomy (UCS), while the second patient received cisplatin-based chemotherapy before the surgery. Radiological follow-up was planned 3 months after the surgery. Both mucinous AC and UC are considered incredibly unusual subtypes, with no defined treatment guidelines. Anterior exenteration with or without neoadjuvant chemotherapy may be opted for advanced PUC affecting the proximal urethra and adjacent organs. Following the previous studies, in this case series, both patients (locally advanced) underwent anterior exenteration. Additionally, the UC subtype received multimodal treatment with neoadjuvant chemotherapy which was shown to improve overall survival. In conclusion, PUC is extremely rare, and the choice of management remained various. Long-term follow-up for these patients is mandatory to improve understanding of this incredibly uncommon disease. • PUC is very scarce, accounting for 0.02 % of all female cancers. • The current treatment for primary urethral carcinoma is still uncertain. • Multimodal treatment is preferred in locally-advanced since it increases OS. • In this case, both underwent anterior exenteration and neoadjuvant chemotherapy. • Long-term follow-up is necessary to better understanding of this rare cancer. [ABSTRACT FROM AUTHOR]

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• Unmarried status was associated with an increased risk of locally advanced stage. • Unmarried female PUC patients more frequently harbored advanced stage at presentation. • Unmarried status was associated with lower rates of bi-/trimodal therapy. • Unmarried male PUC patients less likely to benefit from bi-/trimodal therapy. Unmarried status has been associated with advanced stage at presentation and lower treatment dose intensification rates in several urological and non-urological malignancies. However, no previous investigators focused of the association of unmarried status with locally advanced stage (T 3-4 N 0-2) at presentation and lower bi-/trimodal therapy rates in primary urethral carcinoma (PUC) patients. To address these knowledge gaps, we relied on the Surveillance, Epidemiology, and End Results (SEER) database. Within the SEER database 2000 to 2020, all non-metastatic PUC patients were identified. Logistic regression models (LRMs) tested for differences in stage at presentation and treatment modality in the overall cohort and then in a sex-specific fashion, according to marital status (married vs unmarried). Of all 1,430 non-metastatic PUC patients, 1,004 (70%) were male vs 426 (30%) were female. Of 1,004 male PUC patients, 272 (27%) were unmarried. Of all 426 female PUC patients, 239 (56%) were unmarried. In multivariable LRMs predicting T 3-4 N 0-2 , unmarried status was independently associated with an increased risk of locally advanced stage at presentation in the overall cohort (odds ratio [OR]:1.31; P = 0.03) and in female patients (OR:1.62; P = 0.02), but not in male PUC patients (P = 0.6). In multivariable LRMs predicting bi-/trimodal therapy, unmarried status was an independent predictor of lower bi-/trimodal therapy rates in the overall cohort (OR:0.73; P = 0.02) and in male patients (OR:0.60; P = 0.007), but not in female PUC patients (P = 0.6). Unmarried female PUC patients more likely harbored locally advanced stage at presentation. Conversely, unmarried male PUC patients are less likely to benefit from bi-/trimodal therapy. [ABSTRACT FROM AUTHOR]

Background: Primary urethral carcinoma (PUC) is a rare genitourinary malignancy with a relatively poor prognosis. The aim of this study was to examine the impact of surgery on survival of patients diagnosed with PUC.Methods: A total of 1544 PUC patients diagnosed between 2004 and 2016 were identified based on the SEER database. The Kaplan-Meier estimate and the Fine and Gray competing risks analysis were performed to assess overall survival (OS) and cancer-specific mortality (CSM). The multivariate Cox regression model and competing risks regression model were used to identify independent risk factors of OS and cancer-specific survival (CSS).Results: The 5-yr OS was significantly better in patients who received either local therapy (39.8%) or radical surgery (44.7%) compared to patients receiving no surgery of the primary site (21.5%) (p < 0.001). Both local therapy and radical surgery were each independently associated with decreased CSM, with predicted 5-yr cumulative incidence of 45.4 and 43.3%, respectively, compared to 64.7% for patients receiving no surgery of the primary site (p < 0.001). Multivariate analyses demonstrated that primary site surgery was independently associated with better OS (local therapy, p = 0.037; radical surgery, p < 0.001) and decreased CSM (p = 0.003). Similar results were noted regardless of age, sex, T stage, N stage, and AJCC prognostic groups based on subgroup analysis. However, patients with M1 disease who underwent primary site surgery did not exhibit any survival benefit.Conclusion: Surgery for the primary tumor conferred a survival advantage in non-metastatic PUC patients. [ABSTRACT FROM AUTHOR]

Male primary urethral urothelium carcinoma is a rare clinical case. Here, we detail a case of a 58-year-old man with primary urothelium carcinoma of the distal urethra treated in our hospital. The patient with a neoplasm inside the external urethral orifice for 2 years, which was previously diagnosed as condyloma acuminata, had received photodynamic therapy for 3 times, with initial symptoms of urinary stream bifurcation and dysuria. The exfoliative urine cytology showed negative. Cystoscopy showed a tumor growing around the distal urethra. Biopsy and immunohistochemistry revealed high-grade papillary urothelium carcinoma. The patient received partial urethrectomy, followed by urinary bladder irrigation chemotherapy with epirubicin postoperatively. The corpus spongiosum was invaded while the corpus cavernosa were not. Postoperative pathological examination showed high-grade invasive urothelium carcinoma. There is no evidence of tumor recurrence, metastasis or surgical complications during a 61-month follow-up period. Male primary urethral urothelium carcinoma is a rare clinical case with particular clinical and pathological characteristics. There are still no established treatment guidelines and should be studied further. [ABSTRACT FROM AUTHOR]

Background: Our aim was to identify the independent prognostic factors in patients with primary urethral carcinoma (PUC) and to predict their overall survival (OS) and cancer-specific survival (CSS) at 3, 5, and 8 years. Methods: Patients with PUC identified in the Surveillance, Epidemiology, and End Results (SEER) database were divided into training and validation cohorts. Nomograms were constructed based on the results of Cox regression analysis. The predictive performance of each nomogram was evaluated using the consistency index (C-index), the area under the receiver operating characteristics curve (AUC), and calibration plots. Decision-curve analysis (DCA) was used to test the clinical value of the predictive models. Results: Our study screened 822 patients with PUC. Multivariate analysis showed that the age at diagnosis, race, histology, American Joint Committee on Cancer (AJCC) stage, and surgery status were independent prognostic factors for CSS and age at diagnosis, race, histology, AJCC stage, surgery status, and chemotherapy for OS (all P < 0.05). We used these prognostic factors to construct nomograms. The C-indexes for OS and CSS were 0.713 and 0.741 in training cohorts and 0.714 and 0.738 in validation cohorts, respectively. The AUC and calibration plots demonstrated the good performance of both nomograms. The DCA indicated the presence of clinical net benefits in both the training and validation cohorts. Conclusion: We developed and validated nomograms for predicting OS and CSS in patients with PUC, which can help clinicians make treatment decisions. [ABSTRACT FROM AUTHOR]

• Primary urethral carcinoma is a rare malignancy, accounting for <1% of GU malignancies. • Married status independently predicted lower CSM in the entire cohort of PUC patients. • Married status was associated with lower CSM in female but not in male PUC patients. It is unknown whether married status may be associated with lower cancer-specific mortality (CSM) rates in primary urethral carcinoma (PUC) patients. To test for differences in CSM rates, according to marital status, we relied on the Surveillance, Epidemiology, and End Results (SEER) database 2000–2020. Patient (age, sex, race/ethnicity, marital status), tumor (stage, histology), and treatment (surgery, systemic therapy) characteristics of PUC patients were tabulated. Then, Kaplan–Meier plots, as well as univariable and multivariable Cox regression (MCR) models tested for differences in CSM rates according to marital status in overall cohort and then in sex-specific subgroup analyses. Of all 1,571 PUC patients, 70% were male vs. 30% female. Females were statistically significantly younger (68 vs. 73 years), more frequently unmarried (54 vs. 28%), non-Caucasian (43 vs. 24%), more frequently harbored T 3-4 N 0 M 0 (39 vs. 18%) and less frequently T 1-2 N 0 M 0 (53 vs. 69%) or T any N 1-2 M 0 /T any N any M 1 (8 vs. 13%), relative to males. Moreover, we recorded differences in histotype proportions in females vs. males (urothelial 30 vs. 64%; squamous 24 vs. 22%; adenocarcinoma 36 vs. 7%; others 10 vs. 6%) and surgical treatment (none 22 vs. 17%; excisional biopsy 22 vs. 36%; partial urethrectomy 14 vs. 16%; radical urethrectomy 42 vs. 31%). In MCR models focusing on the entire cohort, married status independently predicted lower CSM (hazard ratio [HR]:0.82; P = 0.02). Similarly, in MCR models focusing on females, married status independently predicted lower CSM (HR:0.73; P = 0.03). Conversely, in MCR models focusing on males, married status failed to independently predict lower CSM (HR:0.89; P = 0.3). Married status was associated with lower CSM in PUC patients. However, this benefit applies to female PUC patients, but not to their male counterparts. [ABSTRACT FROM AUTHOR]

Primary urethral carcinoma is a rare cancer, comprising

This male patient presented with a scrotal abscess and urinary obstruction. The patient’s history included a perineal abscess and the development of urethrocutaneous fistulae (watering-can perineum). He underwent multiple debridement procedures without resolution. During the fifth debridement for Fournier’s gangrene, a biopsy revealed invasive squamous cell carcinoma. The patient was bedridden because of the large mass, a wide en bloc resection with lymphadenectomy and reconstruction was performed revealing a large (22 cm) squamous cell carcinoma originating from the urethra. He also received palliative chemoradiotherapy and hip hemiarthroplasty. Unfortunately, he succumbed to the disease. Given the recognized relationship between inflammation and the development of cancer, it is important to entertain a differential diagnosis of cancer, especially with erosive infections. This case report highlights the all too common late presentation of urethral cancer. Interestingly, despite correction of the bedridden state with palliative surgery, the patient did not perceive an improvement in quality of life based on the FACT-G questionnaire. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate risk factors for survival in a large international cohort of patients with primary urethral cancer (PUC). Methods: A series of 154 patients (109 men, 45 women) were diagnosed with PUC in ten referral centers between 1993 and 2012. Kaplan-Meier analysis with log-rank test was used to investigate various potential prognostic factors for recurrence-free (RFS) and overall survival (OS). Multivariate models were constructed to evaluate independent risk factors for recurrence and death. Results: Median age at definitive treatment was 66 years (IQR 58-76). Histology was urothelial carcinoma in 72 (47 %), squamous cell carcinoma in 46 (30 %), adenocarcinoma in 17 (11 %), and mixed and other histology in 11 (7 %) and nine (6 %), respectively. A high degree of concordance between clinical and pathologic nodal staging (cN+/cN0 vs. pN+/pN0; p < 0.001) was noted. For clinical nodal staging, the corresponding sensitivity, specificity, and overall accuracy for predicting pathologic nodal stage were 92.8, 92.3, and 92.4 %, respectively. In multivariable Cox-regression analysis for patients staged cM0 at initial diagnosis, RFS was significantly associated with clinical nodal stage ( p < 0.001), tumor location ( p < 0.001), and age ( p = 0.001), whereas clinical nodal stage was the only independent predictor for OS ( p = 0.026). Conclusions: These data suggest that clinical nodal stage is a critical parameter for outcomes in PUC. [ABSTRACT FROM AUTHOR]

Background: To investigate the impact of perioperative chemo(radio)therapy in advanced primary urethral carcinoma (PUC). Patients and methods: A series of 124 patients (86 men, 38 women) were diagnosed with and underwent surgery for PUC in 10 referral centers between 1993 and 2012. Kaplan-Meier analysis with log-rank testing was used to investigate the impact of perioperative chemo(radio)therapy on overall survival (OS). The median follow-up was 21 months (mean: 32 months; interquartile range: 5-48). Results: Neoadjuvant chemotherapy (NAC), neoadjuvant chemoradiotherapy (N-CRT) plus adjuvant chemotherapy (ACH), and ACH was delivered in 12 (31%), 6 (15%) and 21 (54%) of these patients, respectively. Receipt of NAC/N-CRT was associated with clinically node-positive disease (cN+; P = 0.033) and lower utilization of cystectomy at surgery (P = 0.015). The objective response rate to NAC and N-CRT was 25% and 33%, respectively. The 3-year OS for patients with objective response to neoadjuvant treatment (complete/partial response) was 100% and 58.3% for those with stable or progressive disease (P = 0.30). Of the 26 patients staged ≥cT3 and/or cN+ disease, 16 (62%) received perioperative chemo(radio)therapy and 10 upfront surgery without perioperative chemotherapy (38%). The 3-year OS for this locally advanced subset of patients (≥cT3 and/or cN+) who received NAC (N = 5), N-CRT (N = 3), surgery-only (N = 10) and surgery plus ACH (N = 8) was 100%, 100%, 50% and 20%, respectively (P = 0.016). Among these 26 patients, receipt of neoadjuvant treatment was significantly associated with improved 3-year relapse-free survival (RFS) (P = 0.022) and OS (P = 0.022). Proximal tumor location correlated with inferior 3-year RFS and OS (P = 0.056/0.005). Conclusion: In this series, patients who received NAC/N-CRT for cT3 and/or cN+ PUC appeared to demonstrate improved survival compared with those who underwent upfront surgery with or without ACH. [ABSTRACT FROM AUTHOR]

Objectives: To describe and compare primary urethral carcinomas in South Taiwan with those in the USA and to explore the influence of chronic arsenic exposure. Methods: From 1988 to 2001, there were 21 pathologically proven primary urethral carcinomas diagnosed and treated at our hospital (14 males, 7 females). Seven of 14 male patients were chronically exposed to arsenic in drinking water for an average of 23 years. We compared our cases to three studies in the USA (80 males, 179 females), and analyzed the influence of chronic arsenic exposure by onset age, histology, staging, and outcome. Results: Male patients with localized tumors had better survival compared to those with advanced tumors (p = 0.0045 in males, p = 0.07 in females). In comparison to the three studies in the USA, there was an unusual higher frequency of bulbomembranous adenocarcinoma at our center (43 vs. 18%, 2 and 0%, respectively, p < 0.0001), particularly among those with chronic arsenic exposure (73 vs. 14%, p = 0.031). Conclusions: In South Taiwan, there was a high frequency of bulbomembranous urethral adenocarcinoma, which might be associated with chronic arsenic exposure. Although the implications of such an observation are minimal owing to its rarity, it is worth exploring. Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Primary urethral carcinoma is a rare cancer, comprising <1% of all malignancies. The location of this lesion presents a certain dilemma of treatment between efficacy and quality of life. We report an 84-year-old male patient, with a history of chronic hepatitis C, hypertension, and transient ischemic accident, who presented with dysuria and acute urinary retention. The intravenous urography showed mild prostatic enlargement, but no stone or filling defect was noted in the upper urinary tract. On urethrocystoscopy, multiple papillary tumors were found at the pendulous urethra, and the pathology of biopsy confirmed urothelial carcinoma. The patient was admitted, and electroresection with fulguration of urethral tumors was performed owing to the patient's old age and poor performance status. Intraurethral and intravesical chemotherapy with mitomycin C was regularly given at the outpatient clinic. Recurrent urothelial carcinomas were noted twice in the first 2 years of follow up, and repeated transurethral resections were done. Unfortunately, liver cirrhosis with hepatocellular carcinoma was diagnosed last June, for which he received transcatheter arterial chemoembolization. No recurrence of urethral cancer has been found on semiannual cystoscopy in the past 3 years. Penile-preserving surgery is a reasonable surgical option for elderly primary urethral carcinoma patients with acceptable oncological outcome and good quality of life. [ABSTRACT FROM AUTHOR]

Primary urethral carcinoma is a rare oncologic condition with limited data to support organ-sparing therapies. Herein, we present a case of primary urethral squamous cell carcinoma in situ of the bulbar urethra treated with intraurethral 5-fluorouracil (5-FU) who exhibited a complete pathologic response observed at the time of dismembered urethroplasty. The clinical features, diagnosis, and treatment course of our case are reviewed. These data may support the use of intraurethral 5-FU for similar cases in the future.

Context: Primary urethral cancer (PUC) is a rare cancer entity. Owing to the low incidence of this malignancy, the main body of literature consists mainly of case reports, making evidence-based management recommendations difficult., Objective: To review reported disease management strategies of PUC and their impact on oncological outcomes., Evidence Acquisition: A systematic research was performed according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement using Medline, Scopus, and Web of Science, to find studies of the past 10yr including ≥20 patients, and investigating treatment strategies and their impact on outcomes of the three most frequent histologies: urothelial carcinoma, adenocarcinoma, and squamous cell carcinoma., Evidence Synthesis: In localized PUC, penis-sparing surgery can be performed in males, while in females, complete urethrectomy with surrounding tissue is advised to minimize recurrence due to positive margins. Radiotherapy (RT) has worse survival and recurrence rates, as well as more adverse effects, than surgery, limiting its use in genital-preserving therapy. Locally advanced PUC should be treated with multimodal therapy, as monotherapies result in inferior recurrence and survival rates. Extent of surgery is still undecided, favoring radical cyst(oprostat)ectomy with total urethrectomy (RCU). Lymph node involvement is a predictor of survival, highlighting the role of lymph node dissection for disease control and staging. RT can improve survival in combination with surgery and/or chemotherapy (CHT). Neoadjuvant platinum-based CHT can improve overall and recurrence-free survival. At recurrence, salvage therapy with surgery and/or CHT can improve survival. Superficial urothelial carcinoma of the prostatic urethra can be treated with transurethral resection. Stromal invasion often features concomitant bladder cancer with a poor prognosis and requires RCU with or without systemic preoperative CHT., Conclusions: PUC is a rare malignancy with an often poor natural course, requiring a stage- and gender-specific risk-based treatment strategy. The role of systematic perioperative CHT and the extent of surgery are becoming more important., Patient Summary: In this review, we looked at the treatment options for primary urethral cancer. We found that while an organ-confined disease can be managed with local resection, growth beyond the organ border makes a combination of different treatment modalities, such as surgery and systematic chemotherapy, necessary to improve outcomes., (Copyright © 2019 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

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. [ABSTRACT FROM AUTHOR]