Primary tumor surgery improves survival in non-metastatic primary urethral carcinoma patients: a large population-based investigation.

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.

A Contemporary Analysis of Urethral Recurrence following Radical Cystectomy.

PURPOSE: Oncologic outcomes following urethral recurrence (UR) remain incompletely described, with reports limited by small cohort sizes. We evaluated risk factors for UR as well as cancer-specific survival (CSS) and overall survival (OS) among patients with UR. MATERIALS AND METHODS: We reviewed our institutional radical cystectomy (RC) registry to identify patients with UR. Cox proportional hazards regression was used to assess risk factors for UR. Kaplan-Meier and Cox models were used to assess the relationship between UR and CSS/OS as well as to compare outcomes following symptomatic vs asymptomatic presentation of UR. RESULTS: Overall, 2,930 patients underwent RC from 1980 to 2018, with a median postoperative followup of 7.1 years (IQR 2.8-13.1), of whom 144 (4.9%) were subsequently diagnosed with UR. Carcinoma in situ (HR 1.98, 95% CI 1.30-3.04), multifocal disease (HR 1.59, 95% CI 1.07-2.36) and prostatic urethral involvement at RC (HR 3.01, 95% CI 1.98-4.57) were associated with increased risk of UR. UR was associated with decreased CSS (HR 7.30, 95% CI 5.46-9.76) and OS (HR 1.86, 95% CI 1.54-2.24). A total of 63/144 patients were diagnosed with UR based on symptoms, while 104/144 patients with UR underwent urethrectomy. Patients with symptomatic UR had higher tumor stage at urethrectomy (≥pT2 in 13.1% vs 3.1%, p=0.007), while patients with asymptomatic UR experienced longer median CSS (12.1 vs 6.1 years) and OS (8.30 vs 4.82 years; p=0.05 for both). CONCLUSIONS: We identified pathological risk factors for UR after RC and report adverse subsequent survival outcomes for these patients. Presentation with symptomatic UR was associated with higher tumor stage and poorer prognosis, supporting a value to continued urethral surveillance after RC.

Incidence rates and contemporary trends in primary urethral cancer.

PURPOSE: We assessed contemporary incidence rates and trends of primary urethral cancer. METHODS: We identified urethral cancer patients within Surveillance, Epidemiology and End Results registry (SEER, 2004-2016). Age-standardized incidence rates per 1,000,000 (ASR) were calculated. Log linear regression analyses were used to compute average annual percent change (AAPC). RESULTS: From 2004 to 2016, 1907 patients with urethral cancer were diagnosed (ASR 1.69; AAPC: -0.98%, p = 0.3). ASR rates were higher in males than in females (2.70 vs. 0.55), respectively and did not change over the time (both p = 0.3). Highest incidence rates were recorded in respectively ≥75 (0.77), 55-74 (0.71) and ≤54 (0.19) years of age categories, in that order. African Americans exhibited highest incidence rate (3.33) followed by Caucasians (1.72), other race groups (1.57) and Hispanics (1.57), in that order. A significant decrease occurred over time in Hispanics, but not in other race groups. In African Americans, male and female sex-stratified incidence rates were higher than in any other race group. Urothelial histological subtype exhibited highest incidence rate (0.92), followed by squamous cell carcinoma (0.41), adenocarcinoma (0.29) and other histologies (0.20). In stage stratified analyses, T1N0M0 stage exhibited highest incidence rate. However, it decreased over time (-3.00%, p = 0.02) in favor of T1-4N1-2M0 stage (+ 2.11%, p = 0.02). CONCLUSION: Urethral cancer is rare. Its incidence rates are highest in males, elderly patients, African Americans and in urothelial histological subtype. Most urethral cancer cases are T1N0M0, but over time, the incidence of T1N0M0 decreased in favor of T1-4N1-2M0.

The epidemiology and role of surgery in the treatment of urethral clear cell carcinoma.

PURPOSE: To perform a retrospective analysis of the epidemiology and role of surgery on survival in patients with urethral clear cell carcinoma (UCCC) using the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database. METHODS: UCCC cases diagnosed from January 1, 1973, to December 31, 2014, were extracted from SEER. Descriptive statistics were calculated for all variables. Univariate analysis to assess for differences in survival with respect to covariates was performed using the log-rank test. Multivariate analysis was performed with Cox proportional hazards regression models to determine the predictive performance of covariates with respect to overall survival (OS) and disease-specific survival (DSS), reported as hazard ratio (HR) with 95% CIs. Comparisons were considered statistically significant at P < 0.05. RESULTS: Sixty-one cases were extracted for analysis. Mean age ± SD was 63.0 ± 13.9 years. Fifty (82%), 18 (29.5%), and 14 (23.0%) patients underwent surgery, radiation, and chemotherapy, respectively. On univariate analysis, the following covariates were associated with both OS and DSS: age, stage, and surgery (all P < 0.001). On multivariate analysis, surgery was a predictor for improved OS and DSS (HR, 0.178; 95% CI [0.068; 0.464]) and HR, 0.166; 95% CI [0.057; 0.484], respectively). Neither radiation nor chemotherapy was significantly associated with OS or DSS. CONCLUSION: Surgery was associated with improved OS and DSS in patients with UCCC. While neither radiation nor chemotherapy was significantly associated with survival, additional studies are necessary to determine how these therapeutic interventions may impact prognosis.

Ultrastructural Analysis of Urethral Polyps against the Background of Urogenital Infection.

We performed an electron microscopic study of samples of urethral polyps obtained from 90 women (mean age 52.5±4.9 years). According to PCR and culture studies, the most common infectious agent in patients with urethral polyps is U. urealyticum (100% cases). In 70% cases, this infectious agent was present as monoinfection, of these, clinically significant concentration (>106 CFU/ml) were found in 53.3% cases. In 30% cases, associations with C. trachomatis, T. vaginalis, and M. genitalium were found. We observed significant ultrastructural heterogeneity of the epithelial cells in urethral polyps, which manifested in a combination of hyperplastic and metaplastic changes and signs of cytodestruction. Detection of mycoplasma-like bodies in connective tissue mononuclear cells and viral particles in epithelial cells during ultrastructural study, including cases with negative PCR results, indicates the pathogenetic role of latent infection in the formation of urethral polyps.

Positive Pre-cystectomy Biopsies of the Prostatic Urethra or Bladder Neck Do Not Necessarily Preclude Orthotopic Bladder Substitution.

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.

Lichen Sclerosus Accompanied by Urethral Squamous Cell Carcinoma: A Retrospective Study From a Urethral Referral Center.

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.

Female Urethra Adenocarcinoma.

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.

Frequency of a positive family history of colorectal cancer in general practice: a cross-sectional study.

BACKGROUND: Evidence on the frequency of a positive family history of colorectal cancer (CRC) among individuals aged <55 years is lacking. General practice setting might be well suited for the identification of individuals in this above-average risk group. OBJECTIVE: To determine the frequency of a reported positive family history of CRC among patients aged 40 to 54 years in a general practice setting. METHODS: We conducted a cross-sectional study in 21 general practices in Germany. Patients aged 40 to 54 years were identified by means of the practice software and interviewed by health care assistants using a standardized four-item questionnaire. Outcome was occurrence of a positive family history of CRC, defined as at least one first-degree relative (FDR: parents, siblings, or children) with CRC. Further measurements were FDRs with CRC / colorectal polyps (adenomas) diagnosed before the age of 50 and occurrence of three or more relatives with colorectal, stomach, cervical, ovarian, urethel or renal pelvic cancer. RESULTS: Out of 6723 participants, 7.2% (95% confidence interval [CI] 6.6% to 7.8%) reported at least one FDR with CRC and 1.2% (95% CI 0.9% to 1.5%) reported FDRs with CRC diagnosed before the age of 50. A further 2.6% (95% CI 2.3% to 3.0%) reported colorectal polyps in FDRs diagnosed before the age of 50 and 2.1% (95% CI 1.8% to 2.5%) reported three or more relatives with entities mentioned above. CONCLUSION: One in 14 patients reported at least one FDR with CRC. General practice should be considered when defining requirements of risk-adapted CRC screening.

Systematic Review on the Fate of the Remnant Urothelium after Radical Cystectomy.

CONTEXT: Urothelial carcinoma is considered a pan-urothelial disease. As such, the remnant urothelium in the upper urinary tract and urethra following radical cystectomy (RC) remains at risk for secondary urothelial tumors (SUTs). OBJECTIVE: To describe the incidence, diagnosis, treatment, and outcomes of patients with SUTs after RC. EVIDENCE ACQUISITION: A systematic search was conducted using PubMed database according to Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines to identify studies between 1970 and 2016 reporting on malignant diseases of the urothelium after RC for bladder cancer. The search strategy separated between upper and lower tract urothelial tumors. EVIDENCE SYNTHESIS: Of a total of 1069 studies, 57 were considered for evidence synthesis. SUTs occured in approximately 4-10% of patients after RC. Carcinoma in situ of the bladder, a history of nonmuscle invasive bladder cancer, and tumor involvement of the distal ureter are the strongest risk factors for secondary upper tract tumors. Risk factors for secondary urethral tumors represent urothelial malignancy in the prostatic urethra/prostate and bladder neck (in women), nonorthotopic diversions, and positive findings on permanent sections. The majority of patients (84%) with SUTs, presented with urothelial recurrence without evidence of metastasis. Of those, 84.0% were treated with surgery, 10.5% with systemic chemotherapy and/or radiotherapy, and 5.6% with topical chemotherapy and/or immunotherapy. After a median follow-up of 91 mo (range: 26-155), 65.9% of patients died of disease and 21.5% died of other causes. Detection and treatment of SUTs at an asymptomatic stage can reduce the risks of cancer-specfific and overall mortality by 30%. A limitation of the study is that the available data were retrospective. CONCLUSIONS: SUTs are rare oncological events and most patients have an adverse prognosis despite absence of distant disease at diagnosis. Therefore, surveillance of the remnant urothelium should be implemented for patients with histological features of panurothelial disease as it may improve timely detection and treatment. PATIENT SUMMARY: Secondary tumors of the renal pelvis, ureters, and urethra occur in approximately 4-10% of patients after radical removal of the bladder for bladder cancer. These patients' prognoses are reduced, likely due to delayed diagnosis. Therefore, routine surveillance might be important to detect tumors at an early stage.

Association between selected dietary scores and the risk of urothelial cell carcinoma: A prospective cohort study.

Studies investigating the association of food and nutrient consumption with the risk of urothelial cell carcinoma (UCC) have produced mixed results. We used three common dietary scores, the Mediterranean Diet Score (MDS), the Alternate Healthy Eating Index 2010 (AHEI-2010) and the Dietary Inflammatory Index (DII) to assess the evidence of an association between diet and the risk of UCC. Over a median follow-up time of 21.3 years, 379 incident UCC cases were diagnosed. Dietary scores were calculated using data from a 121-item food frequency questionnaire administered at baseline. We used Cox models to compute hazard ratios (HR) for the association between dietary scores (per one standard deviation) and UCC risk. In order to reflect overall adherence to a healthy diet, a metascore was constructed by summing the quintiles of each of the three scores. None of the dietary scores was associated with the risk of UCC overall. A healthier diet was found to be inversely associated with the risk of invasive (MDS: HR = 0.86, 95% CI: 0.74-1.00, metascore: HR = 0.84, 95% CI: 0.71-0.98), but not superficial disease (heterogeneity between subtypes p = 0.04 and p = 0.03, respectively). Results were consistent but weaker for the DII and the AHEI-2010. We found some evidence of effect modification by smoking, in particular for the metascore (Current: HR = 0.77, 95% CI: 0.58-1.01, Former: HR = 0.77, 95% CI: 0.64-0.92, Never: HR = 1.01, 95% CI: 0.81-1.26, p for heterogeneity = 0.05). A healthy diet may be protective against the risk of invasive, but not superficial, UCC. Promoting healthy dietary habits may help lower the risk of invasive UCC, especially for current and former smokers.

Patterns, risks and outcomes of urethral recurrence after radical cystectomy for urothelial cancer; over 20 year single center experience.

PURPOSE: To evaluate the factors affecting urethral recurrence after radical cystectomy for bladder cancer and relationship between urinary diversion type and urethral recurrence rates. PATIENTS AND METHODS: In our 504 radical cystectomy series, 287 male patients whose final pathological were urothelial carcinoma were included in the study. The relationship between urethral recurrence and pathological stage, grade, lymph node involvement and diversion type was researched in addition to risk factors for urethral recurrence. RESULTS: A Total of 287 patients. Orthotopic continent urinary diversion (OCD) and ileal conduit (IC) was performed after radical cystectomy in 141 (49.1%) and 146 (50.9%) patients respectively. Urethral recurrence was observed in 11 (3.8%) patients and urethral recurrence rates in OCD and IC groups were 1.4% and 6.2% (p=0.034). Pathological stages of recurrent patients were 2 pT1, 1 pT2 and 8 pT4 respectively (p<0.001). Urethral recurrence was significantly lower in OCD group when compared to IC group (p=0.036). When all parameters were analyzed using Cox multivariate regression analysis, the most important factor that affects urethral recurrence was pathological T stage (p<0.001). Risk factors for urethral recurrence were present in 92 patients. Urethral recurrence rates in patients with and without risk factors were 8.69% and 1.53% (p<0.01). CONCLUSIONS: In this study, pathological stage was found to be the most important factor affecting urethral recurrence and prostatic stromal invasion was an important prognostic factor in these cases. Although risk factors for urethral recurrence were similar in both groups, urethral recurrence rates were significantly lower in OCD group when compared to IC group.

Management of advanced primary urethral carcinomas.

Primary urethral carcinoma (PUC) is a rare malignancy accounting for <1% of genitourinary cancers, with a predilection for men and African-Americans. The sites and histology of urethral carcinoma vary by gender and anatomical location. Squamous cell carcinoma is most common among both genders but adenocarcinomas are noted in 15-35% of cases among women. Obstructive or irritative symptoms and haematuria are common modes of presentation. Clinical evaluation includes cystourethroscopy with biopsy and examination under anaesthesia. Magnetic resonance imaging provides a highly effective method to image the primary tumour while defining the potential involvement of surrounding structures. Most tumours are localised, with regional metastases to nodal sites seen in up to 30% of cases in both genders, while distant metastases at presentation are rare (0-6%), but occur in up to 40% of cases with recurrent disease. Among men, the two most important prognostic factors are disease location and stage. Low-stage tumours (T1-2) and tumours involving the fossa navicularis or the penile urethra have a better prognosis than higher stage tumours (>T2 or N+) and lesions involving the bulbomembranous urethra. In women, in addition to stage and location, the size of the tumour has also prognostic implications. While surgery and radiation therapy (RT) are of benefit in early stage disease, advanced stage PUC requires multimodal treatment strategies to optimise local control and survival. These include induction chemotherapy followed by surgery or RT and concurrent chemoradiation with or without surgery. The latter strategy has been used successfully to treat other human papillomavirus-related cancers of the vagina, cervix and anus and may be of value in achieving organ preservation. Given the rarity of PUC, prospective multi-institutional studies are needed to better define the optimal treatment approach for this disease entity.

Follow-up after radical cystectomy based on patterns of tumour recurrence and its risk factors.

CONTEXT: Following cystectomy, approximately 50% of patients will present tumour recurrence. A recurrence may be local, systemic or occur in the urethra or upper urinary tract. OBJECTIVE: To analyse the characteristics, risk factors and outcomes of patients with tumour recurrence following cystectomy so as to subsequently propose a cancer follow-up protocol. ACQUISITION OF EVIDENCE: Analysis of original articles and reviews related to tumour recurrence and follow-up after radical cystectomy for urothelial tumour. Articles were obtained from Pubmed searches. SUMMARY OF THE EVIDENCE: Systemic and local recurrences following cystectomy appear in 20%-35% and 5%-15% of cases, respectively. Some 80%-90% are diagnosed in the first 3 years, with the majority concentrated in the first 24 months. Common factors related to an increased risk of local and systemic recurrence are a pathologic stage ≥pT3, the presence of positive margins and the extension of the lymphadenectomy. The incidence of recurrence in the upper urinary tract and urethra is 2%-6% and 4%-6%, respectively. Both types of recurrence may appear late and share risk factors such as signs of multifocal disease, a history of non-muscle-invasive bladder cancer, multiplicity, presence of ISC, urinary tract tumours and prostatic urethral tumours. Tumours in the distal ureteral cystectomy specimen and tumours in the prostatic urethra are also risk factors related to the appearance of tumours in the urinary tract and urethra, respectively. CONCLUSION: Understanding the natural history of urothelial bladder carcinoma and the risk factors related to the appearance of tumour recurrence following cystectomy are essential for designing an appropriate follow-up protocol. The follow-up of patients with risk factors for local or systemic recurrence will achieve maximum efficiency during the first 3 years. The follow-up should be extended for patients with risk factors for presenting upper urinary tract or urethral tumours.

Risk assessment of upper tract urothelial carcinoma related to aristolochic acid.

BACKGROUND: Aristolochic acid is a toxin found in plants of the genus Aristolochia, to which humans can be exposed either through certain Chinese herbal medicines or through inadvertent commingling with food crops. Our objective was to estimate cumulative exposures of aristolochic acid associated with increased risk of end-stage renal disease (ESRD), and to conduct a systematic review and meta-analysis on aristolochic acid-induced upper tract urothelial carcinoma (UUC). METHODS: Using epidemiologic studies on aristolochic acid-related disease from multiple different regions of the world, a systematic review was conducted in which relative risks (RR), HRs, and ORs were derived or extracted directly, and a meta-analysis was conducted. One study was used to estimate a benchmark dose lower confidence limit (BMDL) for aristolochic acid-related ESRD. RESULTS: Mean values for risk ratios, ORs, RRs, or HRs, of UUC caused by aristolochic acid ranged from 1 to 49. A meta-analysis of these studies resulted in a pooled OR of 5.97 [95% confidence interval (CI), 2.78-12.84] for this aristolochic acid-related cancer. The obtained BMDL for aristolochic acid-related ESRD was 0.42 g cumulative aristolochic acid exposure. CONCLUSIONS: Aristolochic acid exposure is significantly associated with an increased risk of UUC, and there is a dose-dependent relationship between cumulative aristolochic acid exposure and ESRD risk. IMPACT: Individuals who use certain Chinese herbal medicines may significantly increase their risk of developing UUC and/or ESRD, as would individuals who are inadvertently exposed to aristolochic acid through commingling of Aristolochia plants with harvested food crops.

Primary urethral carcinoma in females: an epidemiologic study on demographical factors, histological types, tumour stage and survival.

PURPOSE: To obtain insight into demographical factors, histology and survival rates of females diagnosed with primary urethral cancer and to determine favourable treatment. METHODS: Data from 91 females with primary urethral carcinoma, age varying from 15 to 85 years, registered between 1989 and 2008 at the National Cancer Registry of the Netherlands were used for this study. Demographical factors, incidence rate, morphology and tumour stage according to TNM classification were analysed. Kaplan-Meier survival curves were constructed and stratified by stage, histological type and treatment modality. RESULTS: The overall crude annual incidence was 0.7 per million women with a peak incidence in the age group of 80-84 years. Analysis of the morphology showed urothelial cell carcinoma (UCC) in 45 %, squamous cell carcinoma (SCC) in 19 %, adenocarcinoma (AC) in 29 %, and unknown or undifferentiated carcinoma accounted for 6 %. Almost half of patients (46 %) had advanced disease at time of diagnosis and was mainly treated with surgery and/or radiotherapy. The 5-year survival rates of stage 0-II, stage III and stage IV were 67, 53 and 17 %, respectively. The 5-year survival rates of SCC, UCC and AC were 64, 61 and 31 %, respectively. CONCLUSIONS: Female primary urethral carcinoma is a rare condition, and the majority of patients were aged above 65 years. Almost half of patients have advanced disease upon diagnosis. TNM stage and histological type of disease are the most determining factors for survival. Extended surgery with or without radiotherapy seems to be the most favourable treatment. Awareness and early diagnosis are important to improve survival.

Melanoma of the female urethra.

Primary melanoma of the female urethra is a very rare malignant tumor with high mortality. Due to its rarity, there are no guidelines and recommendations on the diagnosis and treatment of such patients, so we aimed to review the reported cases and case series, their treatment, and outcome. We searched through PubMed for all articles reporting on female urethral melanoma. We found 73 articles (case reports and case series) reporting on 112 patients. There are no clinical trials on the topic due to the rarity of the condition. Median patient age at presentation is 68 years. Due to the late presentation, the prognosis of the disease is poor, and median survival is 16 months, with 5-year survival in around 10 % (12 reported patients). Regarding treatment, most authors use either less radical approach (partial or total urethrectomy) or radical approach (anterior pelvic exenteration). We found no evidence that either of the treatment modalities results with higher survival. In local excision, there are indications that margins less than 2-2.5 cm result in high percentage of local recurrence suggesting that resection width should be at least 2.5 cm. For localized urethral melanoma, local resection with margins of 2.5 cm can be recommended and there is no foundation to support radical surgery in such patients. Chemotherapy and immunotherapy can also recommend. For locally advanced disease, the prognosis is poor, and radical surgery will not improve survival significantly.

Urethral cancer.

Urethral carcinoma is a rare tumor with predominantly poor survival. Both the disease and its treatment can affect both sexual and urinary function. The natural history of urethral carcinoma varies, therefore the appropriate application of surgery, radiation, and chemotherapy remain unknown. Management of this disease remains driven by individual clinician experience and data derived from small case series. This article discusses the histology and anatomy of the male and female urethra, as well as their natural history. In addition, the epidemiology, clinical presentation, diagnosis, staging, treatment, and future directions of management of cancer arising in the urethra are addressed.

A clinicopathologic study of gynecologic organ involvement at radical cystectomy for bladder cancer.

OBJECTIVE: To report the clinicopathologic analysis of women who underwent radical cystectomy for bladder cancer in Egypt from 1997 to 2005. METHODS: Clinicopathologic data for 250 women who underwent radical cystectomy for bladder cancer at 3 centers in Cairo were retrospectively reviewed from hospital charts and pathology sheet records. Cystectomy specimens were evaluated pathologically for involvement of internal genitalia. RESULTS: The uterus was not available for histopathologic examination in 11 specimens; 1 ovary was absent from 18 specimens; and both ovaries were absent from 2 specimens. Uterine involvement was observed in 1 case of transitional cell carcinoma. Benign uterine pathology was detected in 25 cases. All patients had normal ovaries, and the vagina was involved in 11 cases. There was urethral involvement in 10% of patients. Of the 50 patients available for follow-up, 11 had 1 ovary preserved and 2 had the uterus plus both ovaries preserved. None of them experienced late ovarian or uterine recurrence. CONCLUSION: Involvement of female internal genitalia in bladder cancer is uncommon. Thus, preservation of these organs in young women undergoing radical cystectomy should be considered in selected cases after careful preoperative assessment.